ABSTRACT BOOK 22ND ANNUAL MEETING

Gaylord National on the Potomac WASHINGTON, DC SEPTEMBER 21-24, 2011

Also includes: • Disclosures for all presenters • Speakers’ learning objectives and recommended reading What happens in DC doesn’t have to stay in DC

The webcast of the 2011 NAMS Annual Meeting lets you take advantage of the meeting’s educational riches year-round, at your convenience.

If you miss part of the meeting or just want to revisit some sessions, this free on-demand webcast is your answer. The webcast will capture all plenary sessions as well as the Pre-Meeting Symposium and let you select individual presentations for targeted viewing. It will be freely available to all through September 15, 2012. It’s a great way to reinforce your learning at your leisure and according to your schedule.

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Webcast2011_PreLaunch_Sidebar.indd 1 8/16/11 9:43 AM Contents

Key to Abstracts ...... 4

Invited Speakers’ Abstracts & Learning Objectives ...... 7

Scientific Session Speakers’ Abstracts ...... 32

Basic Science Poster Presentations ...... 40

Clinical Poster Presentations ...... 44

Disclosure Statement...... 67

Key to Disclosures ...... 68

Disclosures ...... 69

Invited Speakers’ Recommended Reading ...... 73

Call for Abstracts 2012 Annual Meeting . . . . . Inside Back Cover

3 Key to Abstracts

Invited Speakers’ Abstracts Scientific Session Speakers’ Abstracts Speakers Page # Speakers Page #

David F . Archer, MD, NCMP ...... 19 Susan E . Appt, DVM ...... 38 Raquel D . Arias, MD ...... 15 David F . Archer, MD, NCMP ...... 38 Gloria A . Bachmann, MD ...... 39 Lauren L . Drogos, MA...... 39 Herbert Benson, MD ...... 31 Kristine Ensrud, MD, MPH...... 36 Janet S . Carpenter, PhD, MSN, FAAN ...... 27 Hadine Joffe, MD, MSc ...... 37 Susan R . Davis, MBBS, FRACP, PhD ...... 26 Matthew Jorgensen, PhD ...... 34 Kristine Ensrud, MD, MPH ...... 27 Kristijan Kahler, PhD, RPh ...... 33 Murray A . Freedman, MS, MD ...... 14 Sobia Khan, MD, NCMP ...... 35 Ellen W . Freeman, PhD ...... 27 Antonio Lombardi, MD ...... 34 Steven R . Goldstein, MD, FACOG, CCD, NCMP ...... 7 Santiago Palacios, MD, PhD ...... 34 Martha Gulati, MD, MS, FACC, FAHA ...... 17 Barbara Parry, MD ...... 37 Steven T . Harris, MD, FACP ...... 23 JoAnn V . Pinkerton, MD, NCMP ...... 32 Candace J . Heisler, JD ...... 29 Hadine Joffe, MD, MSc ...... 12 JoAnn V . Pinkerton, MD, NCMP ...... 36 Ann E . Kearns, MD, PhD ...... 22 David J . Portman, MD ...... 33 Andrea Z . LaCroix, PhD ...... 27 Susan Reed, MD, MPH ...... 33 Gail A . Laughlin, PhD ...... 25 Peter F . Schnatz, DO, FACOG, FACP, NCMP ...... 35 Robert Lindsay, MBChB, PhD, FRCP ...... 24 James A . Simon, MD, CCD, NCMP, FACOG ...... 36 Emma A . Meagher, MD ...... 18 Claudio N . Soares, MD, PhD, FRCPC ...... 39 Alec J . Megibow, MD, MPH, FACH ...... 9 Mary A . Tagliaferri, MD, LAc ...... 38 Mary Jane Minkin, MD, FACOG, NCMP ...... 21 Masakazu Terauchi, MD, PhD ...... 37 Monica Morrow, MD, FACS ...... 8 Rebecca C . Thurston, PhD ...... 32 Lori J . Mosca, MD, MPH, PhD ...... 16 Rebecca C . Thurston, PhD ...... 38 Thomas H . Murray, PhD ...... 28 Michelle P . Warren, MD, NCMP ...... 32 Lila E . Nachtigall, MD, NCMP ...... 39 Miriam T . Weber, PhD ...... 37 Teri B . Pearlstein, MD ...... 13 Susan D . Reed, MD, MPH ...... 27 William E . Reichman, MD ...... 20 James A . Simon, MD, CCD, NCMP, FACOG ...... 19 Patricia M . Speck, DNSc, APN, FNP-BC, ...... 29 DF-IAFN, FAAFS, FAAN Patricia J . Sulak, MD ...... 30 Jonathan L . Tilly, PhD ...... 10

4 In addition to the abstracts accepted for presentation in a Scientific Session, the following abstracts were accepted for poster presentation . These abstracts are eligible for the 2011 NAMS Poster Prizes . The poster numbers listed below correspond with the numbers on the posters displayed at the meeting .

Basic Science Presentations Clinical Presentations Presenting Author Abstract # Poster # Page # Presenting Author Abstract # Poster # Page #

Jan Bohuslav, PhD 1113741 P-1 40 Lucy Abraham 1174677 P-19 44 Hoon Choi, MD 1113942 P-2 40 Wafa R . Al Omari, MD, FRCOG 1173365 P-20 44 Steriani Elavsky, PhD 1116853 P-3 40 Jose Mendes Aldrighi, MD, PhD 1116801 P-21 45 William Fisher, MA 1115666 P-4 40 Jose Mendes Aldrighi, MD, PhD 1116836 P-22 45 William Fisher, MA 1115702 P-5 41 Jose Mendes Aldrighi, MD, PhD 1116814 P-23 45 Tak Kim, MD, PhD 1174347 P-6 41 David F . Archer, MD, NCMP 1114448 P-24 45 Seung-Yup Ku, MD, PhD, NCMP 1116783 P-7 41 David F . Archer, MD, NCMP 1115729 P-25 46 Felicia Ojo, MPH 1090224 P-8 41 Gloria A . Bachmann, MD 1116365 P-26 46 Sophie Pettit 1174581 P-9 41 Jessica P . Brown, PhD 1116525 P-27 46 Peter F . Schnatz, DO, FACOG, 1115113 P-10 42 Carol A . Caico, PhD, OGNP, NCMP 1069444 P-28 47 FACP, NCMP Mindy S . Christianson, MD 1107766 P-29 47 Peter F . Schnatz, DO, FACOG, 1115034 P-11 42 Craig Crandall, PhD 1170986 P-30 47 FACP, NCMP Lori A . Cray, PhD 1116468 P-31 47 Sonali Shah, MBA, MS, RPh 1108042 P-12 42 Sue E . Dasen, MS 1115259 P-32 48 Jose M . Soares, Jr ., MD, PhD 1116545 P-13 43 Lino Del Pup, MD 1093993 P-33 48 Regina Teixeira Gomes, PhD 1114259 P-14 43 Catherine E . Doyle, RN, BScN, 1112361 P-34 48 Regina Teixeira Gomes, PhD 1114827 P-15 43 CON(C), NCMP Regina Teixeira Gomes, PhD 1114818 P-16 44 Cindy M . Duke, BS, MS, MD, PhD 1169466 P-35 48 Carina Verna, MD 1114834 P-17 44 Robert R . Freedman, PhD 1113686 P-36 49 Carina Verna, MD 1114991 P-18 44 Margery L .S . Gass, MD, NCMP 1114850 P-37 49 Linda M . Gerber, PhD 1114740 P-38 49 Carolyn Gibson, MPH, MS 1174016 P-39 50 Miguel Gonzales-Izquierdo, MD 1171889 P-40 50 Miguel Gonzales-Izquierdo, MD 1171910 P-41 50 Vaidyanathan Gowri, MD 1165079 P-42 50 Rhoda Jamadar 1162971 P-43 51 Xuezhi Jiang, MD 1115042 P-44 51 Roksana Karim, MBBS, PhD 1116777 P-45 51 JangHeub Kim, MD 1173593 P-46 52

5 Key to Abstracts (continued)

Clinical Presentations Clinical Presentations Presenting Author Abstract # Poster # Page # Presenting Author Abstract # Poster # Page #

Michael Krychman, MD 1111965 P-47 52 Rekha M . Sathyanarayana, 1114106 P-76 60 MT (ASCP) Seung-Yup Ku, MD, PhD, NCMP 1112933 P-48 52 Lynnette Leidy Sievert, PhD 1116856 P-77 60 Ji Young Lee 1113943 P-49 52 Tasneem Siyam, BSc, Pharm 1115490 P-78 60 Sonia Maria Rolim Lima, MD, PhD 1122444 P-50 53 Michael C . Snabes, MD, PhD 1174650 P-79 61 Sonia Maria Rolim Lima, MD, PhD 1122461 P-51 53 Claudio N . Soares, MD, 1115616 P-80 61 Sara E . Looby, PhD, ANP 1173773 P-52 53 PhD, FRCPC Ricardo V . Maamari, MD, NCMP 1114478 P-53 53 Claudio N . Soares, MD, 1175107 P-81 61 Wendy L . Marsh, MD, MS 1165714 P-54 54 PhD, FRCPC Kelsey E . Mills, HBSc, MD 1116753 P-55 54 Claudi N . Soares, MD, 1116464 P-82 61 PhD, FRCPC Alvaro Monterrosa-Castro 1114136 P-56 54 Lily Stojanovska, BSc, MSc, PhD 1116639 P-83 62 Alvaro Monterrosa-Castro 1114143 P-57 54 Lily Stojanovska, BSc, MSc, PhD 1116643 P-84 62 Laura Moral 1114222 P-58 55 Cynthia A . Stuenkel, MD, NCMP 1115171 P-85 62 Lila E . Nachtigall, MD, NCMP 1170180 P-59 55 Sandra Teixeira 1079511 P-86 62 Eliana Aguiar Petri Nahas, MD 1113743 P-60 55 de Araujo Moraes, MD, PhD Belal Naser, MD 1114933 P-61 56 Sandra Teixeira 1087056 P-87 63 de Araujo Moraes, MD, PhD Katherine M . Newton, PhD, RN 1116563 P-62 56 Sandra Teixeira 1087048 P-88 63 Katherine M . Newton, PhD, RN 1116793 P-63 56 de Araujo Moraes, MD, PhD Alice I . Nichols, PhD 1115235 P-64 56 Kristi A . Tough, MD, NCMP 1163153 P-89 63 Betania Ogando 1116781 P-65 57 Shigeto Uchiyama 1116613 P-90 64 Marcia A . Padua, MD 1115051 P-66 57 Tomomi Ueno 1116615 P-91 64 JoAnn V . Pinkerton, MD, NCMP 1115721 P-67 57 Maria S . Velasco, MD 1112387 P-92 64 David J . Portman, MD 1114310 P-68 57 Maria S . Velasco, MD 1116767 P-93 65 Beth A . Prairie, MD, MPH 1157930 P-69 58 Michelle P . Warren, MD, NCMP 1116010 P-94 65 Beth A . Prairie, MD, MPH 1169825 P-70 58 Catherine J . Wheeler, MD 1164772 P-95 65 Josiane Rocha 1116704 P-71 58 Catherine J . Wheeler, MD 1172778 P-96 65 Josiane Rocha 1116776 P-72 59 Jennifer Whiteley, EdD, MSc, MA 1114622 P-97 66 Josiane Rocha 1116732 P-73 59 Mariano Zacarias-Flores, MD 1116743 P-98 66 Patricia A . Rouen, PhD, FNP 1115258 P-74 59 Jacqueline Zummo, MS, 1115017 P-99 66 Jae Hong Sang, MD 1114916 P-75 59 MPH, MBA

6 The Increased Sensitivity of Transvaginal Ultrasound: Do We See Too Much? Steven R. Goldstein, MD, FACOG, CCD, NCMP. Obstetrics & Gynecology, New York University School of Medicine, New York, NY

The ascertainment of diagnostic medical information through most of the 20th Century relied on techniques like inspection, palpation, and auscultation as noninvasive ways to obtain information about internal anatomy, both normal and abnormal, as well as physiology which when not normal we call “pathology”. Sensitivity of imaging modalities has become so refined that we are seeing structures either never before appreciated or sometimes appreciated but not with such precision. This lecture will deal with my observations of this issue in gynecology using transvaginal ultrasound (TV U/S), although the problems associated with increased sensitivity of imaging exist in many other clinical fields as well. My thesis is that as we see more and more detail the response to what we see has often been based on old and thus preconceived notions, and not on newer well-organized and well-designed studies to Speakers’ Abstracts & Learningdetermine the Objectives prevalence of particular findings and their clinical significance. Information obtained with increasingly refined technology cannot simply be handled according to old established principles. Newer studies must be made before clinical recommendations can be made. We must be careful not to over interpret such findings that may be much more common and less ominous Plenary Symposiumthat previously #1 believed. The vaginal probe has revolutionized gynecology. Higher frequency probes in close proximity to the structure being studied have created a degree of image magnification that is as if we are doing Presidential Symposium—“Incidental Findingsultrasound through on Imaging: a low power microscope Friend (sonomicroscopy).or Foe?” We are seeing things with ultrasound that you cannot see with the naked eye. Furthermore, the ease of performing TV U/S, and its increasingly routine use for surveillance, has resulted, in my opinion, in an explosion of incidental findings that are much more common and more innocuous than previously realized. There are many examples in gynecology but I will concentrate on two that are very common and relevant to menopausal patients. These are 1) The Increased Sensitivity of Transvaginal Ultrasound: Do We See Too Simple ovarian cystic structures and 2) Incidental endometrial “thickening” Much? in non bleeding postmenopausal women. Forty years ago the dictum that a Steven R. Goldstein, MD, FACOG, CCD, NCMP. Obstetrics & Gynecology, palpable postmenopausal ovary was abnormal was put forth by Dr. Hugh New York University School of Medicine, New York, NY Barber. When ultrasound (then transabdominal ultrasound) began to see postmenopausal cystic structures these were promptly removed as potentially The ascertainment of diagnostic medical information through most of the malignant. 25 years ago the first small observational study began to suggest 20th Century relied on techniques like inspection, palpation, and auscultation that unilocular unilateral cysts were invariably benign and could be managed as noninvasive ways to obtain information about internal anatomy, both expectantly. Abundant data from prospective screening studies have normal and abnormal, as well as physiology which when not normal we call confirmed that observation. They have also shown the incidence of unilocular “pathology”. Sensitivity of imaging modalities has become so refined that we cystic adnexal structures in postmenopausal women can be as high as 18%. are seeing structures either never before appreciated or sometimes appreciated The field has “matured” to where almost all clinicians will now counsel such but not with such precision. This lecture will deal with my observations of this patients for conservative management. Twenty years ago the first reports of issue in gynecology using transvaginal ultrasound (TV U/S), although the a thin distinct endometrial echo in postmenopausal patients with bleeding problems associated with increased sensitivity of imaging exist in many other surfaced. Abundant prospective data from multicentered trials showed that clinical fields as well. My thesis is that as we see more and more detail the the incidence of malignancy in postmenopausal patients with bleeding when response to what we see has often been based on old and thus preconceived the endometrial echo measures < 4mm on transvaginal ultrasound is 1/917. notions, and not on newer well-organized and well-designed studies to In 2009 ACOG stated “when transvaginal ultrasound is performed for patients determine the prevalence of particular findings and their clinical significance. with postmenopausal bleeding and an endometrial thickness <4mm is found Information obtained with increasingly refined technology cannot simply be endometrial sampling is not required”. Unfortunately most clinicians who handled according to old established principles. Newer studies must be made understood that a thin distinct endometrial echo in such patients excludes before clinical recommendations can be made. We must be careful not to over malignancy, have still inappropriately assumed that a thick echo in non- interpret such findings that may be much more common and less ominous bleeding patients is abnormal and requires intervention. The prevalence of that previously believed. The vaginal probe has revolutionized gynecology. non thin endometrial echo on TV U/S in asymptomatic postmenopausal Higher frequency probes in close proximity to the structure being studied women is 10-17%. Furthermore13% of asymptomatic postmenopausal have created a degree of image magnification that is as if we are doing women will have an endometrial polyp on TV U/S. The risk of malignancy ultrasound through a low power microscope (sonomicroscopy). We are seeing is such imaged structures, absent bleeding, is less than 1 in 250 yet the things with ultrasound that you cannot see with the naked eye. Furthermore, complication rate from operative hysteroscopy in this elderly group is as high the ease of performing TV U/S, and its increasingly routine use for as 3.6%. The increasing sensitivity of the vaginal probe can and should be a surveillance, has resulted, in my opinion, in an explosion of incidental wonderful tool for the gynecologist. However studies on the prevalence and findings that are much more common and more innocuous than previously significance of the things one can see on such imaging must be carried out if realized. There are many examples in gynecology but I will concentrate on it is to be incorporated appropriately. Remember the credo –“above all else do two that are very common and relevant to menopausal patients. These are 1) no harm! Simple ovarian cystic structures and 2) Incidental endometrial “thickening” in non bleeding postmenopausal women. Forty years ago the dictum that a palpable postmenopausal ovary was abnormal was put forth by Dr. Hugh Barber. When ultrasound (then transabdominal ultrasound) began to see postmenopausal cystic structures these were promptly removed as potentially malignant. 25 years ago the first small observational study began to suggest that unilocular unilateral cysts were invariably benign and could be managed expectantly. Abundant data from prospective screening studies have confirmed that observation. They have also shown the incidence of unilocular cystic adnexal structures in postmenopausal women can be as high as 18%. The field has “matured” to where almost all clinicians will now counsel such patients for conservative management. Twenty years ago the first reports of a thin distinct endometrial echo in postmenopausal patients with bleeding surfaced. Abundant prospective data from multicentered trials showed that the incidence of malignancy in postmenopausal patients with bleeding when the endometrial echo measures < 4mm on transvaginal ultrasound is 1/917. In 2009 ACOG stated “when transvaginal ultrasound is performed for patients with postmenopausal bleeding and an endometrial thickness <4mm is found endometrial sampling is not required”. Unfortunately most clinicians who Learningunderstood Objectives: that a thin distinct endometrial echo in such patients excludes malignancy, have still inappropriately assumed that a thick echo in non- At thebleeding conclusion patients of is thisabnormal presentation, and requires participantsintervention. The should prevalence be ableof to: non thin endometrial echo on TV U/S in asymptomatic postmenopausal • women Describe is 10-17%.how the Furthermore13% use of endometrial of asymptomatic ultrasonography postmenopausal can reduce surgical interventions women will have an endometrial polyp on TV U/S. The risk of malignancy • is State such theimaged prevalence structures, andabsent recognize bleeding, isthe less significance than 1 in 250 of yet postmenopausal the ovarian cysts • complicationState the prevalence rate from operative and hysteroscopyexplain the in significance this elderly group of is “thickened” as high endometrial echo on transvaginal as 3.6%. The increasing sensitivity of the vaginal probe can and should be a wonderfulultrasound tool infor nonbleeding the gynecologist. postmenopausal However studies on the patients prevalence and significance of the things one can see on such imaging must be carried out if it is to be incorporated appropriately. Remember the credo –“above all else do no harm! 7 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #1 Presidential Symposium—“Incidental Findings on Imaging: Friend or Foe?”

MRI for Breast Cancer Screening & Staging Monica Morrow, MD, FACS. Memorial Sloan Kettering Cancer Center, New York, NY

MRI is able to visualize small tumor deposits not evident on mammography or clinical exam that previously could only be identified on pathologic exam. While this presents new opportunities, it also results in problems when MRI findings result in more aggressive surgical treatment in clinical situations in which outcomes are well documented to be good without the use of MRI. In the screening setting, MRI has been shown to have a higher sensitivity for invasive cancer detection than mammography in known or suspected BRCA mutation carriers leading to fewer node positive cancers and detection of smaller cancers in the MRI screened group. In a meta-analysis comparing high risk screening with MRI and mammography, the sensitivity of mammography was 32% (95% CI 23-41) and that of MRI was 75% (95% CI 62-88). Whether these results are specific to the unique biology of breast cancers in BRCA mutation carriers or can be extrapolated to women at increased risk from other causes is uncertain. In women with breast cancer, additional disease is detected by MRI in 16% of cases (95% CI 6-34%). However, two prospective randomized trials (COMICE, MONET) have not shown an improvement in the ability to successfully select patients for breast conservation or to obtain negative margins with the use of MRI. To date, retrospective studies do not show a decrease in local recurrence after breast conservation with MRI use. Downsides of MRI include cost, false positives leading to a delay in cancer treatment during work-up, and an association between pre-op MRI and the increased use of ipsilateral mastectomy and contralateral prophylactic mastectomy. Odds ratios for mastectomy with MRI range from 1.5-3 after adjustment for other variables MRI is useful in problem areas of management such as occult primary cancer presenting as axillary adenopathy, in the BRCA carrier who chooses breast conservation, and in patients receiving neoadjuvant chemotherapy. It may be helpful in clinical problem solving in selected cases, but in the absence of evidence of patient benefit should not be considered a routine part of the pre-operative work-up or follow-up of the breast cancer patient.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Identify and describe groups of women for whom MRI screening has been shown to be beneficial • Recognize the lack of a difference in short- or long-term surgical outcomes for breast cancer patients staged with and without MRI

8 Plenary Symposium #1 Presidential Symposium—“Incidental Findings on Imaging: Friend or Foe?”

Incidental Imaging Findings: Strategies to Minimize Their Impact Alec J. Megibow, MD, MPH, FACH. New York University - Langone Medical Center, New York, NY

For better or worse, some form of imaging has become expected as part of the evaluation of patients for virtually all clinical problems. Current imaging technology provides referring clinicians with a rapid, safe and accurate assessment of patients and has become focal points for decision making. However, as more and more patients undergo imaging tests there is increasing frequency of detection of findings that were likely not sought after, so-called incidental findings. There are occasions where unsuspected findings actually benefit patients, e.g. detection of an unsuspected aortic aneurysm, urinary calculi, and silent hydronephrosis. Yet despite the overwhelming pre-test probability that the findings are of no consequence to the patient, their detection often results in extra (and usually unnecessary) further testing, patient anxiety, referring clinician frustration, cost, radiation, and even-in some cases- surgical sampling. The root cause of the problems associated with these findings is variable security by both radiologists and clinicians to deal with uncertainty, often excused as fear of medico-legal consequences. Radiologists have recognized the significance of these findings and have sought to create some form of guidance to aid the individual confronted with an incidental finding. The approach has been the creation of decision trees that stratify the likelihood that an individual finding is benign, malignant or indeterminate. The decision trees were created in a formal process with teams of imaging experts reviewing the literature and then sharing with the entire group for comment and further refinement. The project required four years to complete; these decision trees have been published in October of 2010. While those of us involved in their creation are convinced that they will be modified over time, we believe that they represent a credible “first pass” from which refinements can be added. This talk will review a radiologist’s perspective of the problem of incidental findings, economic implications of their detection, and review the application of the imaging decision trees in abdominal diseases.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Characterize the problem of incidental findings in the abdomen • Describe the process by which decision trees have been adopted in the literature • Explain how these decision trees can increase the confidence level of interpreting radiologists

9 Speakers’ Abstracts & Learning Objectives (continued)

Keynote Address

Ovarian Aging: Can Science Turn Back the Clock? a comparable population of oocyte-producing stem cells in ovaries of Jonathan L. Tilly, Ph.D. Vincent Center for Reproductive Biology, reproductive age women, and discerning how the aging process affects them. Massachusetts General Hospital/ Harvard Medical School, Boston, MA. Another approach we have taken is dietary caloric restriction (CR), which extends lifespan and attenuates the severity of many aging-related health Ovarian aging is defined by a declining ovarian reserve, decreased ovulation complications in diverse species. Institution of CR in adult female mice results and reduced egg quality. Oocytes are prone to aging-associated aneuploidy in a remarkable near-doubling of natural reproductive lifespan with vast and meiotic spindle abnormalities, leading to increased infertility, fetal loss improvements in offspring survival (Aging Cell 2008 7:622-9). Follow-up and birth defects – most notably Down syndrome. Despite extensive research, studies have revealed that CR prevents the aging-related decline in total and no interventions have been identified that mitigate the deleterious effects of metaphase-II oocyte yield, and completely abolishes aging-related aging on the ovaries. Mice also exhibit an age-related decline in their ovarian increases in oocyte aneuploidy, chromosome misalignment, meiotic spindle reserve, as well as an aging-associated increase in oocyte aneuploidy and abnormalities and mitochondrial dysfunction, all of which occur in oocytes spindle defects. We have therefore used mice to explore approaches for of aging ad libitum-fed control animals (Proc Natl Acad Sci USA 2011 in improving ovarian function in aging females, and then used this information press). This opens the prospects for development of CR mimetic-based for initial validation in studies of human ovaries. For example, we have been approaches to safely circumvent the negative impact of aging on germline exploring the use of female germline or oogonial stem cells (OSCs) as both chromosomal stability and its segregation in eggs. Finally, it is worthwhile agents and targets for increasing the ovarian reserve. Although our initial mentioning that ovarian failure marks a time in life defined by infertility studies identifying the existence of OSCs in adult mouse ovaries (Nature 2004 and a cessation of cyclic hormone secretion from the gonads. Although the 428:145-50) were controversial, OSCs have recently been isolated from ramifications of the loss of fertile potential are clear, the consequences of postnatal mouse ovaries by several labs and shown by intraovarian impaired ovarian endocrine function are much more diffuse because of the transplantation to generate eggs that yield viable offspring (Nature Cell Biol large number of tissues in the body affected by ovarian-derived hormones 2009 11:631-6). Further, aged mouse ovaries devoid of oocytes retain a small such as estrogen. This latter point is exemplified by the diverse spectrum of pool of premeiotic germ cells that remain capable of producing oocytes when health issues that become manifest in women after menopause. Strategies that transferred to a young adult ovarian environment (Aging 2009 1:971-8). prevent or delay ovarian failure therefore hold clinical potential not just for Accordingly, failure of these cells to support the ovarian reserve with age may fertility reasons but also for improving the overall quality of life in women as reflect both germ cell-intrinsic changes as well as deterioration of somatic they age. Although this latter goal may be viewed as unreachable by some, microenvironments that support OSC function. Other studies have focused past work with mice has shown that sustaining ovarian function through on identification of agents that enhance oogenesis in adult ovaries, an maintenance of an adequate ovarian reserve with age does in fact yield objective that will be facilitated by our recent validation of an in-vitro immense health benefits without an increase in cancer, especially in steroid- screening assay that predicts the ability of a given compound to stimulate responsive tissues (Proc Natl Acad Sci USA 2007 104:5229-34). Thus, the oocyte formation when administered to adult female mice in vivo (Cell Cycle concept of an “ovarian replacement therapy” is, in our opinion, at least worth 2010 9:339-49). Our current efforts are now directed at characterizing additional testing. Supported by NIA MERIT Award R37-AG012279.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Explain how increasing chronological age negatively affects ovarian function • Describe approaches currently being developed in mice that can be used to attenuate or prevent aging-associated deterioration of ovarian function • Discuss how work on ovarian aging in mice supports the notion that functional lifespan of human ovaries may be amenable to therapeutic manipulation

10 Plenary Symposium #2 “Staging Reproductive Aging: An Update from STRAW+10” Supported by an unrestricted educational grant from Eli Lilly and Company

Staging Reproductive Aging: An Update from STRAW+10 John F. Randolph, Jr., MD1, Frank J. Broekmans, PhD2, Siobán D. Harlow, PhD1. 1University of Michigan, Ann Arbor, MI; 2Department of Reproductive Biology, University Medical Center Utrecht, Utrecht, Netherlands

This plenary symposium will review the work of a 2-day symposium, “STRAW+10: Addressing the Unfinished Agenda of Staging Reproductive Aging,” convened immediately before the 2011 NAMS Annual Meeting as a collaborative effort among the National Institute on Aging, the Office of Research on Women’s Health, The North American Menopause Society, the American Society for Reproductive Medicine, the International Menopause Society, and The Endocrine Society. The STRAW+10 effort aims to build on the 2001 STRAW (STtaging Reproductive Aging in Women) workshop, which produced a consensus document whose recommendations have been the standard for classifying female reproductive aging through menopause and have significantly framed research in the field over the past decade. In the 10 years since STRAW, our understanding of the ovary–brain interactions that occur before and after the final menstrual period has advanced considerably, as has our understanding of the implications for women’s health. These advances are the impetus for STRAW+10, whose primary objectives are to: (1) discuss criteria for the onset of early menopause in light of new population-based data relating to reproductive hormones and ovarian markers; (2) assess how to apply reproductive staging algorithms to women with higher body mass index and women who smoke; (3) provide recommendations for staging of women following gynecological surgery, chemotherapy, and hormone therapy as well as women with polycystic ovarian syndrome and chronic diseases like HIV/AIDS; and (4) assess potential criteria for staging postmenopause. The individual presentations in this plenary symposium will summarize the STRAW+10 symposium in several ways. The first will review recent advances in our understanding of FSH stages of the menopause transition, including improved modeling of the decline in ovarian reserve and the impact of body mass index. The second will discuss antimullerian hormone and antral follicle count as improved markers of fertility decline and onset of the menopause transition. The final presentation will outline preliminary recommendations from STRAW+10, which will be published in full form in the coming months.

11 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #3 “Identifying & Treating Depression in Midlife Women” Supported in part by grant funding from Pfizer Inc.

Menopause, Depression & Hormones: What’s the Connection? Hadine Joffe, MD, MSc. Department of Psychiatry, Division of Sleep Medicine, Massachusetts General Hospital, Boston, MA

The perimenopause is a period of risk for first-onset of and recurrence of depression in midlife women. While the majority of women who suffer from depression in midlife have previously experienced depression as young adults, some women experience their first episode of depression during the perimenopause. The basis for the increased risk of depression during this period of reproductive life is multi-factorial and varies among women. Common risk factors include a previous history of depression, stressful life events, and the perimenopause itself. Perimenopause may contribute to the increased risk of depression through several pathways, including fluctuating levels of estradiol and other reproductive hormones, and sleep disturbance secondary to hot flashes. Hot flashes and sleep disturbance are strongly associated with depression in perimenopausal women, and women with menopause-associated depression commonly experience hot flashes and sleep disturbance concurrent with their depression. The frequent comingling of these symptoms suggests that they may share a common etiologic pathway in some women. Understanding the potential contribution of perimenopausal hormone changes, menopausal symptoms, stressful life events, and recurrence of depression, to the etiology of depression in midlife women will inform our ability to treat depression in this population. Treatment strategies for individual women will vary with the key risk factors identified for that woman and the relative prominence of specific co-occurring symptoms, such as sleep disturbance. Understanding the pathways that link these frequently commingled symptoms together will enable clinicians to optimize treatment for individual women who experience depression during the perimenopause.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Recognize the role of perimenopause and menopausal symptoms in the risk of depression in midlife women • Describe the association of depression with fluctuating estradiol levels, hot flashes, and sleep disturbance

12 Plenary Symposium #3 “Identifying & Treating Depression in Midlife Women” Supported in part by grant funding from Pfizer Inc.

Depression in Midlife Women: Identification & Treatment Teri Pearlstein, MD. Psychiatry & Human Behavior, Alpert Medical School at Brown University, Providence, RI

Depressive and anxiety symptoms may first appear or increase in midlife women. Although for many perimenopausal women these symptoms are “subsyndromal”, it is important that midlife women be screened for mood and anxiety disorders that negatively impact daily life and functioning. Screening scales can be utilized for both diagnostic assessment and for monitoring response to treatment. Treatment for depression includes both pharmacological and non-pharmacological therapies, such as psychotherapy. Studies have been conducted with antidepressant medications in both perimenopausal and postmenopausal women. The use of antidepressant medications in midlife women should take into account specific symptoms, potential side effects, and concurrent medications. Studies have reported mixed results about a possible differential response to selective serotonin reuptake inhibitors before and after the menopausal transition. Estrogen may have a unique role in the improvement of mood in depressed perimenopausal women, both as a single treatment and as an adjunctive treatment. Augmentation strategies may be considered if depressive symptoms do not respond to antidepressant medication or estrogen. Complementary and alternative treatments may have a role in the treatment of depression in midlife women who do not desire, or do not tolerate, psychotropic medication or hormones.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Effectively evaluate midlife women for depressive symptoms • Identify pharmacologic and nonpharmacologic treatments for depression, and choose among them to address the needs and concerns of individual midlife women

13 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #4 “When Sex Hurts” Supported in part by grant funding from Novo Nordisk Inc., Pfizer Inc., and Warner Chilcott

Prevalence, Etiology & Diagnosis of Vulvovaginal Atrophy Murray A. Freedman, MS, MD. Department of Obstetrics & Gynecology, Medical College of Georgia, Augusta, GA

The classification of painful sex disorder in the DSM IV includes a number of etiologic factors, but because of time constraints (for this NAMS presentation), this discussion of “painful sex” will be limited to dyspareunia as it relates to vulvovaginal atrophy (VVA) and estrogen insufficiency in peri- and postmenopausal women. While the primary focus will address “painful sex”, it should be emphasized that the discussion applies equally to the enhancement of pleasurable sex, not just the prevention of VVA and dyspareunia. While there are 3 inevitable, inexorable factors that adversely effect female sexuality—-age, hormones and relationship issues—-aging and partnership issues will be addressed in only a cursory manner. The prevalence of VVA has been vastly underestimated because most studies and surveys in the literature have typically reported symptoms of sexual complaints and/or dysfunction rather than having been based upon physical examination. There is a paucity of scientific data based on the actual physical findings of atrophy in hypoestrogenic postmenopausal women. 1500 postmenopausal women in a clinical practice were examined for signs of VVA, including measurement of vaginal pH. Data will be presented to suggest that a) the prevalence of VVA in truly hypoestrogenic women (serum estradiol < 20 pg/ mL) is approximately 85 %, and b) up to 15 % of postmenopausal women utilizing ‘adequate’ doses of estrogen supplementation exhibit signs of VVA. Vaginal pH has been found to be a rapid, simple, accurate, inexpensive and reproducible harbinger of VVA, and pH values > 5.0 are almost invariably associated with physical evidence of VVA. Because of its embryologic derivation (endoderm), the introitius is subject to the earliest morphologic changes of VVA, and there are distinctive involutional changes at the vestibule that characterize the atrophic process. While vaginal dryness, erythema and loss of rugation are indicative of VVA, the early anatomic alterations at the intoitus (particularly the contraction and loss of elasticity) are actually more pathognomonic of the atrophic process. It is the introital involution rather than vaginal atrophy per se that is initially responsible for dyspareunia in hypoestrogenic women. While lubricants may assuage dryness and discomfort temporarily, the atrophic process often continues unabated. The combination of diminished or absent sexual activity and estrogen insufficiency compounds the atrophic process, and in a hypoestrogenic environment, VVA becomes an inevitable consequence.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe the incidence and prevalence of vaginal atrophy and its impact on sexual health • Identify and distinguish causes of dyspareunia in peri- and postmenopausal patients • Recognize the various physical changes associated with vaginal atrophy • Implement strategies to ensure that they routinely ask peri- and postmenopausal patients about their vaginal and sexual health

14 Plenary Symposium #4 “When Sex Hurts” Supported in part by grant funding from Novo Nordisk Inc., Pfizer Inc., and Warner Chilcott

Treatment Options for Vaginal Atrophy & Dyspareunia Raquel D. Arias, MD. Obstetrics & Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA

The human vagina is more than a potential space. It is a dynamic, complex micro-ecosystem whose integrity supports symptom-free elimination and urination in addition to sexual function. Maintenance of vaginal health is dependent on gross structural, microanatomic, immunologic, neural and vascular integrity. It is therefore not surprising that intervention targeting a single aspect of vaginal health maintenance yields only modest success. While direct comparisons of hormonal, mechanical and topical (nonhormonal ) treatments are limited, a working knowledge of each will contribute to the clinician’s ability to advise and guide care in the burgeoning demographic at risk for dysfunction.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • .Identify and manage vaginal moisture deficiency with local interventions that are either hormonal or nonhormonal • Counsel peri- and postmenopausal patients on the benefits and risks associated with vaginal estrogen use • Initiate individualized treatment plans for vaginal atrophy and dyspareunia in peri- and postmenopausal patients

15 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #5 “Cardiovascular Disease in Postmenopausal Women: Getting to the Heart of the Matter” Supported in part by grant funding from Astellas

State of the Heart 2011—New Guidelines for Prevention Lori J. Mosca, MD, MPH, PhD. Department of Medicine, Columbia University, New York, NY

Despite enormous progress in the awareness, prevention, and treatment of cardiovascular disease (CVD) over the past decade, it remains the leading cause of death among women and a major contributor to morbidity, decreased quality of life, and health expenditures in the United States (1). One in three adult females has CVD with a disproportionate prevalence of disease among black females. Since 1984 the annual number of deaths due to CVD for women has exceeded those for men. Nearly one half million women die of CVD annually, accounting for nearly half of all their deaths. Nearly 3 million women were discharged from short stay hospitals with CVD listed as the first diagnosis in 2007. These statistics underscore the public health and economic impact of CVD. According to a recent national survey, awareness of CVD as the leading cause of death has nearly doubled among women (30% in 1997 to 54% in 2009) since national educational campaigns were initiated (2). Despite the progress, awareness continues to lag among racial and ethnic minorities compared to white women suggesting targeted educational interventions need to be developed and evaluated to close the gap especially because awareness of CVD risk has been linked to taking preventive action. The majority of CVD in women is coronary heart disease (CHD) and currently about 8 million women in the US are living with CHD (1). An estimated half million women will have a new or recurrent myocardial infarction (MI) or fatal CHD. Among women who have a recognized MI over age 40 years 24% will die within 1 year compared to 18% of men. It is notable that 2 out of 3 women who die suddenly of CHD had no previous symptom which suggests that primary prevention must be a key strategy to reduce the burden of CHD in women. Similar to trends in CVD, the death rate for CHD is higher for black females than white females. Sex differences in the presentation of CHD have been well established with women more likely to present with angina compared to men while the initial presentation of CHD in men is more likely to be MI or CHD death. A recent national survey indicated that only about half of women knew the classic symptoms of heart disease and significantly less knew the atypical symptoms which are more common in women than men (2). Of concern was that only 53% of women said they would call 9-1-1 if they thought they were having a heart attack but 79% said they would call if they thought someone else was. Substantial evidence has documented the benefits of prevention to reduce the morbidity, mortality, and costs associated with CVD in women. The American Heart Association recently updated its guidelines for the prevention of CVD in women (3). A notable change over previous guidelines is the shift from evidence-based to effectiveness-based guidelines. The expert panel emphasized that the efficacy of intervention observed in clinical trial settings is often not realized in clinical practice. This gap may be related to the diversity of women in practice settings and lack of adherence due to side effects and other barriers. Other significant changes in the guidelines were the addition of novel risk factors, such as pregnancy complication and rheumatoid arthritis. The threshold for “high risk” was modified to >10% 10- year absolute risk of CVD owing to the greater prevalence of stroke in some and the data documenting traditional Framingham scores underestimate risk in women. The 2011 guidelines also emphasized the need for more research Learning Objectives: on how to better implement proven preventive strategies in women. At the conclusion of this presentation, participants should be able to: • .Incorporate cardiovascular risk assessment, as established by American Heart Association (AHA) guidelines on cardiovascular disease prevention in women, into patients’ annual examinations • Advise women on how to implement new recommendations for the prevention of cardiovascular disease

16 Plenary Symposium #5 “Cardiovascular Disease in Postmenopausal Women: Getting to the Heart of the Matter” Supported in part by grant funding from Astellas

Coronary Disease & Stroke in Women: Strategies for Intervention Martha Gulati, MD, MS, FACC, FAHA. Preventive Cardiology & Women’s Cardiovascular Health, Ohio State University College of Medicine, Columbus, OH

Coronary artery disease (CAD) remains the leading cause of death in both men and women in the United States. Women differ from men in their clinical presentation of coronary artery disease, their performance on diagnostic tests, and their prevalence of coronary artery disease. The purpose of this talk will be to discuss gender differences in presentation and treatment of cardiovascular disease and stroke, with a focus on recent research and guidelines for women and cardiovascular disease. The discussion will also include cardiac syndrome X and recent research related to this syndrome.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe differences in coronary artery disease patterns in women as compared with men and the impact of these differences on prognosis • Identify women at risk for stroke, recognizing the increased prevalence of stroke in women compared with men • Implement preventive strategies to reduce the risk of cardiovascular disease and stroke in women, and describe the role of aspirin in primary and secondary prevention

17 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #5 “Cardiovascular Disease in Postmenopausal Women: Getting to the Heart of the Matter” Supported in part by grant funding from Astellas

Clinical Challenges in Lipid Management Emma A. Meagher, MD. University of Pennsylvania Health System, Philadelphia, PA

Cardiovascular disease is the primary cause of death in American women, accounting for more than 500,000 deaths per year. More women die from cardiovascular disease (CVD) each year than from the next seven leading causes of death combined. There is a need to better identify and treat women who may be at risk for cardiovascular disease. Dyslipidemia is one of the most important modifiable risk factors for coronary heart disease (CHD). Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid- modifying therapy for the reduction of coronary risk in both genders. However, there are important gender differences in the lipid profile that warrant our attention. A significant body of evidence from numerous, well- controlled, randomized trials demonstrates that treatment with HMG-CoA reductase inhibitors (statins) reduces morbidity and mortality from CVD. Subgroup analyses of both primary and secondary prevention trials have shown that lipid-modifying drugs offer benefits to women comparable to those seen in men. While these observations are important and have resulted in the adoption of standard of care approaches for the management of CVD risk in men, they have not been uniformly adopted in the management of risk in female patients. In addition, when reviewing these landmark statin trials it is clear residual risk for CV events remains despite statin therapy. In women, changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride levels are believed by many to be better predictors of coronary risk than LDL- C or total cholesterol. Despite this, attempts to demonstrate that combination therapy directed at HDL –C raising or triglyceride lowering have failed to improve CVD outcome.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Implement appropriate pharmacotherapy to reduce LDL cholesterol and triglyceride levels in women as indicated by the AHA guidelines • Determine which women are appropriate candidates for pharmacotherapy to raise HDL cholesterol levels according to the AHA guidelines

18 Plenary Symposium #6 “Debate—Is There Ever an Indication for Hormone Therapy in an Asymptomatic Postmenopausal Woman?”

Is There Ever an Indication for Hormone Therapy in an Asymptomatic Postmenopausal Woman? James A. Simon, MD, CCD, NCMP, FACOG. George Washington University School of Medicine, Washington, DC; and David F. Archer, MD, NCMP, The Jones Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA

In a special debate format, two experienced menopause practitioners will present dueling arguments on whether hormone therapy is ever indicated in an asymptomatic postmenopausal woman. Each debater will prepare both affirmative and negative arguments, with supporting evidence, prior to the debate, and their respective positions will be assigned randomly at the start of the debate. The format will allow 15-minute presentations for each position followed by 5-minute rebuttals on each side. An audience vote at the end will determine the winner.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Explain whether, when, and why hormone therapy might ever be an appropriate option for an asymptomatic postmenopausal woman

19 Speakers’ Abstracts & Learning Objectives (continued)

NAMS/Pfizer Wulf H. Utian Endowed Lecture

History & Experience: The Direction of Alzheimer’s Disease William E. Reichman, MD. Psychiatry, Faculty of Medicine, University of Toronto, Toronto, ON, Canada

As the global population is projected to age substantially in coming decades, the number of individuals who will develop Alzheimer’s disease (AD) is expected to rise dramatically. The dementia syndrome arising from AD includes progressive failure in memory and all other cognitive domains, behavioural alterations, functional decline and ultimately, death. We have come to understand that AD is likely to be multi-determined through interactions between heritable causal and susceptibility genes, environmental exposures, mid life health status and lifestyle choices. Additionally, mounting scientific evidence suggests that the neuropathological processes characteristic of AD can be detected several years prior to the onset of clinical signs and symptoms. Thus, AD is now considered to have pre-symptomatic, prodromal (mild cognitive impairment) and dementia phases. Through the use of cerebrospinal biomarkers, volumetric neuroimaging, functional neuroimaging, and cognitive stress tests, individuals at significant risk for developing dementia due to AD can now be identified with greater sensitivity and specificity. Not surprisingly, there is growing attention to successfully identify interventions to halt or delay the clinical onset of AD. The biological capacities of neurogenesis and neuroplasticity and the related concepts of brain and cognitive reserve provide a rationale for developing techniques to strengthen the cognitive abilities of older persons sufficiently to prevent incident dementia. As the normal aging process is also strongly associated with brain changes that lead to a weakening of some select cognitive domains in healthy persons, there has been increasing interest in finding methods to “keep our brains sharp” by maintaining or enhancing cognitive performance. Not surprisingly, interest among the consumer public in learning how to prevent cognitive loss and how to strengthen such abilities in mid and later life appears to be steadily growing. This has led to the emergence of a new “Brain Fitness” commercial industry in which structured, live cognitive training programs, computerized games, internet based course work and other “products” are being marketed and sold to consumers. However, the majority of available brain fitness methods and products have scant scientific evidence to support their effectiveness. Despite this caveat, ongoing research advances do indeed support the potential for memory and other intellectual functions to be strengthened and maintained through cognitive training, physical exercise, dietary choices, social engagement and psychological stress reduction.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Outline recent scientific advances for detecting Alzheimer’s disease prior to the onset of dementia • Summarize the most recent research findings on how to potentially maintain and strengthen cognitive function and reduce the risk for developing dementia due to Alzheimer’s disease • Describe the emerging “Brain Fitness” market and how best to advise patients and their families about preventing Alzheimer’s disease

20 Plenary Symposium #7 “Addressing the Needs of Midlife Women Through & Beyond Breast Cancer” Supported in part by grant funding from Pharmavite LLC

Quality of Life: Alternatives to Hormone Therapy for Vasomotor Symptoms Mary Jane Minkin, MD, FACOG, NCMP. Yale University School of Medicine, New Haven, CT

80% of women experience vasomotor symptoms during the menopausal transition. Women with breast cancer can be even more symptomatic; if they are premenopausal at time of diagnosis, chemotherapy often renders them suddenly hypoestrogenic.. If they are already postmenopausal and on hormonal therapy, they will be required to stop. Virtually all women with estrogen receptor positive tumors will be treated with either tamoxifen or aromatase inhibitors, further exacerbating their vasomotor symptoms. Although the most efficacious of the available therapies for managing vasomotor symptoms, namely estrogen, is contraindicated in this population, several categories of relief do remain available. Lifestyle changes that have been shown to mitigate severity of vasomotor symptoms include smoking cessation, exercise, and weight loss; adoption of healthier lifestyle measures may even impact on the overall survival. Paced respiration and acupuncture have been tried, with mixed results on efficacy, but not controversial on safety.1Herbal and botanical approaches may be helpful. Controversies do exist over both the efficacy and safety of both isoflavones and black cohosh in this population. Non hormonal medications have been prescribed widely; SSRI’s and SNRI’s are widely used in this group of patients. However, given the special emotional vulnerability of the relatively young cancer survivors to potential side effects of anti-depressants, such as decreased libido and weight gain, these medications need to be prescribed judiciously. Special consideration is merited in tamoxifen users, as certain SSRI’s such as paroxetine can interact with tamoxifen’s metabolism, hence risking reduction in chemo-efficacy of tamoxifen. Gabapentin has been used in breast cancer survivors as well. Older therapies such as antihypertensives are rarely used currently, given side effects and minimal efficacy. Given that sleep disruption often accompanies vasomotor complaints, consideration needs to be given to adjunctive use of sleep medications in this population. Vaginal atrophy is a common accompaniment to vasomotor symptoms, and contributor to the overall compromised quality of life particularly in the relatively young experiencing abrupt menopause. Symptoms of vaginal discomfort thus must be enquired in those experiencing vasomotor symptoms; while alternative therapies such as polycarbophil moisturizers have shown promise in providing symptomatic relief, judicial use of vaginal estrogen therapy may be a consideration for some, given the minimal systemic absorption with the use of low dose rings, tablets, and creams. Given the increased use of SERM’s and projected possible use of aromatase inhibitors for breast cancer chemoprevention, alternative therapies for vasomotor symptoms will become even more relevant. Potential use of TSECs in this population may prove beneficial in symptom prevention as well.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Discuss management of hot flashes with their breast cancer patients, ranging from lifestyle changes to nonprescription therapies to prescription medications • Counsel breast cancer patients on the potential risks and benefits of these management options, framing them within the patient’s expectations of symptom relief • Collaborate with the patient’s medical oncology team to maximize her quality of life by ensuring that they understand her menopause symptoms and how they are managed

21 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #7 “Addressing the Needs of Midlife Women Through & Beyond Breast Cancer” Supported in part by grant funding from Pharmavite LLC

Mobility of Life: Skeletal Concerns Ann E. Kearns, MD, PhD. Division of Endocrinology, Mayo Clinic, Rochester, MN

The superiority of third generation aromatase inhibitors over tamoxifen as adjuvant hormonal therapy in postmenopausal women with hormonal receptor positive breast cancer has resulted in improved disease-free survival. The randomized trials unexpectedly showed an association of arthralgia and myalgia with aromatase inhibitors. This symptom complex is common and can be significant enough to affect quality of life. Discontinuation of therapy for this reason is not uncommon. The symptoms abate when the medication is stopped and permanent joint destruction does not occur. There is no proven treatment intervention, but over the counter pain relievers and physical therapy may be helpful. The mechanism by which aromatase inhibitors cause arthralgia and myalgia is not well understood. In contrast, it is understood that the estrogen deprivation caused by aromatase inhibitors is the mechanism underlying the known negative impact on bone mass. Managing the bone health in postmenopausal women with breast cancer being treated with aromatase inhibitors is important for long-term health. There are trials with bisphosphonates that demonstrate efficacy in preventing the bone loss in patients receiving aromatase inhibitors. Women receiving aromatase inhibitors should have screening bone density and fracture risk assessment. Those at intermediate risk may be considered for preventative therapy. In all women receiving aromatase inhibitors, bone density should be monitored and fracture risk reviewed. Understanding and managing the arthralgias and skeletal consequences of aromatase inhibitors is important to optimal long term health outcomes in women being treated with aromatase inhibitors.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Recognize the syndrome of aromatase inhibitor-associated arthralgia and myalgia, as well as identify and select among the management options • Identify and explain the bone loss induced by aromatase inhibitors and select patients for appropriate treatment to ameliorate it

22 Plenary Symposium #8 “Osteoporosis Update: Practical Guidance for the Care of Postmenopausal Women” Supported in part by grant funding from Amgen Inc., Eli Lilly and Company, Merck & Co., Inc., and Warner Chilcott

Secondary Causes of Osteoporosis: When & How to Investigate causes of osteoporosis should be especially common in patients with BMDs Steven T. Harris, MD, FACP. University of California, San Francisco, San below normal for age (i.e., with abnormal BMD Z-scores), the available data Francisco, CA would suggest that that is not true. The most common laboratory abnormality encountered in the evaluation of the patient with low BMD is vitamin D It is common for a low bone mineral density (BMD) to be interpreted as deficiency. For some years, the target serum level for 25-hydroxyvitamin D “osteoporosis,” but the BMD can only provide an estimate of bone mineral has been 30 ng/mL at a minimum. In late 2010, the Institute of Medicine content (BMC), without establishing a specific underlying cause. A BMD suggested that a blood level of 20 ng/mL or higher should suffice for the with a T-score of -2.5 or lower is consistent with primary osteoporosis, but is general population. Nevertheless, many clinicians still feel that a level of 30 not diagnostic of primary osteoporosis. It can be challenging to distinguish ng/mL or higher is desirable in an older patient with low BMD. In general, it between primary osteoporosis due to postmenopausal or age-related changes, is recommended that adults up to age 70 receive 600 IU of vitamin D daily secondary osteoporosis due to other diseases or medications, osteomalacia, and that those over age 70 receive 800 IU of vitamin D daily. Those and other disorders such as osteogenesis imperfecta. There are dozens of recommendations are based on bone health. It is also recognized, however, diseases, conditions and drugs that have been associated with low BMD. that 1500 IU to 2000 IU of vitamin D daily may be required to consistently Many should be obvious from the medical history and physical exam, but raise the blood level of 25-hydroxyvitamin D above the target of 30 ng/mL. some are more subtle or detectable only by judicious laboratory testing. As a The Institute of Medicine set the Tolerable Upper Intake Level of vitamin D general rule, every patient with low BMD deserves at least a limited as 4000 IU daily. The Institute of Medicine also concluded that there is no laboratory evaluation before initiating pharmacologic therapy. In several conclusive evidence linking a particular level of 25-hydroxyvitamin D to any series, roughly 40% to 60% of patients with apparent primary osteoporosis putative extra-skeletal benefit. There are no hard and fast rules regarding the had a previously unsuspected underlying disorder. In the absence of clear referral of patients to clinicians specializing in metabolic bone disease for the national guidelines regarding laboratory evaluation, a consensus among expert further evaluation of possible secondary causes of bone disease. Broadly, clinicians is that testing should/could include a complete blood count, com- however, referral would be reasonable for: •Patients in whom the osteoporosis prehensive metabolic panel, 25-hydroxyvitamin D and a 24-hour urine is unexpectedly severe or has unusual features. Examples include collection for the measurement of calcium excretion. Thyroid function tests premenopausal women with low BMD, young men with low BMD, women and other tests such as parathyroid hormone (PTH) should be done if with unexpectedly low BMD despite long-term estrogen therapy, and patients clinically indicated. Although there is room for debate about the extent of with fractures in the absence of major trauma despite normal BMD •Patients laboratory testing, there is no debate that the cost of that baseline laboratory with significant concurrent diseases that complicate management such as testing is relatively small compared to the cost of many years of malabsorption, hyperparathyroidism, Cushing’s disease or chronic renal pharmacologic therapy prescribed for the presumed underlying primary disease •Patients with statistically-significant bone loss or recurrent fractures osteoporosis. Although it is intuitively appealing to argue that secondary despite bone-protective therapy

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Counsel peri- and postmenopausal women on evidence-based levels of vitamin D and calcium intake for optimal bone and overall health • Recognize the need to test for bone mineral density and consider osteoporosis therapy initiation in postmenopausal women with recent fractures and other risk factors for osteoporosis • Explain when, why, and how to evaluate for secondary causes of osteoporosis in postmenopausal women

23 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #8 “Osteoporosis Update: Practical Guidance for the Care of Postmenopausal Women” Supported in part by grant funding from Amgen Inc., Eli Lilly and Company, Merck & Co., Inc., and Warner Chilcott

Osteoporosis Treatments: What’s New and What’s Coming? Robert Lindsay, MBChB, PhD, FRCP. Helen Hayes Hospital and Columbia University, West Haverstraw, NY

Around the turn of the century there was a move away from estrogen therapy, and a corresponding move toward the use of bone specific agents, primarily bisphosphonates for the prevention of osteoporosis in relatively young women. Recently, that has come under scrutiny with the occurrence of unusual transverse fractures of the femoral shaft several centimeters below the greater trochanter. The realization that many of these fractures were occurring in women on bisphosphonates has led to an evaluation of the use of these drugs in the long term. The use of tools to estimate risk of fracture (e.g. FRAX may mitigate the problem, but the level of risk and the mechanism are still not understood. It appears that for those at high risk of fracture, as ewell as those who have already suffered a fracture, the benefits of intervention still outway any potential risk by a considerable margin. Whether a similar problem occurs with denosumab, the RANK-L inhibitor is not known, but it is worth noting that estrogens, Calcitonin and raloxifene have not been incriminated. Novel agents are in the development pipeline, but face challenges, not only with the development process and the need for fracture data, but also the increasing number of generic agents that will be available. Alternative routes of administration for teriparatide and calcitonin are under study. One estrogen product has been combined with a tissue selective estrogen (CEE + bazodoxifene). Analogues of teriparatide are being evaluated. In addition new targets such as sclerostin and cathepsin K appear amenable to inhibition with increased bone formation and inhibition of bone resorption resulting respectively. It may be at least another 4-5 years before either reaches the market. At present prescriptions continue to decline and it is clear that fracture patient are still not being evaluated or treated. Perhaps the best chance for improvement in management of osteoporosis is the development of guidances (and stronger!) from NCQA, JCAHO, AMA supported by organizations such as NOF, ASBMR and NAMS. This is somewhat of a carrot and stick approach, and might be obviated if HCPs realized that all fractures in postmenopausal women are potentially related to a compromised skeleton and evaluated fracture patients accordingly.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe the relative strengths and drawbacks of available and investigational osteoporosis therapies • Select among osteoporosis therapies to meet postmenopausal women’s individual needs

24 Plenary Symposium #9 “Androgens & Women’s Health” Supported by grant funding from BioSante Pharmaceuticals, Inc.

Androgens in Women: Beyond Libido Gail A. Laughlin, PhD. Department of Family & Preventive Medicine, University of California, San Diego School of Medicine, San Diego, CA

Many studies have investigated the role of estrogen in cardiovascular disease (CVD) in women; less attention has been paid to testosterone. The testosterone-estrogen balance in women increases dramatically at menopause, a time when central adiposity and the incidence of cardiovascular disease also increase, suggesting that higher levels of testosterone relative to estradiol may be atherogenic in women. The combination of hyperandrogenemia, an adverse CHD risk profile and endothelial dysfunction in young women with polycystic ovarian syndrome (PCOS) supports the view that androgen excess may harm the female heart. However, the expected increase in CHD events and mortality in women with PCOS has not been observed and recent studies report low levels of testosterone in women with atherosclerotic disease, raising the possibility that testosterone may have beneficial effects on the heart, or suggesting a U-shaped association with suboptimal levels at both extremes. The limited availability of sensitive and accurate assays for female testosterone levels has impeded resolution of whether testosterone increases or decreases the risk of CHD in older women. In addition, the association may depend on the fraction of testosterone examined, the estrogen milieu, and obesity and obesity-related factors. In contrast to estrogen, the postmenopausal ovary continues to secrete androgens, contributing about 40% of circulating testosterone. Testosterone and estradiol circulate bound to albumin, to sex hormone binding globulin (SHBG), and in the free (unbound) state. The free and non-SHBG bound fractions are widely believed to be the most bioactive forms, although direct evidence supporting this thesis is sparse. An important difference in total and bioavailable (non-SHBG bound) testosterone (BioT) is that the relative proportion of the bioavailable fraction can be metabolically regulated. Central obesity and insulin resistance have strong inhibitory influences on hepatic SHBG production, leading to higher circulating levels of bioavailable testosterone (and estradiol). Epidemiological evidence suggests that total and bioavailable testosterone have opposing associations with some CVD risk factors and outcomes (higher total T is beneficial, higher BioT is harmful) and that higher levels of testosterone relative to estradiol are favorably associated with CVD risk factors and CVD events. Testosterone may influence the development of CVD in postmenopausal women via multiple pathways including effects on adiposity, body fat distribution, and obesity-related molecules; effects on other classic CVD risk factors; and/or direct effects on the vasculature.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe the physiologic changes in endogenous androgens across the menopausal transition and during postmenopausal aging • Draw on current understanding of the cardiometabolic effects of endogenous androgens to counsel postmenopausal women on their possible role in cardiometabolic health and disease

25 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #9 “Androgens & Women’s Health” Supported by grant funding from BioSante Pharmaceuticals, Inc.

Androgen Treatment of Female Sexual Dysfunction: Risks, Benefits & Available Therapies Susan R. Davis, MBBS, FRACP, PhD. School of Public Health & Preventive Medicine, Monash University, Melbourne, VIC, Australia

Androgens are vital hormones in women, circulating in concentrations ranging from nanomolar to micromolar. Not only are androgens the precursor hormones for estrogen biosynthesis in the ovaries and extragonadal tissues, but androgens act directly via androgen receptors throughout the body. Androgen levels decline with age in women with the greatest fall in total and free testosterone occurring before the menopause(1). Large RCTs involving naturally and surgically postmenopausal women presenting with hypoactive sexual desire disorder (HSDD) demonstrate that testosterone therapy, with/without concurrent estrogen therapy, improves the quality of the sexual experience. More recent studies demonstrate the use of testosterone therapy improve sexual wellbeing in premenopausal women with HSDD. The effects appear not to be mediated by aromatization of testosterone to estrogen. The other potential benefits of testosterone in women include favorable effects on bone density, muscle mass, vascular endothelial function and cognitive function. Despite the entrenched belief that higher blood levels of testosterone increase the risk of cardiovascular disease (CVD), data from recent observational studies mostly show an inverse relationship between testosterone and CVD risk. Published randomized controlled trials (RCTs) indicate that non oral testosterone therapy does not adversely affect plasma lipids or other CVD risk markers (2, 3). One pilot RCT suggests favorable effects of non oral testosterone treatment of women with established congestive cardiac failure which merits further evaluation. Virilization is dose dependent with few women discontinuing therapy in RCTs due to acne or hirsutism(4). Preliminary data indicate favorable effects on cognition. The relationship between endogenous testosterone production and breast cancer risk remains contentious, with recent studies indicating no relationship (5). No RCT of testosterone therapy has been sufficiently large or of sufficient duration to establish whether such treatment may influence breast cancer occurrence. There does not appear to be an association between testosterone and endometrial cancer, or other malignancies on review of published studies. Testosterone use has not been approved other than for surgically menopausal women on estrogen therapy in Europe. Despite this, the use of testosterone by women is widespread, with vast numbers of women using testosterone preparations developed and marketed for men, testosterone preparations compounded on individual prescriptions as oral lozenges and creams, and testosterone implants. Hence there is a clear need for a testosterone therapy delivering an appropriate female dose to be approved, so that women have the option of using a product formulated for women.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Recognize the potential impact of androgens on sexual function • Summarize and compare the evidence-based efficacy and safety profiles of androgen treatment options for female sexual dysfunction

26 “New Clinically Relevant Findings from the MsFLASH Research Network: The Escitalopram Trial”

New Clinically Relevant Findings from the MsFLASH Research Network: The Escitalopram Trial A.Z. LaCroix, PhD1, E.W. Freeman, PhD2, K.E. Ensrud, MD, MPH3, S.D. Reed, MD, MPH4, J.S. Carpenter, PhD, RN, FAAN5. 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA; 2Departments of Obstetrics/Gynecology and Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA; 3VA Medical Center/University of Minnesota, Minneapolis, MN; 4University of Washington School of Medicine, Seattle, WA; 5School of Nursing, Indiana University, Indianapolis, IN

The Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) clinical trials network, supported by the National Institute on Aging as a cooperative agreement, is conducting a series of randomized clinical trials designed to test new interventions for menopausal symptoms. Our first randomized trial of escitalopram in healthy menopausal women with hot flashes found that treatment significantly reduced the frequency, severity, and bother of vasomotor symptoms during 8 weeks of treatment. Delving further into the effects of escitalopram on vasomotor symptoms, we then examined the efficacy of escitalopram compared with placebo for: (1) daytime and nighttime hot flash frequency, severity, and bother; (2) number of flash-free days and nights; and (3) hot flash interference (the Hot Flash Related Daily Interference Scale). Escitalopram significantly reduced both daytime (18%; p=0.001) and nighttime (15%; p=0.003) hot flashes compared to placebo. The escitalopram group experienced about one-half more flash-free day (p=0.03) and one-half more flash-free night (p=0.001) compared to the placebo group. Hot flash interference scores were reduced by 18.1 points in the escitalopram group compared to 14.6 points in the placebo group over the course of the trial (p=0.01). Despite these encouraging findings, concerns about the use of SSRIs for hot flashes include potential side effects, especially related to insomnia and sexual function. Further evaluation of the effect of escitalopram versus placebo on insomnia symptoms (Insomnia Severity Index) and subjective sleep quality (Pittsburgh Sleep Quality Index) revealed that escitalopram at 10-20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 4 and 8 weeks of follow-up (p≤0.001 for overall treatment effect for both sleep measures). Escitalopram did not significantly impact the overall Female Sexual Function Index, or a single item from the Female Sexual Distress Scale, although escitalopram decreased lubrication relative to placebo (-0.6 points difference on a 6-point scale; p=0.02) in sexually active women. We conclude that escitalopram provides relief for vasomotor symptoms, does not increase symptoms of insomnia, and does not affect overall sexual function in non-depressed women with bothersome hot flashes. Future MsFLASH trials will test several other therapies for relief of menopause symptoms including yoga, aerobic exercise, omega-3 fatty acid supplementation, low-dose estrogen, and venlafaxine using designs that allow for side-by-side comparison of treatment effects relative to placebo and/or comparison groups.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe the effects of escitalopram on vasomotor symptoms (frequency, severity, bothersomeness, daytime hot flashes, nighttime hot flashes, hot flash interference), symptoms of insomnia, and sexual function in nondepressed women with bothersome hot flashes • Understand the future trials that will be conducted by the MsFLASH clinical trials network using factorial and comparative effectiveness trial designs

27 Speakers’ Abstracts & Learning Objectives (continued)

Kenneth W. Kleinman Endowed Lecture

The Role of Genetic Testing & Genetic Information in Research Thomas H. Murray, PhD. The Hastings Center, Garrison, NY

Spurred in part by Congressional interest in the implications of genetics, the US Human Genome Project early on established an Ethical, Legal and Social Implications (ELSI) Program. The ELSI Working Group consulted with many clinicians, scientists, scholars, advocates and patient organizations in an effort to learn what most concerned people about mapping and sequencing the human genome. Two themes quickly emerged: worries that the privacy of genetic information would be violated, and concerns that genetic information would be used to discriminate against individuals believed to carry genetic risks. The ELSI program established a Task Force on Genetic Information and Insurance, which I chaired. The story of that Task Force carries valuable lessons for clinicians, researchers and policy makers today. In particular, claims about the power of genetic information to predict an individual’s life course were based on a scientifically unjustified belief in genetic determinism. That belief resulted in policy recommendations that tried to treat genetic information as distinct from and more important than other forms of health related information—a stance now known as genetic exceptionalism. Demystifying genetic information, and reassuring clinicians, patients and research subjects that it is not as powerful or predictive in most cases as had been feared (or hoped) can facilitate genetic research and help clinicians provide better counseling and care for their patients.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Explain the concept of genetic exceptionalism and provide a critical assessment of it • Evaluate the implications of genetic risk information for health insurance systems • Accurately appraise for patients and research subjects the risks of genetic discrimination and violations of genetic privacy

28 Abuse, Neglect, & Exploitation of the Older Female: Integrating Healthcare, Legal, & Community Responses Patricia M. Speck, DNSc, APN, FNP-BC, DF-IAFN, FAAFS, FAAN1, Candace J. Heisler, JD2. 1University of Tennessee Health Sciences Center College of Nursing, Memphis, TN; 2Assistant District Attorney for the City & County of San Francisco, Trainer, Office for Victims of Crime, Training & Technical Assistance Center, University of California, Hastings College, San Bruno, CA

The extent of elder abuse is largely unknown due to the varying degrees of cognitive and physical abilities of older persons, research design limitations, and inconsistent definitions among the experts or in publications. However, most agree that elder abuse, neglect and exploitation of older females may include physical abuse, rape, sexual abuse, emotional or psychological abuse, neglect, and financial exploitation where the cost to older persons and society is greater than $2.9 billion. It is also known that older women experience Plenary Symposiumsexual, domestic #10 and financial victimization often committed by persons in trusted and ongoing relationships. In 2010, researchers found that when cognitively capable, the prevalence rate of victimization in persons over 60 “Abuse, Neglect, & Exploitationyears ofof age the is 11.4%, Older and Female: that 65% of reported victims were women. The Integrating Healthcare, Legal,lifetime & Community prevalence of partner Responses” violence is 26.5% and includes physical and sexual violence which are seriously underreported. Low rates of reporting are associated with family dynamics and values, inability to report, disbelief, and lack of awareness that the abusive conduct should be reported. Risk assessments of the older female that evaluate the patient’s ability to understand and exercise informed consent, respecting the patient’s rights to Abuse, Neglect, & Exploitation of the Older Female: Integrating autonomy and self-determination, explore the relationships between family Healthcare, Legal, & Community Responses members and neighbors (which may include the abuser), drug and alcohol Patricia M. Speck, DNSc, APN, FNP-BC, DF-IAFN, FAAFS, FAAN1, use, and the belief that respect for self determination using the least restrictive Candace J. Heisler, JD2. 1University of Tennessee Health Sciences Center alternatives are characteristics of a thorough health care evaluation that should College of Nursing, Memphis, TN; 2Assistant District Attorney for the City be completed at every visit. Health care providers must be familiar with local & County of San Francisco, Trainer, Office for Victims of Crime, Training & community agencies available to assist when abuse, neglect and exploitation Technical Assistance Center, University of California, Hastings College, San are suspected or confirmed, including agencies that support safe havens and Bruno, CA medical treatment of the older person’s ills. The failure of the health care provider to take an active role may subject the vulnerable older woman to The extent of elder abuse is largely unknown due to the varying degrees of continued violence and exploitation. The impact to those exposed to cognitive and physical abilities of older persons, research design limitations, significant childhood or a lifetime of abuse is correlated to diseases that affect and inconsistent definitions among the experts or in publications. However, every biological system and has been shown to contribute to premature death most agree that elder abuse, neglect and exploitation of older females may by as much as 20 years! When older women seek care for vague somatic include physical abuse, rape, sexual abuse, emotional or psychological abuse, complaints or when there are implausible explanations for physical trauma, neglect, and financial exploitation where the cost to older persons and society health care providers have the opportunity to identify, evaluate, and refer is greater than $2.9 billion. It is also known that older women experience individual victims to specialized care and interventions. That said, research sexual, domestic and financial victimization often committed by persons in reveals that health care providers are ill equipped to identify or manage the trusted and ongoing relationships. In 2010, researchers found that when older woman’s needs or the system’s response to the non-medical needs cognitively capable, the prevalence rate of victimization in persons over 60 following abuse, neglect or exploitation. Through case studies of typical years of age is 11.4%, and that 65% of reported victims were women. The scenarios following sexual or domestic abuse, neglect or exploitation in the lifetime prevalence of partner violence is 26.5% and includes physical and older female, this presentation will review the epidemiological data, explain sexual violence which are seriously underreported. Low rates of reporting are the coordinated community response, identify stakeholder agencies, clarify associated with family dynamics and values, inability to report, disbelief, and legal reporting requirements, and discuss common approaches to the ideal lack of awareness that the abusive conduct should be reported. Risk health care provider response of forensic medical management and criminal assessments of the older female that evaluate the patient’s ability to justice obligations. understand and exercise informed consent, respecting the patient’s rights to autonomy and self-determination, explore the relationships between family members and neighbors (which may include the abuser), drug and alcohol use, and the belief that respect for self determination using the least restrictive alternatives are characteristics of a thorough health care evaluation that should be completed at every visit. Health care providers must be familiar with local community agencies available to assist when abuse, neglect and exploitation are suspected or confirmed, including agencies that support safe havens and medical treatment of the older person’s ills. The failure of the health care provider to take an active role may subject the vulnerable older woman to continued violence and exploitation. The impact to those exposed to significant childhood or a lifetime of abuse is correlated to diseases that affect every biological system and has been shown to contribute to premature death by as much as 20 years! When older women seek care for vague somatic complaints or when there are implausible explanations for physical trauma, health care providers have the opportunity to identify, evaluate, and refer individual victims to specialized care and interventions. That said, research reveals that health care providers are ill equipped to identify or manage the older woman’s needs or the system’s response to the non-medical needs following abuse, neglect or exploitation. Through case studies of typical scenarios following sexual or domestic abuse, neglect or exploitation in the older female, this presentation will review the epidemiological data, explain the coordinated community response, identify stakeholder agencies, clarify legal reporting requirements, and discuss common approaches to the ideal Learninghealth care Objectives: provider response of forensic medical management and criminal justice obligations. At the conclusion of this presentation, participants should be able to: • Describe the epidemiology of and latest research addressing abuse, neglect, and exploitation of older/vulnerable persons • Explain the role of coordinated community response, members and roles, and community impact • Discuss the elements of a forensic evaluation of domestic and sexual violence involving the older female • Clarify legal reporting requirements for older/vulnerable person abuse, neglect, and exploitation • Identify common presentations of older/vulnerable person abuse, neglect, and exploitation

29 Speakers’ Abstracts & Learning Objectives (continued)

Plenary Symposium #11 “The Mind-Body Connection: Impact on Health & Disease”

A Healthy Midlife Crisis – Habits That Lead to Wellness Patricia J. Sulak, MD. Scott & White Healthcare, Texas A&M College of Medicine, Temple, TX

Despite the numerous life-saving advances in medicine from improved diagnostic testing to miracle medications to surgical wonders, our waiting rooms are filled with women who are not healthy, not happy, and even depressed, often with numerous self-induced medical conditions. Many are complicating their lives and harming their well being with numerous unhealthy behaviors including a sedentary lifestyle, dietary indiscretion, substance abuse, and self-induced stress. These health risk behaviors can lead to the #l overall killer (cardiovascular disease) and the #l cancer killer (lung cancer). Then comes the dreaded “midlife crisis”. It’s a fact - - as we age, our body wants to deteriorate and atrophy. But, the good news is that we can delay the decay for many years. Another fact - - most disease states can be improved and sometimes even prevented with a healthy lifestyle. The problem is two fold. Number one: What is healthy? With the promotion of miracle supplements, weight loss wonder programs, and even colonics, what is safe, no less healthy? Number two: How do I institute healthy habits and, importantly, maintain them? Healthcare professionals and patients need the facts on components of a healthy lifestyle that can improve the quality and quantity of their lives. What are some of these lifesaving habits? First and foremost, make movement mandatory. With our technologically advanced society, we have become too sedentary necessitating that we become creative in finding enjoyable ways to put healthy movement into our daily lives. The American Heart Association has established guidelines for reducing risk of chronic disease and preventing weight gain. Secondly, critique caloric consumption. While many diets are promoted as the answer, the Mediterranean Diet has been the most studied in terms of disease prevention. Other healthy habits to be discussed include addressing addictions, managing time and money, the power of forgiveness, and spiritual connection.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • State the WHO definition of health • List dietary and exercise guidelines that prevent disease • Recognize and prescribe lifestyle modifications that foster health and happiness

30 Plenary Symposium #11 “The Mind-Body Connection: Impact on Health & Disease”

A Mindful Midlife—Understanding the Mind-Body Connection Herbert Benson, MD. Harvard Medical School, Boston, MA

Stress plays an important role throughout a person’s life. It is related to 60- 90% of visits to health care professionals. The relaxation response (RR) is the counterpart of the stress or fight-or-flight response. The RR is characterized by decreased oxygen consumption, carbon dioxide elimination, and respiratory rate as well as decreased limbic system activity and responsivity to plasma norepinephrine. There are coordinated genetic expression changes in the RR that are opposite to those of the stress response. The genetic changes of the RR are characterized by decreases in oxidative phosphoralization (energy metabolism), inflammation activity as well as apoptotic expression. To the extent that disorders are caused or exacerbated by stress, regular elicitation of the RR is an effective therapeutic intervention. These conditions include: premenstrual syndrome, hot flashes of menopause, infertility, hypertension, depression, anxiety, insomnia, irritable bowel syndrome, inflammatory bowel disease, and rheumatoid arthritis as well as other autoimmune conditions. Two steps are usually practiced to evoke the RR: (1) the repetition of a word, sound, prayer, or physical activity and (2) the disregard of everyday thoughts with a return to the repetition. The two steps break the train of everyday thinking and are linked to millennia old practices that include meditation, yoga, repetitive prayer, tai chi and chi gong. Regular use of the relaxation response is coordinated with appropriate pharmaceutical and surgical therapies. It is an essential feature of self-care that includes nutrition and exercise.

Learning Objectives: At the conclusion of this presentation, participants should be able to: • Describe the physiology of the relaxation response • Identify methods/strategies that elicit the relaxation response • Demonstrate the role of mind/body medicine with regard to managing menopausal symptoms and stress

31 NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 1

Scientific Sessions

PLENARY SCIENTIFIC ABSTRACT SESSION #1 group when the results of WHI were announced are now 57-73 years of age and thus at greater risk for cardiovascular and other chronic disease. This group started HT at the normal age of menopause, unlike two thirds of the women in the WHI study(1). Design: S-1. The aim of this retrospective cohort study was to test differences in the incidence of The Effects of Bazedoxifene/Conjugated Estrogens on Breast Density in obesity, hypertension, and hyperlipidemia, as well as the use of medications among Postmenopausal Women women ages 57 to 73 who used HT for at least 5 years and subsequently stopped its use Jennifer A. Harvey1, JoAnn V. Pinkerton2, Kaijie Pan3, John R. Thompson3, Sebastian compared to those who continued HT use. The study also assessed quality of life and Mirkin3, Arkadi A. Chines3. 1Department of Radiology, University of Virginia Health medical morbidity. The study enrolled women born between 4/1/1938 and 3/31/1953 who System, Charlottesville, VA; 2Department of Obstetrics and Gynecology, Division of previously used HT for at least five years. Recruitment is ongoing; to date 250 women Midlife Health, University of Virginia Health System, Charlottesville, VA; 3Pfizer Inc, have been enrolled of which 209 are considered complete. Interviews and measurements Collegeville, PA were conducted at doctors’ offices in the New York City area. Three groups were Objective: Increased mammographic breast density may be a risk factor for breast cancer, compared: women who have remained on HT (“Continued HT,” n= 101), women who but the etiology of this relationship is not well understood. Certain medications, including discontinued HT use for a minimum of 6 months and have since resumed HT(“Resumed combined estrogen/progestin therapy, have been shown to increase breast density. HT”, n=33), and women who discontinued HT and have not resumed its Published phase 3 studies have demonstrated the efficacy and safety of use(”Discontinued HT,” n=75). Results: Of the women who discontinued HT, 67% cited bazedoxifene/conjugated estrogens (BZA/CE), a tissue selective estrogen complex adverse media as a reason for discontinuation, 29% cited a physician’s recommendation, (TSEC), in the treatment of menopausal symptoms and prevention of postmenopausal and 11% stated other reasons. The overall mean age at interview was 64.8±4.0 years. The osteoporosis without an increase in breast pain or breast cancer. The effects of BZA/CE Discontinued HT group was slightly older than the Continued HT group; 65.7±3.9 vs. on breast density were evaluated in a substudy of the Selective estrogens, Menopause, 64.1±4.0 years (p<.05) but similar to the Resumed HT group (65.1±4.0 years, n.s.). 95% And Response to Therapy (SMART)-5 trial. Design: In this phase 3, double-blind, were Caucasian, and 87% had a college education or greater. Patients started HT at placebo (PBO)-controlled study of postmenopausal women with a uterus (N = 1,843), 49.2±5.0 years. Mean weight was 63.2±11.2 kg and mean body mass index (BMI) was subjects were randomized to receive BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 23.8±4.2. No differences were noted between the groups with respect to weight, height, 0.45 mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO daily for 12 months to BMI, waist/hip ratio, blood pressure, triglycerides or cholesterol levels. Women on HT evaluate efficacy and safety. A subset of these women met inclusion criteria and were (Continued HT and Resumed HT) scored higher than the Discontinued HT group on the enrolled in a breast density substudy. Breast density changes were assessed by digitized 115 point Utian Quality of Life scale (87.7±13.3 vs. 81.8±13.3, p<.01). In particular, mammograms that were centrally read by a single radiologist using specifically developed women on HT scored higher than the Discontinued HT group on the 35 point occupational software. Comparison of the adjusted mean difference in percent breast density at 12 satisfaction scale subset (26.5±7.2 vs. 23.5±7.8, p<.02). The Discontinued HT group months for each group versus PBO was based on a non-inferiority test with a pre-defined scored higher than those on HT with respect to the Greene climacteric vasomotor scale margin of 1.5%. Results: A total of 940 women (mean age ± standard deviation (SD), 54.0 (1.2±1.4 vs. 0.7±1.1, p<.02). Vaginal dryness was also greater (1.9±1.1 vs. 1.4±0.6, ± 4.0 y; mean years since last menstrual period, 4.4 ± 3.6 y) participated in the breast p<<.001). Finally, the Discontinued HT group was on significantly more antihypertensive density substudy: BZA 20 mg/CE 0.45 mg (n = 231), BZA 20 mg/CE 0.625 mg (n = medications (29.9% of the Discontinued HT group vs. 15.9% of Continued HT group 247), BZA 20 mg (n = 122), CE 0.45 mg/MPA 1.5 mg (n = 100), or PBO (n = 240). At and 6.5% of Resumed HT group). Combining the groups on HT, 13.8% of women 12 months (Figure), BZA 20 mg/CE 0.45 and 0.625 mg demonstrated non-inferiority currently on HT were on antihypertensive medications compared with 29.9% of women versus PBO (the upper bound of the 95% confidence interval [CI] was 0.51% and 0.44%, not on HT (p<.01). Conclusion: These results suggest that discontinuation of HT may respectively). However, CE 0.45 mg/MPA 1.5 mg showed a significant increase in mean place some women at risk for the development of hypertension, which may be an early percent breast density at 12 months versus PBO (P <0.001; upper bound of the 95% CI, indication of the metabolic syndrome and those remaining on HT score higher on scale 2.7%). Conclusion: Women treated with BZA 20 mg/CE 0.45 or 0.625 mg for 12 months of quality of life, particularly that which focuses on satisfaction with profession and showed no differences in breast density compared with those treated with PBO, suggesting occupation. REFERENCES: 1. Rossouw, JAMA 2002, 2. Grady, Obstet Gynecol 2003, a potential advantage of BZA/CE over conventional estrogen/progestin therapy. 3. IMS Health, WSJ 2006

S-3. Hot flashes and lipids in the Study of Women’s Health Across the Nation Rebecca C. Thurston, PhD1,2, Samar R. El Khoudary, PhD2, Kim Sutton-Tyrrell, DrPH2, Carolyn Crandall3, Ellen Gold4, Barbara Sternfeld5, Hadine Joffe, MD, MSc6, Karen A. Matthews, PhD1,2. 1Psychiatry, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology, University of Pittsburgh, Pittsburgh, PA; 3Medicine, University of California, Los Angeles, Los Angeles, CA; 4Public Health Sciences, University of California, Davis, Davis, CA; 5Research, Kaiser Permanente, Oakland, CA; 6Psychiatry, Harvard, Boston, MA Objective: Vasomotor symptoms, or hot flashes (HF) and night sweats (NS), reported by 75% of peri- and postmenopausal women, are thought to have quality of life, but few medical, implications. However, recent findings link HF to cardiovascular disease (CVD) risk. The reasons for these associations are not fully understood, but evidence suggests that HF may be associated with an adverse lipid profile. Our aim was to examine the relations between HF and lipids, controlling for other CVD risk factors, estradiol (E2), and follicle stimulating hormone (FSH) over a 7 year period. Design: Participants were 3201 women ages 42-52 years at baseline in the Study of Women’s Health Across the Nation (SWAN). Participants at entry completed interviews (HF and NS: none, 1-5, ≥6 days in past 2 weeks; affect), physical measures (body mass index (BMI)), and a blood draw (low density lipoprotein (LDL), high density lipoprotein (HDL), apolipoprotein(a) (apo(a)), Figure. Mean Adjusted Difference (95% CI) in Percent Breast Density Versus apolipoprotein(b) (apo(b)), lipoprotein(a) (Lp(a)), trigycerides, E2, FSH) at baseline and Placebo at 12 Months. approximately yearly for 7 years thereafter. HF were examined in relation to each lipid with covariates age; site; race/ethnicity; education; BMI; menopausal status; parity; S-2. alcohol use; smoking; physical activity; diabetes status; diagnosed cardiovascular disease; Effect of Estrogen and Hormone Therapy Withdrawal on Health and depression/anxiety symptoms; and anti-hypertensive, anticoagulant, and lipid lowering medication use. E2 and FSH were added in separate steps. Data from visits with reported Quality of Life after Publication of The Women’s Health Initiative in New hormone therapy use were excluded. Results: In linear mixed models adjusted for all York City covariates except hormones, more frequent HF were significantly associated with higher Michelle Warren, Olivia Richardson, Sonal Chaudhry, MD, Aimee Shu, MD, Abigail levels of all of the lipids assessed except Lp(a): LDL [vs. no HF, 1-5 days: β Chua, Nancy L. Sloan, DrPH, MPH. Ob/Gyn, Columbia University Medical Center, New B(95%CI)=1.48(0.57-2.40, p=.002); ≥6 days: B(95%CI)=2.13(0.91-3.35, p=.0006)], York, NY HDL [vs. no HF, 1-5 days: B(95%CI)=.30(-0.06-0.65, p=.10); ≥6 days: Objective: Since July of 2002, when the results of the Women’s Health Initiative (WHI) B(95%CI)=.77(0.30-1.25, p=.001)], apo(a) [vs. no HF, 1-5 days: B(95%CI)=.92(-0.01- were published, a large number of women stopped hormone therapy (HT) due to concerns 1.85, p=.05); ≥6 days: B(95%CI)=1.97(0.76-3.19, p=.002)], apo(b) [vs. no HF, 1-5 days: over risks of heart attacks and breast cancer(1). This sudden discontinuation of therapy is B(95%CI)=1.41(0.61-2.20, p=.0006); ≥6 days: B(95%CI)=2.51(1.45-3.57, p<.0001)], probably the largest single decrease of a medication over a short period of time in the and triglycerides [(vs. no HF, 1-5 days: % change (95%CI)=2.91(1.41-4.43, p=.0001); history of American medicine. The initial drop in sales amounted to 33% and has ≥6 days: % change(95%CI)=5.90(3.86-7.97, p<.0001)]. These associations remained continued at rate of approximately 6% a year(2;3). These events represent an unparalleled significant for LDL, HDL, apo(a), apo(b), and triglycerides after adjustment for E2, and opportunity to answer questions of risk and benefit in women who initiated therapy at for HDL, apo(a), apo(b), and triglycerides after adjustment for FSH. Findings for NS menopause and subsequently chose to stop therapy. Evidence exists that the were consistent with those for HF. Conclusion: HF were associated with higher LDL, hypoestrogenic menopausal state is associated with weight gain and changes in body HDL, apo(a), apo(b), and triglycerides during a 7-year follow up period, controlling for composition. Such changes increase visceral fat and the secretion of inflammatory factors CVD risk factors and E2 concentrations. Lipids should be considered in examining links and predispose women to chronic diseases such as diabetes, heart disease and the between HF and CVD risk. SWAN has support from the NIH, DHHS, through NIA, metabolic syndrome. The time elapsed since 2002 presents an appropriate interval for NINR and NIH ORWH (NR004061; AG012505, AG012535, AG012531, AG012539, observation of the consequences of this experience, as women who were in the 49-64 age

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AG012546, AG012553, AG012554, AG012495). The content of this abstract is solely the in each stratum were randomized to receive 60 mg/d ospemifene or placebo and were responsibility of the authors and does not necessarily represent the views of the NIA, provided with a nonhormonal vaginal lubricant to use as needed (PRN). For each stratum, NINR, ORWH or NIH. changes from baseline to Wk 12 (LOCF) for the four co-primary endpoints were assessed: vaginal pH, percentages of superficial cells and parabasal cells in the maturation index and the severity of the MBS. This abstract reports the Dryness Stratum results. Results: In the S-4. ITT analysis, at Wk 12 ospemifene demonstrated significant efficacy vs placebo for 3 of Does Route of Administration for Estrogen Hormone Therapy and 4 co-primary endpoints from baseline. Significant mean changes from baseline to Wk 12 Estradiol Transdermal System Dosage Strength Impact Risk of Venous for vaginal pH and percentages of superficial (LS mean) and parabasal cells (Median) Thromboembolism were evident (Table 1). Significant improvement was observed as early as 4 wks. Kristijan H. Kahler, PhD, RPh1, Judit Nyirady, MD, MBA1, Eric Beresford, PharmD1, Improved mean change was observed for the MBS vaginal dryness at Wk 12, which François Laliberté2, Katherine Dea, MA2, Mei Sheng Duh, MPH ScD3, Patrick Lefebvre, approached statistical significance (P=0.0803). A higher % of subjects treated with MA2. 1Novartis Pharmaceuticals Corporation, East Hanover, NJ; 2Groupe d’analyse, Ltee, ospemifene reported no vaginal dryness, and the subjects’ self-reported symptom severity, Montreal, QC, Canada; 3Analysis Group, Inc, Boston, MA which was assessed on a 4-point scale improved by 2 to 3 points in 46.3% ospemifene vs Objective: Hormone therapy (HT) is regularly used in the treatment of symptoms 34.4% placebo subjects. The PP analysis showed statistically significant improvement associated with menopause, such as hot flashes and vulvovaginal atrophy. Venous for all 4 co-primary endpoints (pH, % superficial and % parabasal cells, all P<0.0001 and thromboembolism (VTE) is among the most serious complications associated with HT. vaginal dryness, P=0.0143) and similar improvements in dryness severity. The main A recent study has showed that transdermal estrogen administration was associated with difference between the ITT and the PP populations was in study drug compliance, which a lower risk of VTE relative to oral estrogen administration. The objective of the current was higher in the PP population. The numbers of subjects with ≥1 adverse event (AE) at follow-up analysis was to evaluate the impact of high dose estradiol transdermal system Wk 12 in both strata combined is summarized in Table 2. Discontinuation rates were (ETS; Vivelle-Dot®) on the risk of VTE events as compared to the use of oral estrogen- similar in the ospemifene (10.2%) and placebo (11.6%) groups. Endometrial histology only HT agents. Design: A health insurance claims analysis was conducted using the assessments showed no cases of hyperplasia and 2 (1.0%) cases of active proliferation in Thomson Reuters MarketScan database from January 2002 through October 2009. the ospemifene group vs 0% in the placebo group. Vaginal bleeding was reported in 2 Patients ≥35 years old with continuous insurance coverage, newly initiated on an ETS or (0.4%) and 4 (0.9%) subjects in the ospemifene and placebo groups, respectively; 1 oral estrogen-only HT with ≥2 dispensings were analyzed. VTE was defined as ≥1 subject on ospemifene experienced deep vein thrombosis was discontinued from the study. diagnosis code for deep vein thrombosis (DVT; ICD-9 codes: 451.1x, 451.2, 453.4x, There were no cases of myocardial infarction, breast cancer or death. Conclusion: In 453.8, 453.9) or pulmonary embolism (PE; ICD-9 codes: 415.1x). Patients with a prior postmenopausal women with the self-reported MBS of vaginal dryness, these data history of VTE or using any estrogen HT agents within 180 days before the first ETS or demonstrate that treatment with ospemifene 60 mg/d provides clinically and statistically oral estrogen-only HT drug dispensing were excluded. The study observation period significant efficacy and was well tolerated. With greater improvement in symptom severity started on the date of ETS or oral estrogen HT treatment initiation (index date) until 90 scale changes and in markers of vaginal health, this novel SERM may prove to be the days following the index treatment interruption or discontinuation (i.e., continuous use of first non-estrogen to effectively treat the symptoms of VVA. therapy). Cohorts of ETS and oral estrogen-only HT were matched 1:1 based on both exact factor and propensity score matching methods to ensure balanced patient Table 1 Change from BL to Wk 12 LOCF (ITT)* characteristics at baseline. The incidence rates of VTE events were calculated as number of patients with an event divided by patient-years of observation, censored at the time of the first event. The incidence rate ratio (IRR), assessed through Poisson regression was used to compare the rates of VTE events for ETS relative to oral estrogen-only HT cohorts. ETS dosage strength ranged from 0.025 to 0.1 mg/day. To assess the impact of ETS dosage, IRRs of VTE were also reported for subgroups of women initiating high dose * Similar results were reported for the PP analysis. ETS based on two definitions: (i) 0.075 or 0.1 mg/day and (ii) 0.1 mg/day, relative to their corresponding matched oral estrogen-only HT users. Results: Among the 30,547 patients Table 2 Adverse Events treated with ETS and 159,281 receiving oral estrogen-only HT, 27,018 ETS users and an equal number of oral estrogen-only HT users were matched to form the overall study population. The mean ages of the matched cohorts (SD) were 48.9 (7.1) years; in each cohort 6,044 (22.4%) and 1,788 (6.6%) patients had a hysterectomy and an oophorectomy at baseline, respectively. The mean (median) drug exposure for the ETS and oral estrogen- only HT cohorts was 391 (264) and 401 (272) days, respectively. Based on the matched analysis of the overall study population, a total of 115 ETS users developed VTE compared to 164 subjects in the oral estrogen-only HT cohort (IRR: 0.72; 95% CI: 0.57- S-6. 0.91, P=0.006). Furthermore, the lower risk for VTE events associated with ETS relative Vasomotor Symptoms in Premenopausal Women by Race: the LEAVES to oral estrogen-only HT remained statistically significant in women initiating high dose Study ETS. In the matched cohorts of ETS and estrogen-only HT users where ETS was initiated Susan D. Reed, MD, MPH1,2, Katherine M. Newton, PhD3, Johanna Lampe, PhD2, Sharon at 0.075 or 0.1 mg/day (11,570 women in each cohort), 45 ETS users and 80 oral estrogen- Fuller3, Congh Qu, PhD3, Gabrielle Gundersen, MS3. 1Obstetrics and Gynecology, only HT users developed VTE (IRR=0.58; 95% CI: 0.40-0.84, P=0.004), while in the University of Washington, Seattle, WA; 2Public Health Sciences, Fred Hutchinson Cancer matched cohorts where high dose ETS was defined as 0.1 mg/day (8,956 patients in each Research Center, Seattle, WA; 3Group Health Research Institute, Seattle, WA cohort), 32 ETS users and 65 oral estrogen-only HT users developed VTE (IRR=0.52; Objective: Prevalence of vasomotor symptoms among women over age 45 who report 95% CI: 0.34-0.80, P=0.003). Conclusion: This large population-based study of over regular periods have not been well described. Prevalence variability by race/ethnicity is 50,000 patients based on real-world data suggests that patients receiving ETS (Vivelle- expected. Design: We performed a population-based mailed survey of 18,500 women, Dot®) have significant lower incidence of VTE of approx 30% compared to patients ages 45-58, enrolled at Group Health Cooperative in Washington State, identified from receiving oral estrogen-only HT. Data from this study also showed that the lower risk for automated databases as not using hormones (50% response rate). The purpose of this VTE associated with ETS remained significant in women initiating high dose ETS relative analysis was to describe self-reported hot flashes and night sweats, by race/ethnicity to matched oral estrogen-only HT women. among all premenopausal women surveyed who reported regular menses. We excluded women who had had a bilateral salpingo-oophorectomy. Generalized linear models were S-5. used to calculate differences in vasomotor symptoms by race, adjusted for age (*P<0.05; Efficacy of a novel SERM, ospemifene, in the treatment of moderate-to- †P<0.001). Results: There were 1,575 premenopausal women who responded to the survey, 73% were white, the mean age was 48.5±2.5 years, 32% reported ever having hot severe vaginal dryness symptoms of vulvovaginal atrophy associated with flashes and 48% reported ever having night sweats. Premenopausal native menopause Hawaiians/Pacific Islanders were most likely to report ever having hot flashes (46%), 1 2 David Portman, MD , Gloria A. Bachmann, MD , Steven R. Goldstein, MD, FACOG, followed by African American women (39%), American Indian (38%), Hispanic nonwhite 3 4 5 6 6 CCD, NCMP , Vivian Lin , James Liu , Shelli Graham , Michele Giliberti , James A. (37%), white (34%), Filipino (30%), Vietnamese (29%), Japanese (26%), Asian Indian 7 1 Simon, MD, CCD, NCMP, FACOG . Columbus Center for Women’s Health Research, (22%), Chinese (19%), and Hispanic white (18%). Controlling for age, Chinese women 2 Columbus, OH; UMDNJ -Robert Wood Johnson Medical School, New Brunswick, NJ; were 11% less likely to have ever had hot flashes as compared with white women 3 4 New York University School of Medicine, New York, NY; QuatRX Pharmaceuticals (P<0.01). Premenopausal American Indian women were most likely to report ever having 5 6 Company, Ann Arbor, MI; MacDonald Women’s Hospital, Cleveland, OH; Clinical night sweats (62%), follow by African American (61%), white (51%), Hawaiian/Pacific 7 Development, Shionogi Inc., Florham Park, NJ; The George Washington University Islanders (46%), Hispanic nonwhite (41%), Hispanic white (35%), Japanese* and Asian School of Medicine, Washington, DC Indian (33%), Filipino* (30%), and Chinese† and Vietnamese* (24%). Conclusion: Objective: Ospemifene, a novel, selective estrogen receptor modulator (SERM) that Among women over age 45, who were most likely in the early to mid transition, Asian exerts estrogenic, pharmacologic activity in the vaginal epithelium, is presently being women were least likely to report having hot flashes and night sweats. African-American studied for treatment of symptoms of vulvovaginal atrophy (VVA) in postmenopausal reported hot flashes and night sweats more commonly than white or Asian women. women. This study assessed the efficacy, safety and tolerability of ospemifene 60 mg/d in the treatment of VVA symptoms. Design: A 12-wk, 1:1 randomized, double-blind, placebo-controlled, parallel-group study enrolling 919 postmenopausal women 40 to 80 years of age with VVA in two strata based on their self-reported most bothersome symptom (MBS) of vaginal dryness or vaginal pain (dyspareunia). Two study populations were analyzed: the intent-to-treat (ITT) (primary analysis) and per protocol (PP). Subjects

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CONCURRENT SESSION #1 S-8. Treatment with the Cathepsin K Inhibitor Odanacatib in Postmenopausal S-7. Women with Low BMD: 5 Year Results of a Phase 2 Trial Andrew Denker1, N. Binkley2, H. Bone3, N. Gilchrist4, B. Langdahl5, H. Resch6, J. Reproductive Safety of Bazedoxifene in Postmenopausal Women With Rodriguez-Portales7, A. Lombardi1, C. Le Bailly De Tilleghem8, C. DaSilva1, E. Osteoporosis: Results of a 7-year, Randomized, Placebo-controlled, Phase Rosenberg1, A. Leung1. 1Merck, Rahway, NJ; 2U. of Wisconsin, Madison, WI; 3Michigan 3 Study Bone & Mineral Clinic, Detroit, MI; 4Princess Margaret Hospital, Christchurch, New Santiago Palacios1, Tobie J. de Villiers2, Fiorenzo De Cicco - Nardone3, Amy Levine4, Zealand; 5Aarhus U. Hospital, Aarhus, Denmark; 6Medical U. Vienna, Vienna, Austria; Robert Williams4, Teresa Hines4, Arkadi A. Chines4. 1Instituto Palacios, Madrid, Spain; 7Pontificia Universidad Católica de Chile, Santiago, Chile; 8Merck, Brussels, Belgium 2Panorama MediClinic and University of Stellenbosch, Cape Town, South Africa; Objective: The selective cathepsin K inhibitor odanacatib (ODN) progressively increased 3Università Cattolica del Sacro Cuore, Rome, Italy; 4Pfizer Inc, Collegeville, PA BMD at the spine and hip during a 2-year trial and 2-year extension. Here we report the Objective: Endometrial and breast safety are important considerations in the development results of an additional year. Design: Postmenopausal women of mean age 63 yrs, with of selective estrogen receptor modulators (SERMs). Bazedoxifene (BZA) has BMD T-scores -2.0 to -3.5 at the lumbar spine or hip, received weekly placebo (PBO) or demonstrated long-term safety and efficacy for the treatment of postmenopausal women ODN 3, 10, 25, or 50mg for 2 yrs in addition to calcium, if needed, and vitamin D3. In with osteoporosis in a pivotal phase 3 study. Here we describe the reproductive safety of yr 3, women in each treatment group were re-randomized to ODN 50mg or PBO. For yrs BZA in women enrolled in this study during 7 years of treatment. Design: In the 3-year 4-5, women receiving PBO or ODN 3mg in yrs 1-2 and PBO in yr 3 were switched to core study, generally healthy postmenopausal women with osteoporosis (N=7,492; mean ODN 50mg; all others continued with their yr 3 treatments. BMD at the lumbar spine age, 66.4 y) were randomized to receive BZA 20 or 40 mg, raloxifene (RLX) 60 mg, or (primary endpoint), femoral neck, trochanter, and 1/3 radius; bone turnover markers; and placebo daily. All subjects were supplemented with elemental calcium (1,000-1,200 mg/d) safety were assessed. Results: Women entering the yr 4-5 extension receiving PBO and vitamin D (400-800 IU/d). During a 2-year extension (N=4,216; Years 4 and 5), the (n=41) or ODN 50 mg (n=100) had similar baseline characteristics. After 5 yrs, in women RLX 60-mg arm was discontinued, and subjects receiving BZA 40 mg were transitioned who received ODN 50mg continuously from yr 1 (n=13), mean % changes (SE) in BMD to BZA 20 mg. The study remained double-blinded and was extended for an additional 2 from baseline were: lumbar spine 11.9 (2.1) (Figure), femoral neck 9.8 (1.9), trochanter years (Years 6 and 7; N=1,732). All subjects continued to receive BZA 20 mg or placebo. 10.9 (1.4), total hip 8.5 (1.0), and 1/3 radius -1.0 (1.3). In women who were switched Endometrial and breast safety findings at 7 years are reported for BZA 20 mg, BZA from ODN 50mg to PBO after 2 yrs (n=14), BMD mean % changes (SE) from baseline combined (BZA 20-mg group plus the group that transitioned from BZA 40 to 20 mg were: lumbar spine -0.4 (1.3) (Figure), femoral neck -1.6 (1.0), trochanter -1.0 (0.8), total after 4 years), and placebo. Adverse events (AEs) were recorded throughout the study. hip -1.8 (0.8), and 1/3 radius -4.7 (1.7). After 5 yrs, in women continuously receiving Endometrial thickness as measured by transvaginal ultrasound (TVU) at baseline and at ODN 50 mg (n=9-10), geometric mean % changes from baseline (SE) were -67.4 (10.1) Year 7 is presented for subjects in the endometrial safety substudy. Results: Overall, the for urine NTX/creatinine, but only -15.3 (5.9) for serum BSAP. In women switched from reproductive safety findings with BZA at 7 years were favorable and generally consistent ODN 50mg to PBO after 2 yrs (n=10) these changes were 6.0 (7.6) and -11.9 (3.9). with those seen at 3 and 5 years. Transvaginal ultrasound data were available for 90 Administration of ODN over 5 yrs compared to PBO was generally well-tolerated. subjects at baseline and at Year 7 (BZA 20 mg, n=31; BZA combined, n=61; placebo, Conclusion: Women who received ODN 50mg for 5 yrs had a gain in spine and hip BMD n=29). The mean change (± standard error) from baseline in endometrial thickness with over 5 yrs and showed a sustained reduction in urine NTX/Cr and a smaller reduction in BZA 20 mg (–0.23 ± 0.25 mm) and BZA combined (–0.15 ± 0.18 mm) was not serum BSAP. As previously reported, discontinuation of ODN results in reversal of BMD significantly different from that seen with placebo (0.14 ± 0.56 mm) at 7 years. The gains. number of subjects with endometrial thickness >5 mm at any time interval on therapy was similar (range, 5.2%-8.3%) among groups. The incidence of endometrial hyperplasia with BZA was similar to that with placebo. Fewer cases of endometrial carcinoma were reported with BZA 20 mg (n=0) or BZA combined (n=3) than with placebo (n=7; P <0.01 and P <0.05, respectively; Table). The incidences of ovarian cyst, uterine hemorrhage, and vaginal hemorrhage were small and similar among the BZA and placebo groups. There were numerically more cases of histopathologically confirmed ovarian carcinoma in the BZA 20-mg (n=3) and BZA combined (n=4) groups than in the placebo group (n=0; Table); the differences were not statistically significant. The incidence of breast carcinoma in the BZA 20-mg and BZA combined groups was not different from that in the placebo group (Table). Other breast-related AEs, including breast cysts, fibrocystic breast disease, and breast pain were reported with similar frequency among groups (Table). Conclusion: BZA was associated with a neutral effect on the breast and favorable endometrial safety profile, including fewer cases of endometrial carcinoma compared with placebo, in postmenopausal women with osteoporosis over 7 years of therapy.

Table. Incidence of Gynecologic and Breast-related AEs

S-9. Low Plasma Concentrations of Vitamin D3 are Associated with Increased Cardiovascular Risk Factors in a Female Nonhuman Primate Model AE, adverse event; BZA, bazedoxifene. Matthew J. Jorgensen, PhD1, Peter F. Schnatz, D.O.2,3, Lawrence L. Rudel4, Matthew aP <0.01 vs placebo; Fisher exact test. Nudy2, Jay R. Kaplan1, Thomas B. Clarkson1. 1Department of Pathology/Comparative bP <0.05 vs placebo; Fisher exact test. Medicine, Wake Forest School of Medicine, Winston-Salem, NC; 2Department of ObGyn cExcludes 2 cases that were not confirmed as ovarian carcinoma by and Internal Medicine, The Reading Hospital and Medical Center, Reading, PA; histopathology. 3Departments of ObGyn & Internal Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; 4Department of Pathology/Lipid Sciences, Wake Forest School of Medicine, Winston-Salem, NC Objective: Recent studies have suggested that most American women have an adequate dietary intake of vitamin D. Not understood, however, is whether the rather large individual differences in plasma concentrations of vitamin D3 have any patho-physiologic significance. The purpose of this study was to investigate whether, and to what extent, these individual differences in plasma vitamin D concentrations are associated with important cardiovascular risk factors such as: age, abdominal obesity (waist circumference), and high-density lipoprotein cholesterol (HDL-C). Design: A cohort of 155 female vervet/African green monkeys (Chlorocebus aethiops sabaeus), ranging in age from 3-25 years old, were fed a typical Western diet for 7-8 weeks that provided them

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with a woman’s equivalent of approximately 1,000 IU/day of vitamin D3. Measurements of vitamin D3 and HDL-C concentrations, as well as waist circumference were obtained. Results: Among the entire cohort, the range of vitamin D3 concentrations was 19.6 to 142.0 ng/mL (mean ± SE = 66.4 ± 1.7 ng/mL). Plasma vitamin D3 concentrations were inversely associated with age (r=-0.35, p<0.0001). Among young monkeys (aged: 3-6 years) mean plasma vitamin D3 concentrations were 82.3 ± 3.2 ng/ml versus 58.6 ± 2.9 in older monkeys (aged: 16-25 years). Plasma vitamin D3 concentrations were inversely associated with waist circumference (r=-0.19, p=0.016). The females in the lowest quartile of vitamin D3 concentrations had waist circumferences of 34.1 ± 0.7 cm versus the highest quartile with waist circumferences of 31.7 ± 0.6 cm. Plasma vitamin D3 concentrations were positively correlated with HDL-C (r= 0.20, p=0.01). Thus, the lowest quartile of vitamin D3 had mean HDL-C concentrations that were 13.6 mg/dL less than the highest quartile. Conclusion: Lower plasma concentrations of vitamin D3 were significantly associated with older age, increased abdominal obesity, and decreased HDL-C. Therefore, higher plasma concentrations of vitamin D3 were associated with more favorable cardiovascular risk factors.

S-11. Correlation of age, ethnicity and body mass index (BMI) with change in bone mineral density over serial Dual Energy X-Ray Absorptiometry (DXA) scans among postmenopausal women Sobia Khan, M.D., Devorah R. Wieder, MD MPH, Holly Thacker, MD, Benjamin Nutter. Women’s Health, Cleveland Clinic Foundation, Cleveland, OH Objective: Identifying the factors that modify bone health helps determine, the population most at risk for osteoporosis in order to initiate preventive and treatment measures accordingly. The primary goal of this study was to analyze the correlation of age, ethnicity and BMI with change in the Bone Mineral Density (BMD) among postmenopausal women receiving serial DXA scans. BMI has an independent relationship with BMD regardless of age or ethnicity and it is postulated and concluded in various studies that obesity may decrease the risk of osteoporosis by increasing BMD. However, the effect of age and ethnicity in conjunction with BMI on change in bone mineral density over time has not been as well established. Design: Study Group : This retrospective, comparative Vitamin D3 concentrations by age. study was conducted on an initial data set containing 9,727 records for 1,956 patients who underwent Hologic Dual Energy X-Ray Absorptiometry scans at the Cleveland Clinic from April 2002 through February 2008. For purposes of analysis, records were kept only S-10. if the patient’s initial scan occurred post-menopause (age ≥ 50 years), and when a follow- The Quantification of Vitamin D Receptors in the Coronary Vasculature up scan occurred within 2 - 5 years of a previous scan. A significant change in BMD is and Association with Atherosclerosis denoted by an absolute change of more that 0.03 g/cm2. The final data set contained 609 Peter F. Schnatz, D.O.1,2, Matthew Nudy1, David M. O’Sullivan, PhD1, J. Mark Cline, records for 430 patients. Of these patients, 274 had two scans, 133 had 3 scans, and the DVM, PhD3, Susan E. Appt, DVM3, Xuezhi Jiang, MD1, Jay R. Kaplan3, Thomas B. remainder had four scans. The median age of patients was 53.1 years, and the study group Clarkson3. 1ObGyn & Internal Medicine, The Reading Hospital and Medical Center, was primarily Caucasian. The median time between scans was 26.22 months and the Reading, PA; 2ObGyn & Internal Medicine, Jefferson Medical College of Thomas median time since the initial scan was 32.66 months. Statistical Methods: Mixed Effects Jefferson University, Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest modeling approaches were employed to estimate the relationship between outcome University, Winston-Salem, NC variables and age, ethnicity, BMI, and time since initial scan while entering the patient as Objective: The activated vitamin D receptor (VDR) may have an important role in a random effect. Inspection of the random effects variances showed that these variances vascular health. The objective of this study was to evaluate whether there is an association were very small; suggesting that mixed effects techniques could be abandoned without between the abundance of VDR’s in the coronary vasculature and the degree of altering the results. Typical modeling approaches were used for calculation and atherosclerosis. Design: Utilizing a cohort of 39 postmenopausal female cynomolgus interpretation. Linear regression was used to investigate the relationship of the predictors monkeys with varying stages of atherosclerosis, transverse sections of the left anterior with raw BMD change while logistic regression was used to investigate the relationship descending artery (LAD) were analyzed for cross-sectional area, plaque thickness, and with the occurrence of a significant change in BMD. Initially, interaction terms were VDR quantity using immunohistochemical H-score analysis. The quantities of VDR’s included in the models, but were removed when they showed to be non-significant factors. were analyzed as a continuous variable and were divided at the median H-score into higher Variance inflation factors (VIF) were calculated to evaluate the presence of vs. lower groupings. Results: In the LAD, a significant negative correlation was observed multicollinearity. Analyses are performed using R 2.12.2 statistical software. Modeling is between the quantity of VDR and plaque size (both cross-sectional area [p<0.001, see performed using the functions in the lme4 and rms packages. Statistical significance is figure] and plaque thickness [p<0.001]). Monkeys in the low vitamin D receptor group had determined by a p-value ≤ 0.05. Results: Age and ethnicity showed no significant effect a significantly greater cross-sectional plaque area (1.2 mm2) and greater plaque thickness on change in BMD. BMI had a relationship with increased BMD where every unit (0.3 mm) than those in the high VDR group (0.4 mm2, p=0.005; 0.1 mm, p=0.003, increase in BMI was associated with a 0.0004 g/cm2 increase in BMD (p = 0.19), however respectively). Conclusion: Lower concentrations of VDR’s in a main coronary artery BMI showed no significant effect on change in BMD over time. Each month elapsing were associated with greater arterial plaque size in female postmenopausal monkeys. since the initial scan was associated with a -0.0004 g/cm2 decrease in BMD (p =0.002; Given that coronary artery atherosclerosis is a major cause of coronary heart disease in see Table 1.1). Each month elapsing since the initial scan was associated with a 2% postmenopausal women, further research to ascertain the relationship between Vitamin D increase in odds of a significant change (p < 0.001; see Table 1.1). Conclusion: While and atherosclerosis is warranted. BMI does bear a relationship with bone mineral density in postmenopausal women, low BMI was not associated with significantly greater decreases in BMD over time in this study. Decrease in BMD over time was also not correlated with age or ethnicity. This study highlights the need for a more complex risk profile to assist in predicting changes in BMD for an individual patient.

See table on next page.

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Table 1.1: Linear Model Summary for Serial BMD Loss in the Hip 3.6 y) participated in this substudy: BZA 20 mg/CE 0.45 mg (n=115), BZA 20 mg/CE 0.625 mg (n=123), BZA 20 mg (n=49), CE 0.45 mg/MPA 1.5 mg (n=56), or PBO (n=116). At 12 months, the mean change from baseline at Month 12 in scores for sleep adequacy, sleep disturbance, sleep problems overall (sleep problems index I and II), and time to fall asleep was significantly improved with BZA 20 mg/CE 0.625 mg compared with PBO (P <0.05 for all; Table); significant improvement in sleep disturbance and time to fall asleep scores was seen with BZA 20 mg/CE 0.45 mg compared with PBO (P <0.05 for each). Mean change from baseline at Month 12 in scores for sleep adequacy, sleep disturbance, overall sleep problems (sleep problems index I and II), and time to fall asleep was significantly improved with CE 0.45 mg/MPA 1.5 mg compared with PBO (P <0.05 for all). At 12 months, MENQOL results (Table) showed that women treated with BZA/CE 0.45 or 0.625 mg had significant improvement in total and vasomotor scores compared with PBO (P <0.05 for each). In addition, the mean change from baseline in S-12. sexual and physical function scores was significantly improved with BZA 20 mg/CE Efficacy of flibanserin as a potential treatment for Hypoactive Sexual 0.625 mg compared with PBO (P <0.01 for each) at Month 12. Significant improvement Desire Disorder in North American postmenopausal women was also seen in the CE 0.625-mg/MPA 1.5-mg group in the mean change from baseline James A. Simon, MD, CCD, NCMP, FACOG1, Leonard DeRogatis3, Lorraine in total and vasomotor scores compared with the PBO group (P <0.05 for each) at 12 Dennerstein2, Michael Krychman4, Brad Shumel5, Miguel Garcia5, Vladimir Hanes5, months. Conclusion: Symptomatic postmenopausal women treated with BZA/CE had Michael Sand, PhD, MPH5. 1George Washington University, Washington, DC; 2University significant improvement in sleep parameters and HR-QoL over 1 year. These results are of Melbourne, Melbourne, VIC, Australia; 3Center for Sexual Medicine at Sheppard Pratt, consistent with those seen in previous SMART trials, and support BZA/CE as an effective Baltimore, MD; 4Southern California Center for Sexual Health and Survivorship treatment option for menopausal symptoms while protecting the endometrium in Medicine, Newport Beach, CA; 5Boehringer-Ingelheim, Ridgefield, CT postmenopausal women. Objective: To assess the efficacy of 24 weeks’ treatment with flibanserin 100mg qhs for generalized, acquired Hypoactive Sexual Desire Disorder (HSDD) in postmenopausal Table. Mean Change From Baseline in MOS Sleep Scale Measures and MENQOL women. Design: This was a double blind, randomized, placebo-controlled trial of Scores at 12 Months (SMART-5) flibanserin 100mg qhs in postmenopausal women (n=949). Co-primary endpoints were change from baseline to study end in: 1) the number of satisfying sexual events (SSE) and 2) Female Sexual Function Index (FSFI-d) desire domain, both assessed over a 28 day period. Secondary endpoints included: Female Sexual Distress Scale-Revised (FSDS-R) total and FSDS-R Item 13 scores (distress associated with low sexual desire))Efficacy analyses were based on the full analysis set (FAS), which included all women who were randomized, received one dose of study medication and had at least one on treatment efficacy assessment. Intent to treat, last observation carried forward (LOCF) analysis was used for all efficacy analyses. Results: Mean (SD) baseline data were: SSE 2.1 (2.3) and FSFI-d 1.8 (0.7). The mean changes from baseline to study end in the efficacy endpoints are given in the table below. Adverse events leading to discontinuation were experienced by 3.5% of women receiving placebo and 8.1% of women receiving flibanserin 100mg. Serious adverse events were reported by 0.8% of women receiving placebo and 1.7% of women receiving flibanserin 100mg. Conclusion: In this North American trial in postmenopausal women with HSDD, flibanserin 100 mg qhs was associated with clinically meaningful and statistically significant improvements in both co-primary endpoints, the number of SSE and sexual desire (FSFI desire domain), and the secondary endpoints for distress associated with sexual dysfunction (FSDS-R total) and distress associated with low sexual desire (FSDS-R Item 13) compared with placebo.

Mean change from baseline to study end in efficacy endpoints

aP <0.05 vs placebo.

*p=0.004 versus placebo S-14. **p<0.0001 versus placebo ***p=0.0059 versus placebo Effect of Escitalopram on Insomnia Symptoms and Subjective Sleep ****p=0.0083 versus placebo Quality in Healthy Menopausal Women with Hot Flashes: A Randomized Controlled Trial in the MsFLASH Network Kristine Ensrud, MD, MPH1, Joesph Larson2, Katherine Guthrie2, Hadine Joffe, MD, CONCURRENT SESSION #2 MSc3, Andrea LaCroix2, Carol Landis4, Katherine Newton5, Susan Reed4, Barbara Sternfield6, Nancy Woods4, Ellen Freeman7. 1Medicine, University of Minnesota / VA Medical Center, Minneapolis, MN; 2Fred Hutchinson Cancer Research Center, Seattle, S-13. WA; 3Harvard Medical School, Boston, MA; 4University of Washington, Seattle, WA; Effects of Bazedoxifene/Conjugated Estrogens on Sleep Parameters and 5Group Health Research Institute, Seattle, WA; 6Research, Kaiser Permanente, Oakland, Health-related Quality of Life in Postmenopausal Women CA; 7Medicine, University of Pennsylvania, Philadelphia, PA JoAnn V. Pinkerton1, Kaijie Pan2, Lucy Abraham2, Jill Racketa2, Arkadi A. Chines2, Objective: Determine the effect of escitalopram on insomnia symptoms and subjective Sebastian Mirkin2. 1University of Virginia Health System, Charlottesville, VA; 2Pfizer Inc, sleep quality in healthy menopausal women with hot flashes. Design: Randomized, Collegeville, PA double-blind, placebo-controlled, parallel arm, multicenter trial of escitalopram (10-20 Objective: Bazedoxifene/conjugated estrogens (BZA/CE) is a tissue selective estrogen mg/day in a flexible-dose regimen) for 8 weeks in 205 women. By design, nearly half of complex (TSEC) that has been shown in previous studies to be an effective treatment for the study population was African-American. Insomnia symptoms (Insomnia Severity vasomotor symptoms (VMS) while ensuring endometrial safety in women less than or Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]), a priori more than 5 years from menopause. The effects of BZA/CE on sleep parameters and specified secondary outcomes, were collected at baseline and week 4 and 8. Of 205 health-related quality of life (HR-QoL) were assessed in the Selective estrogens, women randomized, 200 (98%) provided ISI data and 198 (97%) provided PSQI data at Menopause, And Response to Therapy (SMART)-5 trial. Design: In this phase 3, double- week 8. Results: At baseline, mean hot flash frequency was 9.78/day (SD 5.60), mean ISI blind, placebo (PBO)-controlled study (N=1,843), postmenopausal women with an intact was 11.4 (SD 6.3), and mean PSQI was 8.0 (SD 3.7). Treatment with escitalopram reduced uterus were randomized to BZA 20 mg/CE 0.45 or 0.625 mg, BZA 20 mg, CE 0.45 ISI at week 8 (mean difference -2.00, 95% CI: -3.43 to -0.57, p <0.001 overall treatment mg/medroxyprogesterone acetate (MPA) 1.5 mg, or PBO daily for 12 months. Sleep and effect), with mean reductions of -4.73 (95% CI -5.72 to -3.75) in the escitalopram group HR-QoL were evaluated in a subset of women with bothersome VMS and sleep problems and -2.73 (95% CI -3.78 to -1.69) in the placebo group. Reduction in PSQI was greater at baseline. The Medical Outcomes Study (MOS) sleep scale was used to evaluate in the escitalopram versus placebo group (mean difference at week 8 -1.31, 95% CI -2.14 individual sleep parameters, including sleep adequacy, sleep disturbance, sleep quantity, to -0.49, p <0.001 overall treatment effect). Clinical improvement in insomnia symptoms somnolence, snoring, shortness of breath or headache, and time to fall asleep; overall and subjective sleep quality (defined as a 50% or greater decreases in ISI and PSQI from sleep problems were measured with 2 summary index scores (sleep problems index I and baseline) was observed more frequently in the escitalopram group versus placebo group II). The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to (ISI: 50.0% versus 35.4%, p=0.04; PSQI 29.6% versus 19.2%, p=0.09). Conclusion: evaluate HR-QoL; the questionnaire comprises 4 domains (vasomotor, psychosocial, Among healthy menopausal women with hot flashes, escitalopram at 10-20 mg/day sexual, and physical function) that were scored individually and averaged for a total score. compared with placebo reduced insomnia symptoms and improved subjective sleep Results: A total of 459 women (mean age, 53.4 y; mean years since last menstrual period, quality at 8 weeks of follow-up.

36 S-15. significantly with most of the depression items (HADS-D) and anxiety items (HADS-A) Hot Flashes Recur Rapidly After Discontinuation of the SSRI in the HADS questionnaire, and the absolute values of correlation coefficients were Escitalopram: Results from the MsFLASH Research Network generally larger in NRS than in DIS. (4) Multiple linear regression analysis was performed Hadine Joffe, MD, MSc1, Katherine A. Guthrie, PhD2, Lee Cohen, MD1, Janet Carpenter, with the NRS severity score as the dependent variable, and the HADS items #2 (“I still PhD, RN3, Joseph Larson, MS2, Andrea LaCroix, PhD2, Ellen W. Freeman, PhD4. enjoy the things I used to enjoy.”) and #3 (“I got a sort of frightened feeling as if something 1Psychiatry, Massachusetts General Hospital, Boston, MA; 2Fred Hutchinson Cancer awful is about to happen.”) scores as representative predictors for depression and anxiety, Research Center, University of Washington School of Public Health, Seattle, WA; 3School respectively. Standardized partial correlation coefficients for depression and anxiety was of Nursing, Indiana University, Indianapolis, IN; 4Department of Obstetrics/Gynecology, -0.248 (p = 0.009) and -0.243 (p = 0.011). Conclusion: Sleep disturbances are highly University of Pennsylvania, Philadelphia, PA prevalent in peri- and post-menopausal women, and are closely related with psychological Objective: Hot flashes are known to recur after hormonal therapy is discontinued. As symptoms rather than somatic ones. Depression and anxiety is more strongly associated non-hormonal medications such as selective serotonin reuptake inhibitors (SSRI’s) are with NRS than with DIS, and the both factors equally contribute to make sleep less used more widely to treat hot flashes, it is important to understand whether hot flashes restorative in these women. similarly recur after SSRI discontinuation. In an 8-week randomized controlled trial of escitalopram, the Menopause Strategies: Finding Lasting Answers for Symptoms and S-17. Health (MsFLASH) Research Network found that escitalopram was more effective than Plasma Melatonin Circadian Rhythms in Menopausal Depressed vs. placebo in treating bothersome hot flashes (p<0.001). In the current analysis, we examine the prevalence and predictors of hot flashes recurring 3 weeks after escitalopram was Normal Control Women Barbara L. Parry, M.D., Charles Meliska, PhD, Diane Sorenson, Ana Lopez, Fernando discontinued under double-blinded conditions. We hypothesized that recurrence of hot Martinez, Henry Orff. Psychiatry, University of California, San Diego, La Jolla, CA flashes would be common and predicted by menopausal and psychological characteristics Objective: The aim was to test the hypothesis that the amplitude or phase (timing) of at treatment initiation. Design: Caucasian and African-American peri- and melatonin circadian rhythms differs in menopausal depressed patients (DP) vs. Normal postmenopausal women with 4+ bothersome hot flashes per day were randomized to Control (NC) women because the constellation of endocrine patterns accompanying escitalopram (10–20mg/day) vs. placebo for 8 weeks. At the end of the trial, there was a menopausal depression remains incompletely characterized. Design: In a university 3-week double-blinded discontinuation phase during which time medication was stopped. hospital setting, we measured plasma melatonin every 30 minutes from 18:00-10:00 h in Hot flash frequency was measured continuously with a daily diary during the screening, dim light (< 30 lux) or dark, serum gonadotropins and steroids (18:00, 06:00 h) and mood treatment, and discontinuation phases of the trial. Hot flash recurrence was defined as hot (Hamilton and Beck depression ratings) in 29 (18 NC, 11 DP) peri- or post-menopausal flash frequency at the end of 3 weeks within 20% of the level reported at baseline. A women. Main outcome measures were plasma melatonin (onset, offset, synthesis offset, subgroup analysis was conducted among those whose hot flashes responded to duration, peak concentration, area under the curve) and mood. Results: Multi- and escitalopram (≥30% decrease in hot flashes from baseline to week 8). Logistic regression univariate analyses of covariance (MANCOVA, ANCOVA) showed melatonin offset time models were developed to determine which a priori characteristics predicted recurrence was delayed (P = .045) and plasma melatonin was elevated in DP compared with NC (P among all randomized to escitalopram and then among those responding to escitalopram. = .044) across time intervals. Multiple regression analyses showed that years past Demographic and menopausal characteristics and baseline symptom levels of hot flashes, menopause predicted melatonin duration, and that melatonin duration, body mass index insomnia [Insomnia Severity Index], depression and anxiety were included in the (BMI), years past menopause, Follicle Stimulating Hormone (FSH) level and sleep end multivariable model if they showed a univariate association. Results: Of 104 assigned to time were significant predictors of baseline Hamilton (P = .0003) and Beck (P = .00004) escitalopram, 97 (93%) completed the 8-week trial, and 93 (89%) provided hot flash data depression scores. Conclusion: Increased melatonin secretion that is phase-delayed into through the end of the discontinuation phase. The mean hot flash frequency was 9.9 (SD the morning characterized menopausal DP vs. NC. Years past menopause, FSH, sleep end 6.2) per day at baseline and 7.2 (SD 6.3) per day at the end of the discontinuation phase. time and BMI may modulate effects of altered melatonin secretion in menopausal Hot flashes recurred in 36 (39%) women after treatment discontinuation, and in 20 (29%) depression. of 68 women who responded to escitalopram. Univariate models showed that Caucasian race, postmenopausal status, and higher levels of insomnia symptoms at baseline predicted hot flash recurrence (all p<0.05). In adjusted models, only higher levels of insomnia S-18. symptoms remained a significant predictor of hot flash recurrence (odds ratio [OR], 95% Cognition in Perimenopause: How menopause transition stage affects the confidence interval [CI] for a 5-point increase in the ISI: 1.60, 1.04–2.47, p=0.03). trajectory of cognitive change over time Analyses restricted to the subgroup of women who responded to escitalopram revealed Miriam Weber1, Leah Rubin2, Pauline Maki2. 1Department of Neurology, University of that Caucasian race, insomnia symptoms, and BMI were associated with hot flash Rochester, Rochester, NY; 2Department of Psychiatry, University of Illinois at Chicago, recurrence in unadjusted models (all p<0.10). However, in adjusted models, only Chicago, IL Caucasian race showed a trend toward an increased likelihood of hot flash recurrence Objective: Studies of objective cognitive performance during the menopausal transition (OR 4.76, 95% CI 0.88–25.0 p=0.07). Conclusion: Hot flashes recurred rapidly—within reveal small, but measurable, declines in verbal fluency, verbal episodic memory and 3 weeks after treatment discontinuation—in approximately one-third of women whose processing speed. The aim of this study was to determine the trajectory of cognitive hot flashes were treated with and responded to the SSRI escitalopram. Women with higher function in perimenopausal women over one year. Specifically, we aimed to determine if levels of insomnia symptoms at baseline were most likely to report recurrence of hot cognitive function declines from baseline to one year follow-up and if cognitive change flashes. These results provide the first evidence that hot flashes recur rapidly in a over time differs according to perimenopausal group status at baseline. Design: 59 significant proportion of women after short-term treatment with non-hormonal SSRI perimenopausal women between the ages of 40 and 60 were categorized into early therapies. (changes in menstrual flow amount, duration and/or cycle length) (n=9), middle (≥ 1 episode of cycle irregularity, with no skipping of periods) (n=16) or late (≥ 1 skipped S-16. period) (n=34) perimenopause based on self-reported menstrual patterns, according to Depression and Anxiety Is Associated with Non-Restorative Sleep in Peri- criteria from the Seattle Midlife Women’s Health Study. We adminstered a comprehensive and Post-Menopausal Women neuropsychological battery and a self-report inventory of depression. Women were evaluated at baseline, 6 months, and one year follow-up. We had a 97% retention rate Masakazu Terauchi, MD, PhD1, Shiro Hiramitsu, MD1, Mihoko Akiyoshi1, Yoko Owa1, (n=57) from baseline to 6 months and a 96% retention rate (n=55) from 6 months to 1 Kiyoko Kato1, Satoshi Obayashi, MD, PhD1, Eisuke Matsushima2, Toshiro Kubota, MD, year. Two women were evaluated at baseline and 1 year, but were not seen at 6 months. PhD1. 1Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Women who participated in at least two evaluations were included in the current analyses Tokyo, Japan; 2Department of Psychosomatics, Tokyo Medical and Dental University, (n=59). Composite z-scores were computed for the following cognitive domains: working Tokyo, Japan memory/attention, executive function, visuospatial function, motor funtion, verbal Objective: To investigate the association of depression and anxiety with sleep learning, and verbal memory. All primary hypotheses were tested using mixed effects disturbances in peri- and post-menopausal women. Design: We retrospectively analyzed regression models, controlling for age, education and self-reported depressive symptoms. the records of 442 peri- and post-menopausal women who were enrolled in the Systematic Results: As a group, women’s performance on all cognitive domains significantly Health and Nutrition Education Program, conducted at the Menopause Clinic of the Tokyo improved from baseline to follow-up (p<.001). However, the trajectory of change over Medical and Dental University Hospital, between May 2005 and December 2010. In this time differed as a function of baseline perimenopausal group status. Women in early program, the physical and mental health of these women was assessed using the perimenopause showed no significant improvement in motor and verbal memory Menopausal Health-Related Quality of Life (MHR-QOL) questionnaire developed in our performance over time, and women in middle perimenopause showed no significant clinic, and the Hospital Anxiety and Depression Scale (HADS) questionnaire developed improvement in verbal learning and verbal memory over time. Women in late by Zigmond and Snaith. The MHR-QOL questionnaire contains 9 somatic and 12 perimenopause significantly improved in all cognitive domains. Women in early psychological items including difficulty in initiating sleep (DIS) and non-restorative sleep perimenopause showed significantly more improvement in verbal learning tasks than (NRS), while the HADS comprises 7 anxiety and 7 depression items. The subjects women in middle perimenopause (p<.001) across time. Conclusion: Cognitive function responded to each item in the questionnaires on a 4-point Likert scale. The following in perimenopause may not be linear, but instead may change over the course of the entire issues were addressed by evaluating the MHR-QOL and the HADS scores of these menopusal transition. The trajectory of this change may differ as a result of women: (1) The prevalence of sleep disturbances; (2) the association of somatic and perimenopausal group status. The cognitive domains of verbal learning, verbal memory psychological symptoms with sleep disturbances; and (3) the association of depression and fine motor speed and dexterity may be particularly vulnerable during perimenopause. and anxiety with sleep disturbances. Results: (1) The percentage of women who reported DIS and NRS more than 3 nights per week was 31.9% and 40.7%, respectively. (2) DIS and NRS severity scores were correlated better with psychological symptom scores (depressed mood, panic attacks, etc.) than with somatic ones (hot flashes, night sweats, etc.) in the MHR-QOL questionnaire. (3) DIS and NRS severity scores were correlated

37 Scientific Sessions(continued)

CONCURRENT SESSION #3 for hepatic events 0.08 (90% CI -3.51, 3.67). Conclusion: There was no evidence of increased risk of cardiovascular, cerebrovascular, or hepatic events for desvenlafaxine vs placebo in this study, indicating that desvenlafaxine was safe for use in women with VMS. S-19. Adiposity and hot flashes in midlife women: Timing is everything Rebecca C. Thurston, PhD1,2, Nanette Santoro, MD3, Karen A. Matthews, PhD1,2. S-21. 1Psychiatry, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology, University of Pulse Wave Velocity is Positively Correlated with Atherosclerosis Extent Pittsburgh, Pittsburgh, PA; 3Obstetrics and Gynecology, University of Colorado, Denver, in Midlife Female Nonhuman Primates CO Susan E. Appt, DVM1, Kylie Kavanagh, DVM1, Haiying Chen1, Jay R. Kaplan1, Jason Objective: It is a long-held belief that adiposity protects women from hot flashes due to Lazar2, Thomas B. Clarkson1. 1Comparative Medicine, Wake Forest School of Medicine, androgen-to-estrogen sex steroid bioconverstion by adipose tissue. However, recent Winston Salem, NC; 2Division of Cardiovascular Medicine, State University of New York findings from epidemiologic investigations suggest that greater adiposity is associated Downstate Medical Center, Brooklyn, NY with increased hot flash reporting. This work is largely based upon questionnaire measures Objective: To determine whether, in midlife females, a non invasive measure of arterial of hot flashes, without the use of real-time self-reporting or physiologic measures of hot stiffness (pulse wave velocity, PWV) is a marker of atherosclerosis extent, and to flashes. Dose-response relations between adiposity and flashes have also been unexplored. investigate the relationships among PWV and plasma cardio-metabolic risk markers. The aim of this study was to use diary and physiologic measures of hot flashes to examine Design: Subjects were 49 socially housed, female cynomolgus monkeys (Macaca associations between body size/composition and hot flashes. Variations in these relations fascicularis) with an estimated mean age of 19 years (~57 women’s equivalent years). by age were also examined. Design: A subcohort of women in the Study of Women’s After consuming a human-like diet containing animal protein and cholesterol for ~two Health Across the Nation (N=52; 25 African American, 27 non-Hispanic Caucasian) who years, PWV, cardio-metabolic risk markers, and Left common iliac artery atherosclerosis reported hot flashes in the past two weeks, had an intact uterus and both ovaries, and were (LCI, via surgical biopsy) were measured. The iliac artery has been validated as a not taking medications impacting hot flashes, were recruited in 2008-2009. Women surrogate for coronary artery atherosclerosis extent in the cynomologus monkey. Pulse completed anthropometric measures (bioimpedence analysis of total percentage of body waveforms were recorded using tonometry (SphygmoCor®) at the brachial and femoral fat, body mass index (BMI), waist circumference), and a blood draw (estradiol (E2), arteries sequentially. Transit time was calculated using the R wave of a simultaneously SHBG, FSH). Women also underwent four days of ambulatory sternal skin conductance electrocardiography recording and the difference in distance between the brachial artery monitoring with a diary, such that physiologic and self-reported hot flashes were both site and the supra sternal notch, and the distance between the supra sternal notch and the recorded simultaneously. Associations between anthropometrics and hot flashes were femoral artery site. Multivariate regression analysis was used and data are reported as estimated with generalized estimating equations, adjusting for factors associated with hot correlations (r) and mean (±SE). Results: PWV for female monkeys was similar to that flashes (age, race, anxiety). Interactions by age were examined in all models. The observed in adult human subjects (7.7±0.28, range = 4.4 – 12 meters/second). Significant influence of menopausal stage was not examined as 90% of the sample was associations were observed between PWV and both LCI atherosclerosis extent (r = 0.33, postmenopausal. Results: Higher BMI (odds ratio (OR), 95% confidence interval p=0.02) and systolic blood pressure (r = 0.33, p=0.02). There was a tendency for positive (CI)=0.97(0.94-0.99), p<0.05) and waist circumference (OR(95%CI)=0.98(0.97-0.99), associations with plasma LDL + VLDL (r = 0.29, p=0.06), BMI (r = 0.27, p=0.06, kg/m2), p<0.01) were associated with fewer physiologic hot flashes. Interactions by age (p’s<0.05) HgA1c% (r = 0.22, p = 0.12) and plasma glucose (r = 0.20, p = 0.14). In addition, a indicated that the inverse associations of body fat, BMI, and waist circumference with multivariate analysis indicated that plasma glucose was an independent predictor of PWV hot flashes were most apparent among the oldest women in the sample. Additionally (p<0.04). No significant associations were observed with diastolic blood pressure or other controlling for E2 and SHBG reduced, but did not eliminate, age-related variations in lipid variables. Conclusion: The results of this study suggest that, like women, arterial relations between body size/composition and hot flashes. Conclusion: Higher adiposity stiffness is a significant predictor of atherosclerosis in nonhuman primates. Further studies was associated with fewer physiologic hot flashes among older women with hot flashes, are indicated to determine whether measures of insulin resistance are similarly correlated suggesting that as ovarian estrogen production ceases, the role of peripheral adiposity as with PWV, as has been reported in postmenopausal women. a source of estrogen becomes more important in predicting hot flashes. A modifying role of age should be considered in understanding the role of adiposity in hot flashes. SWAN has support from the NIH, DHHS, through NIA, NINR and NIH ORWH (NR004061; S-22. AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, Tissue Selective Estrogen Receptor α Agonists Reverse Weight Gain AG012495). This work was also supported by AG029216. The content of this abstract is without Causing Mammary Gland or Uterine Proliferation solely the responsibility of the authors and does not necessarily represent the views of Mary Tagliaferri, MD1, Elise Saunier, PhD1, Omar I. Vivar2, Andrea Rubenstein1, the NIA, NINR, ORWH or NIH. Sreenivasan Paruthiyil1, Scott Baggett1, Richard E. Staub1, Isaac Cohen1, Dale C. Leitman2,1. 1Bionovo, Emeryville, CA; 2Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, CA S-20. Objective: Long-term estrogen deficiency increases the risk of obesity, diabetes and Cardiovascular, Cerebrovascular and Hepatic Safety of Desvenlafaxine metabolic syndrome in postmenopausal women. Menopausal hormone therapy containing Over 1 Year in Women With Vasomotor Symptoms Associated With estrogens might prevent these conditions, but its prolonged use increases the risks of Menopause breast cancer, strokes and thromboembolic events. Animal studies indicate that the David F. Archer1, JoAnn V. Pinkerton2, Christine J. Guico-Pabia, MD, MBA, MPH3, beneficial effects of estrogens in adipose tissue and adverse effects in the mammary gland Eunhee Hwang3, Ru-fong J. Cheng3. 1Eastern Virginia Medical School, Clinical Research and uterus are mediated by estrogen receptor alpha (ERα). One strategy to prevent obesity, Center, Norfolk, VA; 2University of Virginia Health System, Charlottesville, VA; 3Pfizer diabetes and metabolic syndrome is to improve the safety of estrogens by developing Inc, Collegeville, PA tissue selective ERα drugs that act as agonists in adipose tissue, but not in the mammary Objective: Clinical data have shown that the serotonin-norepinephrine reuptake inhibitor gland and uterus. To date, tissue selective ERα agonists have not been identified. Design: desvenlafaxine (administered as desvenlafaxine succinate) is effective for the treatment We considered plant extracts as a source of tissue selective ERα agonists and screened of moderate to severe vasomotor symptoms (VMS) associated with menopause. However, multiple extracts using transfection assays. Numerous plant extracts were screened for one 12-month study noted cardiovascular events in 5/612 women taking desvenlafaxine.1 ERα activity by transfecting U2OS cells with the classic estrogen responsive element The objective of the current study was to examine the safety of desvenlafaxine including (ERE) upstream a minimal thymidine kinase promoter linked to the luciferase reporter estimated incidence of cardiovascular events, cerebrovascular events, and hepatic events gene (ERE tk-Luc) and an expression vector for human ERα. Based on these findings we for desvenlafaxine vs placebo in symptomatic, generally healthy menopausal women selected two plant extracts that we used in a high fat diet fed mouse model to examine if seeking treatment for VMS. Design: This was a multicenter, randomized, double-blind, they reverse weight gain and fat accumulation. Potential adverse proliferative effects of placebo-controlled safety and efficacy study in postmenopausal women seeking treatment the plant extracts in the mammary gland and uterus were assessed in a mouse model where for symptomatic VMS. Following a 1 week titration period, desvenlafaxine 100 mg/d was treatment time was 49 days. Last, to examine the tissue specific effects of the plant extracts administered for up to 1 year. Safety was monitored with physical examinations, adverse at the genomic level, we compared gene expression profiles in gonadal fat, mammary events (AEs) collection, vital sign measurements, laboratory evaluations, and gland and uterus in response to estradiol and the extracts. Results: Extracts from two electrocardiogram results. Potential cases of ischemic cardiovascular events (coronary plants, Radix Glycyrrhiza uralensis (RG) and Radix Pueraria lobata (RP) selectively heart disease-related death, new onset myocardial infarction [MI], or unstable angina activated multiple ERα responsive reporters, and reversed weight gain and fat requiring hospitalization, and unscheduled revascularization procedures) and accumulation comparable to estradiol in ovariectomized obese mice maintained on high cerebrovascular events (definite stroke or probable stroke) identified by investigator fat diet. Unlike estradiol, RG and RP did not induce proliferative effects on the mammary reports and periodic adverse event review based on Standardized Queries of the Medical gland and uterus. Gene expression profiling demonstrated that RG and RP induced Dictionary for Regulatory Activities were reviewed by blinded adjudication boards. estrogen-like regulation of genes in abdominal fat, but not in the mammary gland and Hepatic events (liver function tests [alanine aminotransferase or aspartate uterus. RG and RP also behaved differently than the SERMs, raloxifene and tamoxifen, aminotransferase] >5X upper limit of normal) were identified based on central laboratory because they did not antagonize the effects of estradiol. Conclusion: The compounds in data. Results: A total of 2118 participants took ≥1 dose of study medication (mean extracts from RG and RP might constitute the first class of tissue selective ERα agonists therapy duration of 280 days); 1066 received desvenlafaxine and 1052 received placebo. to prevent and/or reverse weight gain, fat accumulation, metabolic syndrome and other There was 1 event adjudicated to be a cardiovascular event: 1 placebo-treated participant conditions in postmenopausal women. had an MI. One desvenlafaxine-treated participant was adjudicated to have a probable stroke. Two participants in each treatment group had hepatic events. The excess risk of desvenlafaxine compared with placebo per 1000 woman-years for cardiovascular events was -1.07 (90% CI -2.86, 0.72), for cerebrovascular events 1.11 (90% CI -0.68, 2.9), and

38 S-23. our knowledge, this is the first study directly comparing objective hot flashes in women Cortical Thickness Analysis in Depressed, Medication-free, and men undergoing ADT therapy. The finding that the circadian rhythm was similar Perimenopausal and Postmenopausal Women between the sexes, suggests that similar mechanisms might contribute to HF in both Luciano Minuzzi, MD, Ph.D, Benicio N. Frey, Geoffrey B. Hall, Ivan Skelin, Stefanie women and men on ADT. Given previous findings of altered circadian rhythms of hot Attard, Meir Steiner, Claudio N. Soares, MD, PhD, FRCPC. Department of Psychiatry and flashes in breast cancer survivors, our data suggests that HFs in men undergoing ADT Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada may be more similar to HFs in healthy women than HFs in breast cancer survivors. Objective: The menopausal transition and early postmenopausal years have been Understanding overlap in the physiology and circadian rhythm of HFs across patient described as a period of higher risk for the development of depressive symptoms or Major populations might suggest which patient populations might benefit from HF treatments. Depressive Disorders (MDD) in a woman’s life. Previous structural imaging studies conducted in patients with MDD have shown volume reductions in several brain regions that are involved in emotional regulation. However, the impact of MDD on cerebral grey CONCURRENT SESSION #4 matter in midlife women has yet to be determined. In a recent functional magnetic resonance imaging (fMRI) study, we demonstrated that depressed perimenopausal women failed to deactivate the rostral anterior cingulate cortex (ACC) during a response inhibition S-25. task. The objective of the present study is to measure grey matter cortical thickness in the Measurement of Urogenital Symptoms brain of medication-free midlife women with diagnosis of MDD in comparison to healthy Lila E. Nachtigall, MD, NCMP1, Gloria A. Bachmann, MD2. 1Department of Obstetrics controls by using structural MRI. Furthermore, we aim to investigate at regional level & Gynecology, New York University Langone Medical Center, New York, NY; whether grey matter abnormalities in the ACC correlate with depressive symptoms in this 2Department of Obstetrics, Gynecology and Reproductive Sciences, UMDNJ-Robert population. Design: Thirteen medication-free peri/postmenopausal women (mean age = Wood Johnson Medical School, New Brunswick, NJ 49.5 ± 3.8 years) diagnosed with a major depressive episode (mean total MADRS Symptoms of vulvo-vaginal dryness, irritation, itching, and discharge, dyspareunia, dysuria scores=19.2 ± 5.0, mean duration of depressive episode=17.6 months) and 13 healthy and frequent urinary tract infections are associated with the hypoestrogenic state, most (non-depressed), age-matched controls (mean age=50.1 ± 5.3 years, mean total MADRS notable in menopausal women, regardless of etiology. The SWAN study confirmed clinical scores=2.6 ± 1.7) underwent high-resolution structural MRI in a 3T scanner. The images observations that vaginal dryness, especially as it relates to dyspareunia, can be a symptom were pre-processed in order to segment the brain into grey, white and CSF tissue classes during the perimenopausal transition as well. The largest cohort of menopausal women and to align cortical structures across the subjects. Grey matter cortical thickness was studied that reports on the prevalence of self-reported urogenital symptoms is derived from measured using the Laplace method. Volume-of-interests (VOIs) corresponding to ACC the data of 98,705 postmenopausal women enrolled in the observational study and clinical subregions (dorsal, rostral, and subgenual) were manually drawn on the three dimensional trials of the Women’s Health Initiative. These data indicate that as many as one quarter of image. Voxel-wise statistical analysis was performed between the groups using menopausal women will report urogenital symptoms (vaginal or genital dryness, 27.0%; BrainVoyager QX software. Results: Voxel-wise analysis revealed decreases in grey vaginal or genital irritation or itching, 18.6%; vaginal or genital discharge, 11.1%; and matter thickness in subjects with MDD in the temporal lobe (superior and middle temporal dysuria, 5.2%). In addition to vaginal estrogen therapy, other interventions, including oral gyri), angular gyrus, superior frontal gyrus, ACC, anterior midcingulate cortex and Dt56a a phtoestrogen, and vaginal DHEA are being researched to reverse symptoms and precuneus. Depressed subjects presented thicker grey matter in the right dorsolateral signs of urogenital atrophy. To measure the response of a studied intervention, a subjective prefrontal cortex (DLPFC). Moreover, VOI analysis in the ACC showed decreases in measurement of severity is often accomplished by patient self report-using a likert scale cortical thickness in the left hemisphere of depressed subjects (ANOVA, F=6.4, p=0.01). grading, which also is applicable in clinical practice. Although attempts have been made Lastly, left dorsal ACC presented higher cortical thinning in subjects with MDD (< 20%, to document and objectively measure severity of atrophic urogenital changes observed by p=0.02). Depressive symptoms (i.e., MADRS scores) were inversely correlated with pelvic examination, none to date have been validated. Also, there are no biomarkers that cortical thickness in the left ACC (p=0.01). No effect of age on cortical thickness was can be followed for treatment response. For estrogen therapy, efficacy is also measured by found in subjects with MDD or controls. Conclusion: To our knowledge, this is the first the objective endpoints of pH and maturation index. Quantitative measurement of increased study examining cortical thickness in medication-free MDD midlife women with vaginal secretions as an efficacy measure for both estrogen and non-estrogen interventions depression. Depressed, unmedicated midlife women showed reduction in cortical using calcium alginate nasopharyngeal swabs or nylon-flocked cervicovaginal swabs have thickness in a number of brain regions, and an increase in cortical thickness in the right been studied to date only in non-human animal studies. DLPFC compared to healthy age-matched controls. In addition, severity of depressive symptoms was associated with cortical thinning in the left ACC. These results suggest that the untreated depressive disorder in perimenopausal and early postmenopausal women might have a negative impact in discrete brain regions associated with mood and cognitive MsFLASH RESEARCH NETWORK control. Future studies should clarify the potential effects of pharmacologic treatments on cortical brain structure in this population. S-26. New Clinically Relevant Findings from the MsFLASH Research Network: S-24. The Escitalopram Trial Circadian Rhythm of Hot Flashes in Symptomatic Postmenopausal Andrea Z. LaCroix1, Ellen W. Freeman2, Kristine Ensrud, MD, MPH3, Susan D. Reed, Women and Men Undergoing GnRH Analog Therapy MD, MPH4. 1Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Lauren L. Drogos, M.A.1, Rhoda Jamadar2, Leah Rubin2, Stacie Geller3, Lee Shulman4,5, Seattle, WA; 2Departments of Obstetrics/Gynecology and Psychiatry, University of Suzanne Banuvar4, David Walega, M.D.5, Pauline M. Maki1,2. 1Psychology, University of Pennsylvania Medical School, Philadelphia, PA; 3VA Medical Center, University of Illinois at Chicago, Chicago, IL; 2Psychiatry, University of Illinois at Chicago, Chicago, Minnesota, Minneapolis, MN; 4School of Nursing, Indiana University, Indianapolis, IN IL; 3Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL; The Menopause Strategies: Finding Lasting Answers for Symptoms and Health 4Northwestern University, Chicago, IL; 5Northwestern Memorial Hospital, Chicago, IL (MsFLASH) clinical trials network, supported by the National Institute on Aging as a Objective: Hot flashes (HFs) are the most commonly reported and bothersome cooperative agreement, is conducting a series of randomized clinical trials designed to test menopausal symptom, but can also occur in up to 80% of men undergoing androgen new interventions for menopausal symptoms. Our first randomized trial of escitalopram in deprivation therapy (ADT) for prostate cancer. Hot flashes have been associated with healthy menopausal women with hot flashes, found that treatment significantly reduced the memory changes, loss of bone density, cardiovascular disease and depressive symptoms frequency, severity and bother of vasomotor symptoms during 8 weeks of treatment. in women across the menopausal transition. Previous reports have shown a circadian Delving further into the effects of escitalopram on vasomotor symptoms, we then examined rhythm of hot flashes in healthy postmenopausal women, but not breast cancer survivors. the efficacy of escitalopram compared with placebo for: (1) daytime and nighttime hot The current study compared and contrasted circadian rhythm of hot flashes in flash frequency, severity and bother; (2) number of flash free days and nights; and (3) hot symptomatic postmenopausal women and men undergoing ADT. Design: Forty-one flash interference (the Hot Flash Related Daily Interference Scale). Escitalopram subjects provided data, including 14 men (Mean age = 69.7) from a study investigating significantly reduced both daytime (18%; p=0.001) and nighttime (15%; p=0.003) hot HF and cognition in men undergoing GnRH analog therapy for prostate cancer and 54 flashes compared to placebo. The escitalopram group experienced about one-half more women (Mean age = 52.7) from a baseline visit for two clinical trials investigating efficacy flash-free day (p=0.03) and one-half more flash-free night (p=0.001) compared to the of non-hormonal hot flash treatments. Subjects wore an ambulatory sternal skin placebo group. Hot flash interference scores were reduced by 18.1 points in the conductance monitor (Biolog Model 3991x/2-HFI) for 24 hours. Objective (i.e., > 1.8 or escitalopram group compared to 14.6 points in the placebo group over the course of the trial > 2.0 micromho increase in 45 seconds or 30 seconds for men and women, respectively) (p=0.01). Despite these encouraging findings, concerns about the use of SSRIs for hot HF were recorded, with specific cut-offs chosen based on prior validation studies. To flashes include potential side effects, especially related to insomnia and sexual function. reduce inter-individual variability in the time of hot flashes for subjects on different Further evaluation of the effect of escitalopram versus placebo on insomnia symptoms sleep/wake schedules, data were normalized to each subjects’ wake time. Data were (Insomnia Severity Index) and subjective sleep quality (Pittsburgh Sleep Quality Index) collated in 30-minute bins, and a repeated measure ANOVA with polynomial contrasts revealed that escitalopram at 10-20 mg/day compared with placebo reduced insomnia were used to test for changes in hot flash frequency during the recording period. Curve symptoms and improved subjective sleep quality at 4 and 8 weeks of follow-up (p≤0.001 estimate regression was used to determine the presence of a circadian rhythm in frequency for overall treatment effect for both sleep measures). Escitalopram did not significantly of hot flashes across a 24-hour recording period. Results: Women averaged 17 objective impact the overall Female Sexual Function Index, or a single item from the Female Sexual HFs (13.2 daytime, 3.7 nighttime) and men averaged 12.4 HFs (8.9 daytime, 3.5 Distress Scale, although escitalopram decreased lubrication relative to placebo (-0.6 points nighttime) over a 24-hour period. Both men and women showed a circadian rhythm of difference on a 6-point scale; p=0.02) in sexually active women. We conclude that HFs evidenced by a significant quadratic contrast (p<.001). No sex differences were escitalopram provides relief for vasomotor symptoms, does not increase symptoms of observed in the circadian pattern or the frequency of HFs. Hot flash frequency peaked insomnia and does not affect overall sexual function in non-depressed women with over the late afternoon through early evening with a nadir at nighttime. Conclusion: To bothersome hot flashes. Future MsFLASH trials will test several other therapies for relief

39 of menopause symptoms including yoga, aerobic exercise, Omega-3 fatty acid responses from exercise are expected to ensue from moderate intensity exercise rather supplementation, low dose estrogen and venlafaxine using designs that allow for side-by- than vigorous exercise. The main study objectives were (1) to evaluate psychological Basicside comparison Science of treatment effects relative toPoster placebo and/or comparison Presentations groups. (affect, anxiety, self-efficacy) responses to vigorous and moderate intensity exercise in midlife women; (2) to assess whether responses varied by menopausal, vasomotor symptom, weight, and fitness status; and (3) to assess whether affective responses to of menopauseBASIC symptoms SCIENCE including POSTER yoga, aerobic PRESENTATIONS exercise, Omega-3 fatty acid exerciseresponses were from associated exercise are with expected overall to(objectively ensue from measured) moderate physicalintensity activityexercise levels.rather supplementation, low dose estrogen and venlafaxine using designs that allow for side-by- Design:than vigorous Community-dwelling exercise. The main midlife study women objectives of varying were (1)menopausal to evaluate status psychological (age range side comparison of treatment effects relative to placebo and/or comparison groups. 40-60(affect, years; anxiety, M=51.4, self-efficacy) SD=4.2), responses not on hormone to vigorous therapy and were moderate recruited intensity for a exercisedaily diary in P-1. studymidlife of women; PA effects (2) toon assess psychological whether outcomes. responses As varied part by of menopausal, the study, 134 vasomotor women Comparative analysis of estrogenic receptor subtype selectivity of 17β- completedsymptom, weight,a vigorous and intensity fitness status;exercise and bout (3) (maximal to assess graded whether exercise affective test) responses and 121 ofto estradiol,BASIC its metabolites, SCIENCE and POSTERrelated compounds PRESENTATIONS using highly accurate themexercise completed were associated a moderate with intensity overall exercise (objectively bout on measured) a treadmill physical at self-selected activity pace levels. but reporter gene based assay ofDesign: moderate Community-dwelling intensity. Psychological midlife responses women of were varying assessed menopausal before, statusduring, (age and range after 1 1 1 1 2 1 40-60 years; M=51.4, SD=4.2), not on hormone therapy were recruited for a daily diary P-1.Jan Bohuslav, PhD , Sylvia Chow , Sylvia Fong , Isaac Cohen , Dale Leitman . Bionovo each bout and also 20 and 40 minutes post exercise for the moderate intensity bout. Heart 2 study of PA effects on psychological outcomes. As part of the study, 134 women Inc.,Comparative Emeryville, analysis CA; Department of estrogenic of Nutritional receptor Science, subtype University selectivity of California, of 17β- rate, perceived exertion, and oxygen uptake were also monitored to quantify exercise Berkeley, CA intensity.completed Overall a vigorous physical intensity activity exercise levels werebout assessed(maximal objectively graded exercise through test) accelerometry and 121 of Objective:estradiol, Estrogenits metabolites, metabolites and are knownrelated to compoundscirculate in the using female highly body and accurate produce acrossthem completed a 2-week monitoringa moderate intensityperiod. Results: exercise Repeated bout on a measures treadmill ANOVAat self-selected and MANOVA pace but biologicalreporter generesponses. based After assay the discovery of a second estrogen receptor (ER ) it is wereof moderate conducted intensity. separately Psychological for pre and responses post exercise were assessed responses before, and responsesduring, and during after 1 1 1 1 2 1 β importantJan Bohuslav, to distinguish PhD , Sylvia if estrogen Chow , ligands Sylvia Fongproduce, Isaac similar Cohen activities, Dale and Leitman pharmacological. Bionovo exercise.each bout Overall,and also 20there and were 40 minutes more generalpost exercise and more for the positive moderate responses intensity to bout. moderate Heart 2 Inc.,outcomes. Emeryville, Selectivity CA; in Departmentthe transactivation of Nutritional for each Science,ER subtype University may reveal of differencesCalifornia, intensityrate, perceived exercise, exertion, including and significant oxygen uptake enhancements were also in monitoredpositive affect to quantify (d=.47, p<.001),exercise inBerkeley, bio-pharmacological CA activities and provide insights into the physiological actions of feelingsintensity. of Overall energy physical (d=.52, activity p<.001), levels psychological were assessed wellbeing objectively (d=.62, through p<.001), accelerometry and self- selectiveObjective: estrogen Estrogen metabolites metabolites at aredifferent known times to circulate in a woman’s in the female life, as body well and as produceprovide efficacyacross a 2-week(d=.36, monitoringp<.001). Responses period. Results: to certain Repeated mood states measures (anxiety ANOVA and tension)and MANOVA varied informationbiological responses. for pharmaceutical After the development discovery of of a new second estrogens estrogen for menopausalreceptor (ER hormoneβ) it is significantlywere conducted by fitnessseparately and symptomfor pre and status, post withexercise higher responses fit and asymptomaticand responses womenduring therapy.important Design: to distinguish We developed if estrogen a highlyligands sensitiveproduce similarand reproducible activities and reporter pharmacological gene cell- experiencingexercise. Overall, anxiety there reducing were moreeffects general of larger and magnitude more positive as compared responses to lowerto moderate fit and basedoutcomes. assay Selectivity for the measurement in the transactivation of ERα- andfor eachERβ -specificER subtype estrogenic may reveal activities. differences This symptomaticintensity exercise, women. including Responses significant were enhancements more varied in positive for vigorous affect (d=.47, exercise, p<.001), with assayin bio-pharmacological is based on transient activities expression and provide of estrogen insights responsive into the physiological element (ERE) actions based of overweight/obesefeelings of energy and (d=.52, symptomatic p<.001), women psychological generally wellbeing showing significantly(d=.62, p<.001), smaller and mood self- reporterselective gene estrogen together metabolites with estrogen at different receptors times (either in a ERwoman’sα or ER life,β) inas human well as cell provide lines enhancingefficacy (d=.36, effects p<.001). than normal Responses weight to and certain asymptomatic mood states women (anxiety (examples and tension) presented varied in thatinformation do not contain for pharmaceutical endogenous developmentER. Low variability of new ofestrogens the assay for allows menopausal us to determine hormone Figuresignificantly 1). Overweight/obese by fitness and symptom women status, also showedwith higher significantly fit and asymptomatic larger decreases women in concentrationtherapy. Design: of estrogens We developed in unknown a highly samples sensitive with anderror reproducible less than 20% reporter at sub-nanomolar gene cell- calmnessexperiencing following anxiety vigorous reducing exercise.. effects of More larger active magnitude women as chose compared to exercise to lower at fithigher and range.based assayResults: for theIn thismeasurement report, we of compare ERα- and activities ERβ-specific of several estrogenic natural activities. and synthetic This intensitiessymptomatic during women. the moderate Responses self-paced were morebout but varied affective for responses vigorous during exercise, exercise with estrogensassay is based (17β on-estradiol, transient 17expressionα-estradiol, of estrogen estrone, responsive estriol, 2-hydroxyestradiol, element (ERE) based 4- wereoverweight/obese largely unrelated and symptomatic to overall physical women generallyactivity levels. showing Conclusion: significantly From smaller a mood- mood reporterhydroxyestradiol, gene together 2-methoxyestradiol, with estrogen receptors and ethinylestradiol) (either ERα inor fourERβ different) in human mammalian cell lines enhancing effectsperspective, than normalthese results weight indicate and asymptomatic that moderate women intensity (examples exercise presented should bein thatcell linesdo not (HEK contain 293, endogenous U2OS, MCF7, ER. and Low ECC-1). variability The ofrelative the assay estrogenic allows potencies us to determine (REP) promotedFigure 1). for Overweight/obese midlife women. Deconditioned, women also showed overweight significantly or obese women larger decreasesare likely into concentrationof tested compounds of estrogens were incalculated unknown as samples the ratios with between error less EC50 than of 20% 17β -estradiolat sub-nanomolar and the respondcalmness to following vigorous exercisevigorous less exercise.. positively, More creating active the women potential chose for todiscouraging exercise at women higher range.individual Results: compounds In this (REP>1report, we corresponds compare activities to a potency of several higher natural than 17 andβ-estradiol). synthetic fromintensities pursuing during and themaintaining moderate regular self-paced physical bout activity. but affective From aresponses motivational during perspective, exercise Estriolestrogens had (17theβ highest-estradiol, ER β 17specificα-estradiol, REP (REP=34) estrone, and estriol, a low 2-hydroxyestradiol, ERα REP (REP=0.05) 4- womenwere largely should unrelated be also encouraged to overall physicalto engage activity in enjoyable levels. forms Conclusion: of physical From activity a mood- that indicatinghydroxyestradiol, its strong 2-methoxyestradiol, preference to activate and ER ethinylestradiol)β-dependent gene in fourtranscription different as mammalian compared areenhancing personally perspective, meaningful. these results indicate that moderate intensity exercise should be tocell 17 linesα-estradiol. (HEK 293, In contrast,U2OS, MCF7, ethinylestradiol and ECC-1). had The higher relative preference estrogenic for potenciesthe activation (REP) of promoted for midlife women. Deconditioned, overweight or obese women are likely to ERof testedα (ER compoundsα REP = 5.1were vs. calculated ERβ REP as the= 0.15). ratios Basedbetween on EC50 the ERof 17α βspecific-estradiol REP, and the respond to vigorous exercise less positively, creating the potential for discouraging women compoundsindividual compounds can be ranked (REP>1 as ethinylestradiol corresponds >>to a17 potencyβ-estradiol higher >estrone, than 17 estriolβ-estradiol). > 17α- fromP-4. pursuing and maintaining regular physical activity. From a motivational perspective, estradiol,Estriol had 2-hydroxyestradiol the highest ERβ >specific 4-hydroxyestradiol, REP (REP=34) 2-methoxyestradiol. and a low ERα REPThe ER(REP=0.05)β specific womenTwo sternal should be skin also conductanceencouraged to engage monitors in enjoyable for the forms measurement of physical activity of hotthat indicatingranking is its estriolstrong preference >17β-estradiol> to activate ethinylestradiol ERβ-dependent gene >estrone transcription >17α-estradiol, as compared 2- areflashes: personally Comparison meaningful. and evaluation tohydroxyestradiol, 17α-estradiol. In4-hydroxyestradiol, contrast, ethinylestradiol and 2-methoxyestradiol. had higher preference Conclusion: for the activationOur findings of William Fisher, MA, Aimee Johnson, Gary Elkins, Ph.D.. Psychology & Neuroscience, ERα (ERα REP = 5.1 vs. ERβ REP = 0.15). Based on the ERα specific REP, the demonstrate that the most abundant human estrogens, 17β-estradiol, estrone and estriol P-4.Baylor University, Waco, TX compounds can be ranked as ethinylestradiol >> 17β-estradiol >estrone, estriol > 17α- Objective: Hot flashes, the most common and debilitating symptom of the climacteric, have different relative potencies towards ERα and ERβ, and may therefore produce ERα- Two sternal skin conductance monitors for the measurement of hot estradiol,and ERβ-specific 2-hydroxyestradiol responses >as 4-hydroxyestradiol, their levels change 2-methoxyestradiol. during pregnancy orThe menopause. ERβ specific A are studied utilizing subjective and objective measures. The ‘gold-standard’ objective rankinggreater understanding is estriol >17 of howβ-estradiol> the differences ethinylestradiol in the structures >estrone of metabolites >17α-estradiol, leads to ER 2- measureflashes: is Comparison the physiological and measurement evaluation of hot flashes via sternal skin conductance William Fisher, MA, Aimee Johnson, Gary Elkins, Ph.D.. Psychology & Neuroscience, hydroxyestradiol,subtype transcriptional 4-hydroxyestradiol, specifity could leadand 2-methoxyestradiol.to the development of Conclusion: new classes Ourof estrogens findings recording (SSC). This study compares two devices for this measurement, the Biolog® Baylor University, Waco, TX demonstrateto prevent menopausal that the most symptoms. abundant human estrogens, 17β-estradiol, estrone and estriol Hot Flash Monitor, produced by UFI and an experimental hot flash recorder from Bahr™ have different relative potencies towards ERα and ERβ, and may therefore produce ERα- Management,Objective: Hot Inc. flashes, Though the these most two common devices and both debilitating measure sternal symptom skin ofconductance, the climacteric, they and ERβ-specific responses as their levels change during pregnancy or menopause. A doare so studied at different utilizing rates. subjective The Biolog® and Hotobjective Flash measures.Monitor records The ‘gold-standard’ sternal skin conductance objective greaterP-2. understanding of how the differences in the structures of metabolites leads to ER continuouslymeasure is the every physiological second for measurement 24 hours at a of time, hot whereasflashes via the sternal Bahr™ skin Monitor conductance records subtypeThe ability transcriptional of Cyclosporine specifity could (CsA) lead to theinduce development oxigen of free new radicalsclasses of estrogensin a rat sternalrecording skin (SSC). conductance This study samping compares once twoevery devices 10s. Both for thisdevice measurement, are attached the sternally Biolog® by toosteoblast prevent menopausal cell line symptoms. meansHot Flash of standardMonitor, EEGproduced electrodes by UFI placed and an in experimental a proprietary hot electrode flash recorder gel and from adhesive Bahr™ to Hoon Choi1, Heung Yeol Kim2. 1Sanggye Paik Hospital, Inje University, Seoul, Republic theManagement, skin. Design: Inc. InThough a study these of 145two devicespost-menopausal both measure women sternal experiencing skin conductance, severe (50+they 2 do so at different rates. The Biolog® Hot Flash Monitor records sternal skin conductance P-2.of Korea; Kosin University, Busan, Republic of Korea week) hot flashes, participants were asked to wear both of these devices at three different Objective: This study examined the ability of Cyclosporine (CsA) to induce apoptosis in continuouslypoints during everytheir participation second for 24 in hoursa larger at NIH-granteda time, whereas study the of Bahr™ a mind-body Monitor treatment records Thea rat osteoblastability of cell Cyclosporine line. Design: (CsA) Rat osteoblast to induce ROS oxigen 17/2.8 freecells radicalswere cultured, in a andrat sternalfor hot flashes.skin conductance Hot flashes samping were assessed once every subjectively 10s. Both and device objectively are attached using thesternally Biolog® by osteoblasttreated with withcell 0.1-40line g/mL CsA for 24 hours after plating of cells. Cell viability was meansand Bahr™ of standard monitor. EEG Data electrodes were collected placed fromin a proprietary participants electrode and comparison gel and adhesiveof the data to 1 μ 2 1 Hoondetermined Choi ,by Heung the MTT Yeol assay.Kim . WesternSanggye Blot Paik Analysis Hospital, was Inje done University, with primary Seoul, antibodies Republic thefrom skin. the twoDesign: devices In awere study made. of 145 Results: post-menopausal Clear differences women were experiencing visible in thesevere recorded (50+ 2 toof caspase-3Korea; Kosin and University,caspase-8. ReactiveBusan, Republic oxygen speciesof Korea (ROS) synthesis was measured by week)tracks hotfrom flashes, the two participants devices, withwere theasked Bahr™ to wear monitor both of data these showing devices atless three erratic different skin flowcytometry.Objective: This studyResults: examined Cell viabilitythe ability decreasedof Cyclosporine in dose-dependent (CsA) to induce manner apoptosis with in pointsconductance during presentaiton,their participation however, in a larger as this NIH-granted device recorded study ofat a mind-bodytenth the rate treatment of the aincreasing rat osteoblast concentrations cell line. Design:of CsA. TreatmentRat osteoblast of ROS ROS 17/2.8 17/2.8 cells cells with were 0.1, cultured, 0.5, 1, 5, and10, forBiolog®, hot flashes. the clarity Hot flashes of the data were must assessed be viewed subjectively with caution and objectively as the comparison using the of Biolog® the data treated20, or 40with μ g/mLg/mLwith 0.1-40 CsAμg/mL caused CsA for85%, 24 80%,hours after73%, plating 60%, 45%,of cells. 40%, Cell and viability 27% wascell andwas Bahr™not standardized. monitor. Data Adverse were eventscollected associated from participants with toleration and comparison of the electrode of the paste data viability,determined respectively. by the MTT Western assay. Westernblot analysis Blot Analysisshowed reducedwas done caspase-3 with primary expression antibodies and fromwas a the limitation two devices of the were Bahr™ made. monitors, Results: with Clear 14 differences participants were (9.65%) visible reporting in the recorded adverse inducedto caspase-3 caspase-8. and caspase-8. The ROS Reactive in a dose-and oxygen time-dependent species (ROS) synthesismanner were was increasedmeasured by events,tracks fromcompared the two to 5devices, participants with (3.45%)the Bahr™ reporting monitor adverse data showingevents from less the erratic Biolog®. skin CsA.flowcytometry. Conclusion: Results: These results Cell viabilitysuggest that decreased CsA can ininduce dose-dependent oxygen free radicals manner which with Bothconductance monitors presentaiton, showed challenges however, with as thisfloor device and ceiling recorded effects. at a tenthTo date, the therate Bahr™ of the appearsincreasing to concentrationstrigger apoptosis of byCsA. activating Treatment pro-apoptotic of ROS 17/2.8 signals. cells CsA with plays 0.1, 0.5,a role 1, in5, 10,the Biolog®,monitor has the no clarity scoring of thealgorithm, data must and be thus viewed the onlywith interpretationcaution as the ofcomparison the data can of bethe done data post-20, or transplatation 40 μg/mLg/mL bone CsA diseases caused via 85%, the induction 80%, 73%, of apoptosis 60%, 45%, in osteoblast. 40%, and 27% cell wasby exporting not standardized. the data to Adverse alternate events analytical associated programs with or toleration by visual ofclinical the electrode interpretation. paste viability, respectively. Western blot analysis showed reduced caspase-3 expression and wasIn contrast, a limitation the Biolog® of the Bahr™ monitor monitors, utilizes FlashTrax©, with 14 participants a proprietary (9.65%) software reporting that analyzes adverse induced caspase-8. The ROS in a dose-and time-dependent manner were increased by events,the data compared for an change to 5 participantsin change in (3.45%) skin conductance reporting adverseactivity fromevents baseline from the levels. Biolog®. This CsA.P-3. Conclusion: These results suggest that CsA can induce oxygen free radicals which Bothsoftware monitors utilizes showed a default challenges setting of with2 μmho floor change and ceiling / 30 s toeffects. equate To an date,event. the Further, Bahr™ it Psychologicalappears to trigger Responsesapoptosis by activating to Acute pro-apoptotic Exercise insignals. Middle-Aged CsA plays a Women:role in the monitorrecords button-presshas no scoring subjective algorithm, markers and thus of hotthe onlyflash interpretationevents and flags of theevents data as can either be done true Contrastingpost- transplatation the Effectsbone diseases of Vigorous via the induction and Moderate of apoptosis Intensity in osteoblast. bypositive exporting or false the negativedata to alternate based on analytical the HF event programs matching or by temporally visual clinical with interpretation. button-press. Steriani Elavsky, Ph.D.1, Okan Micoogullari, M.Sc.2. 1Department of Kinesiology, Penn InThough contrast, this the algorithm Biolog® hasmonitor been utilizes criticized FlashTrax©, in the literature a proprietary as over-reporting software that hot analyzes flash 2 the data for an change in change in skin conductance activity from baseline levels. This StateP-3. University, University Park, PA; Physical Education and Sports Department, Middle events, the absence of such an algorithm for the Bahr™ monitor is a limitation. Head-to- East Technical University, Ankara, Turkey software utilizes a default setting of 2 μmho change / 30 s to equate an event. Further, it Psychological Responses to Acute Exercise in Middle-Aged Women: head comparisons were made between the two devices on participants who wore both Objective: In spite of the multiple health benefits of physical activity, only 47% of recordsdevices button-presssimultaneously subjective and also markers reported of their hot flashhot flashes events onand a flagsdiary. events Clinical as eitherscoring true of middle-agedContrasting women the Effects report meeting of Vigorous current andphysical Moderate activity (PA)Intensity guidelines and nearly positivethe Bahr™ or false was negativeutilized againstbased on the the Biolog® HF event software-derived matching temporally data comparingwith button-press. results Steriani Elavsky, Ph.D.1, Okan Micoogullari, M.Sc.2. 1Department of Kinesiology, Penn 27% report no leisure-time physical activity at all (BRFSS, 2007). Objective PA Thoughfrom each this device algorithm against has participant been criticized self-reported in the hot literature flashes. asConclusion: over-reporting In our hot sample flash State University, University Park, PA; 2Physical Education and Sports Department, Middle surveillance data paint even bleaker picture with less than 3% of females accumulating events,of 145 post-menopausal the absence of such women an algorithm who experienced for the Bahr™ a minimum monitor of 50is a hot limitation. flashes per Head-to- week, East Technical University, Ankara, Turkey sufficient PA levels (Troiano et al., 2008). Additionally, substantial drop-out rates (50%) headthe Biolog® comparisons Hot Flash were Monitor made between results morethe two closely devices match on participantparticipants self-report who wore of both hot Objective: In spite of the multiple health benefits of physical activity, only 47% of plague most physical activity programs. These statistics seem to be in conflict with the devicesflashes oversimultaneously a 24-hour recording. and also reported their hot flashes on a diary. Clinical scoring of generallymiddle-aged accepted women notion report that meeting physical current activity physical makes activity people (PA) feel good.guidelines One hypothesisand nearly the Bahr™ was utilized against the Biolog® software-derived data comparing results 27%put forth report to explain no leisure-time this contradiction physical regards activity exercise at allintensity, (BRFSS, whereby 2007). more Objective pleasurable PA from each device against participant self-reported hot flashes. Conclusion: In our sample surveillance data paint even bleaker picture with less than 3% of females accumulating of 145 post-menopausal women who experienced a minimum of 50 hot flashes per week, sufficient PA levels (Troiano et al., 2008). Additionally, substantial drop-out rates (50%) the Biolog® Hot Flash Monitor results more closely match participant self-report of hot plague most physical activity programs. These statistics seem to be in conflict with the flashes over a 24-hour recording. generally accepted notion that physical activity makes people feel good. One hypothesis put forth to explain this contradiction regards exercise intensity, whereby more pleasurable

40 P-5. P-8. Ambient Temperature and Hot Flashes: Does the weather influence hot Factors affecting level of preparedness for menopause among flashes in postmenopausal women? premenopausal women in Leo community, Ido Local Government Area, William Fisher, MA, Kathy Amador, Aimee Johnson, Gary Elkins, Ph.D.. Psychology & Oyo State, Nigeria Neuroscience, Baylor University, Waco, TX Felicia O. Ojo, MPH in view, Oyedunni Arulogun, PhD. Health Promotion and Education, Objective: The relationship of ambient temperature and its role in influencing the number University of Ibadan, Oyo State, Ibadan, Nigeria and severity of hot flashes is not yet well-understood. Research into this relationship has Objective: 1. Assess the level of knowledge of respondents about menopause. 2. been mixed and to date the influence of menopausal stage on this relationship has been Determine the perception of respondents about menopause. 3. Identify factors affecting largely overlooked. In this study, the relationship of ambient temperature to the number the level of knowledge and perception of respondents about menopause 4. Discover the of hot flashes in symptomatic post-menopausal women was investigated. Design: This level of preparedness of the respondents for menopause. 5. Identify factors affecting the study consists of 143 post-menopausal women who were recruited as part of a larger NIH- level of preparedness for menopause among respondents. Design: The survey involved the granted study of a non-pharmacological hot-flash treatment. Baseline assessments of hot use of a three-stage random sampling technique in selecting 426 female respondents flash diaries as well as physiological measurement of sternal skin conductance were taken. across six streets in Leo community. Six Focus Group Discussions (FGDs) were The baseline assessments were collected over a span of three years to investigate whether conducted. A validated semi-structured questionnaire with a 33-point knowledge scale or not ambient temperature during the participant’s 24-hour baseline assessment was used for collecting quantitative data and five questions were used to assess influenced the frequency or severity of hot flashes. Results: . Results of this study failed participants’ level of preparedness. Analysis of the quantitative data was done using to show a difference between cold-weather or hot-weather groups in the objective descriptive, Chi-square and ANOVA statistics while the tape-recorded and transcribed measures of hot flashes or diary report of hot flashes. There was, however, a significant FGD data were subjected to content analysis. Results: The mean age of the respondents correlation between membership to the cold-weather group and in perceived impact of hot was 36.6 ± 4.5years and 86.9% were married. Nine percent of the participants had no flashes as evidenced by scores from the Hot Flash Related Daily Interference Scale (r= - formal education while 40.6% had secondary education. Majority (89.0%) of the .582, p<.05). Membership to the hot-weather group did not show a significant relationship. respondents were Yoruba and 76.0% had ever heard about menopause. Their sources of Conclusion: It may be, as the apparently incongruous results of this study may indicate, information included, mother (20.0%), health care provider (18.1%), radio (13.4%), that in the population of post-menopausal women, ambient temperature’s role in the friends (12.0%), sister (5.4%), aunt (5.2%) and internet (2.1%). Respondents’ mean genesis of hot flashes is spurious. knowledge score on menopause was 11.6 ± 2.5 while the mean knowledge score by level of preparedness include: not prepared (5.7 ± 2.1), slightly prepared (10.6 ± 2.9) and very P-6. prepared (18.5 ± 2.5) with a significant difference (p<0.05). Most respondents (97.0%) were of the opinion that menopause brings relief associated with menstruation to women Effect of Klimaktoplan on the proliferation of breast cancer cells: in vitro while 62.4% perceived that menopause reduces physical strength in women. Only 45.8% study of the respondents stated that they were prepared for menopause and of this 97 (49.5%) 1 2 1 1 Tak Kim, MD, Ph.D , Byoung Ick Lee , Ki hoon Ahn . Dept of obgyn, Korea University viewed themselves as very prepared. Over half (52.8%) of the respondents between the 2 Anam Hospital, Seoul, Republic of Korea; Dept of obgyn, Inha University, Incheon, age of 40-45 years and 28.5% between the age of 30-39 years perceived themselves as Republic of Korea prepared for menopause (p<0.05). Level of education was not significantly associated Objective: This study was aimed to investigate the effect of Klimaktoplan on the with level of preparedness for menopause. A large proportion of the FGD participants proliferation of breast cancer (MCF-7) and normal mammary epithelial cells (MCF-10A). expressed concerns about the health challenges related to menopause. A few of them were Design: MCF-7 and MCF-10A cells were cultured in 312.5, 625, and 1250 ug/ml of the opinion that menstrual stoppage is a disadvantage to women who are yet to give Klimaktoplan for experimental group. Beta-estradiol and medroxyprogesterone 17-acetate birth as menopause marks the end of conception. Conclusion: Low level of knowledge were used for comparison with Klimaktoplan. Beta-estradiol only (0.001, 0.01, and 0.1 about menopause is a key factor that is affecting the level of preparedness for menopause uM), and the combination of estradiol and progesterone (0.001, 0.01, and 0.1 uM beta- among premenopausal women. Public enlightenment and community-based education estradiol; 0.01, 0.1, and 1 μM medroxyprogesterone 17-acetate) were treated. Control on menopause are needed to address these challenges especially among young adult cells for Klimaktoplan and beta-estradiol groups were treated by DMSO, and DMSO and women. EtOH for combination group. The proliferation and shape of cells were evaluated by MTT assay after incubation of 4 days. The effect of lactose, an ingredient in Klimaktoplan were also assessed by treating 1250 ug/ml lactose. Results: Klimaktoplan of 625 and 1250 P-9. ug/ml had a concentration-dependent anti-proliferative effect on breast cancer cells, Time is critical for beneficial effects of hormone replacement therapy on although there were no differences of cell proliferation between 312.5 ug/ml Klimaktoplan working memory above other cognitive functions and DMSO. Klimaktoplan had no effect on the proliferation of normal mammary cells in Sophie A. Pettit, Psychology. The Department of Psychology, The University of Plymouth, any concentrations. Beta-estradiol and lactose increased the proliferation of breast cancer Plymouth, United Kingdom and normal mammary cells. The effect of combination of estradiol and progesterone on Objective: Oestrogen decline during the menopause leads to decline in cognitive the proliferation of breast cancer and normal mammary cells were lower than estradiol performance because oestrogen receptor sites are found in the pre-frontal cortex, only, but higher than control. Conclusion: Klimaktoplan had an anti-proliferative effect hippocampus, hypothalamus and cerebellum of the female brain, areas associated with for breast cancer cells, but not for normal mammary epithelial cells unlike the effects of memory and attention functions. Extensive research over the past two decades has tested estradiol only and the combination of estradiol and progesterone the effects of administering HRT to maintain oestrogen levels (Sherwin, 2005). MRI studies with humans have shown improvements in hippocampal volume and frontal P-7. functions with HRT, but these changes were not associated with improved performance on memory tasks. Similar Benefits of HRT on WM and learning have been found in Study on microRNA and its target gene expression using in vitro murine human studies, with an initial focus on verbal long-term memory (Sherwin, 1988). Some ovarian follicular growth and aging model studies have found benefits of HRT for working memory (WM), the ability to temporarily 1,2 2 2 2 Seung-Yup Ku, MD,PhD , Yong Jin Kim , Yoon Young Kim , Sun Kyung Oh , Seok store and manipulate information simultaneously (Duff & Hampson, 2001) but overall 1,2 1,2 1 1,2 1 Hyun Kim , Young Min Choi , Jung Gu Kim , Shin Yong Moon . Obstetrics and the findings are mixed results (Maki & Zonderman, 2001) and some studies have even Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; found detrimental effects of HRT (Grigorova & Sherwin, 2006). Typically, previous 2 Institute of Reproductive Medicine and Population, Medical Research Center, Seoul studies did not control for time of HRT administration until a general pattern was National University, Seoul, Republic of Korea established; that those with administrated with HRT at the peri menopausal stage or mixed Objective: Cyclic ovarian follicular growth is a key mechanism of estradiol production samples have found cognitive benefits of HRT whereas those where HRT was in premenopausal period, and in vitro ovarian follicular growth and aging could be an administrated post menopause have not. This pattern is consistent with the critical period important research model to understand the ovarian aging and menopause. MicroRNA is hypothesis (Khoo, 2010); that HRT will only have a positive effect on cognition if the known to play important roles in development and maturation of eukaryotic cell. This therapy is initiated during the peri menopause. As well as time of administration of the study is to investigate the changes of microRNA and target gene expression using in vitro therapy, inconsistency in the empirical findings may be due to inconsistency in the type murine ovarian follicular growth and aging model. Design: Preantral follicles were of cognitive function being assessed. Recent research suggests that frontally-mediated isolated from ovaries of 2-week-old C57BL6 mouse and cultured in 20 μL-drop of culture working memory functions may be particularly sensitive to effects of oestrogen (Low, media with supplementation of gonadotropin. After full-growth of follicle, oocyte Mille, 2002; Shaywitz et al 2010). Design: The present study, therefore, tested the effect maturation and ovulation were induced with supplementation of hCG. Using TRIzol, total of time of HRT administration on WM function and sustained attention in a naturalistic RNA was extracted from granulosa cells of follicle at pre-, and post-hCG. MicroRNA sample of 121 women who varied in the time they had begun taking HRT, and a sample and its candidate target gene (OCT4, BMP15 and GDF9) were measured with real-time of age-matched controls. Participants were allocated into one of four groups. This included PCR. Results: Maturation rate of oocyte was 45.2% after hCG supplementation. those who begun HRT during their peri menopause, those who begun HRT during their Granulosa cells of post-hCG expressed lower let-7b, higher miR-30a and similar let-7c, post menopause, those who had never taken HRT and were peri menopausal and those miR-16, miR-27a, miR-126, compared to those of pre-hCG. The expression of BMP15 who had never taken HRT and were post menopausal. Mood was measured as a potential and GDF9 were similar in pre- and post hCG. OCT4 was less expressed in post-hCG. covariate and subjective memory function was assessed with items from the Menopausal Conclusion: During in vitro growth and aging of mouse ovarian follicle, profiles of Quality of Life Scale. Participants completed a verbal WM task, a second verbal WM microRNA and its target gene in granulosa cell may change with follicle maturation. task with mathematical components, a spatial WM task and a sustained attention task. Results: A MANCOVA showed a significant difference between task score for both the verbal WM task (p < .001); the verbal WM task with mathematical components (p < .05) but not the spatial WM task (p = .096). On closer look it was identified that HRT users post menopausal scored significantly lower than HRT users peri menopause for the verbal

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Basic Science Poster Presentations (continued)

WM task (p < .001), verbal WM task with mathematical components (p < .005) and the P-11. spatial WM task (p < .05). For the verbal WM task; HRT users post menopause also scored An Inverse Relationship between Plasma Vitamin D Concentrations and significantly lower than non-users post menopause, suggesting that HRT taken post C-Reactive Protein Provides a Potential Mechanism For Cardioprotection menopause could have detrimental effects on WM score. No significant differences were Peter F. Schnatz, D.O.1,2, Sharon Vila-Wright, M.D.1, Xuezhi Jiang, MD1, Thomas C. identified in the sustained attention task yet post menopausal HRT users made the most Register, PhD3, Susan E. Appt, DVM3, Jay R. Kaplan3, Thomas B. Clarkson3. 1ObGyn & mistakes overall. Conclusion: To conclude, it is suggested that HRT can be beneficial to Internal Medicine, The Reading Hospital and Medical Center, Reading, PA; 2ObGyn & WM, especially that with verbal components. However, this may be dependant on time Internal Medicine, Jefferson Medical College of Thomas Jefferson University, of initiation of the therapy. For optimal results, the therapy should be administrated as Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest University, Winston- close to the onset of the menopause as possible. It is also suggested that HRT taken at the Salem, NC post menopausal stage may have detrimental effects on WM. The exact stage at which this Objective: The inflammatory marker C-reactive protein (CRP) has been positively effect may occur has not yet been defined and should be considered when prescribing associated with coronary heart disease (CHD). The purpose of the present study was to HRT. evaluate potential relationships between this inflammatory biomarker and plasma vitamin D concentrations in monkeys consuming atherogenic diets which contained either soy P-10. protein isolate or casein-lactalbumin (C/L) as the primary protein source. Design: Vitamin D Receptor Quantity and Plasma Concentration of Vitamin D: Throughout the study, adult female cynomolgus monkeys (n=74) were administered atherogenic diets with a women’s equivalent of both 1,000 IU/day of vitamin D3 and Their Association with Atherosclerosis 1,200 mg/day of calcium. After 36 months of consuming the soy (n=35) or C/L (n=39) Peter F. Schnatz, D.O.1,2, Matthew Nudy1, David M. O’Sullivan, PhD1, J. Mark Cline, based diets, monkeys underwent oophorectomy to induce surgical menopause and each DVM, PhD3, Susan E. Appt, DVM3, Xuezhi Jiang, MD1, Jay R. Kaplan3, Thomas B. diet group was then re-randomized to receive soy (n=36) or C/L (n=38). After 24 post- Clarkson3. 1ObGyn & Internal Medicine, The Reading Hospital and Medical Center, menopausal months, serum inflammatory markers and 25OH vitamin D concentrations Reading, PA; 2ObGyn & Internal Medicine, Jefferson Medical College of Thomas were assessed. Results: The pre and post-menopausal dietary protein sources had no Jefferson University, Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest effect on post-menopausal concentrations of vitamin D (p=0.63). In all monkeys, there University, Winston-Salem, NC was a statistically significant inverse relationship between vitamin D concentrations and Objective: The objective of this study was to analyze coronary artery vitamin D receptor CRP at necropsy (r=-0.35, p=0.0026), see figure 1. A significant inverse correlation (VDR) abundance, plasma concentration of vitamin D3, and their relationship with between vitamin D concentration and the change in CRP, from premenopause to coronary artery atherosclerosis [CAA]. Design: Premenopausal cynomolgus monkeys postmenopause, was also observed (r=-0.32, p=0.0071). The significant associations (n=39) were fed atherogenic diets containing a woman’s equivalent of both 1,000 IU/day identified between plasma concentration of vitamin D and CRP remained after controlling vitamin D3 and 1,200 mg/day of calcium, and derived their protein from either casein- for postmenopausal diet. Conclusion: Plasma concentrations of vitamin D were inversely lactalbumin (C/L, n= 20) or soy protein isolate (soy, n=19). After 36 months consuming associated with plasma CRP. The association was strong and independent of menopausal the diets, each monkey underwent surgical menopause (oophorectomy). At that time the dietary changes. These findings support the hypothesis that circulating vitamin D entire group of monkeys was re-randomized to one of the two diets. The consequence concentrations are associated with anti-inflammatory properties and offer a potential was that half of the monkeys consumed the same diet and half different diets throughout mechanism by which vitamin D could provide cardio-protection. both the pre- and postmenopausal phase. After 24 post-menopausal months, CAA was measured in the left circumflex artery (LCX) and left anterior descending artery (LAD). VDR abundance was determined for the LAD and plasma 25-OH vitamin D concentrations were assessed. Results: Both the cross-sectional area (mm2) and plaque thickness (mm) in the LCX as well as the LAD were analyzed in these monkeys. Those with higher plasma vitamin D concentrations and higher VDR were compared with those with higher plasma vitamin D concentrations and lower VDR. Smaller plaque sizes were noted with higher plasma vitamin D concentrations and higher VDR [figure]. For the LCX, there was also a significantly lower plaque size (both cross-sectional area [figure] and plaque thickness) in those with higher VDR and lower plasma vitamin D3 concentrations versus those with lower quantities of VDR and higher plasma concentrations of vitamin D3, p=0.009 and p=0.040, respectively. Conclusion: Cynomolgus monkeys with higher quantities of VDR have significantly less atherosclerosis than those with lower quantities of VDR and higher plasma vitamin D3 concentrations. The reason there is an increased plasma vitamin D3 concentration with a decrease in VDR in association with CAA, and which came first, is not known. If these findings translate to humans, it might explain why some individuals with higher plasma concentrations of vitamin D3 have more CAA.

P-12. Comparison of Common Menopause-related Comorbidities and Procedures among Women with and without Diagnosed Menopause Symptoms Nathan Kleinman, PhD1, Nicholas J. Rohrbacker, MS1, Andrew G. Bushmakin2, Jennifer Whiteley2, Wendy D. Lynch1, Sonali N. Shah, MBA, MS, RPh2. 1HCMS Group, Cheyenne, WY; 2Pfizer, Inc., New York, NY Objective: To evaluate the prevalence of osteoporosis, insomnia, depression, anxiety, and specific procedures within a cohort of employed women over age 40 with diagnosed menopause symptoms compared with a matched cohort without menopause symptom diagnoses based on their health insurance claims data. Design: The Human Capital Management Services database of health care, work absence, and payroll data from large employers in various industries throughout the US was used. There were 17,322 employees age 40+ with diagnoses (ICD-9-CM codes 627.xx) in their medical claims data for “menopausal and postmenopausal disorders” (“DX” cohort). The date of first diagnosis was defined as the index date. A group of women from the database without menopause symptom diagnoses (“NoDX” cohort) was matched (1 to 1) to the DX cohort, equating index dates and matching on age, employer, length of medical plan enrollment, and enrollment end date. By 5-year age bands, the post-index enrollment period prevalence of osteoporosis (ICD-9-CM 733.0x), insomnia (307.41, 307.42, 307.49, 327.0x, 780.52), major depression (296.2x-296.3x, 311.xx), other depression (298.0x, 300.4x, 309.0x-309.1x), and anxiety (293.84, 300.0x-300.3x, 309.21) diagnoses was compared between cohorts after the index date. Similarly, the percent of each cohort with chiropractic, acupuncture, and hysterectomy procedures and the number of chiropractic procedures per person were compared. Results: Condition and procedure prevalence values and number of chiropractic services were significantly higher in the DX cohort than in the NoDX cohort in some of the younger age bands from 40 years to 64 years (Table). As age increased, the differences between cohorts diminished. Those over 65 had

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similar prevalences between the cohorts. The prevalence of osteoporosis increased with P-14. age in both cohorts and was significantly higher in the DX cohort than in the NoDX cohort Effects of metoclopramide-induced hyperprolactinemia on the up to the 60-64 age range. For major depression and insomnia, the diagnosed group had hyaluronan acid of murine endometrium after hormonal replacement significantly higher prevalence up to age 55-59. Other depression prevalence and anxiety Gabriela C. Cristofani Maioral, MSc1, Regina C. Teixeira Gomes, PhD2, Carina Verna, prevalence were significantly higher in the DX cohort up to age 50-54. Prevalence of Dr1, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Edmund C. Baracat, PhD3, Helena chiropractic care was significantly higher in the DX cohort up to age 55-59, and the B. Nader, PhD4, José M. Soares Júnior, PhD1. 1Department of Morphology, Federal average number of chiropractic procedures was higher in the DX cohort up to age 50-54. University of São Paulo, São Paulo, Brazil; 2Department of Morphology and Genetics, São Conclusion: Employed women seeking treatment for menopause symptoms were Paulo Federal University, São Paulo, Brazil; 3Department of Gynecology and Obstetrics, associated with a higher prevalence of related conditions and procedures and higher University of São Paulo Medical School of Medicine, São Paulo, Brazil; 4Department of employee costs than similar women without menopause symptom diagnoses. These Biochemistry, São Paulo Federal University, São Paulo, Brazil results highlighting incremental comorbidity, health care utilization, and costs will be Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia on the important for employers sponsoring health care and will aid clinicians in the complex hyaluronan acid in murine endometrium. Design: 80 adult (100 day-old) female virgin care of these individuals. mice were randomly divided into 8 groups of 10 animals each: 1 - group (non- ovariectomized animals, non-Ovx); 2. group (ovariectomized animals, Ovx) treated with Post-Index Condition and Procedure Prevalence between Menopause Symptom Diagnosis the drug vehicle (0.2 ml NaCl 0.9% in distilled water), 3 - group (Ovx); 4 - group (Ovx) (DX) and No Menopause Symptom Diagnosis (NoDX) Cohorts received 200 μg metoclopramide dissolved in 0.2 ml NaCl 0.9% in distilled water; 5. Group Ovx treated with 17β-estradiol; 6. Ovx animals treated with 17β-estradiol; 7. Ovx treated with progesterone; and 8. Ovx treated with metoclopramide plus progesterone. Vehicle and metoclopramide were administered intraperitoneally; the steroid hormones were administered by gavage once daily at 10 a.m. during 50 consecutive days. In the 50th day, the animals were killed, the middle portions of the uterine horns were removed and sectioned into 2 fragments; one of them was fixed in 10% buffered formaldehyde and subjected to routine histologic processing for paraffin inclusion and further sectioning and haematoxylin-eosin staining. The second fragment was prepared for hyaluronan acid determination by an ELISA-like assay method. The results were expressed as mean ± SD and were analyzed by ANOVA. Significance level was set at P<0.05. Results: we found that the hyperprolactinemic state induced and replacement of estrogen and progestin significant alterations on HA concentration of mouse uterus. Conclusion: Our results suggest that replacement of estrogen and progestin may increase the hyaluronic acid in metoclopromide-induced hyperprolactinemia in mice after castration.

P-15. Effects of metoclopramide-induced hyperprolactinemia on the gene expression of hyaluronan synthases in mouse uterine along the different phases of the estrous cycle Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C. Cristofani Maioral, MSc2, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Vivien J. Coulson-Thomas, Dr4, Manuel J. Simões, PhD1, José M. Soares Júnior, MD, Ph.D2. 1Department of Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil; 3Department of Gynecology and Obstetrics, University of São Paulo Medical School of Medicine, São Paulo, Brazil; 4Department of Biochemistry, São Paulo Federal University, São Paulo, Brazil * P<0.05 between DX and NoDX cohorts. Objective: evaluate effects of metoclopramide-induced hyperprolactinemia on the gene expression of hyaluronan synthases 1, 2 and 3 in mouse uterine. Design: 80 adult (100 P-13. days old) female virgin mice were randomly divided into two groups of 40 animals each: Effects of metoclopramide-induced hyperprolactinemia on the on tibial control (Ctr), which received intraperitonela (IP) 0.2 ml of saline solution, and experimental (HPrl), which received IP 6,7 μg/g metoclopramide. After 50 days the epiphyseal growth plate of ovariectomized rats after hormonal animals were properly randomly divided into 8 groups of 10 animals, according to the replacement phase of the cycle: proestrus (Ctr and HPrl), estrus (Ctr and HPrl), metaestrus (Ctr and Roberta B. Wolff, MSc2, Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C. HPrl) and diestrus (Ctr and HPrl). In the 50th day, one hour after the last drug or vehicle Cristofani Maioral, MSc2, Thais C. Rampazo, Graduate Student2, Manuel J. Simões, PhD1, injection, a vaginal smears evaluation was performed in order to verify the estrous cycle Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D3. 1Department of phase. Following euthanasia, the uterine horns were removed, sectioned and immediately Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of frozen in liquid nitrogen for RNA extraction to detect tissue (HAS1, 2 and 3) by Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil; Polymerase Chain Reaction Real Time. Blood was collected for the dosage of prolactin 3Department of Gynecology and Obstetrics, University of São Paulo Medical School of and serum estrogen and progesterone using ELISA-like assay. The results were expressed Medicine, São Paulo, Brazil as mean ± SD and were analyzed by the ANOVA. Results: 80 adult (100 days old) female Objective: To analyse the of metoclopramide-induced hyperprolactinemia on mice virgin mice were randomly divided into two groups of 40 animals each: control (Ctr), epiphyseal disk after ovariectomy Design: 80 adult (100 day-old) female virgin mice which received intraperitoneal (IP) 0.2 ml of saline solution, and experimental (HPrl), were randomly divided into 8 groups of 10 animals each: GI group (non-ovariectomized which received IP 6,7 μg/g metoclopramide. After 50 days the animals were properly animals, non-Ovx) and GII group (ovariectomized animals, Ovx) were treated with the randomly divided into 8 groups of 10 animals, according to the phase of the cycle: drug vehicle/day (0.2 ml NaCl 0.9% in distilled water), GIII group (Ovx) and GIV group proestrus (Ctr and HPrl), estrus (Ctr and HPrl), metaestrus (Ctr and HPrl) and diestrus (Ctr were treated with 6,7 μg/g metoclopramide/day dissolved in 0.2 ml NaCl 0.9% in distilled and HPrl). In the 50th day, one hour after the last drug or vehicle injection, a vaginal water; GV group (Ovx) was treated with drug vehicle/day and 2ug/day 7β-estradiol; GVI smears evaluation was performed in order to verify the estrous cycle phase. Following group (Ovx) was treated with 6,7 μg/g metoclopramide/day and 2ug/day 17β-estradiol; euthanasia, the uterine horns were removed, sectioned and immediately frozen in liquid VII group (Ovx) was treated with drug vehicle/day and 2mg/day progesterone and VIII nitrogen for RNA extraction to detect tissue (HAS1, 2 and 3) by Polymerase Chain group (Ovx). was treated with 6,7 μg/g metoclopramide/day and 2mg/day Reaction Real Time. And another part was fixed in 10% formol for immunohistochemical progesterone.Vehicle and metoclopramide were administered intraperitoneally; the steroid evaluation of HAS1, 2 and 3. The results were expressed as mean ± SD and were analyzed hormones were administered by gavage once daily at 10 a.m. during 50 consecutive days. by the ANOVA. Conclusion: The analysis of immunohistochemistry showed that In the 50th day, following euthanasia the animals were the tibia removed, which was fixed hyaluronan synthases HAS1 and HAS2 increased in phases of proestrus, estrus and in 10% formadehyde, decalcified (10% formic acid) and then submitted to histological metaestrus and HAS3 decreased during the proestrus and increased in phases of estrus and processing for inclusion in paraffin. The sections were stained by haematoxylin-eosin metaestrus. And the gene expression increased HAS1 phases of estrus, metaestrus and (H.E.) evaluated by morphologic methods. The histomorfometric analysis of the disk diestrus. And the gene expression of HAS2 and HAS3 was low. thickness of epiphyseal area was performed using the AxionVision 4.2, RL system (Carl Zeiss) and AxioLab Standart 2.0 microscope. The results were evaluated through statistical analysis by ANOVA tests. Results: The animals ovariectomized and treamented with metoclopramide had significant decrease in the epiphyseal disk thickness when compared to other groups. Conclusion: the morphologic results suggest that the metoclopramide- induced hyperprolactinemia may decrease the thickness of the ovariectomized epiphyseal disk.

43 Basic Science (continued) & Clinical Poster Presentations

P-16. dissolved in 0.2 ml NaCl 0.9% in distilled water; GV group (Ovx) was treated with drug Study of gene expression of prolactin and prolactin receptor in the mice vehicle/day and 2ug/day 7β-estradiol; GVI group (Ovx) was treated with 6,7 μg/g uterus with metoclopramide-induced hyperprolactinemia throughout the metoclopramide/day and 2ug/day 17β-estradiol; VII group (Ovx) was treated with drug estrous cycle vehicle/day and 2mg/day progesterone and VIII group (Ovx). was treated with 6,7 μg/g metoclopramide/day and 2mg/day progesterone. Vehicle and metoclopramide were Regina C. Teixeira Gomes, PhD1, Carina Verna, Dr2, Gabriela C. Cristofani Maioral, administered intraperitoneally; the steroid hormones were administered by gavage once MSc2, Roberta B. Wolff, MSc2, Ricardo S. Simões, MSc3, Edmund Chada Baracat, MD, daily at 10 a.m. during 50 consecutive days. In the 50th day, the animals were killed, the Ph.D3, Helena B. Nader, PhD4, José M. Soares Júnior, MD, Ph.D2. 1Department of middle portions of the uterine horns were removed them was fixed in 10% buffered Morphology, Federal University of São Paulo, São Paulo, Brazil; 2Department of formaldehyde and subjected to routine histologic processing for paraffin inclusion and Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil; further sectioning and haematoxylin-eosin staining.The results were expressed as mean 3Department of Gynecology and Obstetrics, University of São Paulo Medical School of SD and were analyzed by ANOVA. Significance level was set at P<0.05. Results: we Medicine, São Paulo, Brazil; 4Department of Biochemistry, São Paulo Federal University, ± found that the hyperprolactinemic state induced and replacement of estrogen and progestin São Paulo, Brazil significant alteration mice uterus Conclusion: It was observed comparing the groups Objective: To evaluate the metoclopramide-induced hyperprolactinemia impact on the treated with metoclopramide and / or hormones in the control group: treatment with expression of genes prolactin and prolactin receptor in mouse uterus during the estrous estrogen promoted the proliferation of the endometrium as the uterus of the other groups cycle. Design: 80 adult (100 days old) female virgin mice were randomly divided into two were atrophied. groups of 40 animals each: control (Ctr), which received intraperitonela (IP) 0.2 ml of saline solution, and experimental (HPrl), which received IP 6,7 μg/g metoclopramide. After 50 days the animals were properly randomly divided into 8 groups of 10 animals, according to the phase of the cycle: proestrus (Ctr and HPrl), estrus (Ctr and HPrl), CLINICAL POSTER PRESENTATIONS metaestrus (Ctr and HPrl) and diestrus (Ctr and HPrl). Following euthanasia, the uterine horns were removed and fixed in 10% formol. After subjected to histological processing P-19. for inclusion in paraffin. The sections were stained by haematoxylin-eosin (H.E.) How Do Breast Pain and Breakthrough Bleeding Associated with evaluated by morphologic methods. The expression genes prolactin and prolactin receptor Hormonal Treatments for Menopausal Symptoms Impact Post- was quantitative Reverse Transcriptase Polymerase Chain Reaction PCR Analysis Real menopausal Women’s Lives: Qualitative Interviews with Post-menopausal Time. The results were expressed as mean ± SD and were analyzed by the ANOVA. Results: We found that the hyperprolactinemic state induced decrease at proestrus and Women in the USA, China, Mexico and Italy 1 3 4 3 increase estrus the expression of genes prolactin and prolactin receptor, while increase the Lucy Abraham , Rob Arbuckle , Lorraine Dennerstein , Louise Humphrey , Laura 3 2 5 expression of genes prolactin and decrease the expression of genes prolactin receptor. Maguire , Sebastian Mirkin , James A. Simon, MD, CCD, NCMP, FACOG , Tara 1 3 1 Conclusion: The present results show that hyperprolactinemia induces estral cycle- Symonds , Steven Walmsley . PRO Centre of Excellence, Pfizer Ltd, Tadworth, United 2 3 dependent alterations on the expression of genes prolactin and prolactin receptor in mouse Kingdom; Clinical Sciences, Pfizer Inc, Collegeville, PA; Patient Reported Outcomes, 4 uterus. These changes could conceivably help to explain some of the infertility problems Mapi Values Ltd, Bollington, United Kingdom; Dept of Psychiatry and National Aging 5 related to high prolactin circulating levels and/or the observed failures of embryo Research Institute, Melbourne University, Parkville, VIC, Australia; Department of implantation in hyperprolactinemic states. Obstetrics and Gynecology, George Washington University, Washington, DC Objective: Estrogen plus progestin therapies (EPT) represent the current standard of care for post-menopausal women with a uterus for the treatment of symptoms associated with P-17. menopause. While successfully treating climacteric symptoms, the presence of progestin The gene expression prolactin and prolactin receptor’ study in mice is necessary to prevent endometrial proliferation. Progestins contained in EPT are lactimal gland with metoclopramide-induced hyperprolactinemia associated with side effects such as breast pain/tenderness and vaginal spotting/bleeding. Carina Verna, Dr2, Regina C. Teixeira Gomes, PhD1, Gabriela C. Cristofani Maioral, The objective of this study was to conduct qualitative interviews with post-menopausal MSc2, Roberta B. Wolff, MSc2, Vivien J. Coulson-Thomas, Dr4, Helena B. Nader, PhD4, women to better understand the patient experience of breast pain and vaginal bleeding Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D2. 1Department of symptoms associated with EPT and to assess the impact of these symptoms on post- Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of menopausal women’s health-related quality of life (HRQoL). Design: 59 post-menopausal Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil; women in the USA (n=14), China (n=15), Mexico (n=15) and Italy (n=15) (aged 40-63) 3Department of Gynecology and Obstetrics, University of São Paulo Medical School of taking EPT and experiencing breast pain and/or vaginal bleeding/spotting (47/59 were Medicine, São Paulo, Brazil; 4Department of Biochemistry, Paulo Federal University, São experiencing both) participated in in-depth interviews concerning their experiences of Paulo, Brazil EPT and impact on HRQoL. Thematic analysis was conducted to identify concepts Objective: To evaluate the metoclopramide-induced hyperprolactinaemia impact on the describing the experiences of the participants using Atlas Ti. Results: In all 4 countries, expression of genes prolactin and prolactin receptor in mouse lactimal gland. Design: 20 women described a variety of impacts that breast pain and breakthrough bleeding had on adult (100 days old) female virgin mice were randomly divided into two groups of 10 their HRQoL. The largest impact was on sex life with many women avoiding sex or animals each: control (Ctr), which received intraperitoneal (IP) 0.2 ml of saline limiting foreplay when experiencing symptoms, particularly in the USA and China. As solution/day, and experimental (HPrl), which received IP 6,7 μg/g/day one women explained “They want to touch you…and you can’t let them do that because metoclopramide.The 50th day of treatment were anesthetized, sacrificed and removed the of the pain that you’re in”. In terms of psychological wellbeing, some described feeling lacrimal gland was fixed in Bouin, and then subjected to histological processing for angry or annoyed that they were experiencing these symptoms now they were post- inclusion in paraffin. The sections were stained by haematoxylin-eosin (H.E.) evaluated menopausal, while a minority said bleeding made them feel normal “called ‘the old friend’ by morphologic methods. The histomorfometric analysis of the lacrimal gland was in Shanghai dialect, menses give me a cheering message that I won’t get old”. Of concern performed using the AxionVision 4.2, RL system (Carl Zeiss) and AxioLab Standart 2.0 to some women was that breast pain or bleeding was a sign of an underlying health microscope. And a part of the lactimal gland were removed and the expression genes problem, such as cancer “what’s wrong with me? Maybe I - my two aunts died in one year prolactin and prolactin receptor was quantified Reverse Transcriptase Polymerase Chain of breast cancer, so I say maybe I have cancer.” While some felt their symptoms had no Reaction PCR Analysis Real Time. The results were submitted statistical analysis impact on their daily life, others described how symptoms limited their social life, ability ANOVA. Results: the metoclopramide-induced hyperprolactinemia determined to exercise and do chores, and even their choice of clothing “I liked to wear white pants alterations morphologic and increased the expression of genes prolactin and prolactin a lot and since I take these kind of pills, and I started bleeding, well, I don’t wear them”. receptor in lacrimal gland. Conclusion: we found that the hyperprolactinemic state Conclusion: In-depth interviews with a geographically diverse sample revealed how induced increase the expression of genes prolactin and prolactin receptor on proestrus breast pain and bleeding associated with taking EPT can impact HRQoL. The impact of phases. Possibly, this effect is related to reduction in estrogen and progesterone these side effects of EPT on post-menopausal women’s HRQoL should be a consideration production. when reviewing treatment options for menopausal symptoms.

P-18. P-20. Effects of metoclopramide-induced hyperprolactinemia on mice uterus Prediction of Osteoporosis & fracture risk in postmenopausal Emirate after hormonal replacement women. Wafa Al Omari, Anna Karkanis, Jenan Rashid and N Nagelkerke Gabriela C. Cristofani Maioral, MSc2, Regina C. Teixeira Gomes, PhD1, Carina Verna, Tawam Hospital,Al Ain,UAE Dr2, Roberta B. Wolff, MSc2, Mayara R. Silva, Graduate Studant2, Manuel J. Simões, Wafa R. Al Omari, MD, FRCOG1, Anna Karkanis1, Jenan Rashid1, Nickolas Nagelkerke2. PhD1, Ricardo S. Simões, MSc3, José M. Soares Júnior, MD, Ph.D2. 1Department of 1OBG, Tawam Hospital, Al Ain, United Arab Emirates; 2Community medicine, Faculty Morphology, São Paulo Federal University, São Paulo, Brazil; 2Department of of medicine, Emirates university, Al Ain, United Arab Emirates Gynecology and Climaterium, São Paulo Federal University, São Paulo, Brazil; Objective: To explore public awareness of osteoporosis and willingness to manage the 3Department of Gynecology and Obstetrics, University of São Paulo Medical School of problem,with reference to a variety of socio-economic factors. To look for predictors & Medicine, São Paulo, Brazil associates of osteoporosis& high fracture risk in postmenopausal emirate women with Objective: To evaluate the effects of metoclopramide-induced hyperprolactinemia on special reference to social factors in UAE,e.g high parity,birth spacing and sun exposure. mice uterus after hormonal replacement with progesterone and 17β-estradiol. Design: 80 Design: Cross-sectional questionnaire study. The study was carried out in Tawam adult (100 day-old) female virgin mice were randomly divided into 8 groups of 10 animals hospital,Menopause clinic. The study involved 180 post menopausal Emirates women . each: GI group (non-ovariectomized animals, non-Ovx) and GII group (ovariectomized Interventions involved: Questionaire,blood tests, BMD, Fore FR calculator and animals, Ovx) were treated with the drug vehicle/day (0.2 ml NaCl 0.9% in distilled measurement of weight,height. Results: Age and Osteoscale: There is a positive relation water), GIII group (Ovx) and GIV group were treated with 6,7 μg/g metoclopramide/day between Age and risk of lower BMD in postmenopausal women. Years after menopause and Osteoscale: The earlier the menopause take place,the more increase in the risk of

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lower BMD. Parity and osteoporosis: Increased parity lead to increase the risk of prevalence of hypertension and diabetes were estimated with their 95% confidence osteoporosis. Duration of breast feeding and osteoscale: There is no relation between intervals (95%CI) and the Kappa statistic was used to evaluate the agreement between the duration of breast feeding and bone density. BMI and osteoscale: Obesity is common morbidities referred and measured. Results: Measured hypertension was present in among postmenopausal Emirati women with a total mean of BMI of 30.osteoporosis 36.69% of women (95%CI: 33.24 - 40.13%) and it was referred by 40.91% (95% CI: decreased with increase in wt . Medical disorder and Osteoscale: From all medical 37.37 – 44.46%). Diabetes was measured in 22.82% of women (95%CI: 19.27 – 26.37%) disorder, chronic renal disease is the most common disease that affect bone density and 10.84% (95%CI: 8.57 – 13.10%) referred suffering from it. The Kappa coefficient for adversily. Medication and Osteoscale: Steriods is the most common medication that affect hypertension was 34.54% (95%CI: 27.37 – 41.71%) and for diabetes was 42.89% bone density adversily. Cancer drugs has no significant effect on bone density. Sun (95%CI: 34.89 – 50.89%). Conclusion: Hypertension was overestimated in this Exposure,Habits and Osteoscale: All women did not smoke,and have a relatively short population while diabetes was underestimated. Thus, many women may be missing duration of exposure to sun light and even upon exposure they were heavily covered. opportunities for receiving adequate health care assistance. However no relation found between duration of sun exposure and Osteoscale. Biochemical markers and Osteoscale There is no correlation between the serum concentration of 25 OHD,calcium level and alkaline phosphatase when related to osteoscale. Conclusion: In P-24. postmenopausal Emirate Women abnormal bone health was present in 66 % of patients. Transdermal estradiol gel for the treatment of symptomatic More attention to be paid to build up peak bone density before the age of 20. Modifiable postmenopausal women factors has to be looked at from a different angle as duration of sun exposure was not David F. Archer, MD1, James H. Pickar2, Dipali C. MacAllister3, Michelle Warren2. 1Jones related to bone health. Type of culture & costume limit sun exposure benefit. Institute for Reproductive Medicine, Eastern Virginia Medical School, Norfolk, VA; 2Columbia University Medical Center, New York, NY; 3ASCEND Therapeutics, Herndon, VA P-21. Objective: To determine the efficacy, safety, and lowest practical dose of a transdermal Prevalence of depression and associated factors in climacteric in the estradiol gel for the treatment of symptomatic, postmenopausal women. Design: Healthy, “Health Project of Pindamonhangaba” (PROSAPIN) postmenopausal women with at least 7 moderate to severe hot flushes per day or at least Wendry M. Pereira, master1, Débora P. Rezende1, Elaine A. Pereira1, Ana Carolina B. an average of 50 or 60 per week (depending on the trial) were randomized to 1.5 mg Schmitt2, Maria Regina A. Cardoso1, José M. Aldrighi, PhD1. 1School of Public Health, (n=73) or 0.75 mg (n=75) of estradiol in a transdermal 0.06% gel or placebo (n=73) in a University of São Paulo, São Paulo, Brazil; 2School of Medicine, University of São Paulo, phase 3 study, or to 0.375 mg (n=119) or 0.27 mg (n=118) of estradiol in a transdermal São Paulo, Brazil 0.03% gel or placebo (n=114) in a phase 4 study. Hot flush frequency and severity, Objective: To estimate the prevalence of depression and to identify its associated factors responders for frequency, vaginal maturation index (VMI), and adverse events (AEs) were among women in climacteric. Design: The study was cross-sectional, including 875 evaluated. A lower concentration of estradiol gel (0.03%) was used in the phase 4 study women aged 35 - 65 years selected by a probabilistic sampling technique in instead of the currently approved 0.06% concentration used in the phase 3 study, so that Pindamonhangaba city, Brazil. A self-reported questionnaire was applied including lower amounts of estradiol (0.375 mg and 0.27 mg) could be dispensed. Results: A total variables related to socio-demographics characteristics, lifestyle, gynecological and of 89% (196/221) and 79% (277/351) of subjects completed the phase 3 and 4 studies, obstetric history, morbidity and depression, investigated by the Beck’s Inventory. The respectively. Demographics and baseline hot flush number and severity were not notably prevalence of depression was estimated and a multiple logistic regression model was used different between groups within each study. Estradiol and estrone levels increased with to identify its associated factors. Stata, version 10.1, was used in the analyses. Results: estradiol gel application. Frequency of moderate to severe hot flushes and severity of all The prevalence of the depression was 33.7% (95%IC: 30.4% – 37.3%). The associated hot flushes significantly decreased compared with placebo at weeks 4 and 12 with 0.75 factors found were: poor sleep quality (p<0.001), anguish feelings (p<0.001) and mg and 1.5 mg estradiol in the phase 3 study and with 0.375 mg estradiol in the phase 4 insecurity (p<0.001), obstructive sleep apnea (p=0.002), hypertension (p=0.01), referred study. The placebo response was different between the two studies, and the percentages cardiac problem (p=0.03) and falls in the last six months (p=0.04). Conclusion: of responders with the estradiol gel doses studied were higher than with placebo. The Depression affected more than a third of women and its associated factors were sleep overall subject responder rates were generally lower in the phase 4 study than those in the quality, morbidities and feelings of anguish and insecurity. phase 3 study with the approved gel with 0.75 mg estradiol (Table). Significant shifts (P<0.001) in the VMI from baseline to week 12 compared with placebo were also observed with 0.75 mg and 1.5 mg estradiol in the phase 3 study; and significant P-22. improvements in the VMI (P<0.001), increases in superficial cells (P=0.005), and Associated Factors With Insomnia in Climateric Women: PROSAPIN decreases in parabasal cells (P=0.002) were seen with 0.375 mg estradiol compared with (Pindamonhangaba Project Health) placebo in the phase 4 study (no significant changes with 0.27 mg estradiol). The Elaine A. Pereira1, Ana Carolina B. Schmitt2, Wendry P. Pereira1, Debora P. Rezende1, percentages of subjects who experienced at least 1 treatment-emergent AE (TEAE) were Maria Regina A. Cardoso1, José M. Aldrighi, PhD1. 1School of Public Health, University 78.7%, 83.6% and 69.9% with 0.75 mg estradiol, 1.5 mg estradiol, and placebo, of São Paulo, São Paulo, Brazil; 2School of Medicine, University of São Paulo, São Paulo, respectively (phase 3); and 49.6%, 54.3% and 54.0% with 0.375 mg estradiol, 0.27 mg Brazil estradiol, and placebo, respectively (phase 4). The most frequently reported TEAEs (in Objective: To estimate the prevalence of insomnia and to identify associated factors in ≥5% of subjects) were headache, infection, breast pain, and nausea in the phase 3 study; climacteric women. Design: Cross-sectional study with 875 women aged 35 to 65 years and (in ≥2% of subjects) were insomnia and headache in the phase 4 study. A similar registered at the Family Health Strategy from Pindamonhangaba city (São Paulo, Brazil) number of patients discontinued due to AEs in both studies. Three serious AEs not selected by a probabilistic sampling technique. The study estimated the prevalence of considered related to treatment were reported with estradiol in the phase 3 study, whereas symptoms suggestive of insomnia through information contained in the Beck Depression 3 serious AEs were reported with placebo and none with estradiol in the phase 4 study. Inventory. Thus, insomniacs were considered women who referred difficulty falling No deaths occurred in either study. Conclusion: A transdermal estradiol gel with 0.75 mg asleep, keeping asleep or early awakening. To evaluate the associated factors, the women estradiol effectively reduced the frequency and severity of moderate to severe hot flushes, were asked to respond a questionnaire on socio-demographic characteristics, lifestyle, improved VMI, and was well tolerated. Transdermal gel with 0.75 mg of estradiol gynecological history and clinical morbidity and medication and their weight, height and (EstroGel® 0.06%, 1.25 g of gel) is currently indicated in the treatment of moderate to waist circumference were measured. Analysis was performed by a multiple logistic severe vasomotor symptoms and moderate to severe symptoms of vulvar and vaginal regression model using Stata 10.1. Results: Insomnia was reported by 36.6% (95%IC: atrophy due to menopause. The overall efficacy, safety, and responder rates of the 4 studied 33.1 – 40.1) of the study women and the factors associated were: sleeping less than six estradiol doses considered with the currently available formulation, confirm that the hours per night (p=0.043), the presence of poor sleeping quality (p<0.001), polycystic transdermal gel with 0.75 mg of estradiol is the lowest practical dose for treatment of ovary syndrome (p=0.002) and occupational physical activity above the average symptomatic, postmenopausal women. The data from the Phase 4 study do not preclude population (p=0.002). Conclusion: The prevalence of insomnia was high in climacteric further investigation of a lower-dose estradiol gel than what is currently available. women and it was associated with sleeping less than six hours and with poor sleeping quality, the presence of polycystic ovary syndrome and physical activity. Table. Percentage of Responders for Hot Flush Frequency*

P-23. Over- and Under-Reporting of Diabetes Mellitus and Hypertension in Climacteric Women in the “Health Project of Pindamonhangaba” (PROSAPIN) *Responders were subjects with 50% reduction from baseline in moderate to 2 1 1 ≥ Ana Carolina B. Schmitt , Maria Regina A. Cardoso , Wendry P. Pereira , Elaine A. severe hot flushes. Pereira1, Debora P. Rezende1, Rubia G. Guarizi1, Mayra C. Dellu1, Erika Flauzino1, José M. Aldrighi, PhD1. 1School of Public Health, University of São Paulo, São Paulo, Brazil; 2School of Medicine, University of São Paulo, São Paulo, Brazil Objective: To estimate and compare the prevalence of hypertension and diabetes mellitus referred and measured in climacteric women. Design: The study was cross-sectional and investigated a probabilistic sample of 875 women aged 35 to 65 years from Pindamonhangaba city, Brazil. It was asked if they were aware of suffering from hypertension and diabetes mellitus. In addition, both the blood pressure and blood glucose were measured. Women were considered hypertensive when their pressure levels were greater than or equal to 130x85 mmHg, and were considered diabetic those with glucose levels greater than or equal to 100mg/dl, or even the ones under drug therapy. The

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Clinical Poster Presentations (continued)

P-25. ospemifene reported no, or mild dyspareunia and self-reported symptom severity that Safety and Tolerability of Bazedoxifene/Conjugated Estrogens in improved by 2-3 points on a 4-point Likert scale in 52.8% of ospemifene vs 38.8% of Postmenopausal Women: Findings From a 1-Year, Randomized, Placebo- placebo subjects. The PP analysis also demonstrated statistically significant findings for and Active-controlled, Phase 3 Trial each co-primary endpoint, confirming ITT analysis. The % of subjects with at least 1 adverse event (in the ITT population) at Wk 12 for both strata combined is summarized David F. Archer, MD1, Rogerio A. Lobo2, Kaijie Pan3, Arkadi A. Chines3, Sebastian in Table 2. Discontinuation rates were similar in the ospemifene and placebo groups, Mirkin3. 1Clinical Research Center, Eastern Virginia Medical School, Norfolk, VA; 10.2% vs 11.6%, respectively. Endometrial histology assessments showed no cases of 2Columbia University Medical Center, New York, NY; 3Pfizer Inc, Collegeville, PA hyperplasia and 2 (1.0%) cases of active proliferation in the ospemifene group vs 0% in Objective: The tissue selective estrogen complex (TSEC) pairing bazedoxifene (BZA) the placebo group. Vaginal bleeding was reported in 2 (0.4%) and 4 (0.9%) subjects in the with conjugated estrogens (CE) has been shown to be effective in treating menopausal ospemifene and placebo groups, respectively. One subject in the ospemifene group symptoms and preventing osteoporosis while protecting the endometrium in women with experienced a deep vein thrombosis following an 8-hour car ride and was discontinued a uterus. This randomized, double-blind, placebo- and active-controlled, phase 3 study from the study. Conclusion: In postmenopausal women with self-reported MBS of (Selective estrogens, Menopause, And Response to Therapy [SMART]-5 trial) was dyspareunia, this unique study demonstrated that, despite the PRN use of lubricants, conducted to evaluate the efficacy and safety of BZA/CE compared with placebo, treatment with ospemifene 60 mg/d demonstrated clinically and statistically significant medroxyprogesterone (MPA)/CE, and BZA monotherapy in nonhysterectomized efficacy and was well tolerated. postmenopausal women. Here we report findings related to the endometrial safety and overall safety/tolerability profile of BZA/CE during 1 year of treatment. Design: Table 1 Change from BL to WK 12/LOCF (ITT Analysis)* Postmenopausal women (aged 40-65 years) with an intact uterus were randomized to receive daily oral doses of BZA 20 mg/CE 0.45 mg (n = 335), BZA 20 mg/CE 0.625 mg (n = 368), BZA 20 mg (n = 169), MPA 1.5 mg/CE 0.45 mg (n = 149), or placebo (n = 354). Endometrial safety was evaluated by the incidence of endometrial hyperplasia as measured by endometrial biopsy at 1 year. Adverse events (AEs) were recorded throughout the study. Breast tenderness and uterine bleeding (sanitary protection required) or spotting (light or no sanitary protection required) were recorded in daily dairies. Non- cumulative and cumulative rates of amenorrhea (no bleeding or spotting) for 4-week periods over a year were summarized. Results: At Year 1, the incidence of endometrial * Similar results were reported for the PP analysis hyperplasia with BZA 20 mg/CE 0.45 mg (0.30%) and BZA 20 mg/CE 0.625 mg (0.27%) was similar to that with BZA 20 mg (0%), MPA 1.5 mg/CE 0.45 mg (0%), and placebo Table 2 Adverse Events (0.28%). The overall incidence of AEs, treatment-emergent AEs (TEAEs), and serious AEs was similar among treatment groups. There was a higher incidence of AEs leading to study discontinuation in the MPA 1.5-mg/CE 0.45-mg group (14.1%) than in the BZA 20-mg/CE 0.45-mg (7.6%), BZA 20-mg/CE 0.625-mg (7.0%), BZA 20-mg (7.0%), or placebo groups (7.0%; overall P = 0.012). During Year 1, the percentage of subjects who reported at least 1 day of breast tenderness during 4-week cycles with BZA 20 mg/CE 0.45 mg (3.0%-9.4%) and BZA 20 mg/CE 0.625 mg (2.6%-9.1%) was similar to that with placebo (2.0%-8.6%) and lower than that with MPA 1.5 mg/CE 0.45 mg (9.4%-24.3%). For both BZA/CE doses, the rates of spotting (0.5%-5.8%) and bleeding/spotting (0.5%- P-27. 6.2%) during 4-week cycles were generally low and similar to those with placebo Hot Flashes, Sleep Complaints and Depressed Mood in Midlife Women 1 2 1 1 (1.3%-4.8% and 1.6%-4.8%, respectively). MPA 1.5 mg/CE 0.45 mg was associated with Jessica P. Brown , Patti E. Gravitt , J. Kathleen Tracy . Epidemiology and Public Health, 2 higher rates of spotting (8.2%-24.1%) and bleeding/spotting (8.8%-25.6%) compared University of Maryland School of Medicine, Baltimore, MD; Epidemiology, Johns with the BZA/CE and placebo groups. Cumulative rates of amenorrhea for consecutive Hopkins School of Public Health, Baltimore, MD 4-week cycles in women treated with BZA 20 mg/CE 0.45 mg (87.9%-98.3%) and BZA Objective: Prior research has shown that 20% of midlife women report sleepiness 20 mg/CE 0.625 mg (84.9%-98.7%) were similar to those in women treated with placebo consistently interferes with daily life, including augmenting symptoms of depression and (83.9%-98.4%) and higher than those in women treated with MPA 1.5 mg/CE 0.45 mg anxiety. Menopausal women with chronic nighttime awakening report significantly lower (54.4%-91.2%). Conclusion: BZA 20 mg/CE 0.45 and 0.625 mg were associated with a health related quality of life in both physical and mental health domains. Here we favorable endometrial safety and overall safety profile over 12 months. The tolerability examined the relations among hot flashes, sleep complaints and depressed mood as part profile of BZA/CE as measured by rates of amenorrhea and breast tenderness was not of a larger study on midlife women’s genital health. Design: Cross-sectional data were different from placebo and more favorable than MPA/CE. obtained from 179 women (ages 35-60, 79% white). Hot flash experience was obtained from a comprehensive menopausal symptom checklist; it was coded as ever/never as well as ever/never within the past year. Sleep complaints were assessed by the Pittsburgh Sleep P-26. Quality Index (PSQI) and depressed mood was assessed with the Center for Efficacy of a novel SERM, ospemifene, in the treatment of dyspareunia Epidemiological Studies-Depression scale (CES-D). A PSQI total score of 5 or greater symptoms associated with postmenopausal vulvovaginal atrophy suggests clinically meaningful sleep complaints. A CES-D score of 16 or greater indicates Gloria Bachmann, Dr.1, Steven R. Goldstein, MD, FACOG, CCD, NCMP2, Vivian Lin3, depressed mood. Results: The experience of hot flashes was significantly related to the David Portman, MD4, James Liu5, Shelli Graham6, Michele Giliberti6, James A. Simon, total PSQI score for both ever having experienced a hot flash (t=3.60, p<.001) and for MD, CCD, NCMP, FACOG7. 1UMDNJ-Robert Wood Johnson Medical School, New having hot flashes within the past year (t=3.24, p=.001). Depressed mood was not Brunswick, NJ; 2New York University School of Medicine, New York, NY; 3QuatRX significantly related to hot flashes, but was strongly correlated with PSQI total score Pharmaceuticals Company, Ann Arbor, MI; 4Columbus Center for Women’s Health (r=.64, p<.001), with 25% of the sample reporting both elevated PSQI and CES-D scores. Research, Columbus, OH; 5MacDonald Women’s Hospital, Cleveland, OH; 6Clinical Self-rated sleep quality, somnolent medication use, and habitual sleep efficiency did not Development, Shionogi Inc, Florham Park, NJ; 7The George Washington University vary by hot flash experience either ever or within the past year (all p’s>.05). However, ever School of Medicine, Washington DC, DC experiencing hot flashes was related to shorter sleep duration (chi-square=9.55, p = .023), Objective: Currently, only estrogen-based preparations have received regulatory approval longer sleep latency (chi-square=8.26, p=.041), more frequent daytime dysfunction (chi- for prescription treatment of vulvovaginal atrophy (VVA) in postmenopausal women; square = 11.86, p= .008), and greater sleep disturbance (chi-square = 8.46, p=.015). When therefore, exploring alternative treatments for VVA is imperative. Ospemifene, a novel, examining participants with hot flashes within the past year, sleep duration and daytime selective estrogen receptor modulator (SERM), is unique compared with other SERMs dysfunction were no longer significant (p’s>.05), whereas longer sleep latency and sleep due to its estrogenic activity in the vaginal epithelium and is under investigation in disturbance remained significantly more likely in women who reported hot flashes in the postmenopausal women with VVA symptoms. This study assessed the efficacy, safety, past year. Among hot flash sufferers, those reporting less than 7 hours of sleep per night and tolerability of ospemifene 60 mg/d in the treatment of VVA symptoms in were significantly more likely to report an elevated CES-D score, (chi-square = 7.29, postmenopausal women. Design: This 12-wk, randomized, double-blind, placebo- p=.007). Women who reported ever having hot flashes and who experienced daytime controlled, parallel-group study included 919 subjects. Two study populations were dysfunction somewhat or at least weekly were significantly more likely to have an elevated analyzed: intent-to-treat (ITT), the primary analysis, and per protocol (PP). Women (40- CES-D score (chi-square=8.68, p=.003). Among women who reported hot flashes within 80 years of age) were assigned to one of 2 VVA symptom strata (vaginal dryness or the past year, however, there was no relation between sleep latency or sleep disturbance dyspareunia) based on their self-reported most bothersome VVA symptom (MBS);and and elevated CES-D score (p’s>.05) Conclusion: Midlife women with hot flashes within each stratum were randomized 1:1 to receive either ospemifene 60 mg/d or placebo. reported numerous sleep complaints, but not all these sleep complaints were related to Data from each stratum were independently analyzed. All subjects were provided with a depressed mood. In fact, there was no association with difficulty falling asleep or frequent nonhormonal vaginal lubricant to be used as needed (PRN). For each stratum, co-primary trouble sleeping and depressed mood in women with recent hot flashes. Clinically, the efficacy endpoints were measured for change from baseline to Wk 12 (LOCF) in: vaginal experience of hot flashes could be used to prompt a discussion of good sleep hygiene to pH, % superficial cells and % parabasal cells in the maturation index, and the severity of mitigate the potential for future sleep or mood disturbance. the MBS. This abstract reports the dyspareunia stratum results. Results: At Wk 12 ospemifene demonstrated significant efficacy vs placebo for each co-primary endpoint. Changes in the ITT population for vaginal pH (LS mean),% of superficial cells (median), and % of parabasal cells (LS mean) all were p<0.0001 (Table 1); a significant effect was observed as early as 4 wks. Significant mean improvement was also observed for the MBS, dyspareunia (p=0.0001) at Wk 12. A higher percentage of subjects treated with

46 P-28. metabolic syndrome (60.7%). When asked to rate the most preferred modalities to learn Perimenopause and Menopause Support Program about menopause, the top choice was supervised clinics (53.7%), followed by formal Carol Caico, Ph.D., N.P.. Nursing, NYIT, Seaford, NY lectures (21.9%), case presentations (21.4%), small groups (16.4%), web-based learning Objective: The hypothesis was that women who go through a structured support group (8.4%) and independent reading (6.0%). Only 15.2% of residents reported their program will be better prepared to cope with symptoms and be better informed on what health had a formal menopause medicine learning curriculum and 15.6% have a defined care choices they would make. The findings supported the benefits of being part of a menopause clinic as part of their residency. Conclusion: Current American and Canadian perimenopause and menopause support group and the information learned during the 10 OB/Gyn residency training is deficient in menopause medicine education. Based on weeks helped women to feel they are not unique in the way they are coping with this preliminary results of our survey, most residency programs are not fulfilling the period of a woman’s life. Design: Perimenopause and menopause is a period in a womens’ educational goals of their residents in key menopause issues. A majority of residents lives associated with many physical and emotional changes. The severity of the symptoms indicated they have only limited knowledge of common clinical menopause topics and are range from mild to severe and can affect relationships with partners, friends, and barely comfortable in managing patients with menopause-specific problems. A curriculum coworkers. Symptomatic women often try to suffer alone or do not feel supported during is needed to increase knowledge in the areas of pathophysiology of menopausal this sometimes long period of transition. This study will provide a forum of support for symptoms, hormone and non-hormone therapy, bone health, cardiovascular disease and these women which will increase their knowledge and power to effectively cope with this metabolic syndrome. While supervised clinical experience is preferred by most residents transition of life. The support program was conducted by a Women’s Health Nurse as a means to learn how to manage menopausal patients, this opportunity is lacking with Practitioner who holds a certificate as a Menopause Clinician as well as a Specialist in approximately 15% of residents reporting a defined menopause clinic as part of their Adult and Psychiatric Mental Health. Two questionnaires were completed at the first curriculum. support group. One of the questionnaires used was developed by the PI when she completed her doctoral dissertation. The other questionnaire is the Quality of Life P-30. questionnaire developed by Wulf H. Utian. Subjects were invited to attend the support program with inclusion criteria that they be English speaking women between the ages of Reductions in Brain Blood Flow During Hot Flashes in Postmenopausal 45-60 who are currently experiencing symptoms or difficulty coping with perimenopause Women 1,2 1,2 1,2 or menopause. Fliers were distributed to many OB-GYN offices as well as local hospitals Craig Crandall, Ph.D. , Rebekah A. Lucas, Ph.D. , Matthew S. Ganio, Ph.D. , James 1,2 1 and advertisement was be put in local papers. The program was held weekly for 10 Pearson, Ph.D. . Internal Medicine, University of Texas Southwestern Medical Center, 2 consecutive weeks and participants signd a consent which stated that they attend at least Dallas, TX; IEEM, Texas Health Presbyterian Hospital Dallas, Dallas, TX 7 or the 10 sessions and that the information attained from the meeting would be used for Objective: Lightheadedness is occasionally reported during hot flashes. Such a response research. The consent also informed the women that any information used in research may be due to reductions in brain blood flow during the hot flash, although it is unknown would assure anonymity. The venue for the support program was at a large community whether this occurs. This study tested the hypothesis that hot flashes are accompanied by hospital education center who agreed to provide refreshments for all sessions. The same a reduction in brain blood flow in postmenopausal women. Design: Eleven healthy, questionnaires were answered by participants at the end of the sessions. This was a normotensive, postmenopausal women prone to having frequent hot flashes (Age: 53±3 phenomenological study of women living through symptoms of perimenopause and years, Weight: 62±6 kg; BMI: 24±2 kg; mean±SD) rested in the supine position in a menopause.The researcher also started each meeting with a topic that was used as temperature-controlled laboratory (~25°C) for approximately 120 minutes while waiting education for the women, utilizing NAMS slides, and then women were free to talk about for hot flashes to occur. The onset of each hot flash was objectively identified by an abrupt any topic pertaining to what they were experiencing. This was to be a triangulated study increase in sternal skin blood flow (laser Doppler flowmetry) and/or sternal sweat rate as there was a qualitative study based on themes from the sessions and a quantitative (capacitance hygrometry), and was subjectively identified by the subject pressing a switch analysis of questionnaires from the start of the program correlated with the questionnaires at the beginning and end of each hot flash. Brain blood flow was evaluated via transcranial at the end. Results: The findings supported the benefits of being part of a perimenopause Doppler of middle cerebral artery blood velocity (MCAvmean) prior to and throughout and menopause support group and the information learned during the 10 weeks helped hot flashes. Each hot flash was divided into 8 segments of equal duration, with the average women to feel they are not unique in the way they are coping with this period of a MCAvmean being obtained for each segment. For each hot flash, the segment with the woman’s life. Another form which asked for the women to make comments on the lowest MCAvmean was identified and was quantified as a percent reduction relative to program as the researcher found that the during the program, questionnaires that were MCAvmean prior to that hot flash. Hot flashes were categorized as either “responders” used would not show significant change due to the support groups therefore the or “non-responders”, with the criterion for a responder being ≥10% reduction in quantitative piece did not indicated significance. The information gleaned from the field MCAvmean, relative to pre-hot flash baseline, in at least one segment during the hot flash. notes from each sessionand the form that allowed the participants to anonymously fill out Results: Twenty-eight hot flashes were evaluated amongst these 11 subjects. Seventeen the comment form demonstrated overwhelmingly positive results. Conclusion: The of these hot flashes exhibited at least a 10% reduction in MCAvmean and thus were information from this research confirmed that support groups are very important during categorized as responders. The average decrease in MCAvmean for the responder group this period in women’s life and the research on the topic found many on-line lay support of flashes was 19±5% (mean±SD; range: 10 to 31%), while the average decrease in but not many face to face support groups let by experts. MCAvmean for the non-responder group of flashes was only 4±3% (range: 0 to 8%; P<0.001 between responder and non-responder flashes). Conclusion: These data demonstrate that approximately 60% of hot flashes are accompanied by a clear reduction P-29. in brain blood flow. Based upon these findings, it is possible that lightheadedness during Needs Assessment of American and Canadian Obstetrics and Gynecology hot flashes is due to inadequate cerebral perfusion and thus cerebral oxygenation. The Residents Regarding Menopause Education: Areas for Improvement and mechanism(s) responsible for the reduction in brain blood flow during the postmenopausal Learning Preferences hot flash warrants further investigation. Supported by NIH Grant AG030189 Mindy S. Christianson, MD1, Jennifer A. Ducie, M.D.1, Kristiina Altman, M.D.2,1, Wen Shen, M.D.1. 1Gynecology and Obstetrics, Johns Hopkins University School of Medicine, P-31. 2 Baltimore, MD; Obstetrics and Gynecology, Johns Hopkins Bayview Medical Center, Symptom clusters across the menopausal transition and postmenopause: Baltimore, MD Objective: To understand the current teaching of menopause medicine in American and observations from the Seattle Midlife Women’s Health Study Lori A. Cray, PhD1,2, Ellen S. Mitchell, PhD2, Jerald R. Herting, PhD3,2, Nancy F. Woods, Canadian Obstetrics and Gynecology (OB/Gyn) residency programs. In particular, as PhD2. 1College of Nursing, Seattle University, Seattle, WA; 2School of Nursing, University curriculum developers, we sought to identify specific areas for improvement and assess of Washington, Seattle, WA; 3Sociology, University of Washington, Seattle, WA learner preferences for different educational methods. Design: Our team developed and Objective: To differentiate subgroups of women across the menopausal transition stages piloted a 24-item web-based survey. We then sent an e-mail message to all American and and postmenopause who experience similar symptom clusters. Design: A secondary data Canadian OB/Gyn residency directors in April, 2011, inviting them to complete the web- analysis of the Seattle Midlife Women’s Health Study. Sample: participants who provided based survey and forward it to their current residents. While program directors were self-report data on symptoms experienced between 1990 and 2005. Latent class analysis supplied with the web-link to the survey, they were requested to reply with how many (LCA) two-level mixture modeling was used to identify subgroups of women who residents were forwarded the survey link. This survey is still actively in progress with experienced similar clusters of vasomotor, sleep, pain, cognitive, mood and tension planned reminders scheduled at two- and four-week intervals prior to closing the survey. symptoms. Results: Three subgroups of women were identified: 1) asymptomatic Results: Of 311 residency program directors contacted via e-mail, 34 (10.9%) confirmed subgroup (80.2%); 2) highly symptomatic hot flash subgroup (5.2%); 3) low symptomatic forwarding the survey to their residents. Based on program director responses, 693 hot flash subgroup (14.7%). Women in the highly symptomatic hot flash subgroup also residents received the survey with 306 residents completing the survey for a response rate experienced moderate sleep and pain symptom clusters, while women in the low of 44.1%. Of those completing the survey, 28.3% were first-year residents, 19.8 % second- symptomatic hot flash subgroup experienced moderately higher clusters of sleep, pain, year, 25.4% third-year, 15.9% fourth-year residents and 10.6% program directors. When mood, cognitive and tension symptoms. Conclusion: Although intervention studies tend asked to rank their experience during residency among the areas of gynecology, obstetrics, to target only one symptom, this analysis demonstrates that women experience clusters of reproductive endocrinology, menopause medicine and gynecologic oncology, 59.4% of symptoms with varying degrees of severity. Shifting the focus from single symptoms to residents reported they had the least amount of experience in menopause. The majority of symptom clusters will facilitate the identification of the unique symptom experience for residents reported they had limited knowledge and needed to learn more about these individual women. aspects of menopause medicine: pathophysiology of menopause symptoms (62.2%), hormone therapy (60.8%), non-hormone therapy (73.9%), bone health (60.0%), cardiovascular disease (64.1%) and metabolic syndrome (62.3%). Similarly, a majority of residents reported being not comfortable/barely comfortable in managing patients in these areas: pathophysiology of menopause symptoms (59.3%), hormone therapy (66.4%), non- hormone therapy (67.9%), bone health (60.6%), cardiovascular disease (62.1%) and

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Clinical Poster Presentations (continued)

P-32. P-34. Effectiveness of Two Doses of a Monthly Oxybutynin Vaginal Ring in Validation of the MENQOL for use with Women who have been treated Menopausal Women with Symptoms of Overactive Bladder for Gynaecological Cancer or Breast Cancer Sue E. Dasen, MS1, Kathleen Z. Reape, MD1, Howard I. Hait, MS2. 1Teva Women’s Health Catherine Doyle, Lauran Adams, Tracey Das Gupta, Margaret Fitch, Alison McAndrew, Research & Development, Horsham, PA; 2Edenridge Associates, LLC, Wilmington, DE Stephanie Burlein-Hall, Jennifer Blake. Sunnybrook Health Sciences Centre, Toronto, Objective: As part of a larger Phase 2 clinical trial in adult women with overactive bladder ON, Canada (OAB) and symptoms of predominant or pure urge incontinence, urinary urgency, and Objective: To determine if the Menopause Quality of Life (MENQOL) is a valid and elevated urinary frequency, a targeted subset analysis of menopausal women was reliable instrument for use in a population of women whose menopause is a consequence conducted to evaluate the effectiveness of two doses of a monthly oxybutynin (oxy) of treatment for gynaecological or breast cancer. Validation will allow the use of this tool vaginal ring (VR) compared to placebo. Design: In this Phase 2, multicenter, randomized, to measure the effect of menopause on the quality of life of these women. Design: This double-blind, placebo-controlled study of both pre- and post-menopausal women aged is a psychometric evaluation of the MENQOL. To determine face validity, a purposively 21.3 to 85.7 years, subjects were randomized to one of three treatment groups (placebo selected sample of 10 women who met the inclusion criteria reviewed the MENQOL in VR, 4 mg/day oxy VR, or 6 mg/day oxy VR) at 68 investigational sites in the US and order to assess how well it measures quality of life after cancer treatment. To determine Canada. Randomized subjects entered a three-week placebo VR run-in period, during content validity, a purposively selected group of ten experts in gynaecological or breast which they completed a 3-day OAB voiding diary. Upon successful completion of the cancer, menopause or quality of life reviewed the MENQOL for omissions and run-in phase, eligible subjects entered a 12-week treatment period, during which OAB appropriateness. To determine reliability and construct validity, a cross-sectional voiding diaries were completed prior to study visits at Weeks 4, 8, and 12. Vaginal rings convenience sample of 80 women who met the eligibility criteria completed: were changed once a month during the treatment period. The primary measure of efficacy Demographic items, MENQOL, EORTC-30, SVQ-Extended Version, and a Visual Analog was the change from baseline to Week 12 (end-of-treatment) in the total weekly number Scale for Hot Flashes. The same women completed the MENQOL and the Visual Analog of incontinence episodes, with the two active treatment groups each being compared to Scale for Hot Flashes two weeks later Results: Women with a confirmed diagnosis of placebo. Among the 719 randomized participants was a subset of 249 post-menopausal breast or gynaecological cancer who experienced menopause as a result of their cancer subjects (87 received placebo VR, 87 received oxy 4 mg/day VR, and 75 received oxy 6 treatment were asked to participate in this study. Women who were taking hormone mg/day VR) who met the following criteria at the end of the run-in period: >10 urge replacement therapy were excluded. Accrual for this study is ongoing. This abstract will incontinence episodes per week, average urinary frequency of > 8 voids/24 hours and report the characteristics of the first 54 participants. We anticipate accrual will be average total void volume of < 3.0 L/24 hours. The purpose of this analysis was to evaluate completed by July 2011. The women’s ages ranged from 29 to 58 with a mean of 47 years. the consistency of treatment effects in a post-menopausal subject population with a most 81% reported a breast cancer diagnosis; 19% were diagnosed with a gynaecological rigidly defined baseline symptomatology. Results: Both active treatment groups cancer. 78% of the women were married or in a common law relationship and 72% demonstrated statistically significant reductions in the total weekly number of reported completing college or university. The items on the MENQOL that had the highest incontinence episodes from baseline to the end-of-treatment, when compared to placebo. number of ‘yes’ responses included those items measuring vasomotor symptoms. 85% of The mean change for the oxy 4 mg/day VR was -16.90, p=0.0172; the mean change for women reported experiencing hot flashes; 75% reported night sweats and 79% reported the oxy 6 mg/day VR was -16.36, p=0.0246, while the mean change for those women on sweating. 83% of women reported feeling tired or worn out and 83% of women reported placebo was -12.63. These results were similar to what was observed in the overall study trouble sleeping. 75% of women reported feeling a lack of energy. Mean scores for population, i.e., regardless of menopausal status. Conclusion: In this Phase 2 study, both symptoms indicate the level of bothersome. Participants indicated on scale of 0 (not at all the 4 mg/day and 6 mg/day doses of a monthly oxybutynin vaginal ring demonstrated bothered) to 6 (extremely bothered) for each symptom. Reported are mean and standard statistically significant treatment effects and similar efficacy when compared to placebo deviation for each symptom. Vasomotor symptoms were among the highest, including for the primary outcome measure of reduction in the weekly number of reported hot flashes 4.07(1.68), night sweats 3.88(1.86); and sweating 4.00 (1.65). Weight gain incontinence episodes in menopausal women with symptoms of predominant or pure urge was the item that women were most bothered by, with a mean score of 4.62(1.79). Other incontinence, urinary urgency and elevated urinary frequency. That such effects were items that women ranked as bothersome were the items measuring sexual and intimacy similar to the results demonstrated in the overall study population implies that the changes including change in sexual desire 4.24(1.99); vaginal dryness during intercourse treatment effect is maintained when considering post-menopausal women as candidates 4.20 (1.98), and avoiding intimacy 4.12(2.09). Feeling tired or worn out also scored high for therapy. at 4.02(1.59). Conclusion: The consequences of cancer treatment, including menopause, has a significant effect on the quality of life for women diagnosed with breast or Menopausal Subjects: MITT Cohort - Total Number of Incontinence Episodes: Change gynaecological cancer. In particular, women were bothered by vasomotor symptoms, from Baseline to End-of-Treatment changes in sexuality and vaginal dryness. The high incidence and interrelationship of night sweats, feeling tired, difficulty sleeping, and a lack of energy, in conjunction with how high women rank these items in terms of affecting their quality of life may provide a focus for directing interventions at this group of cancer survivors.

P-35. *Change = Change in total number of incontinence episodes from initiation of There is a Sustained Decrease in Pap Smear and HPV Concordance with treatment to end-of-treatment **Difference = Difference between active treatment groups and placebo Increasing Age: When Should we Stop Screening the Low Risk ***P-Value: Significance between active treatment groups and placebo was tested Perimenopausal Patient? on raw data analysis Cindy M. Duke, BS, MS, MD, PhD1, Wen Shen, M.D.1, Kathryn Chang2, Michelle Silver2, Raphael Viscidi4, Anne Burke1, Patti E. Gravitt2,3. 1Department of Gynecology & Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD; 2Department of P-33. Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Vaginal estrogen therapy with promestriene in oncology patients 3Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg Lino Del Pup, Medicine. Gynecological Oncology, National Cancer Institute, Aviano, School of Public Health, Baltimore, MD; 4Department of Pediatrics, Johns Hopkins Italy Medical Institutions, Baltimore, MD Objective: The estradiol diether derivative, promestriene, was tested in oncology patients Objective: The majority of women participating in cervical cancer screening programs suffering from severe vaginal dryness and dyspareunia because of its presumed absence in the United States today are over age 35 and have generally been well screened in the of significant absorption. Labrie (1) reported a relevant increase in serum estrone of about past. Despite their low risk (and no new risk factors) many women and their providers are 500% and 150% folds with vaginal estrogens (CEE and with E2 tablets respectively). As reluctant to deviate from the tradition of ‘Annual Pap Smears’. Current pap testing compared to both E1 and E2 precursors, E1S is present at 10-50 fold higher plasma guidelines for the perimenopausal woman, even when she is low risk, recommend concentration that enables its more sensitive quantification with a better inter-assay screening every three years after a documented history of three consecutively negative variation. Futhermore it is characterized by a prolonged half-life that makes its paps and reflex human papillomavirus (HPV) testing if abnormal cytology on pap screen. measurement independent from the blood sampling time and from the problems We conducted a study to evaluate HPV and cytological abnormalities in a population of associated to the diurnal variations suffered by E1 and E2. The circulating pool of E1S can perimenopausal women (age 35-60) attending routine screening at gynecologic clinics to thus be considered as a “reservoir” and a marker for assessing changes in women’s overall assess the concordance between ASCUS (or worse) pap and high risk HPV (HR-HPV) estrogen pool during promestriene therapy. Design: 15 menopausal patients followed in prevalence to determine whether current practice guidelines, as they relate to the a gynecological oncology department used promestriene 10 mg soft vaginal capsules daily perimenopausal woman, should be revised. Design: A prospective cohort of women age for at least one month. Mean age was 51.9 years. Symptoms, vaginal pH, colposcopy 35-60 years who received routine care at one of four primary Baltimore, Maryland GYN were assessed at the beginning and one month later together with estrone sulfate plasma clinics was enrolled according to institutional IRB guidelines. Participants were seen at levels, used as a marker of overall estrogenicity and measured with very sensitive and semi-annual clinic visits from 2008 to 2011. Exclusion criteria included previous precise liquid chromatography-tandem mass. Results: vaginal lubrication [3 (2-4) to 5 (4- hysterectomy, current pregnancy, history of organ transplant or HIV infection, unwilling 8)] (p= 0.008) and dyspareunia improved [3 (2-5) to 6.4 (6-8)] (p=0.007). Mean vaginal to provide contact information, non-English speaking, or inability to provide informed pH decreased [5.5 (4.8-6.2) to 4.4 (4.2-5.4)] (p= 0.043). Colposcopic evaluation of atrophy consent. Demographic data including socioeconomic status, menstrual history, improved. Estrone sulfate plasma levels, did not change significantly [362 (22-1220) to reproductive history, past pap history, use of exogenous hormones, sexual history, smoking 393 (81-856) pg/ml] (p=0.22). Conclusion: promestriene was very effective to cure and alcohol use were collected. HPV genotyping was performed using Roche Linear vaginal dryness and dyspareunia and to restore vaginal trophism, while plasma estrone Array VLP serology for HR-HPV and pap smear data including reflex HPV testing was sulfate levels did not change significantly. retrieved from the medical record. After adjusting for age, race, education, marital status and clinic, statistical analyses were performed using chi squared analysis. Results: A

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total of 882 women were enrolled. The majority of study participants have a college Society to questions about their use of compounded and off-label hormone therapy. degree. Median household income was $80,000-$100,000. Approximately 70% of Design: A brief survey was distributed to all attendees of the 2010 Annual Meeting of The participants were white and approximately 20% were black. 46.7% reported having an North American Menopause Society at the time of registration. In addition to age and abnormal pap in the past, and in over half of these women, the last abnormal pap was gender, the questions included the following: Do you ever prescribe compounded hormone over 10 years ago. Only 6.0% reported having an abnormal pap within the last year. 18.7% products? If no, do you prescribe FDA-approved testosterone products off-label for of women reported having had treatment for abnormal pap in the past (laser, cryotherapy, women? Please indicate which compounded hormones you prescribe: estradiol, estrone, cone or leep). At baseline, 9.0% of women tested positive for HR-HPV and 18.8% tested estriol, progesterone, testosterone, DHEA. Does your compounding pharmacist include positive for any HPV. The prevalence of any pap abnormality >= ASCUS was 4.7%. Of a list of hormone risks and benefits for the patient? What percentage of your hormone these, 62.5% were ASCUS, 5% were ASC-H, and 32.5% were LSIL. The overall prescriptions is compounded? Do you personally use compounded hormones? Results: concordance between HR-HPV positivity and pap abnormality was 89.9% (p<0.001) with Of 1,299 attendees, 576 were clinicians; 318 attendees (235 of whom were female) a low positive concordance of 13.9%. The ratio of HR-HPV positive to normal pap completed the survey (24% of the total in attendance, 55% of clinicians). Among the discordant results were significantly more common than the ratio of HR-HPV negative to respondents, 69% indicated they had prescribed compounded hormones. Among those abnormal pap results (test for symmetry p=0.0002). Seven out of twenty-six women with who answered no (91), 45% indicated they had prescribed FDA-approved testosterone a HR-HPV negative abnormal pap result (26.9%) had low risk HPV infection, but the off label for women. Testosterone was the most frequently compounded hormone. 53% majority of pap+/HR-HPV negative results were completely negative for HPV. The were not sure if their compounding pharmacist provided product information concordance of pap abnormality and HR-HPV status among women positive by either or (risks/benefits) to the patient; 15% indicated the pharmacist did not. More than 1/3 both methods declined with increasing age: age 35-39 =22.6%, age 40-44 =16.0%, age (n=135) reported compounding represented 10% or more of their prescriptions. Only 8% 45-49 =8.0%, age 50-54 =6.3%, age 55-60 = 0% (all HR-HPV positive patients in this age personally used compounded hormones. Sixty-five comments provided by respondents group had a normal pap). Conclusion: In a population of 882 women participating in indicated compounding is an important issue in their practice: “Only prescribe for patients routine pap screening, no high-grade disease was detected suggesting that perimenopausal who insist or come to me already on them.” “Please have FDA approve testosterone women with a history of negative cervical cancer screening are at low risk for developing transdermal for women!” “For HT, only for patients that really push for this.” “ I will be cervical cancer. The relatively high prevalence of HR-HPV and the declining concordance very interested in these results.” “ I look forward to not needing to use compounded between pap and HPV test results with increasing age suggests a re-evaluation of the anything!” Conclusion: The results of this survey indicate that among clinicians seeing meaning and risk of positive screening test results in well-screened perimenopausal menopausal women, compounding hormones is a significant issue. More data are required women is needed. to determine the extent of this practice, the need that it fills, and the efficacy, safety and financial impact in our society. P-36. Escitalopram Treatment of Menopausal Hot Flashes Robert R. Freedman, Ph.D.1,2, Michael L. Kruger, M.S.2, Manuel E. Tancer, M.D.1. 1Psychiatry, Wayne State University School of Medicine, Detroit, MI; 2Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI Objective: To determine the effects of 10 mg and 20 mg/day of escitalopram on objectively-recorded hot flashes (HFs) and on the rectal temperature threshold for sweating. Design: Two studies were performed: 16 women received 10 mg/day and 26 women received 20 mg/day escitalopram in double-blind fashion for eight weeks. They were required to report at least six HFs/day, be in the age range of 44-59 years, be free of any antidepressant drugs, hot flash treatment drugs or supplements (soy, herbs), have BMI under 32, and be nondepressed as determined by Dr. Tancer using the M.I.N.I. International Neuropsychiatric Interview, a short, structured, psychiatric interview. The rectal temperature threshold for sweating was measured in the laboratory, using published methods, during the first and eighth weeks of the investigation. HFs were physiologically measured by a miniature, ambulatory recorder for the first three weeks and the eighth week of the study. Data from the preliminary study were analyzed using a 2-way, repeated- measures, analysis of variance. Data from the second study were analyzed with a 2-way (Group x Time), repeated-measures, analysis of covariance using BMI as a covariate. To Number prescribing DHEA, E1, E3, E2, P4, and Testosterone. control for differences in HF frequency at baseline (week 1), data from subsequent weeks were expressed as percentages of the week one data. Results: For the first study, there P-38. were no significant effects whatsoever for any measure. The results for the second study are shown in the table below. There were no significant differences between the two The hopeless age?: An exploration of the experience of menopause in Arab groups for hot flash frequency or for rectal temperature sweating threshold at any time women living in Qatar 1 2 1 point. Conclusion: At 10 mg or 20 mg/day, escitalopram is not effective in the treatment Madhuvanti Murphy, Dr.P.H. , Mohamud A. Verjee, MBChB , Linda M. Gerber, Ph.D. . 1 2 of menopausal HFs. (Supported by AG-05233 from NIH) Public Health, Weill Cornell Medical College, New York, NY; Weill Cornell Medical College in Qatar, Doha, Qatar Hot Flash Frequencies by Week as Percent of Baseline Adjusted for BMI Objective: Given that there is no published literature to date on how Qatari women conceptualize and experience menopause, this research aimed to qualitatively describe and examine the expectations and experiences of the midlife transition in Arab women living in Qatar. Design: This qualitative research was the first phase of a larger mixed- method study modeled after the SWAN study. Six focus groups of approximately 7 women each were conducted with Arab women living in Qatar; 3 groups were made up of local Qatari women only, and the other 3 groups with non-Qatari Arab women originating from neighboring countries. A purposive sample of 41 pre-, peri-, and post- menopausal women aged 40 to 60 participated. The semi-structured group format encouraged discussion around knowledge about menopause; physical, emotional and social experiences related to menopause; and, opinions on cultural differences that may exist related to menopause. Focus groups were audio-taped and conducted in Arabic, and were later translated into English. Transcripts were imported into Atlas.ti software and examined for the creation of codes and emerging themes. Comparisons were conducted between Qatari and non-Qatari groups. Information from the groups was used to inform the development of the survey for the quantitative phase of the study. Approval was received from the Institutional Review Boards of Weill Cornell Medical College-Qatar and the Hamad Medical Corporation, Qatar. Results: The majority of women (Qatari and non-Qatari) considered menopause a maturing experience, but preferred not to use the P-37. term ‘menopause” as it translates as “hopeless age” in Arabic, which was considered to Results from 2010 NAMS Survey on use of Compounded and Off-label have negative connotations. Post-menopausal women described menopausal symptoms Hormone Products consistent with general knowledge, such as hot flashes, tiredness and mood swings, but Margery Gass, MD1,2, Cynthia Stuenkel, MD3. 1The North American Menopause Society, many pre-menopausal women were unaware of the symptoms associated with menopause, Mayfield Heights, OH; 2Cleveland Clinic, Cleveland, OH; 3University of California San even if they knew someone who had experienced menopause. Women acknowledged that Diego, San Diego, CA the experience of menopause affected their relationships with their children and husbands, Objective: There are no published data on the extent to which compounded hormone particularly the mood swings, as they would become very emotional. Some women had therapy is being used in the United States. Prescriptions for hormone therapy approved by been recommended hormone replacement therapy by their doctors in order to continue the Food and Drug Administration are tracked and reported intermittently, but having their periods, but many refused as they did not want more children. Diseases such compounded prescriptions are not tracked on a national level. This report reflects the as osteoporosis and vitamin D deficiency were considered linked to menopause. Post- responses of attendees at the 2010 Annual Meeting of The North American Menopause menopausal women were more socially active than before, and were thankful to be able

49 Clinical Poster Presentations (continued)

to travel, spend more time with their families and friends, and participate in religious their cardiovascular and bone metabolic markers. Serum levels of carboxyterminal activities that they previously could not attend during menses. The role of the husband was telopeptide of type 1 collagen (beta-crosslaps, B-CTX, electrochemiluminescence Elecsys a very important theme as how a woman experienced menopause depended on the 2010, Roche Diagnostics, GmbH, Mannheim, Germany) were used as indicators of bone husband’s level of support. Many women initially did not tell their husbands they were resorption. Serum levels of total alkaline phosphatase, creatinine, phosphate, total calcium, menopausal fearing they would marry younger wives, and some believed that menopause magnesium, cholesterol, triglycerides, and glucose were determined with the use of an was brought on by disputes with husbands. Some women also believed that Western autoanalyzer Olympus AV 5200, Tokyo, Japan). Insulin and parathyroid hormone (PTH) women did not have the appropriate support from husbands and families that Arab women were measured by conventional immunoradiometry Results: The mean age of women have during menopause, and felt this lack of support could lead to negative outcomes was 57.9 years. The average age of menopause was 46.3 years. The mean baseline vitamin such as being at an increased risk for suicide caused by depression during menopause. D was 23.3ng/ml. We analyzed the relationship of serum vitamin D levels with type of Conclusion: Qatari and non-Qatari women have many similarities in how they perceived menopause (natural/surgical), and with the above mentioned cardiovascular and bone and experienced menopause, although they collectively believe the experiences of Western metabolism parameters. We found only a trend, although not significant (p=0.054), of women are different. The fact that menopause allowed ladies to devote more time to negative correlation between PTH values and 25(OH) D. Of the total 133 women, we religion, which plays an important part in daily life activities in Qatar, seems to be one of measured 25(OH) D values of 38 in winter, with a mean value of 23,1ng/ml; of 40 in the reasons why this period is looked upon favorably. When developing instrumentation spring with a mean of 21,9ng/ml; of 20 in summer with a mean of 26,7ng/ml; and of 35 for future women’s health-related research in this culture, researchers need to take into in autumn with a mean of 23,1ng/ml. Despite the slight increase in summer no statistical consideration questions on spousal and familial influence in order to be culturally differences were found between the seasonal groups Conclusion: In this Mediterranean appropriate. area we found a high prevalence of inadequate levels of vitamin D, and this was not substantially modified by the season of the year. There was a trend of negative correlation between 25(OH)D and PTH. We could not detect any significant relationship between P-39. cardiovascular or bone metabolic markers and the serum levels of 25(OH) Anxiety and Depressive Symptoms Following Natural Menopause, Hysterectomy with Ovarian Conservation, and Hysterectomy with Bilateral Oophorectomy P-41. Carolyn Gibson, MPH, MS1, Hadine Joffe, MD, MSc2, Joyce Bromberger1, Rebecca C. Effects of Supplmentation With 25-OH-D3 (Calcifediol), A Vitamin D Thurston, PhD1, Tené Lewis3, Naila Khalil4, Karen Matthews1. 1University of Pittsburgh, Analogue, On The Serum Levels of Vitamin D in Postmenopausal Women Pittsburgh, PA; 2Massachussetts General Hospital, Harvard Medical School, Boston, MA; Miguel Gonzalez-Izquierdo1, Sílvia Tamarit Bordes1, Aitana Monllor Tormos1, Maria 3Yale University School of Medicine, New Haven, CT; 4Wright State University, Dayton, Tarrazó Millet1, Aitana Gisbert Vicent1, Maria An García Pérez2, Antonio Cano1,3. OH 1Obstetrics and Gynecology, Hospital Dr Peset, Valencia, Spain; 2Reserch Foundation, Objective: Cross-sectional studies suggest an association between negative affect and Hospital Clínico Universitari, Valencia, Spain; 3Department of Pediatrics, Obstetrics and hysterectomy, but whether negative mood states may be a result of hysterectomy and/or Gynecology, University of Valencia, Valencia, Spain oophorectomy is unclear. We used prospective data to examine mood trajectories in the Objective: To describe the change in the levels of vitamin D after calcifediol, a vitamin years prior to and following natural menopause, hysterectomy with ovarian conservation, D analogue, and the effects on serum parameters of bone metabolism in a group of and bilateral oophorectomy among women in midlife. Design: Data were from the Study community-based healthy postmenopausal women Design: We recruited 260 of Women’s Health Across the Nation (SWAN), a multi-site community-based prospective postmenopausal women, determined their value of 25(OH) D in blood (Roche cohort study of the menopausal transition (n=1,997). Depressive and anxiety symptoms electrochemiluminescence system, Elecsys 2010, Roche Diagnostics, GmbH, Mannheim, were assessed at each of up to 11 annual visits with the Center for Epidemiological Studies Germany), and collected data about bone metabolic markers. Serum levels of Depression Index (CES-D) and four questions about anxiety symptoms. Piecewise carboxyterminal telopeptide of type 1 collagen (beta-crosslaps, B-CTX, hierarchical linear growth models were used to relate natural menopause, hysterectomy electrochemiluminescence Elecsys 2010, Roche Diagnostics, GmbH, Mannheim, with ovarian conservation, and hysterectomy with bilateral oophorectomy to linear growth Germany) were used as indicators of bone resorption. Serum levels of total alkaline trajectories of depressive and anxiety symptoms before and after the final menstrual period phosphatase (U/L), creatinine (mg/dl), phosphate (mg/dl), total calcium (mg/dl), and (FMP) or surgery. Covariates included body mass index, self-rated health, hormone magnesium (mg/dl) were determined with the use of an autoanalyzer Olympus AV 5200, therapy, and antidepressant use, reported at each visit; educational attainment and Tokyo, Japan). The circulating concentration of parathyroid hormone (PTH, pg/ml) was race/ethnicity, assessed at baseline; menopausal status the year prior to FMP or surgery; measured by immunoradiometry (DiaSorin, Stillwater, USA). Forty seven women were and age at the time of FMP or surgery. Results: Between annual visits 1-10, 1,816 (90.9%) supplemented with calcifediol (15000 IU every two weeks). Both treated and untreated of participants reached natural menopause, 78 (3.9%) reported hysterectomy with ovarian women were investigated after 6 months Results: The mean age of the women was 57.9 conservation for benign conditions, and 103 (5.2%) reported hysterectomy with bilateral years and the average menopausal age was 46.3 years. The mean baseline level of 25(OH) oophorectomy for benign conditions. For all women, depressive symptoms decreased in D was 23.3ng/ml. The mean baseline level of 25(OH)D in the supplemented group was the years leading up to (B= -.13, p<.001) and following (B = -.21, p<.001) FMP or surgery. 20,1ng/ml, and increased significantly to a mean value of 40,4ng/ml after 6 months. There Anxiety symptoms decreased in the years following FMP or surgery (B = -.05, p<.001). was a considerable variation in the circulating levels achieved by each woman. In the These trajectories did not significantly differ by hysterectomy or oophorectomy status. non-supplemented women, the mean baseline 25(OH)D value of 25.1ng/ml remained Additional factors related to higher depressive symptoms were poorer self-rated health (B unchanged (25.7ng/ml) at the 6th month. The supplementation with calcifediol was = 1.65, p<.001) and antidepressant use (B = 1.87, p<.001), while depressive symptoms associated with a 2 % increase in the the calcemia, from 9.8mg/dl to 10mg/dl, with a were lower with hormone therapy use (B = -.38, p=.03) and advanced educational stadistical signification, and a decrease in PTH levels from 55,8pg/ml to 50,5pg/ml attainment (B = -1.74, p<.001). Anxiety symptoms were higher with antidepressant use without stadistical signification. We could not detect any other biochemical change in the (B = .41, p<.001) and poorer self-rated health (B = .36, p<.001), and lower with hormone remainder of the bone parameters that were assessed Conclusion: In this Mediterranean use (B = -.09, p=.04) and among African American (B = -.27, p=.01) and Chinese (B = - area we found a high prevalence of inadequate levels of vitamin D. Supplementation with .41, p=.02) women. Conclusion: In this prospective examination, mood symptoms calcifediol achieved mean levels of 25(OH)D, which exceeded the recommended improved before and after the final menstrual period. Trajectories of mood symptoms threshold of 30 ng/ml. This change was associated with a slight increase in the level of before and after hysterectomy, with or without ovarian conservation, were not significantly serum calcium, but PTH serum levels did not modify significantly different than those of naturally menopausal women before and after their final menstrual period. The Study of Women’s Health Across the Nation (SWAN) has grant support from P-42. the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research Etiological profile of women presenting with premature ovarian failure on Women’s Health (ORWH) (Grants NR004061; AG012505, AG012535, AG012531, in Sultan Qaboos University hospital, Sultanate of Oman 1 2 2 1 AG012539, AG012546, AG012553, AG012554, AG012495). The content of this abstract Vaidyanathan Gowri , Jayakumar D. Dennison, MD , Anil V. Pathare . obstetrics and 2 is solely the responsibility of the authors and does not necessarily represent the official gynecology, Sultan Qaboos University, Muscat, Oman; Haematology, Sultan Qaboos views of the NIA, NINR, ORWH or the NIH. University, Muscat, Oman Objective: study the etiological factors of women presenting with premature ovarian failure and their hormonal profile in Sultan Qaboos university hospital Sultanate of Oman P-40. Design: A retrospective study from electronic patient records form Jan 1998- Dec 2010 Baseline and Seasaonal Variation in the Serum Levels of Vitamin D in Results: There were a total of 53 patients during the study period. 40 of them were Postmenopausal Women. Relationship With Cardiovascular and Bone following bone marrow transplant BMT) treatment for hematological disorders and the Metabolic Markers remaining 13 presented with either amenorrhea or infertility. Of the 13 patients, three Miguel Gonzalez-Izquierdo1, Sílvia Tamarit Bordes1, Aitana Monllor Tormos1, Marta patients had other endocrine disorders like hypothyriodism and or diabetes and one had Ferrer Piquer1, Lorena Sabonet Morente1, Maria An García Pérez2, Antonio Cano1,3. a chromosomal abnormality of deletion (46Xdel (x) q24-25, interstitial deletion). The 1Obstetrics and Gynecology, Hospital Dr Peset, Valencia, Spain; 2Research Foundation, mean age of the patients at the time of menopause who did not have bone marrow Hospital Clinico, Valencia, Spain; 3Obstetrics and Gynecology, University of Valencia, transplant was 35.8 years, mean Follicle stimulating hormone was 63IU, Luteinizing Valencia, Spain hormone was 30 IU, prolactin was173 IU and Thyroid stimulating hormone was 2.35 IU. Objective: To measure the circulating levels and the seasonal variation of 25 (OH) In women/girls who received bone marrow transplant for various reasons including acute vitamin D in a population of healthy postmenopausal women living in a Mediterranean and chronic leukemia, Thalasemia, Sickle cell disease and Paroxysmal nocturnal area. To disclose any relationship between 25(OH) D levels and cardiovascular parameters hemoglobinuria the age range was from 4 years to 40 years. The mean Follicle stimulating or bone metabolic markers Design: We recruited 133 postmenopausal women, determined hormone, Luteinizing hormone and Thyroid stimulating hormone in the BMT group is their value of 25 (OH) vitamin D in serum (Roche electrochemiluminescence system, shown below in a table. There was no significant difference in the hormonal profile though Elecsys 2010, Roche Diagnostics, GmbH, Mannheim, Germany), and collected data about the age of onset was significantly different between the groups by Mann- Whitney test (

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p value =0.000) Girls who received bone marrow transplant after 2010 with Reduced (HH) under the oversight of the HH IRB. Between July 2004 and May 2007, seventy intensity conditioning regimen (RIC) resumed periods and one of them even got pregnant three resident physicians completed a rotation which included attending a once a week Conclusion: The most common etiology of premature ovarian failure in this study was menopause clinic. At their first visit, and before the clinic began, they were each given a following BMT for hematological disorders. Recent changes like RIC therapy might help pre-test. At the end of the rotation, a post-test was given that was different from the pre- to avoid this problem and preserve ovarian function test (Test A was sometimes given first and Test B was sometimes given first). Each test contained questions on topics covering menopause, perimenopause, and general women’s health (important for menopause clinicians to know but not specific to menopause). At the end of each testing session, each resident was given a total score (evaluating menopause and non-menopause related questions) and a menopause score (pertaining to menopause related questions only). Results of the post-test were compared to the pre-test in order to determine the efficacy of the clinic in educating the participants on menopause related issues. Results: The mean (+/- SD) pre-test menopause score and total score were 63.2% (+/- 13.3%) and 63.7% (+/- 11.3%), respectively. The mean post-test increase in the menopause score was 14% with a median score increase of 10.2%. The range of post-test results went from a maximum decrease of 7.8% to a maximum increase of 47.1% FSH- Follicle stimulating Hormone (p<.0001, figure 1). The mean increase in the total score was 13% with a median increased LH- Luteinizing hormone of 10.7%. For the total score, the range went from -7.2% to 39.3% (p<.0001, figure 1). TSH- thyroid stimulating hormone There was no correlation between the score changes and the number of clinic sessions attended, the specialties of resident training (OB/GYN vs. non OB/GYN), the level of P-43. training (PGY1 or PGY2), or the order in which the examinations were taken (test A vs. test B taken first). Conclusion: The number of menopausal women, and the demand for Patterns of Brain Activation and the Neural Effects of Objective Hot physicians to care for them, continues to grow. Results of this study suggest that overall, Flashes in Highly Symptomatic Postmenopausal Women the menopause clinic successfully added to the breadth of knowledge of resident 1 4 1 1 Rhoda Jamadar , Deborah M. Little , Leah H. Rubin , Deanne Fornelli , Lauren L. physicians about menopause related matters. Menopause clinics may provide hope for 2 3 5,6 5 1,2 Drogos, M.A. , Stacie Geller , Lee P. Shulman , Suzanne Banuvar , Pauline M. Maki . women, and the medical community, that creative and innovative educational programs, 1 2 Department of Psychiatry, University of Illinois at Chicago, Chicago, IL; Department of such as a menopause clinic, may help educate future physicians in their ability to care for 3 Psychology, University of Illinois at Chicago, Chicago, IL; Department of Obstetrics menopausal women. and Gynecology, University of Illinois at Chicago, Chicago, IL; 4Department of Neurology, University of Illinois at Chicago, Chicago, IL; 5Northwestern University, Chicago, IL; 6Northwestern Memorial Hospital, Chicago, IL Objective: Functional neuroimaging studies provide insight into the cognitive processes and brain areas influenced by the menopausal transition. We previously reported that verbal memory performance on a paragraph recall test was negatively associated with objective hot flashes (HF) as measured by an ambulatory skin conductance monitor in midlife women with moderate to severe hot flashes. In contrast, subjective hot flashes were unrelated to memory. In the present study we used functional magnetic resonance imaging (fMRI) to investigate brain circuitry during a verbal memory task in midlife women and in relation to objective and subjective hot flashes. Design: Fourteen postmenopausal women (mean age= 54, 64% African-American) with moderate to severe vasomotor symptoms (>35 HF/week) completed fMRI assessments of verbal memory. A delayed recognition memory task requiring encoding and recognition of novel (experimental) and frequently repeated (control) words was used. A subset of 9 women wore an ambulatory sternal skin conductance monitor for 24 hours. Objective and subjective (button press) HF were recorded. Participants also completed a neurocognitive battery including verbal memory measures outside the scanner including paragraph recall. Imaging data were pre-processed and analyzed using Statistical Parametric Mapping (SPM5). A whole brain voxel-wise analysis was used to identify brain regions activated during encoding and recognition (novel words minus repeated words). A priori regions of interest included the hippocampus and prefrontal cortex (PFC). In the subset of 9 women with hot flash data, we related objective and subjective hot flashes to patterns of brain activation. Results: Significant regions of activation during the encoding condition included bilateral prefrontal cortex (PFC), right ventral lateral prefrontal cortex (vlPFC), right thalamus, right amygdala and left hippocampus. Significant regions of activation during recognition included bilateral PFC, left vlPFC, bilateral dorsal lateral prefrontal P-45. cortex (dlPFC) and posterior cingulate cortex (PCC). Participants subjectively reported Average concentration of endogenous sex hormones in healthy 60% of objective hot flashes. On the neurocognitive battery, objective (but not subjective) postmenopausal women not taking hormone therapy hot flashes correlated significantly with delayed paragraph recall scores (r= -.697 p<.05). 1 2 3 4 During the experimental (novel words) minus control (repeated words) condition of the Roksana Karim, MBBS, PhD , Wendy J. Mack , Howard N. Hodis , Chun-Ju Chien , Frank Z. Stanczyk5. 1Pediatrics and Preventive Medicine, University of Southern encoding task, objective hot flashes were negatively correlated (p<.01) with activation in 2 the dlPFC and orbitofrontal cortex. There were no correlation between subjective hot California, Los Angeles, CA; Preventive Medicine, University of Southern California, Los Angees, CA; 3Medicine, University of Southern California, Los Angees, CA; flashes and activation during encoding of experimental minus control conditions. 4 5 Conclusion: To our knowledge, this is the first neuroimaging study of objective hot Preventive Medicine, University of Southern California, Los Angees, CA; Obstetrics flashes in relation to brain activation patterns during a cognitive task. Consistent with and Gynecology, University of Southern California, Los Angees, CA previous studies in asymptomatic women, symptomatic postmenopausal women show Objective: While reference ranges of sex hormone concentrations are well defined for activation in a neural network that included PFC, hippocampus, and cingulate cortex. We women of reproductive age, such ranges are not well established for postmenopausal are the first to report that objectively measured hot flashes are negatively correlated with women. Peripheral adipose tissue serves as an important source for sex hormones in the PFC during performance of a cognitive task. Notably, activity decreased in women postmenopausal women. Therefore, the reference concentrations of sex hormones in with more objective hot flashes during effortful memory processing (experimental minus postmenopausal women need to be controlled for obesity. Although the associations of sex novel conditions). Subjective hot flashes did not relate to activation in this network. hormone concentrations with age and body mass index (BMI) are well known, the average Combined with our previous report that objective but not subjective hot flashes predict concentrations of endogenous sex hormones have not been identified in a reasonably large verbal memory declines, this fMRI study underscores the importance of measuring sample of healthy postmenopausal women by age groups, controlled for BMI and type of physiological hot flashes in relation to cognitive function. menopause. Design: Serum concentrations of estrone (E1), total and free estradiol (E2, FE2, respectively), total and free testosterone (T, FT, respectively) and sex hormone binding globulin (SHBG) were assessed in 857 healthy postmenopausal women not taking P-44. hormone therapy. E1 and E2 concentrations were also measured in baseline samples of Menopausal Medicine Clinic: An Innovative Approach to Enhancing the another ongoing trial (n = 350). E1, E2, and T were measured by validated Effectiveness of Medical Education extraction/chromatographic RIAs, whereas SHBG was measured by direct Xuezhi Jiang, MD1, Shiv Sab1, Peter F. Schnatz, D.O.1,2. 1ObGyn&Internal Medicine, The chemiluminescent immunoassay. FE2 and FT levels were calculated by using a validated Reading Hospital and Medical Center, Reading, PA; 2ObGyn&Internal Medicine, algorithm. Sex hormone and SHBG levels were log transformed. Linear regression models Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA were used to obtain mean (SD) sex hormone concentrations for each 5-year age group Objective: Despite a large number of menopausal women in the United States, education adjusted for BMI (continuous) and type of menopause (natural vs. surgical). Results: The in this area of medicine has been limited. The purpose of this study was to assess the study participants were on average(SD) 60.4(7) years old, predominantly white (65%), effectiveness, using a pre- and post-test, of a menopausal medicine clinic to enhance with average BMI of 27.3(5.4) kg/m2. There was a significant positive association of all trainees’ medical knowledge. Design: This study was performed at Hartford Hospital the hormones, except T, with BMI. SHBG was also significantly associated with BMI, but

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Clinical Poster Presentations (continued)

inversely. T and FT levels were lower among surgically menopausal women. Average indicated. For post menopausal women who demonstrates vulvovaginal and clitoral concentrations of sex hormones by 5-year age group, adjusted for BMI and/or type of atrophic changes, including architectural changes and phymosis, topical compounded menopause are shown in Table A. Endogenous concentrations of T and SHBG show testosterone cream may be added for incremental benefit. Phase 3: a) Identify medications significant increasing trend with increasing age. Conclusion: We report BMI-adjusted that may negatively impact sexual orgasmic response, and attempt to change, decrease or average concentrations of sex hormones and SHBG by age group in healthy alter dose. If selective serotonin reuptake inhibitor (SSRI) is the offending agent, patients postmenopausal women, which can be used for reference values in research studies as (or health care professionals) should consider adding a dopamine agonist to the SSRI well as in clinical practice. regimen or changing to a new antidepressant. Women can also consider adding a phosphodiesterase inhibitor “antidote” precoitally. b) Phosphodiesterase Inhibitors Table A: Levels of sex hormones and SHBG by age, adjusted for BMI (PDE5I) Agents: Medications like phosphodiesterase inhibitors may prove to be helpful for SSRI induced orgasmic changes as well as for selected women who have orgasmic changes. Compounded PDE5I applied to clitoral tissues or 25-50 mg of oral Sildenafil 40- 60 minutes prior to intercourse might result in improved sexual response. Results: Presented is a treatment paradigm to help ameliorate the issues related to postmenopausal changes in orgasmic latency and frequency. The paradigm shifts from minimally invasive to more systemic therapeutic options, which can minimize potential side effects. This model has proven beneficial in over 75 postmenopausal women in two large busy sexual medicine practices on two coasts of the USA. Conclusion: Female Orgasmic Disorder is complex and multifaceted in the cancer survivor and further research is needed to confirm its utility of proposed paradigms in large scale populations.

P-48. The change of the 8-hydroxydeoxyguanosine concentrations according to hormone therapy and association with Ser326Cys polymorphism of OGG1 gene in postmenopausal women receiving hormone therapy Seung-Yup Ku, MD,PhD1, Hoon Kim, MD,PhD2, Seok Hyun Kim, MD,PhD1, Young Min Choi1, Jung Gu Kim, MD,PhD1, Shin Yong Moon1. 1Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Republic of Korea; 2Department of Obstetrics and Gynecology, Incheon Medical Center, Incheon, Republic of Korea Objective: The 8-hydroxydeoxyguanosine (8-OHdG) is excised from oxidative damaged *Adjusted for BMI DNA by endonuclease repair enzymes 8-oxoguanine DNA N-glycosylase gene (OGG1) ** Adjusted for type of menopause and widely used for determination of DNA damage. The present study aimed at *** Adjusted for BMI and type of menopause investigating whether estrogen may influence on the blood/urinary 8-OHdG levels and whether the level of blood/urinary 8-OHdG is different according to OGG1 Ser326Cys polymorphism in postmenopausal women receiving HT. Design: In 102 postmenopausal P-46. women receiving HT, the 8-OHdG levels were measured in the blood and urine using Comparison of the Effects of Hormone Replacement Therapy on Bone high performance liquid chromatography (HPLC) before HT and 3 months after HT. The Mineral Density, Lipid Profiles, and Biochemical Markers of Bone genotyping of the Ser326Cys polymorphism of the OGG1 was performed by polymerase Metabolism in postmenopausal women chain reaction (PCR) and restriction enzyme fragment length polymorphism (RFLP) JangHeub Kim, Jeong Namkung, Young-Ok Lew, Mee-ran Kim. The Catholic University, analysis. Results: Clinical characteristics and serum concentration of 8-OHdG were not Seoul, Republic of Korea different according to OGG1 genotypes. The level of blood 8-OHdG after HT was Objective: Objective: To assess the effects of hormone replacement therapy on bone significantly lower compared to that before HT (P=0.003). Although blood and urinary 8- mineral density (BMD), biochemical markers of bone turnover, and lipid profiles in OHdG concentration were not significantly influenced by OGG1 genotypes in this postmenopausal women. Design: Methods: We retrospectively reviewed the medical population, it has been shown that post-HT blood 8-OHdG levels were lower in three records of 199 postmenopausal women who had received care at the Department of OGG1 genotypes (P=0.01). Conclusion: : These findings imply that hormone therapy Obstetrics and Gynecology of Catholic University Seoul St. Mary’s Hospital between can reduce blood 8-OHdG concentrations, one of the markers of oxidative damage. January 1994 and December 2008. The patients were divided into the following three However, the level of 8-OHdG were not different according to OGG1 Ser326Cys groups: group 1 received combined estrogen and progesterone therapy (n=91); group 2 polymorphism in Korean postmenopausal women receiving HT. Further study is needed received estrogen only (n=65); and group 3 received tibolone (n=43). We compared the to confirm this association in larger population. changes in biochemical markers of bone turnover, lipid profiles, and BMD during therapy. Results: Results: The BMD of the lumbar spine increased in groups 1 and 3 by 2.0% and Comparison of clinical characteristics and 8-OHdG concentrations among the three 1.2%, respectively, and the BMD of the total femur increased in groups 1 and 2 by 2.3% genotypes of OGG1 Ser326Cys polymorphism in postmenopausal women receiving and 0.5% from the initial values after 3 years, respectively. However, the BMD of the hormone therapy (HT) femoral neck and total femur decreased significantly in group 3 by 4.8% and 1.9%, respectively, 3 years after treatment initiation (p<0.05). Serum osteocalcin and urinary deoxypyridinoline decreased in all groups 1 year after treatment. In groups 1 and 3, the total cholesterol level decreased and the triglycerides level increased. However, there were no definite changes in the total cholesterol and triglycerides levels in group 2. The HDL- cholesterol level increased in groups 1 and 2, but decreased in group 3. As a result, the BMD of the lumbar spine increased and the total cholesterol level decreased in the combined therapy and tibolone groups. Tibolone had no beneficial effect on the BMD of the femoral neck. Conclusion: Conclusions: Our results suggest that each therapy has different effects on BMD, biochemical markers of bone metabolism, and lipid profiles. A prospective study involving a larger group, and considering multiple factors, will be 8-OHdG: 8-hydroxydeoxyguanosine, OGG1: 8-oxoguanine DNA N-glycosylase required to obtain more clinically meaningful conclusions. gene ET: estrogen therapy, BMI: body mass index Data are mean±SD. P-47. P value by analysis of variance (ANOVA) between the genotypes of OGG1 Treatment Protocol for Postmenopausal Orgasmic Changes Ser326Cys polymorphism Michael Krychman1,2, Susan Kellogg3. 1Southern California Center for Sexual Health, P* value by repeated measures of ANOVA before and after HT Newport Beach, CA; 2Obstetetrics and Gynecology, University of Southern California, Los Angeles, CA; 3Obstetetrics and Gynecology, Drexel University, Philedelphia, PA Objective: Orgasmic complaints are common for postmenopausal women who present P-49. with orgasmic changes in latency and frequency with respect to orgasmic potential. To Decreased Bone Mineral density in Patients With Invasive Cervical date no treatment paradigm exists that offers the health care provider some guidance in Cancer order to manage these troublesome issues in women living with cancer. Design: Presented Ji Young Lee1, Min-Hyung Jung2. 1Konkuk University, Seoul, Republic of Korea; here is a proposed paradigm for the treatment of orgasmic complaints that affect latency 2KyungHee Medical Center, Seoul, Republic of Korea and intensity of orgasm. Phase 1: a) Bibliotherapy, Sexuality Education, Self Stimulation, Objective: In women, osteoporosis is a common chronic disease that induces spinal Use of Vibrator/Stimulator - Begin a sexual response educational program which includes compression and femoral neck fractures, resulting in life-threatening complications. It is education about anatomy and physiology of sexual response. Phase 2: a) Topical very important to identify risk factors in order to prevent this disorder. Bone destruction Nutraceuticals; Products that may enhance genital sensitivity and increase sexual is a well-recognized complication in a variety of neoplasms without bone metastasis. satisfaction include Zestra® Essential Arousal Oils™. b) Topical Hormonal Agents. Therefore, in the present study, we investigated the spinal bone mineral density (BMD) Minimally absorbed local vaginal estrogen creams may be beneficial, if not contra- in patients with cervical cancer without bone metastases. Design: We measured spinal

52 bone mineral densities by dual-photon absorptiometry is 119 patients with invasive uterine Ninety days treatment with isoflavones derived from Glycine max (L.) Merr. and cervical cancer and compared them with measurements from 135 control women. conjugated equine estrogens through the vagina of women after menopause demonstrated Results: When adjusted for age and menopause duration, mean bone mineral density in that there was an improvement in the symptoms of vaginal atrophy and a significant patients with uterine cervical cancer was 13.9% lower (p=.0003) and age-matched increase in the values of cell maturation similar to conjugated equine estrogen. When percentiles were 9.2% lower (p=.0003) than in control women. The deficits in bone comparing Isoflavone and conjugated equine estrogen to placebo, there was a rise in the mineral density and age-matched percentiles were confined to the uterine cervical cancer Index of Meisels with significant difference. After the treatment, all groups showed no patients in their fifties, ie, less than 5 years’ menopause duration. Conclusion: Our study increase in endometrial thickness, changes in vaginal pH, and serum concentrations of results suggest that patients with invasive cervical cancer have a lower BMD, resulting in FSH and estradiol. an increased risk of osteoporosis. P-52. P-50. Assessment of Menopause-Related Symptoms among Perimenopausal The effects of Tribulus terrestris on sexuality in post-menopausal women Women with HIV Sonia Maria Rolim R. Lima, MD, PhD1, Sóstenes Postigo, MD1, Benedito F. Reis, MD1,2, Sara Looby, PhD, ANP1, Hadine Joffe, MD, MSc2, Alison M. Rope1, Jan L. Shifren, MD, Silvia Saito, MD1, Sheldom R. Botogoski, PhD3, Camila P. Martins1, Guazzelli Renata1, NCMP3, Steven Grinspoon1. 1Program in Nutritional Metabolism & Neuroendocrine Unit, Tsutomu Aoki, PhD1. 1Obstetrics and Gynaecology, FCMSCSP, São Paulo, Brazil; Massachusetts General Hospital and Harvard Medical School, Boston, MA; 2Center for 2Obstetrics and Gynaecology, UNIVÁS, Pouso Alegre, Brazil; 3Obstetrics and Women’s Mental Health, Massachusetts General Hospital and Harvard Medical School, Gynaecology, UFPR, Curitiba, Brazil Boston, MA; 3Department of Obstetrics and Gynecology, Massachusetts General Hospital Objective: To study the effects of Tribulus terrestris on sexuality in post-menopausal and Harvard Medical School, Boston, MA women. Design: A prospective, randomized, placebo-controlled, double-blind trial Objective: HIV-infected women are living longer and entering the menopausal transition. involving 60 post-menopausal women with sexual dysfunction was carried out. Study Hot flashes, insomnia, anxiety and depressive symptoms are common menopause- participants were split into two groups: Group I (control) n = 30, and Group II (Tribulus) associated symptoms that can affect all women during the perimenopause. Collectively, n= 30. Both groups were assessed for three months based on two questionnaires: the these symptoms can be burdensome, interfering with daily function and reducing quality- Inventory of Sexual Satisfaction – Female Version (GRISS), and the Female Intervention of-life. However, little is known about the presence and intensity of such symptoms among Efficacy Index (FIEI). Statistical analyses were performed using Student’s t test, the Chi- the growing number of HIV-infected perimenopausal women. The objective of this study squared test with Yates correction, and the Mann-Whitney test. Results: No significant is to evaluate menopausal symptoms including hot flashes, insomnia, anxiety, and difference was found between Groups for age, age at menopause, or time elapsed since depression among perimenopausal HIV-infected women compared to perimenopausal menopause. Results on the GRISS questionnaire showed a significant improvement in non-infected women carefully matched by age, race, and menstrual patterns. We global scores in Group II compared to Group I (p<0.001). A significant improvement on hypothesize that perimenopausal HIV-infected women are more likely to experience hot the GRISS domains of Infrequency, Non-communication, Female sexual avoidance, flashes, insomnia, anxiety, and depression compared to the matched control subjects. Female non-sensuality, Vaginismus and Anorgasmia, was seen in Group II compared to Design: In this cross-sectional evaluation, subjects reported the number of days they Group I (p<0.05). No significant improvement in the Female dissatisfaction domain (p= experienced hot flashes in past month and completed the Menopause Rating Scale (MRS; 0.845) was found. Results on the FIEI questionnaire (post-treatment) revealed a significant range 0-44), Hot Flash Related Daily Interference Scale (HFRDIS; range 0-100), improvement (p<0.001) in vaginal lubrication during intercourse and/or foreplay: Group Insomnia Severity Index (ISI; 8-14 sub-threshold insomnia, 15-21 moderate clinical I (20%) versus Group II (83.3%); improvement in genital sensation during sexual insomnia), Generalized Anxiety Disorder Assessment (GAD-7; scores 5= mild, 10+= intercourse or other stimuli: Group I (16.7%) versus Group II (76.7%); improvement in moderate-to-severe anxiety), and Center for Epidemiologic Studies Depression Scale sensation in the genital region: Group I (20%) versus Group II (70%); improvement in (CES-D; >16= significant depressive symptoms). Results: 48 women (26 HIV+, 22 HIV- sexual relations and/or other sexual stimulation: Group I (13.3% pleasant, 56.7% ) were studied and were similar in age (47+0.4 vs. 48+0.5), race (65% vs. 55% unpleasant and 30% indifferent) versus Group II (43.3% pleasant, 16.7% unpleasant and non-Caucasian), and menstrual patterns (# of periods in past year: 6+0.5 vs. 6+0.5). 40% indifferent)(p=0.003); ability to reach organism: Group I (20% improved and 80% Although the number of days with hot flashes and MRS scores were similar between indifferent) versus Group II (73.3% improved and 26.7% indifferent) (p<0.001). In Group groups (HIV+: 18+4.2 vs. Control 12+2.3, P=0.21; MRS: median 14, interquartile range I, 20% of women reported improvement in their sexual experience and wished to continue [IQR] 6.5-22, vs. 9, IQR 5.8-17.3, P=0.27, respectively), perimenopausal HIV-infected taking the medication, 23.3% noted no change in their sexual experience but wished to women experienced greater interference of their hot flashes with daily function, compared continue taking the medication, while 56.7% stated their sexual experience was unchanged to matched controls (HFRDIS: HIV+ 37, IQR 10-61 vs. 9, IQR 0-42.8, P=0.03), and had and did not wish to continue taking the medicine. In Group II, 80% reported improvement more insomnia (ISI: 12, IQR 8-18.3 vs. 9, IQR 2-13.3, P=0.02), anxiety (GAD-7: 7, IQR in their sexual experience and wished to continue taking the medication, 10% noted no 4.8-13.3 vs. 4, IQR 2-8, P = 0.03), and showed a trend toward more depressive symptoms change but wished to continue taking the medication, while 10% reported no change and (CES-D: HIV+ 20, IQR 10-25 vs. 11.5, IQR 5-19.5, P=0.08). Conclusion: did not wish to remain in use of the medication (p<0.001). In terms of collateral effects, Perimenopausal women with HIV experience greater distress related to hot flashes and no significant difference was detected between the two Groups. No improvement was have more severe insomnia, anxiety, and depressive symptoms than matched seen in the Female sexual dissatisfaction domain on the GRISS assessment. Conclusion: perimenopausal controls, despite experiencing a similar number of days with hot flashes. A ninety-day treatment using Tribulus terrestris in post-menopausal women with sexual These data suggest that clinicians should assess common menopause-associated dysfunction led to improvements in several aspects of sexuality according to scores on the symptoms among perimenopausal HIV+ women because of their deleterious effects on GRISS questionnaires, applied before and after the treatment. Analysis of post-treatment quality-of-life. responses on the FIEI questionnaire also revealed positive results. These results allow us to conclude that use of Tribulus terrestris at the doses administered proved effective for treating sexual disorders in post-menopausal women. P-53. Safety, efficacy and use of ultra-low dose 10 mcg vaginal estradiol tablets JoAnn V. Pinkerton1, Ricardo Maamari, MD, NCMP2, Jeffrey Goldstein2. 1University of P-51. Virginia, Charlottesville, VA; 2Novo Nordisk Inc, Princeton, NJ The effects of isoflavones derived from Glycine max (L.) Merr. and Objective: Professional medical societies and regulatory agencies recommend that the conjugated equine estrogen on the vaginal epithelium and endometrium lowest effective dose of estrogen consistent with postmenopausal (PM) treatment goals of postmenopausal women and benefits and risks for the individual woman should be the therapeutic goal. Thus, Sonia Maria Rolim R. Lima, MD, PhD1, Silvia Saito, MD1, Benedito F. Reis, MD1,2, development of the 10 mcg estradiol (E2) vaginal tablet, which provides the lowest FDA Sostenes Postigo, MD1, Sheldom R. Botogoski, PhD3, Tsutomu Aoki, PhD1. 1Obstetrics approved dose to treat atrophic vaginitis, addresses these recommendations. The and Gynaecology, FCMSCSP, São Paulo, Brazil; 2Obstetrics and Gynaecology, UNIVÁS, objectives were 1) To summarize the efficacy, safety and pharmacokinetic (PK) profile of Pouso Alegre, Brazil; 3Obstetrics and Gynaecology, UFPR, Curtiba, Brazil the 10 mcg E2 vaginal tablets 2) to understand the utilization and perception of the 10 mcg Objective: To compare the effects of isoflavones derived from the extract of Glycine max E2 vaginal tablets in clinical practice after the discontinuation of the 25 mcg E2 vaginal (L.) Merr.. and conjugated equine estrogen on the vaginal epithelium and endometrium tablets. Design: Data from 3 previously published pivotal trials that evaluated the of postmenopausal women. Design: Prospective, controlled and not randomized clinical effectiveness, safety and PKs of the 10 mcg E2 vaginal tablets are presented. Additionally, trial in 90 postmenopausal women, aged from 45 to 68 years old, assessed during three new data from a survey of 35 health care providers (HCPs, identified by an independent months and divided into three groups: Group 1 (Isoflavone) n = 30, Group 2 (placebo) n market research company as prescribers of the 10 mcg E2 vaginal tablet), conducted = 25 and Group 3 (Conjugated Equine Estrogen) n = 20, in which the index of Frost and between September 30 and October 15, 2010 are presented. The survey used a hybrid the maturation index of vaginal cytology were evaluated, and by transvaginal approach that integrated quantitative components with qualitative interviewing techniques. ultrasonography the endometrium was evaluated. The results were expressed by the Index The survey assessed 1) type of patients treated with 10 mcg E2 tablets - newly diagnosed, of Meisels and the endometrial thickness measurement in different times (T) 0, 1 and 2. those switched from 25 mcg E2 tablet or another vaginal estrogen therapy (ET) and 2) For statistical analysis, we used the Wilcoxon, Friedman or Kruskal-Wallis test and the HCPs’ clinical impression of the 10 mcg E2 vaginal tablets. Results: Results of a one-year correlations by analyzing the post-hoc Dunn. Results: Group 1: age: 58 years old, efficacy/safety trial (205 subjects randomized to 10 mcg E2 and 104 to placebo) showed menopausal age: 48 years old, time elapsed since menopause: 9 years. Group 2: age: 57 statistically significant improvements in both objective (vaginal maturation, pH, and years old, menopausal age: 48 years old, time elapsed since menopause: 9 years. Group vaginal health score at week 2) and subjective parameters (composite score of the most 3: age: 56 years old, menopausal age: 46.5 years old, time elapsed since menopause: 6 bothersome symptoms at week 8) of vaginal atrophy in the 10 mcg E2 vaginal tablet years (median values). The start and end values of the index of Meisels in Group 1 were treatment group compared to placebo. The proportions of subjects experiencing adverse T0 to T2 3.7: 46.2, Group 2 T0: 0 to T2: 20 and in Group 3 T0: T2 0 to 50 (median values). or serious adverse events were comparable across the two treatment groups. To further The measurements of endometrial thickness at baseline and after 90 days in Group 1 were evaluate endometrial safety, biopsy data from this trial (n=205) was pooled with biopsy T0: 3 and 2 mm, Group 2 T0 to T2 2: 2 mm, and Group 3 T0: T2 3 to 2 mm. Conclusion: data from 336 women from an open-label 12-month endometrial safety trial to yield 386

53 Clinical Poster Presentations (continued)

evaluable endometrial biopsies. In this pooled analysis, the observed incidence rate of P-55. hyperplasia/carcinoma was 0.52%. Compared with the reported background incidence Menopausal symptoms by age and therapy type in women with premature rate of 0 1% in PM women, this indicated that use of 10 mcg E2 vaginal tablets for one ovarian failure year was not associated with an increased risk of endometrial proliferation. A PK study Kelsey E. Mills, H.BSc, MD1, Maria Velasco2, Wendy L. Wolfman, MD, FRCSC2. in 29 PM women with vaginal atrophy evaluated the systemic absorption of 10 mcg E2 1Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; 2Menopause tablets (dosed once daily for 2 weeks, followed by twice weekly for 10 weeks) using the Unit, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada highly sensitive assay method of gas chromatography mass spectrometry. The mean Objective: Premature ovarian failure (POF) affects 1% of women and causes infertility plasma E2 concentrations remained within the typically defined postmenopausal range (≤ and menopausal symptoms. Women may experience long-term health issues including 20 pg/ml) at all timepoints revealing minimal systemic absorption of E2. Shortly after cardiac disease and low bone mineral density unless they receive estrogen therapy. The the availability of the 10 mcg E2 tablets, a research survey with 35 HCPs revealed that objective of this study was to evaluate womens’ vasomotor, urogenital, and psychological 97% of the HCPs accepted the discontinuation of the higher dose 25 mcg E2 tablets. Of symptoms using the validated Menopausal Rating Scale (MRS). We also sought to the patients treated with 10 mcg E2 tablets, 39% were newly diagnosed with atrophic determine whether any differences existed in symptom severity based on the patient’s vaginitis, and 42% represented patients switching from 25 mcg to 10 mcg E2 tablets. The age, as well as the type of estrogen therapy (oral contraceptive pill vs. hormone therapy). remaining patients (19%) included those switched from other vaginal ET, those that were Design: Patients in the POF clinic at Mount Sinai Hospital, Toronto, Canada, were hormone-hesitant and had previously refused local ET and those receiving 10 mcg refills. administered a questionnaire containing demographic and etiologic data as well as the The reasons stated for treating new patients with 10 mcg E2 tablet included validated MRS to assess menopausal symptoms. A total score > 9 reflects moderate to discontinuation of the 25 mcg E2 tablet, minimal systemic absorption of estrogen, severe symptoms. A small chart review was done to collect additional data. Data was availability of a new lower dose option and ease of use. An additional reason given for expressed as mean +/- standard deviation and percentages. Analysis was performed using switching patients from other local estrogen therapies was that the 10 mcg E2 vaginal OpenEpi (Open Source Epidemiologic Statics for Public Health, 2009). T-tests were used tablets were easier for patients to dose correctly. The majority of HCPs expressed positive to analyze continuous data for significance, and Fisher’s Exact Test was used to analyze perceptions about the 10 mcg E2 tablet and reported good treatment response. categorical data. This study received research ethics approval from Mount Sinai Hospital, Conclusion: In conclusion, this review reinforces the effectiveness, safety and minimal Toronto, Canada. Results: N=44, with 10 people declining to participate. Average age systemic absorption of the 10 mcg E2 vaginal tablets in the treatment of symptoms of was 30.9+/- 8.1 years and average age of presentation with POF 26.5+/-9.8 years. Forty- vaginal atrophy with an annual estrogen exposure of only 1.14 mg. In addition, results of one percent of participants had idiopathic POF. Forty seven percent of respondents used the preliminary survey with HCPs indicate a favorable clinical response and acceptance. an oral contraceptive pill (OCP) and 41% of patients used hormone therapy (HT). Ninety- two percent of women on HT were > than 30 years and 69% of women on OCPs were <30 P-54. years. The average MRS total score of all women was 10.4 +/- 6.4. By MRS domain, the Lifetime Estradiol Exposure and Risk of Depression during the average symptom score for psychological domain was 4.2+/- 2.9, for somatic symptoms was 3.7 +/-2.8 and for urogenital symptoms was 2.5 +/- 2.8. A comparison by therapy type Menopausal Transition: The Study of Women’s Health Across the Nation (OCP vs. HT) revealed no significant difference between total MRS scores as well as Wendy Marsh, MD MS1, Joyce Bromberger2, Sybil Crawford, PhD3, John Randolph, domain scores. A comparison by age (< vs. > 30yrs) also revealed no significant difference MD4, Hadine Joffe, MD, MSc5, Howard Kravitz, MD6, Claudio N. Soares, MD, PhD, in total MRS and domain scores. In the analysis of all symptoms evaluated in the MRS, FRCPC7. 1Department of Psychiatry, University of Massachusetts, Worcester, MA; sexual symptoms and sleep disturbance overall, were the symptoms receiving the highest 2Epidemiology and Psychiatry, University of Pittsburgh, Pittsburg, PA; 3Preventive and scores in our participants. Conclusion: The results show that the overall total MRS score Behavioral Medicine, University of Massachusetts, Worcester, MA; 4Obstetrics and in our participants was in the moderate range for symptom severity. In comparing the Gynecology, University of Michigan, Ann Arbor, MI; 5Psychiatry and Center for Women’s total MRS and different domain scores by age category as well as by type of estrogen Mental Health, Massachusetts General Hospital, Boston, MA; 6Psychiatry and Preventive therapy, we found no statistically significant differences. The symptoms receiving the Medicine, Rush University, Chicago, IL; 7Psychiatry and Behavioral Neurosciences, highest scores in our patients were sexual and sleep disturbance, which may promote McMaster, Hamilton, ON, Canada further assessment and management of these symptoms in women with POF in the future. Objective: It is unclear why some women are at increased risk of depression while undergoing the menopausal transition. Endocrinological factors, particularly changes in estrogen levels, have been hypothesized as contributing to vulnerability to depression P-56. during this reproductive phase. Herein, we examined whether duration of lifetime estrogen Assessment of quality of life in a large female Colombian sample using exposure may be associated with perimenopausal depression risk. Design: Data from the the Cervantes Scale* Study of Women’s Health Across the Nation (SWAN) a multi-site longitudinal, Faustino R Pérez-López1, Alvaro Monterrosa-Castro2, Ivette Romero-Pérez2, Katherin epidemiologic study designed to examine the physical, biological, and psychological Portela-Buelvas2, Peter Chedraui3, Ana Maria Fernández-Alonso4. 1Obstetrics and changes of women during their middle and menopausal years was analyzed. In women Gynecology, University of Zaragoza, Zaragoza, Spain; 2Grupo de Investigación de Salud who were premenopausal at study entry, premenopausal lifelong estrogen exposure was de la Mujer, Facultad de Medicina. Universidad de Cartagena, Cartagena, Colombia; estimated as age of first peri- or postmenopausal SWAN visit, minus age of menarche. The 3Instituto de Biomedicina. Facultad de Medicina, Universidad Católica de Santiago de association of duration of estradiol exposure with time to peri- or postmenopausal Guayaquil, Guayaquil, Ecuador; 4Servicio de Obstetricia y Ginecología, Complejo depression was estimated using pooled logistic regression (which approximates survival Hospitalario Torrecárdenas, Almeria, Spain analysis for interval-censored data) to model time to first annual visit with Center for Objective: To assess quality of life (QoL) with the Cervantes Scale (CS) in a large mid- Epidemiologic Studies Depression (CES-D) scale score >=16. Results: Of 1727 aged Colombian female sample. Design: In this cross sectional study, 1,739 healthy premenopausal women at entry, 1282 had complete data (N=8495 observations). Average women aged 40-59 were requested to simultaneously fill out the CS and a general survey duration of estradiol exposure was 35.6±3.2 S.D. years. A longer duration of exposure containing demographic female and partner data. The CS has four domains: the prior to the menopausal transition was associated with a lower risk of having a CES-D menopause and health (15 items), sexuality (4 items), couple relationship (3 items) and score >=16 during the transition. In the model adjusted for pre-menopausal depression, psychic domain (9 items). The CS total score may range from 0 to 155 with higher score current and ever antidepressant use, site, ethnicity, baseline education, baseline smoking, indicating worse QoL. The Kruskall-Wallis test was used for comparisons. Results: baseline age, time in study (to endpoint or censored), the hazard ratio was 0.847 (95% CI Median CS scores (total and all 4 domains) significantly increased with age, body mass (0.814-0.881), P<0.0001), giving a decrease of 15.3% in the hazard of experiencing index (BMI) values and menopausal status (post vs. premenopausal women, p<0.0001). depression for each additional year of premenopausal estradiol exposure. Conclusion: A Alpha Cronbach values were high (internal consistency) for the total CS (0.813) and its longer duration of estradiol exposure prior to the menopausal transition is protective domains: menopause and health (0.813), psychic (0.804), sexuality (0.845), and couple against experiencing depression during the transition. Estradiol has been shown to relationship (0.838). Conclusion: This is the first report of QoL assessment using the CS modulate monoaminergic systems involved in mood regulation (serotonin, in a large mid-aged Latin American (Colombian) female population in which age, BMI norephinephrine); it is unknown how such modulatory effect during premenopausal years and menopausal status were factors impairing QoL. *This research is a part of the would lead to a protective effect against depression during the menopausal transition. CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) Research Program. Additional analyses will further qualify and quantify other variables related to estrogen exposure, including use of oral contraceptives, pregnancies and lactation. Acknowledgments: The SWAN has grant support from the National Institutes of Health P-57. (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Ethnical and socio-demographical influences on quality of life in middle- Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) aged Colombian women* (Grants NR004061; AG012505, AG012535, AG012531, AG012539, AG012546, Alvaro Monterrosa-Castro1, Angel Paternina-Caicedo1, Liezel Ulloque-Caamaño1, Ana AG012553, AG012554, AG012495). The content of this abstract is solely the Maria Fernandez-Alonso2, Peter Chedraui3, Faustino R Pérez-López4. 1Grupo de responsibility of the authors and does not necessarily represent the official views of the Investigación Salud de la Mujer. Facultad de Medicina, Universidad de Cartagena, NIA, NINR, ORWH or the NIH Cartagena, Colombia; 2Servicio de Obstetricia y Ginecologia, Complejo Hospitalario Torrecárdenas, Almeria, Spain; 3Instituto de Biomedicina. Facultad de Medicina, Universidad Católica Santiago de Guayaquil, Guayaquil, Ecuador; 4Obstetrics and Gynecology, University of Zaragoza, Zaragoza, Spain Objective: To evaluate quality of life (QoL) in middle aged Colombian women using the Cervantes Scale (CS) in order to determine differences according to ethnical and socio- demographical background. Design: A total of 1,739 otherwise healthy women (40 to 59 years) fill out the CS and a general survey containing demographic female/partner data. Total CS score may range from 0 to 155, higher scores reflecting worse QoL. Comparisons were performed between mestizo and Afro-descendents (A-d) women using

54 NAMS11_Regular-LB_Abstracts-2 8/29/11 4:13 PM Page 24

U Mann Whitney or the Kruskall-Wallis test as appropriate. Results: Median scores for P-59. the total CS, and psychical, sexuality and couple relationship domains were significantly A Prospective Study of DT56a (Femarelle®) for the Treatment of lower in A-d women as compared to mestizo ones (p<0.0001). Health and ageing sub- Postmenopausal Vaginal Atrophy domain scores (included in menopause and health domain) were also significantly lower Margaret Nachtigall1, Frederick Naftolin, MD PhD1, Richard Nachtigall1, Israel Yoles, in A-d women. Housewives and retired women presented higher total CS scores. MD2, Lila E. Nachtigall, MD, NCMP1. 1Ob/Gyn, NYU Medical School, New York, NY; Conclusion: This study found that QoL was related to female ethnical and socio- 2Se-cure pharmaceuticals, Dalton, Israel demographical characteristics. *This research is a part of the CAVIMEC (Calidad de Vida Objective: Symptomatic vaginal atrophy affects one out of three menopausal women. en la Menopausia y Etnias Colombianas) Research Program. Hormone therapy, both systemic and local, is effective and indicated for the relief of this problem but may not be acceptable to all patients. DT56a (Femarelle®), a selective P-58. estrogen receptor modulator derived from botanical source, was found to be effective at Analysis of the Indication of Treatment of Osteoporosis in Women of a decreasing menopausal hot flushes and increasing bone mass. We performed a pilot study testing the use of DT56a for vaginal atrophy. Design: 12 post-menopausal women with Primary Care Unit of Spain vaginal atrophy (<5% superficial cells on cervical cytology) with at least one moderate- Laura Moral1, Rosa Ayuso1, Raimundo Hernando1, Amanda Lopez2. 1Primay Care to-severe symptom, were recruited for an IRB-approved 12-week open-label pilot study. Medicine, OSAKIDETZA, Vitoria, Spain; 2Research Unit, OSAKIDETZA, Vitoria, Spain DT56a (322mg) was given by mouth 2X/day for 12 weeks. At each visit (0&q4 weeks) Objective: Assess whether the indication of osteoporosis drug therapy is suited to the subjects had a vaginal atrophy assessment (speculum exam, vaginal pH) and completed NAMS recommendations in 2010 included in our clinical practice guideline. Design: questionnaires on atrophy symptoms and quality of life (Utian QoL scale).At weeks 0 Sectional study conducted in an urban health center (CS Olaguibel, Vitoria, Spain) The and 12, a pap smear with maturation index and vaginal cultures were performed. Results: participants were all postmenopausal women who have been treated with The main bothersome symptoms were: Dyspareunia- 5 Patients,Vaginal soreness- 3 bisphosphonates, raloxifene, strontium ranelate or teritapamida between May 18, 2009 Patients,Vaginal dryness- 2 Patients,Vaginal irritation-1 Patient and Bleeding with coitus- and May 18, 2010 In order to determine the appropriateness of the treatment, we set 1 Patient. All patients reported significant improvement in their most bothersome parameters such as hip fracture or vertebral, densitometric values, risk factors and FRAX. symptom. All women had a significant reduction in vaginal pH. The average pH went Given the heterogeneity of the origin of the limitation in our field, it seemed interesting from baseline 7.7±2.2 to 4.9±1.4 on week 12,p<0.0001. The maturation index also to sort by specialty, to determine if significant differences between them regarding the improved as shown in the figure below: Parabasal cells that were 100% at entry were 43% appropriateness of prescribing. Results: Of the 1021 patients included, the average age following 12 weeks of treatment, Intermediate cells were changed from 0 to 47% and was 71.5 11 years. 25 were excluded from analysis by cessation of therapy during the ± Superficial cells that were 0 at entry, were 10% following 12 weeks of treatment with study period. In the final sample (996 patients) the most prescribed drugs were risedronate DT56a (all statistically significant, p<0.001). A significant improvement was found in (33%) and alendronate (26.7%). Among the gynecologists the most prescribed drugs were UQoL index from mean pre-treatment of 75.4±22.7 points to mean post-treatment of ibandronate (22.6%), alendronate + Vitamin D (20.4%) and raloxifene (18.3%)while in 88.9±26.8, p<0.001.In the sexual domains of the UQoL there was a significant primary care were alendronate (38.7%) and risedronate (33.5 %), raloxifene was improvement from 6.5±2 points (mean pre-treatment) to 10.6± 3.2 (mean post-treatment), prescribed only in 1,9%. An analysis of the prescription by densitometry, 59.1% (n = 55) p<0.001. Conclusion: In this open-label prospective study DT56a was effective against of patients were successfully treated by gynecologists versus 40.2% (n = 188) primary and symptomatic vulvo-vaginal atrophy in both subjective and objective measures. The 40.7% (n = 135) of specialist (p = 0.002). About the proper prescription including FRAX changes in symptoms and pH were prompt and paralleled symptomatic relief. DT56a and previous fractures, 66.7% (n = 60) of patients cared in gynecology were correctly furnished a significant improvement in UQoL. As the placebo effect on the maturation treated compared to 62.9% (n = 288) primary and 69% (n = 227) without detecting index and vaginal pH is negligible, this 12 patient study provides an indicative significant differences. Conclusion: Despite the current ease of access by the doctor for measurement of the positive effect of DT56a for the treatment of vulvo-vaginal atrophy diagnostic tests, one third of women are treated inadequately. No significant differences and a large double blind placebo controlled trial is planned. were found regarding the origin of the prescription, however, the pharmacological pattern is variable. Primary Care is to be the best suited to the treatment recommendations of the guidelines, prescribing bisphosphonates as first choice. On the contrary, there is a preference of gynecologists and ibandronate as the drug of first use and no evidence of their effectiveness in reducing the risk of hip fracture, with a high percentage of prescription of raloxifene (indicating an alternative to bisphosphonates in our country) Assess treatment adherence barriers and promote adherence; provide clear information about fracture risk and treatment purpose.

Comparison of correct treatment between gynecology and primary care

Gynecology prescribe better but the difference is statistically significant

Drugs prescribed by primary care and gynecology

P-60. Estimation of cardiovascular risk in postmenopausal women Eliana A. Nahas, MD, Aline M. Andrade, Jorge Nahas-Neto, Mayra C. Jorge, Claudio L. Orsatti, Ana Paula Tardivo. Gynecology and Obstetrics, Botucatu Medical School-Sao Paulo State University, Botucatu, Brazil Objective: to compare estimation of cardiovascular risk using the Framinghan risk score (FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women in primary cardiovascular disease (CVD) prevention. Design: In this cross-sectional study, a total of 497 Brazilian postmenopausal women, with age ≥ 45 years and amenorrhea >12 months were included. Those had been diagnosed with or were being treated for heart The prescription pattern differs by specialty. Primary care is who best suited to disease, cerebrovascular disease, chronic kidney disease, or diabetes were excluded. The the recommendations of the guidelines. percentage risk of coronary heart disease (CHD) was calculated using the FRS that includes age, total cholesterol, HDL-cholesterol, systolic blood pressure, and ciga¬rette smoking. A risk greater than 20% is considered high; a risk of 10% to 20% is intermediate; and a risk of less than 10% is low. According to the US National Cholesterol Education Program Adult Treatment Panel III guidelines, MetS was diagnosed in subjects with three or more of the following: waist circumference (WC) >88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, HDL-cholesterol <50 mg/dl and glucose >100mg/dl. Data on antecedents, anthropometric indicators, and values of C-reactive protein (CRP) were collected. For statistical analysis were used: Chi-square test or Fisher’s exact test, and logistic regression method (odds ratio-OR). Results: The mean age of the patients

55 Clinical Poster Presentations (continued)

included was 55.3 ± 7.0 years, time since menopause of 7.2 ± 5.9 years, and BMI values 8 days with hot flashes in the last two weeks (43%, 39%, 42%); bothered by hot flashes of 28.2 ± 5.3 kg/m2. According to FRS, among 497 women, mean absolute risk for moderately/a lot vs. little/not at all (58%, 56%, 57%); night sweats ever (72%, 75%, 72%); developing coronary events in 10 years of 3.0%, of which 72.4% (360/497) of women night sweats in the last two weeks (35%, 30%, 34%); mean night sweats per night (2.18± were classified as low risk, 16.5% (82/497) of intermediate risk and 11.1% (55/497) 2.17, 1.96± 1.64, 2.08± 4.12); > 8 days with night sweats in the last two weeks (35%, 30%, presenting a high risk for CHD. The MetS was identified in 40% (199/497) of the women. 34%); or bothered by night sweats moderately/a lot vs. little/not at all (62%, 64%, 62%). Among the patients at risk for CHD by FRS 46.2% had MetS while 84.9% of women Conclusion: We found little evidence of variation in vasomotor symptoms by total soy without MetS were classified as low risk (p<0.001). The risk for CHD increased isoflavone consumption in a large, population-based study. Further analyses will focus on significantly with age at menopause (OR 1.10; CI 95% 1.04-1.17), time since menopause isoflavone type (genistein, daidzein) and, in a subset of women, whether these associations (OR 1.13; CI 95% 1.08-1.18), elevated triglycerides (OR 1.03; CI 95% 1.0-1.10), and are influences by equol producer status. presence of MetS (OR 1.72; CI 95% 1.48-1.84). The BMI, WC, exercise, use of hormone therapy and elevated CRP did not influence the risk. Conclusion: Using only the FRS in estimation of cardiovascular risk, a substantial number of postmenopausal women P-63. showing evidence of the MetS were not identified, even though women with the MetS are Self-Reported Vasomotor Symptoms and Pain by Detailed Race/Ethnicity: at higher risk of CVD. *Financial support by FAPESP with scientific initiation Results from the LeAVES Study scholarship; process number 2009/15659-2. Katherine M. Newton, PhD1, Johanna Lampe, PhD2, Susan D. Reed, MD, MPH3,2, Congh Qu, PhD2, Sharon Fuller1, Gabrielle Gundersen, MS1. 1Group Health Research Institute, Seattle, WA; 2Public Health Sciences, Fred Hutchenson Cancer Research Center, Seattle, P-61. WA; 3Obstetrics and Gynecology, University of Washington, Seattle, WA Are Case Reports of Black Cohosh Hepatotoxicity Conclusive? No Objective: Differences in menopause symptoms by race/ethnicity have been reported in Evidence by Metaanalysis of Randomized Controlled Clinical Trials the literature, but broad categories often used, particularly for “Asian/Pacific Islanders”. Belal Naser1, Susana Garcia DeArriba1, Klaus-Ulrich Nolte1, Jörg Schnitker2, Mary Jane It has been reported that Japanese women may be more likely to experience aches and Minkin3, Rüdiger Osmers4. 1Pharmacovigilance, Schaper & Brümmer GmbH & Co. KG, pains than vasomotor symptoms during the menopause. The purpose of this study was to Salzgitter, Germany; 2Institute for Applied Statistics, IAS Dr. Schnitker, Bielefeld, describe self-reported hot flashes, night sweats, bother from hot flashes and night sweats, Germany; 3Obstetrics and Gynecology, Yale University School of Medicine, New Haven, and joint pain, by more detailed categories of race/ethnicity. Design: We conducted a CT; 4Obstetrics and Gynecology, Hildesheim General Hospital, Hildesheim, Germany population-based postal survey of women aged 45-58 at Group Health Cooperative in Objective: Black cohosh (BC; Actaea racemosa), is a popular and safe treatment option Washington State; 9,273/18,500 responded (50% response rate). The questionnaire in the management of menopausal complaints. Despite of the long-term experience with included information on reproductive stage, frequency and bother of hot flashes and night BC-based preparations, a number of case reports among its users with suspected sweats, whether women were bothered by headaches or body aches and pains, hepatotoxicity have been put into the center of attention in recent years. This, however, demographic characteristics, and a detailed questionnaire on race/ethnicity. A total of is in clear contrast to results from randomised clinical trials (RCTs), where no signs of 5,645 women were eligible for this analysis after excluding women who were liver toxicity risk have been observed until now. Design: To study this discrepancy, a premenopausal, using contraceptive or non-contraceptive hormones, or were missing data metaanalysis of RCTs on the efficacy and safety of black cohosh was conducted regarding on hot flashes, night sweats, or race/ethnicity. Analyses were controlled for age and liver function tests. In a second step, the data was analysed in light of evaluations of case hysterectomy. Analyses used descriptive statistics and logistic regression models reports and events from the spontaneous reporting. Results: A total of forty studies were controlling for age and hysterectomy. (*P<0.05; †P<0.01; ‡ P<0.001) Results: The identified in the scope of the metaanalysis. Seven studies on breast cancer survivors were number of participants by race was: non-Hispanic white (n=4,422); Hispanic white excluded. From the remaining 33 studies on relatively healthy peri- and post-menopausal (n=139); Hispanic non-white (n=64); African-American (n=230); American Indian patients, 17 RCTs (n= 2486 patients) were considered for further evaluations, and 5 RCTs (n=92); Asian Indian (29); Chinese (n=161); Filipino (n=126); Japanese (n=127); (test population = 517 and reference population = 503) could finally be included in the Vietnamese (n=46); other Asian (n=81); Native Hawaiian (n=15); other Pacific Islander metaanalyses. No significant effect of the tested isopropanolic BC containing preparations (n=20); and other (n=93). After controlling for age and hysterectomy, as compared with on liver functions could be demonstrated. Whereas our findings are in agreement with non-Hispanic white women (84%), Chinese (64%‡), Filipino (74%†), Japanese (63%‡), other results of numerous RCTs with treatment durations of 3-12 months and doses of 40- Vietnamese (54%‡) and other Asian (68%‡) women were significantly less likely to report 128 mg BC/d, there is a clear contrast to the quantity of case reports published in the ever having had hot flashes. As compared with non-Hispanic white women (58%), literature and/or spontaneously received by manufacturers and medicinal agencies. Hispanic non-white (47%†), Chinese (37%‡), Filipino (40%‡), Japanese (45%‡), Depending on the causality assignation scales, however, assessments of these reports were Vietnamese (29%‡), other Asian (63%‡) and native Hawaiian (67%†) women were extremely variable. Initial causality assessments have primarily been based on an ad hoc significantly less likely to report every having had night sweats. As compared with non- evaluation. However, thorough analysis based on quantitative and liver specific methods Hispanic white women (58%), African American women reported significantly more disclosed many confounding variables, which can explain the inconsistencies between bother from hot flashes (69%†), while Chinese (37%†) and Filipino (40%†) women findings from the spontaneous reporting and clinical studies. Adulteration, unclear reported significantly less bother from hot flashes. As compared with non-Hispanic white declaration of BC products, low quality of clinical data, undisclosed co-medication, co- women (65%), Hispanic non-white (38%†), Asian Indian (41%†), Chinese (44%†), morbidity, lack of temporal association, and other fea-tures are some of the confounding Filipino (40%‡) and Japanese (40%†) women reported significantly less bother from night variables. Conclusion: In contrast to case reports, our metaanalysis did not detect any sweats. As compared with non-Hispanic white women (61%), African-American (70%*) adverse effect of the isopropanolic BC-extract on liver functions. In addition, there is a and women categorized as “other” (75%†) were significantly more likely to report being growing body of recent re-evaluations using structured causality scales, which confirm the bothered by joint pain, while Chinese (52%*), Japanese (51%*), and other Asian (49%*) findings of RCTs regarding the lack of BC-hepatotoxicity. women were significantly less likely to report being bothered by joint pain. Conclusion: In this population-based study of women residing in the Pacific Northwest, we found significant variation in the reporting of vasomotor symptoms, degree of bother related to P-62. these symptoms, and complaints of bother related to joint pain among women of differing Self-Reported Vasomotor Symptoms and Dietary Isoflavones: Results race/ethnicities. While our study confirms that reporting of vasomotor symptoms is higher from the LeAVES Study among African American women, and lower among Asian women, than among white Katherine M. Newton, PhD1, Johanna Lampe, PhD2, Susan D. Reed, MD, MPH3,2, Congh women, we found that, contrary to other reports, Japanese women were less likely to Qu, PhD3, Sharon Fuller1, Gabrielle Gundersen, MS1. 1Group Health Research Institute, report being bothered by aches and pains than were white women. Seattle, WA; 2Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; 3Obstetrics and Gynecology, Univeristy of Washginton, Seattle, WA Objective: Questions remain about the impact of soy isoflavones on vasomotor P-64. symptoms. Many of the studies to date have evaluated the effects of isoflavone dietary An Evaluation of the Effect of Desvenlafaxine 100 mg on the supplements. We sought to describe self-reported hot flashes, night sweats, and bother Pharmacokinetics of Tamoxifen in Postmenopausal Women by dietary (non-supplement) isoflavone consumption among women who were in the Alice I. Nichols, PhD1, Shannon Lubaczewski, PharmD, MS1, Yali Liang, MS1, Kyle menopause transition or postmenopausal. Design: We conducted a population-based Matschke, MAS1, Gabriel Braley2, Tanya Ramey, MD, PhD2. 1Pfizer Inc, Collegeville, postal survey of women aged 45-58 at Group Health Cooperative in Washington State; PA; 2Pfizer Inc, Groton/New London, CT 9,273 of 18,500 women responded (50% response rate). The questionnaire included Objective: Because the efficacy of the selective estrogen receptor modulator tamoxifen information on reproductive stage, frequency and bother of hot flashes and night sweats, is partially dependent on cytochrome P450 2D6 (CYP2D6) mediated metabolism to form demographic characteristics, and soy food intake (validated Lampe Soyfood 2 primary active metabolites (ie, 4-hydroxy-tamoxifen and endoxifen), there is a concern Questionnaire). At total of 5,635 were eligible for these analyses after excluding women about the potential risks associated with coadministering any potent CYP2D6 inhibitor who were premenopausal, who were using contraceptive or non-contraceptive hormones, with tamoxifen. A body of data is developing that suggests tamoxifen patients receiving who were missing data on hot flashes or night sweats, or who did not complete the concomitant treatment with a CYP2D6 inhibitor, such as the antidepressant paroxetine, Soyfood Questionnaire. Mean daily isoflavone intake (genistein plus daidzein) was have poorer treatment outcomes compared with those with normal levels of CYP2D6 categorized as none (n=1821), low (<=4.3mg/day, n=1928), or high (>4.3mg/day, activity. Design: This open-label study was designed to determine the effect of n=1886). Values were set, by design, to divide women into tertiles of isoflavone coadministering desvenlafaxine on tamoxifen pharmacokinetics. The study enrolled consumption. Analyses used descriptive statistics and generalized linear models healthy, postmenopausal women and had a 2-period inpatient (period 1: 3 days; 2 nights; controlling for age and race/ethnicity. Results: Despite some statistically significant period 2: 9 days; 8 nights) and outpatient (period 1: 11 visits; period 2: 21 visits) design. differences, there were no clinically meaningful differences between women with no, low, On study day 1 of period 1, subjects were administered tamoxifen 40 mg followed by 23 or high isoflavone intake (respectively) in any study measures of vasomotor symptoms, days of blood sampling for pharmacokinetic analyses. During period 2, subjects were including : hot flashes ever (82%, 83%, 81%); hot flashes in the last two weeks (54%, administered desvenlafaxine 100 mg alone for 7 days to reach steady state, then a single 56%, 57%); mean number of hot flashes per day (4.14± 5.72, 3.95± 6.12, 4.23± 6.04); > dose of tamoxifen 40 mg was coadministered followed by 23 days of blood sampling.

56 The primary outcomes were the pharmacokinetics of tamoxifen and endoxifen (ie, AUC physical and mental health, with more than 70% of favorable answers to the items over infinite time (AUCinf), AUC to the last measurable concentration [AUClast], and analysed, including degree of pain, vitality, physical aspects, functional capacity, social peak plasma concentration [Cmax]). Secondary outcomes included the pharmacokinetics and emotional aspects, and mental health. In spite of that, 92.5 % declare little leisure of 4 hydroxy-tamoxifen and N desmethyl-tamoxifen, concentrations of tamoxifen and its time. Conclusion: The reduction of Vitamin D was positively related with low sun metabolites (4 hydroxy-tamoxifen, N desmethyl-tamoxifen and endoxifen). Safety and exposure, not associated with skin color or quality of life. Based on these results, the high tolerability of desvenlafaxine and tamoxifen were also assessed. Comparisons between incidence of hypovitaminosis D in women from a tropical country leads us to suggest the monotherapy and combination therapy were made using the ratio of adjusted mean importance of a routine dosage of Vitamin D. differences and corresponding 90% confidence intervals (CIs). The test for interaction was considered negative if the 90% CIs for the ratios of (Test [desvenlafaxine + tamoxifen]/Reference [tamoxifen]) were within 80% to 125%. Results: Coadministration P-67. of tamoxifen with steady state desvenlafaxine did not alter tamoxifen AUCinf, AUClast One-year Maintenance of Efficacy and Safety of Desvenlafaxine in and Cmax, as reflected by the ratio of adjusted geometric means (90% CI) of Women With Vasomotor Symptoms Associated With Menopause approximately 100.7% (96.7%, 104.9%), 103.5% (100.2%, 106.9%), and 99.4% (94.0%, Joann V. Pinkerton1, David F. Archer2, Christine J. Guico-Pabia, MD, MBA, MPH3, 105.2%). The AUCinf, AUClast, and Cmax for 4-hydroxy-tamoxifen were not altered as Eunhee Hwang3, Ru-fong J. Cheng3. 1University of Virginia Health System, reflected by the ratio of adjusted geometric means of 105.6% (99.7%, 111.8%), 109.3% Charlottesville, VA; 2Eastern Virginia Medical School, Norfolk, VA; 3Pfizer Inc, (103.5 %, 115.5%), and 108.5% (103.5%, 113.7%). Because concentrations of endoxifen Collegeville, PA and N-desmethyl-tamoxifen were detected immediately prior to the second dose of Objective: Desvenlafaxine (administered as desvenlafaxine succinate) is a nonhormonal tamoxifen, the pharmacokinetic parameters for these 2 analytes were adjusted for serotonin-norepinephrine reuptake inhibitor under development for treatment of moderate carryover. In addition, only AUClast and not AUCinf could be accurately calculated for to severe vasomotor symptoms (VMS) associated with menopause. The 12-month efficacy these 2 metabolites. Coadministration of desvenlafaxine and tamoxifen did not alter N- and safety of desvenlafaxine 100 mg/d were assessed in a multicenter, double-blind, desmethyl-tamoxifen AUClast and Cmax, as reflected by the ratio of adjusted geometric randomized, placebo-controlled trial in postmenopausal women seeking treatment for means of 104.2% (100.9%, 107.6%) and 112.1% (107.4%, 116.9%). Endoxifen AUClast bothersome VMS. Design: The reduction in average daily frequency and severity of hot and Cmax decreased by approximately 11.8% and 8.0%, as reflected by the ratio of flushes (HF) at week 12 and maintenance of effect at months 6 and 12 were evaluated in adjusted geometric means of 88.2% (82.6%, 94.2%) and 92.0% (84.7%, 100.0%). a subset of women experiencing ≥7 moderate to severe HF a day or ≥50/wk for ≥2 weeks However, this change was not significant as the 90% CI for the ratio of adjusted means (modified intent to treat [MITT] efficacy substudy population) and analyzed using analysis fell wholly within the prespecified acceptance range (80%, 125%). There were no new, of covariance with treatment as a factor and baseline value as a covariate. Greene unexpected safety concerns observed in this study. The most common adverse events were Climacteric Scale (GCS), Patient Global Impression Symptom Rating (PGI-R), and constipation, nausea, and insomnia. Conclusion: There was no interactive effect on Patient Global Impression of Change (PGI-C) scores, and safety data were also evaluated tamoxifen pharmacokinetics with steady state of desvenlafaxine 100 mg compared with in the entire population. Results: A total of 2186 patients were randomly assigned to tamoxifen alone. For tamoxifen, 4-hydroxy-tamoxifen, N-desmethyl-tamoxifen and treatment. Primary short-term (week 12) outcomes for the subset of 365 women in the endoxifen, the 90% CIs for the ratios of adjusted mean for AUCs and Cmax lie within the MITT efficacy substudy population have been presented earlier. Mean frequency of prespecified acceptance range of 80% to 125%. Due to the lack of effect of desvenlafaxine moderate and severe HF at baseline was 12/d, and mean HF severity score was 2.4. At on tamoxifen pharmacokinetics, usage of desvenlafaxine in women being treated with months 6 and 12, the frequency and severity of HF were significantly reduced for tamoxifen may offer a treatment option that will unlikely alter the efficacy of tamoxifen. desvenlafaxine vs placebo (P≤0.003). At 1 year, desvenlafaxine reduced HF frequency by 7.7 moderate and severe HF/d and severity score by 0.75 (placebo, −4.8/d and −0.44). For the entire population (main study efficacy population: n=964 desvenlafaxine, n=986 P-65. placebo), reductions in GCS total score and 4 of 6 subscales (anxiety, depression, Mamimal Oxygen Uptake and Body Composition in Non-Obese and psychological symptoms, and VMS) were significantly greater with desvenlafaxine Obese Postmenopausal Women compared with placebo at 6 and 12 months (P<0.001). Women taking desvenlafaxine Betania Ogando1,2, Josiane Rocha1,2, Ronaldo Gabriel2, Helena Moreira2. 1Unimontes, reported greater improvement vs placebo at 6 and 12 months based on PGI-C scores and Montes Claros, Brazil; 2University of Trás-os-Montes and Alto Douro, Vila Real, Portugal change in PGI-R scores (all P<0.001). Treatment-emergent adverse events were reported Objective: The purpose of this study was to compare maximal oxygen uptake (VO2max) by 84% of women taking desvenlafaxine and 79% taking placebo. Serious adverse events and variables of body composition in non-obese and obese postmenopausal women, as occurred in 4.0% of women in the desvenlafaxine group and 3.4% in the placebo group. well as to verify the effect of these variables on cardiorespiratory fitness in the two Laboratory test values, vital sign measurements, and ECG results did not suggest any examined groups. Design: The sample was composed of 208 postmenopausal women adverse safety signal during the 12 months of the study. Full safety results are reported (55.57±6.62 years), 56% (75.5%) with a menopause period inferior to 10 years, 55% were separately. Conclusion: Treatment efficacy achieved at week 12 with desvenlafaxine 100 non-users of hormone therapy and 74% were obese. Weight (W), fat mass (FM), visceral mg/d in postmenopausal women with VMS was maintained for one year. fat area (VFA), skeletal muscle mass (SM) and regional soft lean mass (arms, trunk and legs) were evaluated by octopolar bioimpedance InBody 720 (Biospace) and the basal metabolic rate (BMR) was measured resorting to the use of the Cunningham equation P-68. (1991). Skeletal muscle mass index (SMI) was calculated with the formula SMI= (SM/W) Positive Effect of Gabapentin Extended-Release (G-Er) on Sleep in Post- x 100 and VO2max was assessed with the Modified Bruce protocol. The cutpoints for Menopausal Women with Vasomotor Symptoms in Breeze 1 Study obesity and high visceral adiposity were, respectively, FM≥35% and VFA ≥100 cm2. The Risa Kagan, MD1, Verne E. Cowles, PhD2, David Portman, MD3, Rekha M. degree of association between variables was calculated with the Pearson’s correlation Sathyanarayana, MS2, Michael Sweeney, MD2. 1Alta Bates Summit Medical Center, coefficient and a multiple linear regression analysis was performed. Student’s t test was Berkeley, CA; 2Product Development, Depomed, Inc, Menlo Park, CA; 3Columbus Center used to compare the means and the level of significance was set at 5%. Results: Obese for Women’s Health Research, Columbus, OH women presented higher values (p≤0.01) of age (2.25 years), FM (12.20%) and VFA Objective: To evaluate the effects of G-ER 1200mg (single evening dose) & 1800mg (39.37 cm2) and lower values of SMI (-6.42%), VO2max (-4.77 ml/kg/min), compared daily (dosed asymmetrically) on sleep using the Pittsburgh Sleep Quality Index (PSQI) to nonobese women, not being differences identified on BMR. Regardless of age, in post-menopausal women with vasomotor symptoms. Design: This was a Phase 3, characteristics of menopause and other variables of body composition, VFA explains 13% double-blind, placebo-controlled study conducted at 48 sites in the US. Post-menopausal (β=-0-356, p=0.01) and 19% (β= -0.434, p<0.01) of VO2max in non obese and obese women with ≥ 7 moderate to severe hot flashes per day during a 7 day baseline period women, respectively. The former presented a worsening in the levels of VO2max and were randomized in a 1:1:1 ratio to either 1200 mg QD or 1800mg (600mg AM/1200 mg approximately 3.30 ml/kg/min in the presence of an increased level of central adiposity. PM) of G-ER or placebo. Additional inculsion criteria were no history of malignancy In what regards obese women, the average difference of VO2max among women with a within 2 yrs, and amenorrhea for at least 1 yr or amenorrhea for 6-12 mos with FSH > 40 high VFA (between 100 and 150 cm2) and very high VFA (superior to 150 cm2) was 3.72 mIU or ≥ 6 mos post bilateral oophorectomy with or without hysterectomy Patients were ml/kg/min (p< 0.01). Conclusion: The study suggests that visceral fat area is a significant titrated to their randomized dose over 1 wk. The study medication was taken with a meal. independent predictor of cardiorespiratory fitness in non-obese and obese postmenopausal The PSQI consists of 7 components and a derived Global score. PSQI was administered women. Obesity tends to be related to a high VFA and a low SMI. during clinical visits at randomization and wk 4, 12 & 24 of the stable dosing period. An ANCOVA model which included treatment and center factors, and the corresponding baseline value as the covariate was used to determine the pairwise difference between G P-66. ER treatment and placebo treatment. Results: Out of 541 patients randomized 531 were Evaluation of the deficiency of Vitamin D in a population of climacteric included in the ITT population for evaluation of PSQI. For both the 1200 mg and the women in Brazil – Pilot Study 1800 mg doses the Global Score was improved throughout the study. For the 1800 mg Marcia A. Padua, Ji H. Yang, Roberta Vasconcelos, MD, Carolina Martins, MD, Clarissa dose the components of sleep disturbance, quality, latency, duration, and efficiency were Fujiwara, MD, Maria Cristina Stefano. Multidisciplinary Study Group in Quality of Life, significantly improved compared to placebo at wk 4. At wk 12 sleep disturbance, and Clinica Synesis, São Paulo, Brazil quality were significantly different from placebo, while at wk 24 sleep duration, quality Objective: Vitamin D serum dosage evaluation in 70 climacteric women submitted to and efficiency were significantly different from placebo. For the 1200 mg dose sleep the World Health Organization Healthy Life Quality – SHORT FORM 36 (SF-36). disturbance, quality, duration, efficiency and medication were significantly different from Design: Cross-sectional, random study of 70 climacteric patients in a private practice, placebo at wk 4, while at wk 12 quality, duration, and efficiency were significantly submitted to the SF-36 questionnaire and to a Vitamin D serum dosage. Results: Average different from placebo and at wk 24 sleep quality and efficiency were significantly age is 51,15 years (± 7,31); 94 % of participants have a college degree. The great majority different from placebo. Conclusion: The results from this study suggest that G-ER may displays skin pigmentation between levels II (40 %) and II/III (55 %), according to the have a beneficial effect on sleep as measured by the PSQI in post-menopausal women Fitzgerald Skin Types, and 75,7 % of them relate scarce sun exposure. The average dosage with vasomotor symptoms. of Vitamin D is 21,10 ng/mL (± 7,11); insufficient levels of Vitamin D was detected in 86 % of the patients. However, the analysis of the SF-36 revealed positive perception of both See table on next page.

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Clinical Poster Presentations (continued)

Summary of PSQI Components. Mean Difference from Placebo for Gabapentin ER P-70. Sexual function and breast cancer: the elephant in the bedroom Beth Prairie, MD, MPH1, Sybil Crawford2, Rakhshanda Layeequr Rahman3, Marjorie Jenkins4,5. 1Ob/Gyn, University of Pittsburgh, Pittsburgh, PA; 2Preventive and Behavioral Medicine, University of Massachusetts Medical School, Worcester, MA; 3Surgical Oncology, Texas Tech University Health Sciences Center School of Medicine, Amarillo, TX; 4Women’s Health and Gender Specific Medicine, Texas Tech University Health Sciences Center School of Medicine, Amarillo, TX; 5Laura W. Bush Institute for Women’s Health, Texas Tech University Health Sciences Center, Amarillo, TX Objective: Understanding disease-related quality of life (QOL) issues is important for breast cancer survivors. Women are frequently affected by menopausal symptoms, which may include vaginal dryness or other sexual function problems, following breast cancer treatment. Sexual function is an important, but under-recognized, component of survivor quality of life. We sought to evaluate the impact of sexual function on health-related quality of life in breast cancer survivors. We hypothesize that poor sexual function will significantly affect overall quality of life. Design: Women who were known breast cancer survivors not currently receiving hospital-based treatment were identified in a single hospital system through chart review. Eligible women were offered participation in a P-69. cross-sectional study to identify significant determinants of QOL in breast cancer survivors. Informed consent was obtained. Demographic information and detailed Symptoms of depressed mood, disturbed sleep and sexual problems in information regarding the women’s breast cancer history and treatment were obtained. midlife women: cross- sectional data from the Study of Women’s Health Women were asked to complete the Functional Assessment of Cancer Therapy-Breast Across the Nation (SWAN) (FACT-B), a self-administered quality of life survey specific to breast cancer survivors in Beth Prairie, MD, MPH1, Stephen R. Wisniewski, PhD2, James Luther, MA3, Rachel which higher scores indicate better QOL. Initial analysis indicated that menopausal Hess4, Rebecca C. Thurston, PhD7,5, Robin Green6, Katherine Wisner7,1, Joyce symptoms had a significant effect on FACT-B scores, and women were subsequently Bromberger7,2. 1Ob/Gyn, University of Pittsburgh, Pittsburgh, PA; 2Epidemiology, asked to complete the Menopausal Rating Scale (MRS), a questionnaire designed to elicit University of Pittsburgh, Pittsburgh, PA; 3Epidemiology Data Center, University of menopausally-related symptoms in the domains of psychological symptoms, Pittsburgh, Pittsburgh, PA; 4Medicine and Center for Research on Health Care, University somatovegetal symptoms, and urogenital symptoms. Higher scores indicate higher of Pittsburgh, Pittsburgh, PA; 5Psychology, University of Pittsburgh, Pittsburgh, PA; symptom level. Both the FACT-B and MRS contain specific items related to sexual 6Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, NY; 7Psychiatry, functioning. Summary statistics, means and standard deviations for continuous variables University of Pittsburgh, Pittsburgh, PA and percentages for discrete variables, were used to describe the sample. Spearman Objective: Depression is known to be associated with both sleep disturbance and sexual correlations, nonparametric analysis of variance, chi-square test and 2-sample Wilcoxon problems in midlife women. These three symptoms may co-occur and represent a were used to evaluate associations between the sexual function variables and BMI, age, particular symptom complex during midlife. These symptoms are commonly reported but and endocrine treatment. Results: Average age of participants (N=92) was 62.8 years. there are minimal data to examine whether they co-vary in individual women. We sought The majority had Stage 0 or 1 tumors. Almost 70% underwent endocrine treatment, 67.4% to evaluate the interrelatedness of symptoms of depressed mood, disturbed sleep and underwent radiation, 40.2% received chemotherapy, and only 19.6% underwent breast sexual problems in the SWAN cohort at single study visit and to characterize women reconstruction. Average FACT-B score was 113.7, similar to the US population mean of exhibiting this symptom complex with respect to demographic, psychosocial and clinical 111.8. The average total score on the MRS was 13.0 (SD=8.2), which is significantly characteristics. We hypothesized that women with this complex of symptoms would have higher than the general population sample mean of 9.1 (p<0.0001). 60% of women had more stressful life events, lower social support, and be in the late peri-menopausal stage. either no or only mild sexual problems, while only 17% had severe or very severe sexual Design: SWAN is a multi-ethnic observational cohort study of the menopausal transition problems. This is in contradistinction to vaginal dryness, where 28% had very severe in women across the United States. Demographic information was acquired at baseline, symptoms, and 38% had moderate or severe dryness. Vaginal dryness was not significantly and menopausal status was assessed at the time of the study visit. Depression was assed associated with age, BMI, or history of endocrine treatment in this sample. Women had using the Center for Epidemiological Studies Depression Scale (CES-D) with a total score significantly lower well-being on the sexual function questions on the FACT-B than their >= 16 indicating high levels of depressive symptoms. Sleep disturbance was defined as overall scores reflect. 44% were not at all satisfied with their sex lives, and 32% did not reporting waking at night, waking early, or difficulty falling asleep at least 3 times in each feel sexually attractive at all. BMI was inversely associated with perceived sexual of the past 2 weeks. Sexual function was assessed by self-report on a 20-item attractiveness, with women with higher BMIs having lower sexual attractiveness questionnaire derived from several sources and addressing multiple domains of sexual (p=0.006), but not associated with sexual satisfaction. Conclusion: Breast cancer function, including desire, arousal, satisfaction, orgasm and vaginal dryness. Women were survivors in this cohort had high levels of vagina dryness, low levels of sexual satisfaction, identified as having a sexual problem if they had a problem in any of these five domains. and low levels of feeling sexually attractive. Low scores in these domains reduced their Women who reported all 3 symptoms were compared to those who did not. Logistic overall quality of life scores on the two measures used (MRS and FACT-B). Focusing on regression models were used to estimate the association of the demographic, psychosocial overall QOL may miss an import contribution of sexual well-being to long, healthy and clinical characteristics with the symptom complex. P values <=0.05 were considered survivorship. statistically significant. Results: Study subjects (N=1716) were 49.8 years old on average, 49.7% Caucasian, 24.2% African-American, 10.1% Japanese, 9.3% Chinese and 6.7% Hispanic. The majority were either early or late peri-menopausal, married, not using P-71. hormone therapy, and rated their overall health as excellent or very good. 16.5% had CES- Effect of a Moderate-to-Vigorous Intensity Exercise Program in Body D scores >=16, 36.6% had a sleep problem, and 42.2% had any sexual problem. Five Composition and Basal Metabolic Rate of Postmenopausal Women: The percent of the women (N=90) experienced all 3 symptoms. In multivariable models, Role of Hormone Therapy women with the symptom complex were more likely to have lower household incomes, Josiane Rocha1,3, Betania Ogando1,2, Ronaldo Gabriel2, Marco Monteiro2, Helena less education, be surgically postmenopausal (OR 3.37 (95% CI: 1.56, 7.26))or late peri- Moreira2. 1Physical education, unimontes, montes claros, Brazil; 2Universidade Tras os menopausal (OR 1.99 (95% CI: 1.06, 3.75), rate their general health as fair or poor, have Montes e Alto Douro, Vila Real, Portugal; 3Faculdades Integradas Pitagoras, Montes a higher number of stressful life events and lower social support. No effect was noted for Claros, Brazil race/ethnicity or for hormone therapy, although few women (19.8%) were using Objective: – The present study intended to analyse the effect of an exercise program of hormones. Conclusion: In this cross-sectional analysis of the SWAN cohort, 5% of step, weight-training and flexibility on the levels of adiposity and on muscle condition of women were affected by the complex of symptoms of depressed mood, disturbed sleep postmenopausal women, based on the conduction of an investigation with a 12-month and sexual problems. The predicted prevalence of this symptom complex in this sample intervention, aiming the influence of hormone therapy (HT). Design: : One hundred sixty- if each of these symptoms were completely independent would be 2.6%. The higher nine women (56.80±6.47 years old), 55% with HT, were randomly introduced into an prevalence found in this analysis suggests that these symptoms do co-vary within exercise group (EG, n=91) and a control group (CG, n=78). Height (H) was measured in individual women and are interrelated. The association with menopausal stage supports anthropometric position, as well as body composition (W, weight, FM, fat mass; FFM, fat- the hypothesis that this complex is related to the menopausal transition, with surgically free mass, SM, skeletal muscle mass) and basal metabolic rate (BMR) by using octopolar post-menopausal at particularly high risk for having this complex. Psychosocial factors bioimpedance (InBody 720). The skeletal muscle mass index was calculated (SMI= which are known risk factors for depression, including poor social support and more [SM/W] ×100) and the food record method was used. The EG performed a 60-minute stressful life events, were also risks for having the symptom complex. Thus, during exercise set, three times a week, involving step (50% to 85% heart rate reserve), weight midlife, these symptoms may be more likely to cluster in peri-menopausal women with training (8-10 repetitions at submaximal intensity for two sets) and stretching.The t-test these risk factors. and analysis of variance (age control) were employed to compare groups. Results: No differences were found among the averages of the variables in both groups at the beginning of the study, except for age. In absolute terms the CG revealed (p<0.01) an increase of FM (1.86%) and a decrease in SM, SMI (-1.06%), FFM and BMR (-27.95 kcal/day). Differences were identified in the percentage of changes of these variables between the two groups, having these always been more favourable in the EG in relation to the CG. Height presented a significant increase in EG (0.59 cm, p<0.01). Exercise influenced (p< 0.01) the variation of H (p=0.03) SM and of SMI (p=0.04), while the HT

58 affected the variation of the SM (p=0-02), not having an interactive effect been identified veterans with and without a DM diagnosis receiving care in the Veterans Affairs (VA) concerning those two factors. In the absence of HT, the EG and the CG revealed healthcare system. Design: A comparative group design was used to evaluate diabetes differences (p≤0.01) in the percentage change of the SM. In relation to women that symptoms in three groups of postmenopausal women veterans (aged 45-60 years): women documented the use of HT, the EG displayed better percentage change of SM, SMI, H and without DM (No DM; n=90), women with controlled DM (DM-C; A1c ≤ 7%; n=135) FFM in relation to those of the CG Conclusion: The research findings suggest that both and women with poorly controlled DM (DM-PC; A1c >7%; n=102). Participants attenuation in the loss of muscle mass and improvement of stature in postmenopausal responded to a national mailed survey on menopause and consented to clinical data access. women take place with possible beneficial effects in posture and functional capacity, Data collected by the self-administered survey included diabetes status, self-care especially in women with HT. behaviors and DM symptom assessment. DM symptoms were evaluated with the Diabetes Symptom Checklist – Revised (DSC-R), a 34-item tool that measures the burden of DM- related symptoms over the past 4 weeks. A standardized DSC-R global score and eight P-72. symptom subscale scores (hyperglycemia, hypoglycemia, cardiovascular, ophthalmologic, Effects of Physical Exercise Programs on Adiposity and Muscle Condition psychological-fatigue, psychological-cognition, neuropathic-sensation, neuropathic-pain) of Post-Menopausal Women: A Randomized Study were calculated and compared between the groups. Clinical data to characterize the Josiane Rocha1,3, Betania Ogando1,2, Ronaldo Gabriel2, Marco Monteiro2, Helena metabolic state were obtained from VA national laboratory files with consent. Categorical Moreira2. 1State University of Montes Claros, Montes Claros, Brazil; 2University of Trás- data were compared by Chi square with Fisher’s exact test; differences in continuous os-Montes and Alto Douro, Vila Real, Portugal; 3Faculdades Integradas Pitagoras, Montes variables were evaluated by t test and ANOVA with post-hoc analyses. Results: On Claros, Brazil average, participants were 55.0 ± 0.2 years of age, obese (body mass index [BMI] 33.9 ± Objective: analyze the effect of an exercise program on fat mass, visceral fat area (VFA), 0.4 kg/m2), and 11.3 ± 0.2 years postmenopause. Women with controlled and poorly skeletal muscle mass (SMM), and skeletal muscle mass index (SMMI) of post- controlled DM were older, of higher BMI and had more co-morbidities than women menopausal women. Design: One hundred sixty-nine women (56.80±6.47 years) were without DM. A1c levels were lower in DM-C women (6.4%) compared to those with poor randomized into an exercise group (EG, n=91) and the control group (CG, n=78). The EG glucose control (8.9%; p < 0.05). The average age of DM diagnosis was 47.9 ± 0.5 yrs. performed 60 minutes of exercise, 3 times a week (step, weight training and flexibility). Diagnosed at an earlier age (45.4 ± 0.8 yrs vs. 49.8 ± 0.5 yrs; p < 0.001) than their DM- Body composition (W, weight; FM, fat mass; FFM, fat-free mass; VFA, visceral fat area; C peers, DM-PC women also had the illness longer (10.1 ± 0.7 yrs vs. 5.7 ± 0.5 yrs; p < and SM, skeletal muscle mass) and basal metabolic rate (BMR) were evaluated by using 0.001). Higher DSC-R global scores (24.5 ± 1.2 vs. 20.2 ± 1.7; p < 0.05) were octopolar bioimpedance before and after a 12-month period. Skeletal muscle mass index demonstrated in women with DM (n=227) compared to those without DM (n=90). was calculated (SMI= SM/W×100) and the food record method was used. The variable However, seven of the eight DM symptom subscale scores were similar between the averages (absolute values and rates of change) were compared by using t-tests and the groups; only the hyperglycemia subscale score was higher in women with DM (29.9 ± 1.7 degree of statistical significance considered was 5%. Results: In absolute terms, the CG vs. 19.9 ± 2.4, p < 0.05). By ANOVA, DM-PC women had higher DSC-R global scores increased (p <0.01) the FM (1.86%) and the VFA (3.92 cm2). The CG also aggravated the compared to their controlled peers and non-diabetic women (DM-PC: 27.8 ± 2.1 vs. DM- muscle condition (-1.06%), with adverse reflexes in the BMR (-27.95 kcal / C: 22.2 ± 1.4 vs. No DM: 20.2 ± 1.7; p < 0.05), while scores between DM-C and day).Differences were found (p ≤ 0.05) between the EG and the CG for the Δ% FM (- non-diabetic women were similar. Psychological-fatigue symptoms were perceived as the 4.23%), ΔVFA (-4.00%), ΔSM (3.09%), ΔSMI (0.03%) and ΔBMR (2.99 %). most burdensome by all participants. There were no differences in subscale scores for Conclusion: The results suggest that the exercise program attenuated the increase in the hypoglycemia, psychological-fatigue, psychological-cognition, neuropathic-sensation, levels of total and central adiposity and muscle loss associated with menopause and aging, and neuropathic-pain symptoms among the study groups. Hyperglycemia subscale scores conditions that may result in a lower cardiovascular risk and osteoporosis among this were higher in DM-PC women than those without DM but similar to DM-C women (DM- population. PC: 33.2 ± 2.7 vs. DM-C: 27.5 ± 2.3 vs. No DM: 19.9 ± 2.4; p < 0.05). Greater ophthalmologic subscale scores were noted in DM-PC women compared to DM-C and P-73. women without DM (DM-PC: 20.0 ± 2.3 vs. DM-C: 13.3 ± 1.6 vs. No DM: 11.7 ± 1.9; p < 0.05). Cardiovascular subscale scores were higher in DM-PC women compared to Effect of a 12-Month Exercise Program on Body Composition of the DM-C group but similar to women without DM. Conclusion: Diabetes related Postmenopausal Women: Effects of the Nature of Menopause psychological, neuropathic, hypoglycemic and cardiovascular symptoms are present in 1,3 1,2 2 2 Josiane Rocha , Betania Ogando , Ronaldo Gabriel , Marco Monteiro , Helena women without a DM diagnosis and perceived to be of similar severity compared to 2 1 Moreira . Physical Education, State University of Montes Claros, Montes Claros, Brazil; women with DM. Women with poor glucose control had more burdensome 2 Sports and Science, Universidade Tras os Montes e Alto Douro, Vila Real, Portugal; hyperglycemic, ophthalmologic and cardiovascular symptoms. Symptoms related to 3 Faculdades Integradas Pitagoras, Montes Claros, Brazil hyperglycemia provided the best assessment of glucose status across the groups. These Objective: The aim of this study was to investigate the effect of a 12-month moderate- data reinforce the need to screen postmenopausal women for type 2 DM. Further studies to-vigorous exercise program on body composition of postmenopausal women, analyzing are warranted to confirm these findings in non-veteran populations and women of leaner the influence of the nature of menopause. Design: : A total of 169 postmenopausal women body size. (aged 40-77 years old) were randomly selected to an exercise (EG, n = 91) or a control group (CG, n = 78), both with women of induced menopause (27.5% and 26.9%, respectively) and users of hormone therapy (54.9% and 55.1%). Body composition (W, P-75. weight; FM, fat mass; VFA, visceral fat area; SM, skeletal muscle mass; regional SLM, Overactive bladder in postmenopausal women soft lean mass arms, trunk and legs) and basal metabolic rate were evaluated by using Jae hong Sang, Hyoung moo Park. Obstetrics & Gynecology, Chung-Ang University octopolar bioimpedance (InBody 720) at baseline after a 12-month period of exercises. hospital, Seoul, Republic of Korea Skeletal muscle mass was calculated by the formula: SMI = SM/W×100 and all the sample Objective: Recent studies in Korea have shown that the prevalence of overactive bladder elements completed a 3-day food intake documentation. The EG performed 60 minutes in women over 40 was 18.4%. Overactive bladder syndrome is a urinary urgency, usually of exercise, 3 times a week involving step (twice a week, 20 to 25 minutes, 50% to 85% accompanied with frequency and nocturia, with or without urgency urinary incontinence, heart rate reserve), weight training (twice a week, 20 to 25 minutes, 8-10 repetitions at in the absence of urinary tract infection or other obvious pathology. This study was submaximal intensity for two sets) and stretching (once a week, 45 minutes). The t-test performed to investigate the prevalence of overactive bladder and the effect of hormone and analysis of variance (control of age) were employed to compare groups. Results: treatment in menopausal women in Korea. Design: The frequency, nocturia, urgency, and There were no statistically significant differences between means of variables in both urgency incontinence were examined in menopausal women aged 45 years and older groups at baseline except for age. In absolute terms, the CG showed increases (p≤0.01) among patients who visited the Department of Obstetrics and Gynecology, Chung-Ang of the %FM and of the VFA, as well as a worsening in the muscle condition, being University Hospital, between November 2010 and February 2011. Results: Among 350 differences identified (p≤0.05) between them both in what regards rates of changes. The menopausal women responded to the study, 50 women had urgency, with 14.3% of exercise has influenced (p≤0.04) the variation of the SM, SMI and SLM (p=0.02) in trunk prevalence. Among the group with urgency, 28 women showed urgency incontinence, and legs. The EG showed, as compared to the CG, a better SM, regardless of the NM, and with 56% frequency. Urgency did not show statistical significance for old age (over 65 of the VFA, SMI and SLM at the level of the trunk and lower limbs, in the presence of a years) or the presence of hormone treatment, but showed statistical significance among natural menopause. Conclusion: These findings suggest that in healthy postmenopausal the periods of menopause (odds ratio 3.451, 95%CI 1.422-8.377, p=0.004). Also, higher women a 12-month exercise program combining cardiovascular, muscle strength and risks for both frequency (odds ratio 2.921, 95%CI 1.587-5.375, p=0.001) and nocturia flexibility positively influenced body fat distribution and muscular condition, namely (odds ratio 2.469, 95%CI 1.069-5.702, p=0.037) were observed in the group with urgency SLM in legs and trunk. compared to the group without urgency. Conclusion: The results of this study can be meaningful in studying overactive bladder only in menopausal women for the first time in the country. Also, older age or hormone treatment did not affect the prevalence of P-74. overactive bladder, and the hormone treatment was not effective in treating the symptoms The Diabetes Masquerade: Symptoms in Non-Diabetic Postmenopausal of overactive bladder. It is considered that factors affecting overactive bladder in Women menopausal women will be understood if further studies with a large number of subjects Patricia A. Rouen1, Sarah L. Krein, PhD3, Nancy Reame2. 1McAuley School of Nursing, on lifestyles and the types of hormones and administration routes are to be performed in Univ of Detroit Mercy, Novi, MI; 2School of Nursing, Columbia University, New York, the future. NY; 3VA Center for Clinical Management Research, VA Healthcare System, Ann Arbor, MI Objective: Women are disproportionately affected by type 2 diabetes mellitus (DM) with See table on next page. higher lifetime risk of disease incidence and greater severity of complications. Symptoms of this chronic illness are vague and often not recognized in midlife women. The purpose of this study is to examine the diabetes symptom experience of postmenopausal women

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Incidence of overactive bladder according to menopause duration P-77. Menstrual Experience and Midlife Symptoms in Puebla, Mexico Lynnette L. Sievert, PhD1, Elizabeth R. Bertone-Johnson, ScD2. 1Anthropology, UMass Amherst, Amherst, MA; 2Public Health, UMass Amherst, Amherst, MA Objective: The purpose of this study was to examine recalled symptom experience before or during menstrual periods in relation to symptom experience two weeks prior to interview among 755 women aged 40-60 drawn from a general population in Puebla, Mexico. Design: Face-to-face interviews lasting 25 to 50 minutes queried if, during the past two weeks, women experienced one of 22 complaints, including hot flashes and “sadness or desire to cry.” All women were also asked if they experienced abdominal cramps during menstruation, and if they had other symptoms during or before their Other symptoms in overactive bladder menstruation. All were prompted with the examples of irritability and “desire to cry.” Relationships between symptoms associated with menstruation, and between menstrual and midlife symptoms, were examined by chi-square analyses. Logistic regression was used to assess whether abdominal cramps and other symptoms associated with menstruation were determinants of hot flashes at midlife after controlling for relevant variables. A similar model was used to determine if depression and/or irritability with menstruation was a determinant of depressed mood at midlife. Results: Fifty-four percent of women reported cramps during menstruation, 9% reported depressed mood, and 8% reported irritability before or during menstruation. Women volunteered a range of symptoms before or during menstruation, including breast tenderness, waist pain (dolor de cintura), leg pain, headache, GI complaints, and tiredness. Women who reported P-76. depressed mood with menstruation tended to be more likely to report depressed mood in Efficacy of Gabapentin Extended-Release (G-ER) on Vasomotor the past two weeks, and women who volunteered waist pain and abdominal cramping Symptoms in Post-Menopausal Women in Breeze 2 Study with menstruation were significantly more likely to report hot flashes. Among women Mira Baron, MD1, Verne E. Cowles, PhD2, Wulf Utian, MD, PhD, DSc1, William Koltun, who had menstruated within the past 12 months (n=279), parity and abdominal cramps MD3, Rekha M. Sathyanarayana, MS2, Michael Sweeney, MD2. 1Rapid Medical Research, were significant determinants of hot flashes after controlling for education, BMI, and Cleveland, OH; 2Product Development, Depomed, Inc, Menlo Park, CA; 3Medical Center other potential determinants. Among postmenopausal women (n=418), only “waist pain” for Clinical Research, San Diego, CA was a significant determinant of hot flashes after controlling for education, BMI, history Objective: To evaluate the efficacy of G-ER 1200mg & 1800mg daily on the frequency of hysterectomy, HT use, and other relevant variables. For depressed mood, current and severity of moderate to severe hot flashes (HF) from baseline to each treatment wk symptoms of hot flashes, trouble sleeping, and SES were significant determinants of in post-menopausal women. Design: This was a Phase 3, double-blind, placebo-controlled depressed mood among pre-menopausal women after controlling for education, irritability study conducted at 45 sites in the US. Post-menopausal women with ≥ 7 moderate to with menstruation, depressed mood with menstruation, smoking, parity, and other severe HF per day during the baseline period were randomized to either 1200 mg QD or potential determinants. Hot flashes and trouble sleeping were also significant determinants 1800mg (600mg AM/1200 mg PM) of G-ER or placebo. Additional inclusion criteria of depressed mood among postmenopausal women. Depressed mood and irritability with were no history of malignancy within 2 y,and amenorrhea for at least 1 y or amenorrhea menses were not significant determinants of depressed mood at midlife after controlling for 6-12 mos with FSH > 40 mIU or ≥ 6 mos post bilateral oophorectomy. Patients were for other variables. Conclusion: Abdominal cramping and hot flashes may both be titrated to their randomized dose over 1 wk. The study medication was taken with a meal associated with drops in levels of steroid hormones. Alternatively, women who experience and daily HF & their severity were recorded using an electronic diary throughout the and report discomforts associated with menstruation may be more likely to experience and study. The efficacy measure was the mean change in observed average daily frequency and report discomforts associated with menopause. severity score of moderate to severe HF from Baseline and to each follow-up week. An ANCOVA model which included treatment and center factors, and the corresponding baseline value as the covariate was used to determine the pairwise difference between G P-78. ER and placebo treatments. Results: Out of 565 randomized patients, 559 were included Bioidentical Hormone Therapy: A Survey of Pharmacists Beliefs in the ITT population, 190, 186, & 183 in the 1800mg, 1200mg & placebo groups Tasneem Siyam, BScPharm, Nese Yuksel, BScPharm, PharmD. Faculty of Pharmacy and respectively, with 148, 149, and 147 subjects, respectively, completing the study through Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada stable dosing wk 12. The mean (range) age was 53.2 y (28.0 - 70.0), with 66.0% being Objective: In light of the controversy surrounding the term Bioidentical Hormone Caucasian, 27.5% Black, and 4.7% Hispanic. The mean age at menopause was 44 y (18- Therapy (BHT), health care providers may provide information to patients based on their 62) and the mos since the last menstrual period was 109 (1-492). Overall, 49% of subjects personal beliefs with BHT. The objective of our study was to assess pharmacists’ belief had been amenorrheic for at least 12 mos and 45% had undergone surgical sterilization. on the definition, as well as safety and efficacy of BHT and determine potential factors The subjects had an average daily frequency of moderate to severe HF of 12.0 (6.7-41.7), influencing these beliefs. Design: This was a cross-sectional survey design. Community 13.0 (4.43-40.7) and 12.6 (4.9 – 59.6) in the 1800 mg, 1200 mg and placebo groups, pharmacists in Edmonton, Alberta and surrounding areas were asked to participate in a respectively at baseline. Even with a substantial placebo effect, both the 1800mg and written, self-administered survey. A 32-item questionnaire was created with sections on 1200mg group had significantly greater reductions in observed average daily frequency demographics, beliefs on BHT definition, efficacy and safety information sources, and of moderate to severe HF during the titration wk, and at stable dosing wks 1-4 and 8-12. comfort level with BHT. Summary and inferential t test statistics were used for analysis. In addition, the 1200 mg group also had a significant reduction at wk 7 (Figure). The Approval was received by the University of Alberta Health Ethics Research Board. 1800mg group had a significantly greater reduction in observed average daily severity Results: One hundred and thirty four pharmacists were approached for participation in scores of moderate to severe HF during the titration wk, and at wks 1-5 and wks 7-12. In the survey and 95 pharmacists completed the questionnaire (71% response rate). contrast, the 1200mg group only had a significant reductions at wks 3, 9, & 12. Respondents were mostly female (65%) and less than 30 years (33%). Fifteen percent Conclusion: The results form this study suggest that G-ER at 1800mg or 1200mg are worked in a pharmacy that compounded BHT. Majority of pharmacists believed hormone similar in their ability to reduce the frequency of HF while the 1800mg dose has a greater therapy (HT) had a role in treating vasomotor symptoms and vaginal dryness (96%and effect on reducing the severity of vasomotor symptoms. 92% respectively), but only 51% believed HT prevented factures. Forty one percent of the respondents believed BHT included only compounded hormones. Over half (54%) believed BHT to be equally effective as other HT for vasomotor symptoms. Similarly, 54% believed BHT to have equal effects on CVD, VTE and breast cancer risk, while 29% believed BHT to have lower risk of side effects. Furthermore, 39% of pharmacists believed that natural progesterone cream could be used to prevent endometrial hyperplasia. Pharmacists who worked in compounding pharmacies were more likely to believe in less risk of BHT compared to other HT (p<0.05, use of natural progesterone cream to prevent endometrial hyperplasia (p=0.001) and the use of saliva testing in BHT dosing (p<0.05) as compared to pharmacists who worked in other settings. Similarly, BHT compounding pharmacists were more confident recommending and providing patient education on BHT (p<0.05). Conclusion: Community pharmacists had varying beliefs with BHT and these beliefs were strongly influenced by practice setting. This study helps identify areas for targeted education.

Frequency of Hot Flashes.

60 P-79. P-81. LibiGel® (Testosterone Gel) Safety Study Completes Enrollment and Antidepressant Effects on Brain Activation During the Emotional Conflict Continues With a Low CV Event Rate Task in Perimenopausal Women: a Functional MRI Study Michael C. Snabes, M.D.1, Scott Berry2, Joanne G. Zborowski1, Deborah Grady, M.D.3, Luciano Minuzzi, MD, Ph.D, Benicio N. Frey, Geoffrey B. Hall, Ivan Skelin, Stefanie William White, M.D.4. 1BioSante Pharmaceuticals, Inc., Lincolnshire, IL; 2Berry Attard, Meir Steiner, Claudio N. Soares, MD, PhD, FRCPC. Department of Psychiatry and Consultants, College Station, TX; 3University of California, San Francisco, CA; Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada 4Cardiology Center, University of Connecticut School of Medicine, Farmington, CT Objective: Neuroimaging studies have identified brain regions involved with emotional Objective: LibiGel® is in Phase III development for treatment of postmenopausal women conflict and emotional resolution. In a previous functional magnetic resonance imaging with Hypoactive Sexual Desire Disorder (HSDD). FDA approval requires demonstration (fMRI) study, we have demonstrated that peri/postmenopausal women present a distinct of long-term cardiovascular (CV) and breast safety. Herein we report on study progress. brain network for emotional regulation using an Emotional Conflict task. Despite the The objective of the study is to establish the safety of LibiGel treatment of menopausal transition being associated with a higher risk for the development of Major postmenopausal women. Design: This is a Phase III, randomized, double-blind, placebo- Depressive Disorders (MDD), little is known about the impact of MDD and its treatment controlled, multi-center CV events-driven, adaptive design comparison of daily LibiGel® on the emotional regulatory circuit in midlife women. In this study we evaluated the brain testosterone gel verses identical placebo gel in postmenopausal women with HSDD and correlates of emotional regulation in peri- and postmenopausal women before and after CV risk. Design of the study incorporated enrollment completion prior to the maximum antidepressant treatment and in age-matched controls. Design: Nine peri/postmenopausal of 4,000 subjects if the unblinded, independent Data Monitoring Committee (DMC) women (mean age = 52.2 ± 4.3 years) diagnosed with MDD and 18 healthy age-matched statistician calculated the predictive probability of study success to be > 90% after controls (mean age=51.7 ± 5.5 years) underwent 3T fMRI scanning while performing the continuing the study for an additional 12 months after enrollment completion using Emotional Conflict task (Etkin et al., 2006). After a 2-week placebo lead-in phase, placebo prospectively designed Bayesian modeling of the distribution of endpoint CV events. The non-responders received 8 weeks of treatment with SNRIs (Duloxetine 60-120 mg/day or primary safety outcome measure is the effect of treatment on the incidence of a composite Desvenlafaxine, 50 mg/day). fMRI scanning was performed at baseline and after 8 weeks of adjudicated CV events. Results: Based on the results of the adaptive design sample size in treated participants and matched controls. Brain activation was contrasted according to algorithm, enrollment was completed at 3,656 randomized subjects. In addition, the DMC the emotional conflict resolution paradigm (high conflict resolution > low conflict has recommended that the study continue as planned after each of the 6 separate unblinded resolution) using BrainVoyager QX software. Results: Unmedicated MDD patients data evaluations. The mean age of subjects at randomization is 58.6 years: two thirds are presented deactivation of dorsolateral prefrontal cortex (DLPFC) during the emotional hypertensive, 65% dyslipidemic, 21% smokers and 20% diabetic. More than 4,000 conflict resolution. Age-matched controls showed deactivation in a number of cortical subject-years of exposure already have been accrued. The rate of adjudicated, protocol- regions including DLPFC, rostral anterior cingulate, and temporal regions. After eight mandated CV events of subjects is 0.58% and the breast cancer rate is 0.24%. Conclusion: weeks of antidepressant treatment, MDD patients showed clinical improvement (mean The LibiGel safety study continues to accrue event and other safety data and is blinded total MADRS scores = 5.9 ± 5.8, p<0.05). Compared to baseline, healthy controls did to all except the DMC. Even with an enhanced-risk patient population, the CV event rate not present any changes in brain activation during the Emotional Conflict task whereas remains quite low. Successful completion of the LibiGel clinical program could result in treated MDD participants showed increased activation of DLPFC. Conclusion: These the first approved pharmacologic therapy for women with HSDD. Sponsor: BioSante novel but preliminary fMRI findings suggest that MDD in perimenopause and early Pharmaceuticals, Lincolnshire, Il. postmenopause might be associated with changes in the network involved in emotional regulation. Compared to healthy volunteers, untreated subjects with MDD failed to deactivate a number of brain regions in response to the paradigm. After receiving P-80. treatment, MDD patients showed activation of DLPFC, a brain region that was deactivated Effects of Quetiapine Extended-Release on Sleep and Quality of Life in under the same emotional test pre-treatment. The distinct active brain area after Midlife Women With Major Depressive Disorder antidepressant treatment might indicate neuroplasticity due to treatment or compensatory Benicio N. Frey, MD, PhD2, Erika Haber2, Gustavo C. Mendes3, Meir Steiner1, Claudio effect against the disease. Future studies should investigate the impact of hormone N. Soares, MD, PhD, FRCPC1. 1Psychiatry and Behavioural Neurosciences, Obstetrics @ variations on these cortical networks in this population. Gynecology, McMaster University, Hamilton, ON, Canada; 2Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada; 3Psychiatry, Sao Paulo Federal University, Sao Paulo, Brazil P-82. Objective: Existing data support a heightened risk for the development of depression in A Pooled Analysis of the Effect of Desvenlafaxine on Sleep in Women With perimenopausal and early postmenopausal women. Depression during this “window of Vasomotor Symptoms Associated With Menopause risk” is commonly associated with other complaints, including vasomotor symptoms, Claudio N. Soares1, Howard M. Kravitz2, Ru-fong J. Cheng3, Rana Fayyad3, Dale Grothe3, sleep disturbances and other conditions that adversely impact wellbeing and overall Christine J. Guico-Pabia, MD, MBA, MPH3. 1McMaster University, Hamilton, ON, quality of life measures. Quetiapine extended-release (XR) has been shown to alleviate Canada; 2Rush University Medical Center, Chicago, IL; 3Pfizer Inc, Collegeville, PA mood symptoms and improve sleep parameters in individuals with unipolar and bipolar Objective: Desvenlafaxine (administered as desvenlafaxine succinate) reduces the depression. Recent preliminary data also support antidepressant properties of quetiapine number and severity of hot flushes in women with moderate to severe vasomotor XR for the treatment of symptomatic, depressed midlife women. To date, no studies have symptoms (VMS) associated with menopause. Desvenlafaxine 100 mg/d was examined the effects of quetiapine XR on sleep and quality of life in peri/postmenopausal demonstrated to be the lowest effective dose for moderate to severe VMS. An exploratory women with major depressive disorder (MDD). Design: Forty peri- and postmenopausal analysis of the effect of desvenlafaxine 100 mg/d on sleep was carried out using pooled women (defined by STRAW criteria), ages 40-60 years and meeting criteria for MDD data from 5 multicenter, double-blind, randomized, placebo-controlled trials of were enrolled into a clinical trial that included a 2-week, placebo lead-in phase; those desvenlafaxine efficacy and safety for VMS. Design: Postmenopausal women seeking who remained significantly depressed after completion of the placebo lead-in phase then treatment for VMS were randomly assigned to receive desvenlafaxine (50 mg/d–200 entered an 8-week open trial with quetiapine XR, flexible dose, 150-300 mg/day. mg/d) or placebo in 5 trials; all 5 studies included a desvenlafaxine 100-mg arm. Data Depressive symptoms were measured with Montgomery-Asberg Depression Rating Scale from women treated with desvenlafaxine 100 mg/d or placebo were pooled for analysis. (MADRS). Sleep parameters and quality of life were assessed using the Pittsburgh Entry criteria for all 5 studies included ≥7 moderate to severe hot flushes per day or ≥50 Insomnia Rating Scale (PIRS) and the Menopause-Specific Quality of Life Questionnaire per week at baseline. One study had additional inclusion criteria requiring a Greene (Meno-Qol), respectively. Results: Twenty-three subjects were eligible for the modified Climactic Scale (GCS) total score ≥12 and hot flush item score ≥2 at baseline. Study intent-to-treat, last observation carried forward analyses (i.e., those who had at least one durations were 12 weeks (2 studies), 26 weeks (1 study) or 52 weeks (2 studies). The follow-up assessment while receiving treatment with quetiapine XR). Results of these primary endpoint of interest was change from baseline in the number of nighttime analyses revealed significant sleep improvement with quetiapine XR based on PIRS awakenings due to hot flushes at week 12 and across the 12-week time period (pooled domains of subjective sleep distress, overall sleep parameters and sleep-related quality of from 3 studies with these data). Number of nighttime awakenings was analyzed using a life (p<0.001 for all comparisons). Moreover, quetiapine XR led to a significant mixed-effects model for repeated measures, with treatment, baseline, and study in the improvement in all Meno-Qol domains (i.e. vasomotor, physical, sexual and model and week the repeating factor, as well as using last observation carried forward psychological; p<0.05 for all comparisons). Lastly, global improvement in sleep (LOCF). Secondary exploratory measures included change from baseline to week 12 for parameters (changes in total PIRS scores) was strongly correlated with improvement in GCS sleep item score (difficulty in sleeping; 3 studies) and score at week 12 on depressive symptoms (changes in total MADRS scores) (rS=0.79; p<0.001). Conclusion: Menopause Symptoms Treatment Satisfaction Questionnaire (MS-TSQ), item 3 Treatment with quetiapine XR may not only alleviate depressive and menopause-related (satisfaction with effect of treatment on sleep; 2 studies). The incidence of selected sleep- symptoms but also lead to significant improvement in sleep and subjective quality of life related treatment-emergent adverse events (TEAEs) was determined for pooled data from in peri- and postmenopausal women with MDD. Further, larger studies should confirm the all 5 studies. Results: A total of 3323 women took at least 1 dose of desvenlafaxine 100 efficacy and tolerability of quetiapine XR for the management of the depression in this mg (n=1711) or placebo (n=1612) and were included in the safety population for this population. analysis. Nighttime awakenings data were available for 881 women from 3 studies, 475 treated with desvenlafaxine 100 mg/d and 406 treated with placebo. Mean number of nighttime awakenings at baseline was 3.56 for the desvenlafaxine group and 3.34 for placebo. Women treated with desvenlafaxine achieved an adjusted mean (± standard error) reduction of 2.22 ± 0.07 awakenings due to hot flushes per night at 12 weeks with a mean reduction of 2.06 ± 0.06 per night across 12 weeks of treatment; significantly greater than the reductions of 1.65 ± 0.08 and 1.47 ± 0.06 awakenings due to hot flushes per night for women treated with placebo (P<0.001). Difficulty sleeping was significantly reduced in desvenlafaxine-treated women compared with placebo; adjusted mean decrease in GCS sleep item score at week 12 of 0.79 ± 0.04, from a baseline mean of 1.87, compared with

61 Clinical Poster Presentations (continued)

a reduction of 0.56 ± 0.04 for placebo (baseline = 1.83; P<0.001), respectively. At week P-85. 12, 66% of women treated with desvenlafaxine and 44% of women treated with placebo Results from 2010 NAMS Survey on Secondary Transfer of Transdermal reported that they were “satisfied” or “extremely satisfied” with the effect of treatment on Estrogen Preparations sleep (P<0.001). The most common selected sleep-related TEAEs (reported by ≥5% Cynthia A. Stuenkel, MD1, Margery Gass, MD2. 1Medicine, Endocrinology and desvenlafaxine-treated women in the safety population and at least twice the placebo rate) Metabolism, University of California, San Diego, La Jolla, CA; 2The North American were fatigue (9.2%; placebo, 3.3%) and somnolence (6.8%; placebo, 1.2%). Conclusion: Menopause Society, Mayfield Heights, OH In women with moderate to severe VMS, Desvenlafaxine 100 mg/d significantly reduced Objective: As the use of transdermal estrogen preparations has increased, inadvertent the number of nighttime awakenings due to hot flushes, reduced reported difficulty transfer of cutaneous estrogen from women to pets and children has rarely been reported sleeping, and led to reports of greater treatment satisfaction compared with placebo. and is unfamiliar to most clinicians. In the summer of 2010, the Veterinary Information Network, a subscription online resource for veterinarians, compiled nearly 50 reports of P-83. cats and dogs presenting with signs and symptoms of estrogen excess linked to use of Quality Of Life Questionnaires: Translation and Linguistic Adaptation cutaneous estrogens, primarily compounded preparations, by their owners. Concurrently, the Food and Drug Administration issued a safety communication based on 8 cases of from English into Traditional Chinese estrogen excess in children and 2 in pets resulting from transfer of estrogen from women Lily Stojanovska, PhD1, Cindy Law, RN2, Christopher Haines, PhD2. 1School of using Evamist, an FDA approved estrogen preparation. This report reflects the responses Biomedical and Health Sciences, Victoria University, Melbourne, VIC, Australia; of the attendees at the 2010 Annual Meeting of The North American Menopause Society 2Department of Obstetrics and Gynaecology, The Prince of Wales Hospital, Chinese to questions about their experience with transfer of transdermal estrogen preparations to University of Hong Kong,, Hong Kong, Hong Kong children or pets. Design: At the time of registration, a brief survey was distributed to all Objective: The Women’s Health Questionnaire (WHQ) and the Utian Quality Of Life attendees of the 2010 Annual Meeting of The North American Menopause Society (UQoL) are reliable and valid instruments designed to measure the quality of life (QOL) (NAMS). The questions included the following: Do you know of a child or pet affected among English-speaking climacteric women. To describe the translation and cultural by secondary estrogen exposure? If ‘Yes’ to the child query, then describe the approximate adaptation of the UQOL and the WHQ for the Chinese postmenopausal women from age of child and signs of hormone effect. If ‘Yes” to the pet query, please describe the pet Hong Kong Design: The English version of the UQOL and the WHQ were translated into and signs of hormone effect. For either child or pet, please describe the nature of hormone Chinese and cross-culturally adapted to the Chinese from Hong Kong environment, exposure (which hormone products and how/where they were being used). The according to standard internationally recommended methodology of translation. This questionnaire also asked: Did you submit FDA Form 3500 (persons) or 1932a (pets) to process involved several steps: (a) forward translation; (b) reconciliation; (c) back report the findings? Results: Of 1,299 attendees, 576 were clinicians; 312 attendees translation into Chinese and its review, followed by (d) harmonization. The adapted completed the survey (24% of the total in attendance, 54% of clinicians). Among the version from each scale was administered to thirty postmenopausal women with the respondents, 98% indicated they did not know a child or pet affected by secondary purpose of assessing the level of comprehension and cognitive equivalence of this version. estrogen exposure; 7 attendees (2% of responders) indicated they knew of affected A full validation study involving over 100 participants is currently underway. Permission children (n=1) or pets (n=6). The child was between ages of 10 and 12 years and presented to use the instruments by the original authors was obtained. Results: The translated with early signs of puberty. Estrogen cream had been used by the child’s mother. Of the version of both scales was straightforward. In the cognitive debriefing, results were 6 pets that were reported, 5 were described as ‘small dogs.’ The 6th animal was not analyzed and incorporated in the report, showing that all the questions were adequately described. Gynecomastia, enlarged/darkened nipples, or breast development was reported understood by more than 88% of the women interviewed. Despite of this, the viability of in 4 of the 6 pets. One dog also experienced a loss of chest hair; another was the instrument and the difficulties mentioned by the volunteers were analyzed by a five “sick/lethargic.” In 2 dogs, the veterinarian documented elevated serum member committee, and logical, fluent, conceptual and experiential equivalences were estrogen/progesterone levels. Among the 6 pets reported, 4 were exposed to Evamist obtained. Conclusion: The present study fulfills an important step in the process of (applied to forearm in one case and abdomen in another), one was exposed to Estrogel translation and cultural adaptation of the UQOL and the WHQ scales, leading to its (applied to forearm), and 1 was exposed to compounded estradiol cream and compounded subsequent validation and utilization in clinical practice and scientific research in Hong 10% progesterone cream (applied to forearm). FDA reporting had been completed for Kong and mainland China. This methodology can serve as a model for translation of one pet by the veterinarian; no other cases were reported. In summary, one clinician out UQOL and the WHQ into other languages. of 50 who attended the NAMS Annual Meeting and completed the questionnaire had observed secondary transfer of transdermal estrogen from patients to pets or children. In P-84. the experience of NAMS clinicians, 5/6 pet exposures followed use by the owner of FDA The use of Maca (Lepidium meyenii) on plasma glucose and cytokine approved transdermal therapies: Evamist and Estrogel. One of the pets and the only child patterns in postmenopausal Hong Kong Chinese women reported were exposed to compounded hormone therapy. Conclusion: The results of the Lily Stojanovska, PhD1, Kristina Nelson, BSc1, Vasso Apostolopoulos, PhD2, Stephanie survey indicate that among clinicians seeing menopausal women, cases of secondary Day, PhD2. 1School of Biomedical and Health Sciences, Victoria University, Melbourne, transfer of transdermal estrogen preparations may be more common than anticipated from VIC, Australia; 2Department of Immunology, Macfarlane Burnet Institute for Medical pre-marketing safety studies. These findings underscore the importance of educating Research, Melbourne, VIC, Australia patients about appropriate hygiene measures to avoid transfer of estrogen to children and Objective: Maca is a nutritious plant used historically as a therapeutic compound in pets when using any cutaneous estrogen preparations. Should findings of breast alleviating symptoms of menopause transition. Whilst Macas’ mechanism of action is enlargement in children or nipple or vulvar enlargement in pets occur, promptly unknown limited studies indicate that it is not directly correlated with hormonal changes. communicate to the pediatrician or the veterinarian the possibility of secondary transfer Complex interactions between endocrine and immune systems are emerging in menopause of estrogen. physiology, in particular altered cytokine profiles and inflammation with decreasing oestrogen levels. The aim of this study is to determine the effects of supplemental Maca P-86. during a 12-week double-blind cross-over trial, on selected biological markers (Th1/Th2 Construction and Validation of an instrument that breaks the silence: The cytokines) and plasma glucose in post-menopausal Chinese women Design: Twenty- impact of domestic and/or sexual violence on womens health as shown seven healthy postmenopausal women were recruited in a randomised, double-blind, placebo-controlled crossover trial. Women received 3.3g/day of Maca and matching during climactery placebo for six weeks each. At baseline, 6 and 12 weeks, blood was taken for Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da Fonseca, MD, Ph.D, measurements of plasma cytokines (IL-2, IL-4, IL-5, IL-10, IL-12 (p70), IL-13, GM- José M. Soares Júnior, MD, Ph.D, Vicente R. Bagnoli, MD, Ph.D, Marilena A. Sousa, MD, Wilson Maça Yuki Ariê, MD, Ph.D, Edmund Chada Baracat, MD, Ph.D. Ginecology, CSF, IFN-λ and TNF-α) as well as plasma glucose. Results: Three analytes (IL-5, IL-10 and IL-13) were detectable within range, whilst six analytes (IL-2, IL-4, IL-12, GM-CSF, University of São Paulo, São Paulo, Brazil Objective: construction and validation of a questionnaire able not only to measure the IFN-λ, TNF-α) were found to be in concentrations beyond detectable range. Overall, there was minimal variation in detectable cytokines between baseline, placebo and Maca consequences of domestic and/or sexual violence on womens health at climactery but (p>0.05). The mean fasting plasma glucose was marginally but not significantly elevated also to break the silence of these women. Design: application of a questionnaire at the in both placebo and Maca treatments when compared to baseline (p>0.05). Conclusion: Outpatient Clinic Climactery of the General Hospital - University of São Paulo (FMUSP), Maca does not alter cytokine markers nor plasma glucose levels in Chinese Brazil, performed during 2009 for 124 women aged between 40 and 65 years, who were postmenopausal women. This is not unexpected given the healthy menopausal cohort victims of domestic and/or sexual violence, distributed in three groups: 1. Violence studied. In addition we only measured nine cytokines, which may not capture the complex exclusively during childhood/adolescence; 2. During adulthood; 3. Throughout all phases. interactions within an extensive cytokine network. Further studies are required in a larger The instrument encompasses 34 items evaluating: 1. Place of residence and who the cohort, for a longer duration and larger cytokine panel in to explore Maca’s effect in woman lives with; 2. Start, frequency and type of violence; 3. Search for health assistance menopause. and report of the violence; 4. Violence and number of comorbidities; 5. Violence and Menopausal Kupperman Index (IMK). Results: The instrument presented Cronbach Alpha=0.82, reliability among examiners (+0,80), and good possibility to be reproduced. Average menopause age -45,4 years in average, in the control Group (GC) it was 48,1 years and average BMI (Body Mass Index) 28,5 (±2,8), similar to the GC, but frequent violence during adulthood showed a BMI of 30,0 (±2,8).Women subjected to violence during childhood/adolescence presented an average of 5,1 comorbidities during adulthood, 4,6 and 4,4 for both phases. Sexual violence (43,5%) and other types of violence both present average comorbidities (4,60) but represent a significative impairment of sexual life. For those submitted to domestic and/or sexual violence we find: osteoporosis 85,5%; depression/psychiatric disorders 69,4%; hypertension 54%; rheumatic diseases and

62 diseases of the joints 47,7%; allergies 37,9%; fibromyalgia 33,1%; varicose veins in the intervention in a group context, we applied a semi structures questionnaire, self appliable, legs 29,8%; Labyrintitis 29,8%; diabetes 15,3%; disk hernia 14,5%; uterine/ovarian/breast with epidemiological data and the major social determinants acting on the lives of these cancer 13,7%, in which braet neoplasies represents 47,05% of these cancers; other women. Average age was 55,8 years (± 6), menarcha 13 years (± 2), first sexual cancers: 2,4%. Regarding the intensity of climacteric symptoms, 53,2% of the women intercourse 19,4 years (± 5,5), menopause 45,4 years (± 6,3 ). During the period in which present moderate IK moderado, 25,8% light IK e 21% serious IK. Higher percentages of they suffered violence, 68% lived in the urban region. Answers to the open questions were serious Kupperman Index (IK) were observed in women submitted to violence in both life grouped by subject similarity (Minayo, 2004) Results: Type of violence suffered during phases (29,3%), moderate IK in childhood/adolescence (75%) and during adulthood light any phase of life: Physical (75,8%), Sexual (59,75), Psychological (59,3%), Physical IK (33%). There were significative associations between suffering any type of violence Neglect (75,8%), Emotional Neglect (31,41%). Women suffering sexual violence (59,7%) during all phases of their lives, sexual violence during any phase of their lives and a serious report most of the episodes occurring during childhood/adolescence. Regarding the IMK. Among those women, 80,6% did not search health services due to the violence violence they suffered, 88,0% was perpetrated by an intimate partner, and was most suffered. Number of comorbidities and Kuperman Index are not associated to tobacco frequent during 20 to 29 years of age. White women (56%) have more difficulties to relate use (Mann-Whitney test). Among the diverse violence episodes suffered by women, the violence suffered, contrary to afro-descendents (43,58%) and Orientals (3,84%). There ones that most impair their physical and psychological health was the category “Having was no significative relationship between skin color or income and having suffered been hit/suffered because of a man who is the father of my child” (38,7%), followed by domestic and/or sexual violence, but having more than 11 years of schooling was a “Suffering many traumas/violence by someone who raised or adopted me” (33,1%), protective factor. There was a significant relationship between domestic violence and use “Suffering humiliation, verbal abuse, calumnies…” (25%), “Having been hit/suffering of alcohol and/or other drugs by the victimizer. Among the many types of domestic because of someone I loved or still love” (24,2%), and “Having been abused/raped by violence it is possible to outline: demeaning the woman, menaces to deprive the child someone close to me and/or from my family” (17,7%). Regarding the actions of health from basic needs, menaces of aggression or death and privation of freedom, unleashing professionals approaching violence, 75% of the women say they would have asked for diverse degrees of anxiety. Unmarried women or women who are separated, as well as help if the professional had brought the theme during the consultation and 17,7% said those living alone present higher spanking rates than married women. Psychological they would not tell the violence they were subjected to, even if they were questioned about violence is more frequent among married women. Reproductive health: no children it. These women suggested that: 58,1% “professionals must open spaces for people to 3,85%, one child 15,75%, two children 28,29%, three children 21,54 %, four children talk, they must give us more security”, 20,2% “Professionals must stimulate women to not 17,04 %, five or more children 13,50% of the women: never had an abortion 53,37%, one accept violence and to report violence”. Violence suffered had a negative influence on abortion 24,11%, two abortions 12,54%, three abortions 3,21%, four abortions 3,53%, the way of living and acting for 90,3% of the women in these study. Conclusion: The five or more abortions 3,21%. Women having active sexual life amounted to 28,3% and, questionnaire presents good internal consistency and a validated construction, can be among these, only 7,87% consider it to be satisfactory. Smokers are 15,0% and 3,1% are easily reproduced and is indicated to evaluate the consequences of domestic and/or sexual alcohol users. Women with higher schooling look for health assistance (especially violence on womens health during climactery. psychotherapy or psychiatric services) and for the police more often, while those who have less schooling (less than 8 years of schooling) look for the hospital only when suffering major physical hazards, like fractures, bleeding and pain that does not respond P-87. to regular medicine. Women who did not look for health services when suffering violence Life quality in women victims of gender vilence during climactery amounted to 80,6% of the sample and, when they looked for these services, due to other Eli M. Moraes, Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da reasons, they would have told about the violence if the health professional had questioned Fonseca, MD, Ph.D, Vicente R. Bagnoli, MD, Ph.D, Josefina O. Polak Massabki, Jucilene or if the consultation was more humane. Those who did not look for the police explain Sales da Paixão, Pérsio Yvon Adri Cezarino, Edmund Chada Baracat, MD, Ph.D. they do not trust the efficiency of the service, mentioning a degree of gender violence by Ginecology, University of São Paulo, São Paulo, Brazil the teams offering this kind of assistance. Conclusion: This study renders evident Objective: Characterizing a group of women in climactery who were victims of gender breeches in women’s health attention in which professionals lost the opportunity to break violence by information level, depression and quality of live, verifying the results of a the cycle of violence and also shows the importance of assistance humanization, in which psychological intervention on these subjects. Design: Subjects were 62 women aged “caring” includes a way to live, to be and to express oneself. In the individual between 40 and 60 years. A psychological intervention was developed, and a group psychotherapy it is possible to suppose women who are victims of sexual violence during context, with the objective to inform about climacteric syndrome, supporting and their childhood tend to choose inadequate intimate partners, repeating the violence in psychologically preparing the patients. Intervention comprised 12 weekly encounters of their lives. This may be due to factors such as a combination of beliefs, negative 1h30 hours each. In order to render easier the discussion and the experience of the expectations, misadjusted behaviors, low self esteem, lack of self-protective techniques proposed themes (definition of climactery and menopause, sexuality, post trauma stress, and the cultural approach that renders violence as banal, regarding abuse as a normal familiar and amorous relationships) we employed group dynamic techniques. Participants, experience. at the start and at the end of the intervention, were evaluating to assess their information level, anxiety, depression and life quality. Instruments employed were: Beck Depression Inventory, Instrument for Evaluation of Life Quality (WHOQOL-Bref) and a P-89. questionnaire, designed by the researcher, on knowledge about climactery, menopause, The State of the Breast Cancer Vaccine sexuality and healthy habits. Results: At the first evaluation of the knowledge Kristi Tough, MD, Holly Thacker. Cleveland Clinic, Cleveland, OH questionnaire, questions regarding climactery, menopause and sexuality presented the Objective: To survey the literature on the state of clinical advancement of prophylactic higher percentages of incorrect answers. On questions about the consequences of violence and adjuvant breast cancer vaccinations. Developments in immunotherapy, our aging on women’s health, analyzed during the climactery phase, most of the participants state population and the growing prevalence of cancer make cancer vaccination a leading edge they would have told health professionals, during consultation, about the violence of clinical research. Design: Literature review was conducted via PubMed search for suffered, if they had been approached in a more humane way. In the first evaluation of phase II trials of breast cancer vaccines. Search terms used were: human, breast cancer depression, participants presented alteration in their moods (disphoria). Regarding quality vaccine and phase II trial. The reference lists from selected articles were searched for of life, in the evaluation previous to the intervention, scores presented by the participants, relevant contributions to breast cancer vaccine research. The National Cancer Institute when compared to the normative study, were lower in psychological and social aspects. website was reviewed for ongoing clinical trials. Results: No prophylactic or therapeutic Comparison of the evaluation results previous and posterior to the intervention, shows vaccine exists for breast cancer which affects 1 in 8 women by aged 90 or 12% of the that, in the knowledge questionnaire, there was significative increase in the percentage of general population, with higher incidences in BRCA patients and kills 40,000 women adequate answers, in questions dealing with the difference between climactery and yearly. Despite the absence of an approved breast cancer vaccine, there is no dearth of menopause, concepts of climactery and menopause, purpose of the hormonal reposition animal and human research, particularly on various adjuvant vaccines used in the therapy, beauty and sensuality during climactery. Final evaluation signaled a reduction in metastatic setting. The first FDA approved autologous vaccine was the prostate cancer the average of anxiety when compared to the first application, which may indicate a vaccine (sipuleucel-T or Provenge®) which confers survival benefit of 4.5 months for contribution of the intervention to this result. Regarding depression, average reduction of men who failed hormonal therapy. Synergy of immunotherapy and modalities of scores shows that, after the intervention, patients fit into the category with no depression. chemotherapy or hormonal therapy is also employed in breast cancer vaccine research. Conclusion: From these results it is possible to conclude that interventions designed to Four delivery systems are currently being widely studied for effective vaccination which approach the violence suffered, to inform and to prepare women to live climactery is an include: dendritic cell, viral, peptide and whole cell based vaccines. Published phase II intervention that may contribute to improve their life quality. trials exist for peptide and viral vaccines. Peptide vaccines stimulate T cell and antibody cascade against tumor cells expressing the same antigenic protein (mostly HER2 proteins). Published results of 177 metastatic or locally advanced breast cancer patients with E75 P-88. vaccination showed disease free survival advantage of 85% in immunized patients (24/29 Social Determinants of Domestic Violence Among Women During patients) and 59% in the placebo arm after 22 month follow up and recurrence rate 8% Climactery verses 21% respectively (P<0.19). A larger follow up trial showed waning immunity after Sandra D. Teixeira de Araujo Moraes, MD, Ph.D., Angela Maggio da Fonseca, MD, Ph.D, 6 months post vaccination but in vivo T cell response and clinical recurrence rate are not Vicente R. Bagnoli, MD, Ph.D, Eli M. Moraes, Eliana Guimarães Labes, Érica Mendonça always linearly related. Recent data on 48 month follow up revealed decrease recurrence das Neves, Edmund Chada Baracat, MD, Ph.D. Ginecology, University of São Paulo, São rate after 6 months of E75 vaccination (NeuVax®) with booster compared with control. Paulo, Brazil A phase III trial, Prevention of Recurrence in Early Stage, Node Positive Breast Cancer Objective: Analyzing social determinants interacting in the lives of climacteric women with Low to Intermediate HER2 Expression with NeuVax® Treatment is planned for subjected to domestic and/or sexual violence. Design: Descriptive exploratory study with 2012. Viral based vaccines are another vaccination strategy that show promise for clinical qualitative approach including 124 women aged between 40 to 65 years, victims of relevance. Placement of antigens (mucin 1) within a virus or plasmid vector naturally domestic violence, profiting from their weekly therapeutic group encounters, in the ECOS elicits an immune response. Mucin 1 (MUC 1) is an ideal target for its over-expression Space of the University Hospital (Hospital das Clínicas) of the Medicine College of the in breast tumors, glycosolated membrane and strong immunogenicity. Phase I/II clinical University of São Paulo, between August and December, 2010. Before this psychological trials showed the vaccine Sailyl-Tn- keyhole limpet hemocyanin (STn-KLH) or

63 Clinical Poster Presentations (continued)

Theratope® (a synthetic antigen that mimics mucin expression) conferred positive elasticity, thickness and hydration in skin, while reducing the wrinkles in postmenopausal humoral response and significant survival benefit (19.1 months vs 9.2 months, p=0.001) women. Soy isoflavones (daidzein, genistein and glycitein) have similar structures to in vaccine versus control groups respectively. Unfortunately phase III trials showed no estrogen and exhibit estrogenic activity by binding to estrogen receptors. Equol, which is impact on overall survival or time to progression in1030 women. New research with both an active metabolite of daidzein, can be produced in approximately 50% of the Japanese MUC1 and carcinoembryonic antigen (CEA) genes placed into poxviruses are ongoing. and 20–30% of the US population after consumption of soy. The ability to produce equol The idea of a prophylactic vaccine is not novel, but begets complex issues of depends on the presence of certain intestinal microorganism. We recently isolated and autoimmunity. Pre-clinical work with alpha- lactalbumin (a self protein expressed in the identified a lactic acid bacterium, Lactococcus 20-92, that metabolizes daidzein to S- breast) shows vaccination provides robust T cell mediated immune response and equol. Using this strain, we successfully produced a fermented soy food containing natural protection from tumor growth in transgenic mice. This is promising evidence that primary S-equol. Clinical studies have shown the beneficial effects of natural S-equol supplement prevention with vaccination may stave of breast cancer. Clinical trials with alpha on menopausal symptoms and bone metabolism in postmenopausal Japanese women. lactalbumin are pending. References: Will be provided on poster presentation if abstract However, the efficacy of oral intake of S-equol on skin aging in humans is unknown. In provided. Conclusion: Breast cancer vaccination research has exciting advancements in the present study, we investigated the effects of natural S-equol on the skin aging in immunology and oncology, however we lack evidence of benefit in clinical trials. Japanese postmenopausal women. Design: The study was conducted with a double- Promising phase II clinical trials show that vaccination with peptide based HER2, E75 blinded, randomized, placebo-controlled design. Healthy postmenopausal women aged provided survival benefit and decreased recurrence. Thus far, most vaccinations 45-65 years, who were equol non-producers, were recruited for the study. The women complement the myriad of treatments for advanced breast cancer. A prophylactic breast were less than 5 years since the onset of menopause One hundred and one subjects were cancer vaccination is still in preclinical years, but hopefully the thriving research milieu divided into three groups, namely, EQL10 group (n =34, 10mg of equol/d), EQL30 group will eradicate this prevalent cancer in women. (n = 33, 30mg of equol/d), and placebo group (n = 34, 0mg of equol/d). Placebo or natural S-equol supplement were orally ingested twice a day for 12 weeks. Skin parameters of crow’s feet wrinkles (area and depth), hydration, transepidermal water loss (TEWL) and P-90. elasticity were measured at baseline, 4, 8, and 12 weeks during treatment. Blood Distribution of 24 hours urinary equol excretion as an indicator for the biochemical and endocrinological (sex and thyroid hormones) tests were carried out at the physiological range in healthy Japanese equol excretors same time as skin parameters measurements. For the assessment of reproductive organs Shigeto Uchiyama1, Atsuko Onoda1, Tomomi Ueno1, Belinda H. Jenks2, Soh Iwashita1,2, (uterus) and breasts safety of natural S-equol supplement, vaginal cytodiagnosis, James Brooks2, Yoshiko Ishimi3. 1Otsuka Pharmaceutical Co.,Ltd., Saga, Japan; endometrial thickness and mammography were performed before and after treatment. 2Pharmavite LLC, Northrige, CA; 3National Institute of Health and Nutrition, Tokyo, Results: No statistically significant difference was observed at baseline values of wrinkle Japan area and maximum largest wrinkle depth between groups. Wrinkle area in the EQL30 Objective: Soy bean, which is a traditional food in the Asian countries, is consumed more group was significantly lower compared to or vs. the placebo group at 12 weeks. The in Asia compared to the Western countries. The difference in soy consumption between wrinkle areas in both the EQL10 and EQL30 groups were significantly decreased over the Asia and Western is involved in the health status in each area. Previous studies showed that treatment period (P = 0.029 and P = 0.004, respectively). The maximum largest wrinkle the incidence of breast and prostate cancers is much lower in Asian than in the Western depth was significantly lower in EQL30 group compared to placebo group at 4 (P = 0.002) population, which might suggest that intake of soy relates to the reducing risk of those and 12 weeks (P = 0.015). In addition, the change in maximum largest wrinkle depth over cancers in Asian countries. Soy isoflavones (daidzein, genistein and glycitein) have been the treatment period was significantly different between EQL30 and placebo group (P = reported to prevent the hormone-related cancers, although people still have not a few 0.001). Both of the area and maximum largest depth in wrinkle showed a dose-dependent concerns of their estrogenic effects. Equol is a metabolite of the soy isoflavone daidzein, improvement by natural S-equol supplementation (P = 0.001 and P = 0.017, respectively). which was produced by intestinal bacteria, then equol may be involved in the prevalence No statistically significant differences were observed in skin hydration, TEWL or skin of these types of cancer as well as soy isoflavones. The frequency of equol producers is elasticity among the groups. There are no serious gynecological adverse events on uterine approximately 30% in Western population while approximately 50% in Japanese. Tiny or breast tissues, and no significant effects on hormone status during consumption of and ignorable amount of equol is existed in the limited foods (i.e. milk and egg yolk). natural S-equol for 10 or 30 mg/day. Conclusion: Oral administration of 10 mg and 30 Thus, only produced amount of equol from daidzein in the body can affect the amount of mg S-equol/day for 12 weeks improved crow’s feet wrinkles in equol non-producing equol exposure. To date, only a few studies have been reported in terms of the produced Japanese menopausal women without serious adverse events. The data of this study amount of equol in Japanese. Therefore, this study was developed to understand the levels suggest that natural S-equol supplementation has potential to improve quality of life for and potential benefits for a safety and effective amount of equol exposure in healthy postmenopausal women by slowing the skin aging. Findings from this current study Japanese adults. Data of the 24h urinary excretion of equol was evaluated as potential warrant further investigation in a longer treatment period, different ethnicities and scientific data point for evidence regarding the typical daily dose of exposure. So, we statistically powered study. could know daily physiological range of equol exposure in healthy Japanese adults. Design: 13 epidemiological studies, 1,345 subjects (545 men, 492 premenopausal women, and 308 postmenopausal women) participated, were conducted from 1996 to 2010. All P-92. subjects had no current or past history of serious illness. A questionnaire survey was used Characteristics of Patients attending a Dedicated Premature Ovarian to confirm the health and menopause status. The 24h urine of the participants was Failure (POF) Clinic collected under the conditions of their normal daily life (no restrictions of soy foods). Maria Velasco1,3, Taryn Becker2,3, Kelsey E. Mills, H.BSc, MD1,3, Wendy L. Wolfman, Alcohol intake was prohibited during the 24h urine collection. The urine samples were MD, FRCSC1,3. 1Department of Obstetrics and Gynaecology, Mount Sinai Hospital, enzymatically deconjugated, and daidzein, genistein, and equol were measured by high Toronto, ON, Canada; 2Division of Endocrinology and Metabolism, Women,s College performance liquid chromatography (HPLC). The 24h urinary excretions of the Hospital, Toronto, ON, Canada; 3University of Toronto, Toronto, ON, Canada isoflavones and equol were determined using the values measured by HPLC. If the Objective: The clinical characteristics of patients presenting with POF seem to be subjects had equol levels that were above the detection limit (0.27 nmol/mL), they were evolving, with an increasing proportion of patients having POF secondary to cancer defined as equol excretors. All studies were performed with the approval of the human therapies. The objective of the study is to describe the clinical characteristics of the studies institutional review board for each participating institution. Results: The patients attending a dedicated POF Clinic. Design: We conducted a retrospective study frequency of equol excretors was 36.3% among men, 33.3% among premenopausal of patients evaluated at the POF clinic at Mount Sinai, Toronto, Canada, from January women, and 52.6% among postmenopausal women. The total number of equol excretors 2008 to March 2011. A chart review was performed to collect the following data: was 524, then the minimum amount of 24h urinary excretion of equol was 0.4 μmol/day demographics, etiology, hormonal therapy and bone mineral density (BMD) scores. (0.1 mg/day), the maximum was 318.0 μmol/day (77.0 mg/day), the 50th percentile was Descriptive data is presented as median and standard deviation or percentage. BMD was 12.5 μmol/day (3.0 mg/day), and the 95th percentile was 119.2 μmol/day (28.9 mg/day). measured using dual-energy x-ray absorptiometry or DXA. BMD was considered low For equol, daidzein and genistein, premenopausal women had significantly lower values when the Z-score was -2.0 or lower. Data were compared using Chi square tests for than men or postmenopausal women (equol; P<0.001, daidzein: P<0.001, and genistein: categorical variables and Student’s t-test for continuous variables. Results: 179 patients P<0.001 versus men or postmenopausal women, respectively). The 24h urinary excretion attended the POF clinic during the study period, and the data was available for 172 of the of equol in postmenopausal women was significantly higher than that of men (P=0.004), patients. 144 women were included in the analysis, as the remainder did not have POF. but there were no differences for daidzein or genistein between these groups. Conclusion: The remainder of women were perimenopausal, had normal cycles, had hypothalamic or The results of the present study showed that the 24h urinary equol excretion was 0.1-77.0 pituitary amenorrhea or had polycystic ovary syndrome. The mean age was 27.7 years. mg/day in the equol excretors. This range would be physiological exposure of equol in The etiology of POF was unknown in 74 (51%) of women seen in our clinic. 39 women healthy Japanese population. These results could help understand to determine a safety (27%) had received cancer therapy either as a combination of chemotherapy and radiation and effective levels of equol exposure in a body. (n=21), chemotherapy alone (n=13), bilateral salpingoophorectomy (n=4) and radiation alone in 1 patient. Of the group that had POF of unknown etiology, 25 (33%) had evidence of autoimmunity as demonstrated by the presence of thyroid antibodies, hypothyroidism P-91. and/or other autoimmune disease. The patients with unknown etiology presented at an The effects of natural S-equol supplementation on skin aging in older age than the patients with POF secondary to therapy for cancer (29.9+/-8 and 22.8+/- postmenopausal women: A pilot randomized placebo-controlled trial 8.9 years, p<0.001). 27 patients presented with primary amenorrhea (19%), 9 of them Tomomi Ueno1, Atsuko Onoda1, Shigeto Uchiyama1, Belinda H. Jenks2, Soh Iwashita1,2, secondary to cancer therapy. Thirteen women had Turner’s syndrome (9%), and 4 had James Brooks2, Takeshi Aso3, Kayoko Matsunaga4. 1Otsuka Pharmaceutical Co.,Ltd., Fragile X premutation (3%). Of the total group, 85% (n=122) were receiving estrogen Saga, Japan; 2Pharmavite LLC, Northrige, CA; 3Tokyo Medical and Dental University, therapy, 67 (47%) with the oral contraceptive pill (OCP) and 55 (38%) with hormone Tokyo, Japan; 4Fujita Health University School of Medicine, Aichi, Japan therapy (HT), while 22 (15%) declined therapy. 18% used vaginal estrogens although Objective: A factor of skin aging in postmenopausal women is loss of estrogen. they were taking OCP or HT. Twelve patients (8%) had pregnancy after diagnosis, with Approximately 30% of dermal collagen is diminished during the first 5 years after egg donation in 10 women and spontaneous pregnancy in 2 patients. Conclusion: This menopause. Some studies have shown that hormone therapy increases collagen content, study demonstrates that the most common etiology for POF patients is still unknown. Of

64 this group, one third showed evidence of autoimmunity. One hypothesis is that the desvenlafaxine achieved similar reductions in HFs. However, among women treated with etiology could be autoimmune oophoritis on this subgroup. The second most common placebo, obese women had greater HF reduction compared with women with normal BMI etiology of POF is cancer therapy, with the combination of chemotherapy and radiation at week 12. as the treatment that most frequently produces POF. One third of patients presenting with primary amenorrhea are cancer survivors, thus studies focused on preserving ovarian function on young patients are needed. Most of the patients in our study are receiving P-95. hormonal therapy in the form of an oral contraceptive or hormone therapy, to minimize Development of a Multidisciplinary Comprehensive Women’s Midlife morbidities associated with long-term estrogen deprivation. Assessment Clinic Catherine J. Wheeler, MD, Angela Deneris, CNM, Ph.D., Shanna M. Salmon, BS. Ob/Gyn, University of Utah Health Sciences Center, Salt Lake City, UT P-93. Objective: To develop and evaluate satisfaction with a multidisciplinary, comprehensive Incidence of Low Bone Density in Patients Presenting to a Premature health assessment clinic for midlife women ages 40-65, and to provide in one setting: Ovarian Failure (POF) Clinic health education to promote wellness and early disease identification, age-appropriate Maria Velasco1,3, Taryn Becker2,3, Wendy L. Wolfman, MD, FRCSC1,3. 1Department of evidence-based screening, multidisciplinary evaluation and risk assessment, a Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, ON, Canada; 2Division of personalized health plan, and coordination of additional care. Design: According to the Endocrinology and Metabolism, Women,s College Hospital, Toronto, ON, Canada; Office on Women’s Health, Utah ranks 47th or below in key health indices pertinent to 3University of Toronto, Toronto, ON, Canada women, including Pap smear screening, cholesterol screening, mammograms, and routine Objective: Women with untreated POF may have increased morbidity, particularly from check-ups. A potential factor in accessing healthcare is inconvenience, and not having bone fractures and cardiac disease. For these reasons they are treated with estrogen enough time. In one response to this, the University of Utah and its Center of Excellence therapy, either with an oral contraceptive (OCP) or hormone therapy (HT). Currently, in Women’s Health (COE) developed a multidisciplinary comprehensive women’s midlife there is no consensus on which regimen is better. The objective of this study is to evaluate assessment clinic. A steering committee comprised of, primary care and specialty baseline bone mineral density (BMD) in patients presenting to a premature ovarian failure providers and representative administrators, identified current women’s health services at clinic. Other objective is to evaluate the relationship between type of estrogen therapy the University of Utah campus, learned about midlife women’s health programs at other and age. Design: This was a retrospective study of patients evaluated at a dedicated POF COE sites, and commissioned a survey of local women to measure an interest in a clinic at Mount Sinai Hospital, Toronto, Canada, from January 2008 to March 2011. After comprehensive wellness center and to identify the most important specialties and services establishing the need for estrogen replacement, patients are given the option of OCP or to include. The steering committee reviewed guidelines and literature to identify evidence- HT. A chart review was conducted to extract the following data: age at presentation, based recommendations for age-appropriate routine health screens in women. Consecutive etiology of POF, estrogen replacement therapy and BMD. Descriptive data is presented midlife women attending two gynecology clinics over a two week period were surveyed as median and standard deviation or percentage. BMD was measured using dual-energy about health issues of concern to them. A comprehensive questionnaire to assess health x-ray absorptiometry or DXA. BMD was considered to be low when the Z-score was -2.0 and risk behaviors was developed. The clinic model was developed to include: 1. Pre- or lower. Data was compared using Chi square tests for categorical variables and Mann- clinic preparation: Participants completed the questionnaire which was reviewed by clinic Whitney U test was used for continuous variables. Results: 179 women were seen at the staff. Based on responses, appropriate health screens were recommended, which, with POF clinic during the study period. 144 women included in the analysis, as the remainder the exception of colonoscopy and pap smear, were completed before the clinic visit. The did not have POF. Mean age was 27.7 (+/- 9.6) years. The etiology of POF was unknown clinic staff developed a visit plan for each participant based on each participant’s goal for in 74 patients (51%), secondary to therapy for cancer in 39 (27%), Turner syndrome in the clinic, her current health habits and conditions, risk factors, and abnormal results from 13 (9%), Fragile X Premutation in 4 (3%) and other etiologies in 14 patients (10%). Of the pre-clinical testing. 2. Three clinic components: shared education, individual the total group, 85% were receiving estrogen therapy, 47% in the form of an OCP and 38% assessment, and wellness coaching. Each clinic began with a two hour education session were receiving HT. The age of patients taking an OCP was significantly lower than the during which experts discussed memory, heart health, stress reduction, menopause, and age of patients taking HT (22.5 +/- 9.19 versus 29.3 +/- 8.19 years, p < 0.001). BMD was intimacy (issues identified by women as their top concerns). Next, each participant had a available for 78 patients at presentation (54%), with 28 (36%) presenting with low BMD. thorough health assessment from providers specializing in primary care, and gynecology, We did not find a difference between BMD and age of diagnosis (p=0.59). Conclusion: as well as full skin cancer screen by dermatology, and hearing assessment. Participants In this series, the majority of women with POF are receiving estrogen therapy, with consulted with a health coach regarding an area of their life they are working to improve. younger patients preferring OCPs and older patients choosing HT. More than one third 3. After the visit, participants received a complete summary of their visit, results of testing, have low BMD at presentation, suggesting either longstanding hypoestrogenemia or other and a personalized health plan, which was also forwarded to their primary providers for factors as etiologies for low bone density. Further studies are required to evaluate if there continuity of care. Additional recommended testing and/or referrals were also coordinated. is a longer-term impact of type of estrogen therapy (OCP vs. HT) and BMD. 5. About two weeks after the clinic, every participant was surveyed by phone. Immediately after the clinic, all providers were surveyed. This information was used to improve subsequent clinics. Results: Four Women’s Midlife Assessment Clinics were held P-94. between November 2009 and February 2011. There were 6 to 12 women in each clinic. Effect of Baseline Body Weight on the Efficacy of Desvenlafaxine for Commercial insurance reimbursed most of the cost of this care, with participants paying Vasomotor Symptoms Associated with Menopause copays and a small fee for the education component. Post clinic surveys revealed Michelle Warren1, Ru-fong J. Cheng2, Weihang Bao3, Michael J. Louie3, Christine J. participants were uniformly satisfied with their experience and the thoroughness of the Guico-Pabia, MD, MBA, MPH2. 1Columbia University Medical Center, New York, NY; clinic. Among the most valuable aspects were: seeing multiple providers in the same visit; 2Pfizer Inc, Collegeville, PA; 3Pfizer Inc, New York, NY time to address all concerns and questions; discussing results during the clinic; and the Objective: High body weight or body mass index (BMI) and weight gain are associated education. Conclusion: The development of this innovative multidisciplinary and with increased reporting of hot flushes (HFs) in the menopausal transition. Desvenlafaxine comprehensive clinic provides convenient, same-day access to a variety of healthcare (administered as desvenlafaxine succinate) at the 100-mg dose has demonstrated efficacy professionals, and information specific to women. Participants were highly satisfied with for the treatment of moderate to severe vasomotor symptoms associated with the model. menopause.The objective of this analysis was to examine effect of baseline body weight or BMI on the efficacy of desvenlafaxine 100 mg/d for treating moderate to severe HFs in pooled data from 4 double-blind, randomized, placebo-controlled trials. Design: Data P-96. from 4 similarly designed studies assessing the effect of desvenlafaxine on number and Capturing Undiagnosed Health Problems in a Multidisciplinary severity of HFs were pooled for this analysis. Postmenopausal women experiencing ≥7 Comprehensive Women’s Midlife Assessment Clinic: A Pilot Study moderate to severe HF/d (or ≥50/wk) and with BMI ≤40 kg/m2 (3 studies) or ≤34 kg/m2 Catherine J. Wheeler, MD, Angela Deneris, CNM, Ph.D., Shanna M. Salmon, BS. (fourth study) were randomly assigned to receive desvenlafaxine (50 mg/d to 200 mg/d) Ob/Gyn, University of Utah Health Sciences Center, Salt Lake City, UT or placebo in the 4 trials; all 4 trials included a desvenlafaxine 100-mg arm. Study Objective: To evaluate the health risks, symptoms, and behaviors in women who attended durations were 12 (1 study), 26 (1 study), or 52 weeks (2 studies). The percentages of four pilot Women’s Midlife Assessment Clinics held between November 2009 and women classified as normal (BMI<25 kg/m2), overweight (BMI 25 to <30 kg/m2), or February 2011 at the University of Utah. Design: As women age they tend to experience obese (BMI≥30 kg/m2) at baseline were determined. To assess the association between chronic health problems, but many do not adequately access healthcare. The University baseline weight or BMI and efficacy at weeks 4 and 12, analysis of covariance (ANCOVA) of Utah developed a comprehensive multidisciplinary Women’s Midlife Assessment was used with change in number and severity of HFs as the dependent variables. Clinic, including education, assessments by primary care, gynecology, dermatology, Independent variables included treatment, study, and baseline weight or weight category audiology, and consultation with a health coach. The model included pre-clinic (normal, overweight, or obese). Treatment by weight interaction was examined in the preparation. Participants completed a comprehensive questionnaire and evidence-based same model by adding the interaction term. Results: A total of 661 women treated with testing in advance, and the assessment team developed a visit plan. Four pilot clinics were desvenlafaxine 100 mg/d and 588 with placebo were included in the analysis. Mean held from November 2009 to February 2011, with 6 to 12 women attending each consult weight at baseline was 72 kg for each group; 37.6% of participants were overweight at clinic. During quality assurance reviews, several trends were noted, highlighting baseline and 26.6% were obese. Regardless of baseline weight, women on desvenlafaxine opportunities for early identification of illness and symptoms, which may improve with 100 mg/d had a larger reduction in number of HFs than women on placebo (P<0.001). The intervention. Results: A total of 34 women participated in the clinics. Most participants treatment effect was more apparent in non-obese women. The treatment by baseline were employees at the University of Utah, all from an urban setting, 31 were Caucasian, weight and treatment by weight category interactions were significant at week 12 (P= and 3 were of Asian descent. The mean age of these women was 52 years; all were high 0.033, and 0.021). The reduction from baseline in number of moderate and severe HFs was school graduates with 19 women having post graduate degrees. All of the women had similar for desvenlafaxine-treated women of different weight categories, but heavier medical insurance. Fifteen women were pre-menopausal and nineteen were post- women appeared to have a larger response to placebo (Figure). A similar pattern of results menopausal. Most of these women (29) had a primary care or gynecology provider, and was observed for HF severity. Conclusion: Normal and obese women treated with 26 of them had been seen by their providers within the last 2 years; 27 had never had an

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Clinical Poster Presentations (continued)

audiology exam (79%), and 13 had never had a dermatology evaluation (38%), Problems and total plasma antioxidant status [TAS] using Randox Laboratories, Ltd kits; ED was identified included risk factors for heart disease, and under-treatment for depression or determined using Zung’s depression scale. The tests were carried out at the beginning anxiety. More than half of the women (53%) had past or current risk factors for heart and at 6 months of treatment. An alternative cut-off value of LPO ≥0.320 μmol/L was disease including: hypertension, abnormal lipids, or diabetes mellitus. Fourteen of the defined on the basis of the 90th percentile of young healthy subjects. Results: women (41%) had a body mass index (BMI) of 30 or above, and 13 (38%) had waist Lipoperoxides levels were significantly higher in HT and P groups than PRE women (HT circumference (WC) of greater than 35, also risk factors for heart disease. Of the 34 0.348±0.05 and P 0.358±0.05 vs. 0.310±0.03 μmol/L, p<0.001) and antioxidant markers women, 29 (85%) had a family history of heart disease, including hypertension, abnormal were low in POS. LPO levels decreased after 6 months in HT group (0.309±0.07 μmol/L, lipids, diabetes, heart attack, heart failure, and sudden death. Excluding BMI and WC as p<0.05); GPx increased (71.2±18 U/gHb, p<0.01); in PRE and P groups were similar to risk factors, 33 of the 34 women (97%) had a personal and/or family history risk for heart basal. We found 9 (28%) women in PRE, 10 (31%) in HT and 9 (24%) in P, with ED in disease. Twenty-one of the women carried a diagnosis of depression (62%), with 10 of basal time, and the POS women with ED had high LPO levels. After 6 mo. decreased them currently on medication; yet 13 of these women (62% of those being treated) women with distress in HT group (6 [18%], p<0.05), and LPO also diminished in this indicated current symptoms of depression, consistent with inadequate treatment. Seven group (Figure). Conclusion: Our findings suggest that HT decreases OS and emotional women (21%) did not carry a diagnosis of depression, but had symptoms diagnostic for distress in posmenopausal women. This work was supported by grant DGAPA-UNAM depression. Despite 76% of participants having had preventive care within 2 years, a new IN302809 and sponsored by Laboratorios Senosiain SA de CV. Trial registration: diagnosis was identified in 25 of the 34 participants (73%). Previously undiagnosed health COF000120. problems identified in the clinic included: melanoma (1), cardiomegaly (1), breast mass (1), cervical polyp (2), osteopenia (4), abnormal lipids (9), pre-diabetes with a fasting glucose >110 (1), heart murmur (2),eczema (1), abnormal TSH (2),vitamin D deficiency (7), vitamin D insufficiency (6). Conclusion: Although the 34 women who participated in the pilot clinics were educated, insured, and 3/4 had received preventive services within 2 years, the clinic identified a significant number of health problems that needed to be addressed. Possible explanations include: 1. Completion of a thorough questionnaire prior to the clinic; 2. Testing performed prior to the clinic; 3. Pre-clinic visit planning, including identifying positive health and habits, identifying risks for intervention, positive review of systems for evaluation, and abnormal results; 4. Adequate time with providers to allow for thorough assessments and to review risk factors and symptoms; 5. Participants also prepared for the visit in advance, which allowed them to be clear on what they wanted to accomplish at the clinic, their goals, and their concerns. This unique health care model has the potential to improve health care for women in midlife by allowing early diagnosis of disease, improvement of symptoms, wellness and prevention counseling, education, improved lifestyle, and early intervention.

P-97. The Impact of Severity of VMS on Health Status, Resource Use and Productivity Jennifer Whiteley, Ed.D, MSc., M.A.1, Jan-Samuel Wagner2, Andrew Bushmakin1, Lewis Kopenhafer2, Jill Racketa1. 1Health Economics, Pfizer Inc, New York, NY; 2Kantar Health, Figure. Lipoperoxides levels in premenopausal, and postmenopausal women with New York, NY hormone therapy or placebo, with and without ED, basal and after 6 months. Objective: The current study characterizes health-related quality of life (HRQoL), work *Repeated measures ANOVA, p<0.001). productivity, and resource use among post-menopausal women by severity of vasomotor (VMS) symptoms. Design: Participants were selected from the 2010 US National Health and Wellness Survey which is a cross-sectional, internet-based survey representative of the P-99. adult US population. Women age 40-75 years, who did not report a history of menstrual Results from the 2010 Insomnia Related to Menopause Survey bleeding or spotting for one year, were considered post-menopausal and eligible for Jacqueline Zummo, MS, MPH, MBA, Todd Grinnell, William Spalding, Randall analysis (N=3,267). Cohorts of women with no (n=1740), mild (n=931), moderate Marshall. CRMA, Sunovion Pharmaceuticals, Inc., Marlborough, MA (n=462), and severe (n=134) vasomotor symptoms (VMS) were compared, controlling Objective: Research suggests that 40-50% of women report difficulty sleeping during for demographic and health characteristics. Outcomes measures included health status menopausal transition.1,2 A survey in women 40-65 years of age evaluated trouble (EQ-5D), work productivity (WPAI) within the past 7-days, and healthcare resource use sleeping/insomnia during the transition. Design: Manhattan Research administered an within the past 6-months and were assessed using linear models Results: The mean age online, 27-question, multiple-choice survey between 7/16/10-7/22/10 to women ages 40- (SD) for women experiencing severe VMS was 57.92 years (7.84), 58.76 (7.64) for 65. Eligible respondents self-identified as peri-menopausal or post-menopausal, and moderate VMS, 60.47 (7.35) for mild VMS, and 64.46 (7.12) for women not experiencing reported “trouble sleeping/insomnia” during menopause (N=927). The questionnaire VMS. After controlling for demographic and health characteristics, women experiencing assessed the impact of sleep disturbances on quality of life (QoL), daily function, severe and moderate VMS reported significantly lower mean health status scores interactions with healthcare professionals (HCPs), and experience with insomnia compared to women with no symptoms (severe=0.77, moderate=0.82, mild=0.85, treatments. Results: The most common complaints were trouble staying asleep (79%), none=0.86; p<.0001). In addition, the mean number of menopause symptom-related tiredness/fatigue during the day (67%), and trouble falling asleep (63%). 75% reported physician visits was significantly greater among women with severe, moderate or mild insomnia during menopause having moderate-high impact on QoL and daily function and symptoms compared to women with no symptoms (severe=2.73, moderate=2.37, 56% reported a negative impact on relationships. More than half (53%) had seen their mild=1.63, none=0.724; p<.0001). Among employed women experiencing VMS, women HCP within the last 6 months, only 38% of whom discussed difficulty sleeping/insomnia. with severe and moderate symptoms had adjusted presenteeism (percent impairment while This discussion was rarely initiated by the HCP (8%). About 1/3 (31%) of respondents had working due to a problem) of 24.28% and 14.3% compared to 4.33% in women with mild been prescribed a sleep-aid, and 77% felt it was helpful. At the time of the survey, 55% symptoms (p<.001), and activities of daily living impairment of 31.66% and 17.06% of respondents prescribed a sleep-aid were still taking one, and most (93%) planned to compared to 6.16% for women with mild symptoms (p<.0001). Conclusion: Among continue treatment. Conclusion: In the eligible population, sleep disturbances during post-menopausal women, those reporting greater severity of VMS symptoms was menopause impacted daily function, relationships, and quality of life, with trouble staying significantly associated with lower levels of health status and work productivity, and asleep identified as the most common sleep problem. Less than half of sufferers discussed greater healthcare resource utilization. sleep issues with their HCP, and almost entirely at their own initiative. Insomnia during menopausal transition may be frequently under-recognized and undertreated by HCPs. References: 1. Shaver J.L. Women and sleep. Nurs Clin North Am. 2002;37:707-718. 2. P-98. Soares, C.N. Insomnia in women: an overlooked epidemic? Arch Women Ment Health. Antioxidant effect of hormone therapy on oxidative stress and emotional 2005; 8: 205-213. distress in posmenopausal women Mariano Zacarias-Flores, MD ObGyn1, Martha Sánchez-Rodríguez, PhD2, Alicia Arronte- Rosales, M Sc2, Víctor Manuel Mendoza-Núñez, PhD2. 1Hospital Gustavo Baz Prada, Instituto de Salud del Estado de México, Nezahualcoyotl, Edo. México, Mexico; 2Facultad de Estudios Superiores Zaragoza, Unidad de Investigación en Gerontología, UNAM, México, DF, Mexico Objective: To determine the effect of hormone therapy (HT) on oxidative stress (OS) and emotional distress (ED) in postmenopausal women (POS). Design: A randomized, double blind controlled trial was carried out in 100 women: 1) control, 33 premenopausal [PRE] (46±3.7 years, estradiol (E2) 102.0±67 pg/mL, FSH 10±7 pg/mL); 2) HT (0.625 mg/d of synthetic conjugated estrogens [Sixdin®] plus 5 mg/10d of medroxiprogesterone [MPA]), 33 POS (52±3 years, E2 20±4 pg/mL, FSH 55±21 pg/mL); 3) placebo [P], 34 POS (53±3 years, E2 21±3 pg/mL, FSH 53±22 pg/mL). We measured lipoperoxides [LPO] by TBARS assay, erythrocyte superoxide dismutase [SOD], glutathione peroxidase [GPx]

66 Disclosure Statement

The North American Menopause Society (NAMS) is a provider Following the review of disclosure forms, the Society may find of continuing medical education (CME) accredited by the that a faculty member has a conflict of interest. This does not Accreditation Council for Continuing Medical Education necessarily mean that he/she is automatically excluded from (ACCME) and is committed to: participating in the activity . Rather, depending on the nature of the conflict, NAMS will undertake every effort to resolve • Ensuring balance, independence, and objectivity in all of any conflict, including but not limited to communicating its educational programs; requiring that advantages and obligations and restrictions to the participant, altering his/her disadvantages of specific therapies be presented and role within the activity, reviewing his/her content for possible that activities are free of commercial bias for or against revision, or monitoring his/her participation. Resolving any product; and implementing safeguards against bias conflicts of interest may include identifying an alternate when the content is relevant to the commercial interest faculty member, assigning a different topic, or having an • Aligning the content of educational activities with the effective peer review of the content of the activity so that any interests of learners substantial promotional content can be eliminated . • Ensuring that commercial supporters of any activities NAMS has included disclosure information as submitted by have no control over the planning, content, or execution participants, members of the Scientific Program Committee, of the activity and the Society’s Board of Trustees . • Signing written agreements documenting the terms of any commercial support • Limiting any faculty honoraria to reasonable and customary levels plus reimbursement of out-of-pocket expenses • Requiring disclosure forms from those being considered as faculty and resolving any conflicts of interest prior to the activity • Disclosing the sources of commercial support to learners prior to the activity

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67 Key to Disclosures

1 Abbott 46 Lundbeck 2 Agile 47 Lupin 3 Allergan 48 Medical Diagnostic Laboratories 4 American Institute of Ultrasound in Medicine 49 Meditrina 5 Amgen 50 Menopause 6 Archives of Women’s Mental Health 51 Merck 7 Arkochim 52 Merrion 8 Arkopharma 53 NAMS 9 Ascend 54 National Alliance for Research on Schizophrenia and Depression 10 Astellas 55 National Institute of Mental Health 11 Astra Zeneca 56 National Institute on Aging 12 Azur 57 National Institutes of Health 13 Bayer 58 NDA Partners 14 Bionovo Inc . 59 New England Research Institutes 15 BioSante Pharmaceuticals, Inc . 60 Novartis Pharmaceuticals Corporation 16 Boehringer-Ingelheim Pharmaceuticals 61 Noven 17 Canadian Institute of Health Research 62 Novogyne 18 Chemo 63 Novo Nordisk 19 Cleveland Clinic Foundation Innovations Center 64 NYU School of Medicine Alumni Corporation 20 Climacteric 65 OBG Management 21 Columbus Center for Women’s Health Research 66 Own The Bone Advisory Board 22 Cook Ob/Gyn 67 Pfizer, Inc 23 Corcept 68 Pharmavite Inc . 24 Daiichi-Sankyo 69 Philips Ultrasound 25 Depomed Inc . 70 Physicians Service Incorporated 26 Duramed/Barr 71 Procter & Gamble 27 EDP Technologies 72 QuatRx 28 Eli Lilly and Company 73 Roche 29 Endoceutics 74 Rowpar 30 Enzymatic Therapies 75 sanofi-aventis 31 Fabre-Kramer 76 Schaper & Brummer GmbH & Co . KG 32 Faith Care, Inc . 77 Se-cure Pharmaceuticals 33 Ferring 78 Semprea Labs 34 Forest Laboratories 79 Servier 35 Foundation for Osteoporosis Research & Education 80 Shionogi 36 Genentech 81 Solvay 37 Gilead 82 SonoSite, Inc . 38 GlaxoSmithKline 83 Sunovion Pharmaceuticals, Inc . 39 Hamilton Community Foundation 84 Teva Women’s Health 40 Healthywomen .org 85 University of Virginia 41 Hormone Foundation of The Endocrine Society 86 Upsher-Smith Laboratories 42 Hygeia/Orcas Therapeutics 87 Warner Chilcott 43 Journal of Women’s Health 88 Watson 44 Johnson & Johnson 89 Wyeth 45 KV Pharma 90 Yoplait

68 Disclosures

Board of Consultant/ Grants/ Directors/ Advisory Stock/ Research Speaker's Royalties/ Editorial Name Trustees Employment Board Shareholder Support Bureau Patents Board Other Abraham, L • 67 • • • • • • • Al Omari, W • • • • • • • • • Aldrighi, J • • • • • • • • • Appt, S • • • • • • • • • Archer, D • • 1, 2, 13, 18, 23, 51, • 1, 13, 26, 67, 2, 13, 67 • • 2 67, 87, 88 87, 88 Arias, R • • 13, 63, 67, 84 • • • • • • Avis, N • • • • • • • • • Bachmann, G • • 10, 16, 26, 44, • 13, 16, 26, 29, • • • • 51, 60, 63, 67, 71, 81 33, 44, 51, 60, 63, 67, 72, 84 Benson, H • • • • • • • • • Bohuslav, J • • • • • • • • • Broekmans, F • • 51 • • • • • • Brown, J • • • • • • • • • Caico, C • • • • • • • • • Carpenter, J • • • • • • • • • Choi, H • • • • • • • • • Christianson, M • • • • • • • • • Crandall, C • • • • • • • • • Cray, L • • • • • • • • • Dasen, S • 84 • • • • • • • Davis, S • • 15, 87 • 15 • • • • Del Pup, L • • • • • • • • • Doyle, C • • • • • • • • • Drogos, L • • • • • • • • • Duke, C • • • • • • • • • Elavsky, S • • • • • • • • • Ensrud, K • • • • • • • • • Fisher, W • • • • • • • • • Freedman, M • • 84 • • 12, 62, 84 • • • Freedman, R • • • • • • • • • Freeman, E • • • • • • • • • Gass, M • • • • • • • • • Gerber, L • • • • • • • • • Gibson, C • • • • • • • • • Goldstein, S 4, 64, 82 • 5, 13, 22, 63, 67, • • 5, 63, 87 • • • 69, 80 Gonzalez-Izquierdo, M • • • • • • • • • Gowri, V • • • • • • • • • Gulati, M • • • • • • • • •

69 Disclosures (continued)

Board of Consultant/ Grants/ Directors/ Advisory Stock/ Research Speaker's Royalties/ Editorial Name Trustees Employment Board Shareholder Support Bureau Patents Board Other Harlow, S • • • • • • • • • Harris, S • • 5, 28, 37, 51, 73 • • 5, 28, 36, 37, • • • 60, 73, 75, 87 Heisler, C • • • • • • • • • Helmrich, G • • • • • • • • • Jamadar, R • • • • • • • • • Jenkins, M • • • • • • • • • Jiang, X • • • • • • • • • Joffe, H • • 83 • 13, 34, 38, 55, • • • • 56, 57 Jorgensen, M • • • • • • • • • Kagan, R • • 5, 14, 25, 35, 51, 63, • 14, 15, 16, 5, 62, 63 • • • 66, 67, 80 25, 67 Kahler, K • 60 • 60 • • • • • Karim, R • • • • • • • • • Kaunitz, A • • 13, 51, 84 • 2, 13, 29, 48, • • • • 61, 84 Kearns, A • • • • • • • • • Khan, S • • • • • • • • • Kim, JH • • • • • • • • • Kim, T • • • • • • • • • Klein, W • • • • • • • • • Krychman, M 27 • 67, 78 • • 87 • • • Ku, SY • • • • • • • • • LaCroix, A • • • • • • • • • Laughlin, G • • • • • • • • • Lee, JY • • • • • • • • • Lima, SM • • • • • • • • • Lindsay, R • • 5, 28 • 28 5, 28, 60, 87 • • • Lombardi, A • 51 • • • • • • • Looby, S • • • • • • • • • Maamari, R • 63 • • • • • • • Maki, P • • • • • • • • • Marsh, W • • • • • • • • • Meagher, E • • • • • • • • • Megibow, A • • • • • • • • • Mills, K • • • • • • • • • Minkin, MJ • • 13, 30, 62, 63, 67 • • • • • • Monterrosa-Castro, A • • • • • • • • • Moral, L • • • • • • • • • Morrow, M • • • • • • • • •

70 Board of Consultant/ Grants/ Directors/ Advisory Stock/ Research Speaker's Royalties/ Editorial Name Trustees Employment Board Shareholder Support Bureau Patents Board Other Mosca, L • • 74, 75 • • 37 • • • Murray, T • • • • • • • • • Nachtigall, L • • 63, 77 • 77 12, 62, 86 • • • Nahas, E • • • • • • • • • Naser, B • 76 • • • • • • • Newton, K • • • • • • • • • Nichols, A * 67 • • • • • • • Ogando, B • • • • • • • • • Ojo, F • • • • • • • • • Pace, D • • 63 • • 63 • • • Padua, M • • • • • • • • • Pal, L • • • • • • • • • Palacios, S • • 5, 8, 13, 79 • 5, 7, 13, 67, 79 • • • • Parry, B • • • • • • • • • Pearlstein, T • • • • 67 • • • • Pettit, S • • • • • • • • • Pinkerton, J 16, 40 85 5, 16, 25, 63, 67, 84 • 25, 29, 67 • • 20, 43, 50, 65 • Portman, D • 21 13, 25, 29, 61, 67, • 13, 29, 67, 72, 84 67, 84 • • • 72, 80, 84 Prairie, B • • • • • • • • • Randolph, J • • • • • • • • • Reame, N • • • • • • • • • Reed, S • • • • • • • • • Reichman, W • • • • • • • • • Rocha, J • • • • • • • • • Rouen, P • • • • • • • • • Sang, JH • • • • • • • • • Sathyanarayana, R • 25 • • • • • • • Schiff, I • • • • • • • • • Schnatz, P 32, 53 • • • • • • • • Shah, S • 67 • • • • • • • Shapiro, M • • 13, 30, 62, 63, 67 • • • • • • Shifren, J • • 59 • 16 • • • • Sievert, L • • • • • • • • • Simon, J • • 1, 2, 5, 9, 12, 16, • 15, 16, 29, 62, 5, 9, 13, 16, • • • 25, 31, 49, 51, 52, 63, 84 45, 51, 60, 62, 58, 62, 63, 67, 80, 63, 84, 87 84, 87, 88 Siyam, T • • • • • • • • • Snabes, M • 15 • • • • • • •

71 Disclosures (continued)

Board of Consultant/ Grants/ Directors/ Advisory Stock/ Research Speaker's Royalties/ Editorial Name Trustees Employment Board Shareholder Support Bureau Patents Board Other Soares, C • • 11, 13, 28, 46, • 3, 11, 17, 28, 11, 13, 28, • 6, 43, 50 • 67, 89 39, 54, 67, 70 46, 67, 89 Soares, J • • • • • • • • • Speck, P • • • • • • • • • Stojanovska, L • • • • • • • • • Streicher, L • • • • • • • • • Stuenkel, C • • 41 • • • • • • Sulak, P • • • • • • • • • Tagliaferri, M • 14 14 14 • • • • • Teixeira de • • • • • • • • • Araujo Moraes, S Teixeira Gomes, R • • • • • • • • • Terauchi, M • • • • • • • • • Thurston, R • • • • • • • • • Tilly, J • • • • • • • • • Tough, K • • • • • • • • • Uchiyama, S • • • • • • • • • Ueno, T • • • • • • • • • Utian, W • • 13, 14, 19, 42, 47, • • • • • • 51, 62, 68 Velasco, M • • • • • • • • • Verna, C • • • • • • • • • Warren, M • • 67, 72, 90 • 33, 67 5, 86, 87 • • • Weber, M • • • • • • • • • Wheeler, C • • • • • • • • • Whiteley, J • 67 • • • • • • • Zacarias-Flores, M • • • • • • • • • Zummo, J • 83 • • • • • • •

72 Invited Speakers’ Recommended Reading

NOTE: References have been included as submitted by Murray A. Freedman, MS, MD speakers and have not been edited. Freedman MA, Nolan TE . Genital Atrophy: An Inevitable Consequence of Estrogen Deficiency . Female Patient 1996;21:62-66 . Raquel D. Arias, MD Freedman MA . Sexuality and the Menopausal Woman . Contem Obstet Gynecol Labrie F, Archer D, Bouchard C, et al . Intravaginal dehydroepiandrosterone 2000;45(suppl):4-18 . (Prasterone), a physiological and highly efficient treatment of vaginal atrophy. Menopause 2009;16:907-922 . Freedman MA . Vaginal pH, Estrogen and Genital Atrophy . Menopause Manage 2008;17:9-13 . Shulman LP . Selective estrogen receptor modulators and vulvovaginal atrophy: can we improve the lives of our patients with new therapeutic Sturdee DW, Panay N . On behalf of the International Menopause Society options? Menopause 2010;17:452-453 . Writing Group . Recommendations for the Management of Postmenopausal Vaginal Atrophy . Climacteric 2010;13:509-522 . Chollet JA, Carter G, Meyn LA, Mermelstein F, Balk JL. Efficacy and safety of vaginal estriol and progesterone in postmenopausal women with atrophic Pinkerton JV . Vaginal Impact of Menopause-related Estrogen Deficiency . OBG vaginitis . Menopause 2009;16:978-983 . Manage 2010;11(suppl):S2-7 . Lee YK, Chung HH, Kim JW, Park NH, Song YS, Kang SB . Vaginal pH-balanced Goldstein I . Recognizing and Treating Urogenital Atrophy in Postmenopausal gel for the control of atrophic vaginitis among breast cancer survivors: a women . J Women’s Health 2010;19(3):425-432 . randomized controlled trial . Obstet Gynecol 2011;117:922-927 . Steven R. Goldstein, MD, FACOG, CCD, NCMP Herbert Benson, MD Goldstein SR . The endometrial echo revisited: have we created a monster? Am Kagan L, Kessel B, Benson H . Mind over menopause . New York: Free Press, 2004 . J Obstet Gynecol . 2004;191:1092-6 . Benson H, Proctor W . Relaxation Revolution . New York: Scribner, 2010 . Levine D, Brown DL, Andreotti RF, Benacerraf B, Benson CB, Brewster WR, Coleman B, DePriest P, Doubilet PM, Goldstein SR, Hamper UM, Hecht JL, Samuelson M, Foret M, Baim M, Lerner J, Fricchione GL, Benson H, Horrow M, Hur HC, Marnach M, Patel MD, Platt LD, Puscheck E, Smith- Dusek J, Yeung A . Exploring the effectiveness of a comprehensive mind body Bindman R . Management of asymptomatic ovarian and other adnexal cysts intervention for medical symptom relief . J Altern Complement Med, 2010: imaged at US Society of Radiology in Ultrasound consensus conference 16(2):1-6 . statement . Ultrasound Q 2010;26:121-31 . Dreisler E, Stampe Sorensen S, Ibsen PH, Lose G . Prevalence of endometrial Susan R. Davis, MBBS, FRACP, PhD polyps and abnormal uterine bleeding in a Danish population aged 20-74 Davison SL, Bell R, Donath S, Montalto JG, Davis SR . 2005, Androgen levels years . Ultrasound Obstet Gynecol . 2009;33:102-8 . in adult females: changes with age, menopause, and oophorectomy . J Clin Ferrazzi E, Zupi E, Leone FP, Savelli L, Omodei U, Moscarini M, Barbieri M, Endocrinol Metab, 90:3847-3853 Cammareri G, Capobianco G, Cicinelli E, Coccia ME, Donarini G, Fiore S, Litta P, Davis SR, Papalia MA, Norman RJ, O’Neill S, Redelman M, Williamson M, Sideri M, Solima E, Spazzini D, Testa AC, Vignali M . How often are endometrial Stuckey BGA, Wlodarczyk J, Gard’ner K, Humberstone A . 2008, Safety and polyps malignant in asymptomatic postmenopausal women? A multicenter Efficacy of a Testosterone Metered-Dose Transdermal Spray for treatment study . Am J Obstet Gynecol . 2009;200:235 . of decreased sexual satisfaction in Premenopausal Women: A Placebo-Controlled Randomized, Dose-Ranging Study . Annals Internal Med, Martha Gulati, MD, MS, FACC, FAHA 148:569-577 . Gulati M, Cooper-DeHoff RM, McClure C, et al . Adverse cardiovascular Davis SR, Goldstat R, Papalia MA, Shah SM, Kulkarni J, Donath S, Bell R . outcomes in women with nonobstructive coronary artery disease: a report 2006, Effects of aromatase inhibition on sexual function and wellbeing in from the Women’s Ischemia Syndrome Evaluation Study and the St James postmenopausal women treated with testosterone: a randomized placebo Women Take Heart Project . Arch Intern Med 2009;169:843-50 . controlled trial . Menopause, New York, NY 13:37-45 . Bugiardini R, Bairey Merz CN. Angina with “normal” coronary arteries: a Davis SR, Moreau M, Kroll R, Bouchard C, Panay N, Gass M, Braunstein GD, changing philosophy . JAMA 2005;293:477-84 . Linden-Hirschberg A, Rodenberg C, Pack S, Koch H, Moufarage A, Studd J . 2008, Testosterone for Low Libido in Menopausal Women Not Taking Estrogen Shaw LJ, Bugiardini R, Merz CN . Women and ischemic heart disease: evolving Therapy . N Eng J Med, 359:2005-2017 knowledge . Journal of the American College of Cardiology 2009;54:1561-75 . Danforth KN, Eliassen AH, Tworoger SS, Missmer SA, Barbieri RL, Rosner BA, Mosca L, Benjamin EJ, Berra K, et al . Effectiveness-based guidelines for the Colditz GA, Hankinson SE . 2010, The association of plasma androgen levels prevention of cardiovascular disease in women--2011 update: a guideline with breast, ovarian and endometrial cancer risk factors among from the american heart association . Circulation 2011;123:1243-62 . postmenopausal women . International Journal of Cancer, 126:199-207

73 Invited Speakers’ Recommended Reading (continued)

Steven T. Harris, MD, FACP Ann E. Kearns, MD, PhD Tannenbaum C, Clark J, Schwartzman K, et al . Yield of laboratory testing to Khan QJ, O’Dea AP, Sharma P . Musculoskeletal adverse events associated with identify secondary contributors to osteoporosis in otherwise healthy women . adjuvant aromatase inhibitors . J Oncol 2010;2010 . pii: 654348 . Epub 2010 J Clin Endocrinol Metab . 2002;87:4431-7 . Aug 24 . Watts NB, Bilezikian JP, Camacho PM, et al . American Association of Clinical Loibl S, Lintermans A, Dieudonné AS, Neven P . Management of menopausal Endocrinologists medical guidelines for clinical practice for the diagnosis symptoms in breast cancer patients . Maturitas 2011;68:148-154 . and treatment of postmenopausal osteoporosis . Endocr Pract 2010;16(Suppl 3):1-37 . Markopoulos C, Tzoracoleftherakis E, Polychronis A, et al . Management of anastrozole-induced bone loss in breast cancer patients with oral risedronate: Ross AC, Manson JE, Abrams SA, et al . The 2011 report on Dietary Reference results from the ARBI prospective clinical trial . Breast Cancer Res 2010;12:R24 . Intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know . J Clin Endocrinol Metab 2011;96:53-8 . Van Poznak C, Hannon RA, Mackey JR, et al . Prevention of aromatase inhibitor-induced bone loss using risedronate: the SABRE trial . J Clin Oncol 2010;28:967-975 . Candace J. Heisler, JD Patricia M. Speck, DNSc, APN, FNP-BC, DF-IAFN, FAAFS, FAAN Din OS, Dodwell D, Wakefield RJ, Coleman RE . Aromatase inhibitor-induced arthralgia in early breast cancer: what do we know and how can we find out Bonnie RJ, Wallace RB (Eds .) 2003 . Panel to Review Risk and Prevalence of more? Breast Cancer Res Treat 2010;120:525-538 . Elder Abuse and Neglect . Committee on National Statistics and Committee on Law and Justice, Division of Behavioral and Social Sciences and Education National Research Council . Elder mistreatment: Abuse, neglect, and exploitation Gail A. Laughlin, PhD in an aging America . Washington, DC: National Academies Press . Laughlin GA, Barrett-Connor E, Kritz-Silverstein D, von Muhlen D . Brandl B, Dyer CB, Heisler CJ, Otto JM, Stiegel LA, Thomas RW . 2007 . Elder Hysterectomy, oophorectomy, and endogenous sex hormone levels in older abuse detection and intervention: A collabora¬tive approach . New York: women: The Rancho Bernardo Study . J Clin Endocrinol Metab 2000;85:645-651 . Springer . Laughlin GA, Barrett-Connor E. Sexual dimorphism in the influence of Dong X . 2005 . Medical implications of elder abuse and neglect, Gorbien MJ, advanced aging on adrenal hormone levels: The Rancho Bernardo Study . J Ed . Clinics in geriatric medicine, 21(2), 293–313 . Clin Endocrinol Metab 2000;85:3561-3568 . Dyer CB, Connolly MT, McFeeley P . 2003 . The clinical and medical forensics of Laughlin GA, Barrett-Connor E, May S . Sex-specific association of the elder abuse and neglect . In Bonnie RJ & Wallace RB (Eds .) Elder mistreatment: androgen to estrogen ratio with adipocytokine levels in older adults: The Abuse neglect and exploitation in an aging America, pp . 339 . Rancho Bernardo Study . Clin Endocrinol (Oxf) . 65(4):506-13, 2006 . Mosqueda L, Burnight K, Liao S . 2005 . The life cycle of bruises in older Laughlin GA, Barrett-Connor E, Bergstrom J . Low serum testosterone and adults/ Journal of the American Geriatrics Society, 53, 1339–1343 . mortality in older men . J Clin Endocrinol Metab, 2008;93:68-75 . Ramsey-Klawsnik H, Teaster P, Mendiondo M, Marcum J, Abner E . 2008 . Sexual Laughlin GA, Goodell V, Barrett-Connor E . Extremes of endogenous predators who target elders: Findings from the first national study of sexual testosterone are associated with increased risk of incident coronary events abuse in care facilities . Journal of Elder Abuse & Neglect, 20(4), 353–376 . in older women . J Clin Endocrinol Metab 2010;95:740-747 .

Hadine Joffe, MD, MSc Emma A. Meagher, MD Joffe H, Petrillo L, Koukopoulos A, Viguera AC, Hirschberg A, Nonacs R, Somley Mosca L, Benjamin EJ, Berra K, et al . Effectiveness-based guidelines for the B, Pasciullo E, White DP, Hall JE, Cohen LS . Increased estradiol and improved prevention of cardiovascular disease in women—2011 Update: a guideline sleep, but not hot flashes, predict enhanced mood during the menopausal from the American Heart Association . Circulation 2011;123:1243-1262 . transition . J Clin Endo Metab 2011 Jul;96(7):E1044-54 . Baigent C, Keech A, Kearney PM, et al, for the Cholesterol Treatment Trialists’ Joffe H, Partridge A, Giobbie-Hurder A, Li X, Habin K, Goss P, Winer E, Garber (CTT) Collaborators. Efficacy and safety of cholesterol-lowering treatment: J . Augmentation of venlafaxine and SSRI’s with zolpidem improves sleep prospective meta-analysis of data from 90,056 participants in 14 randomised and quality-of-life in breast cancer patients with hot flashes: a randomized trials of statins . Lancet 2005;366:1267-1278 . double-blind placebo-controlled trial . Menopause 2010;17(5):908-16 . Kearney PM, Blackwell L, Collins R, Keech A, Simes J, Baigent C, for the Joffe H, Petrillo L, Viguera A, Koukopoulos A, Silver-Heilman K, Farrell A, Yu G, Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy of Silver M, Cohen LS . Eszopiclone improves insomnia, depressive and anxious cholesterol-lowering therapy in 18,686 people with diabetes in 14 symptoms in perimenopausal and postmenopausal women with hot flashes: randomised trials of statins: a meta-analysis . Lancet, 2008;371:117-125 . a randomized, double-blinded, placebo-controlled cross-over trial . Am J Ridker PM, Danielson E, Fonseca FA, et al . Rosuvastatin to prevent vascular Obstet Gynecol 2010;202(2):171 .e1 .e11 . events in men and women with elevated C-reactive protein . N Engl J Med Joffe H, Soares CN, Thurston RC, White DP, Cohen LS, Hall JE . Depression 2008;359:2195-2207 . is associated with worse objectively and subjectively measured sleep, Miller M, Stone NJ, Ballantyne C, et al . Triglycerides and cardiovascular but not more frequent awakenings, in women with VMS . Menopause disease: a scientific statement from the American Heart Association . 2009;16(4):671-9 . Circulation 2011;123:2292-2333 . Payne JL, Teitelbaum-Palmer J, Joffe H . A reproductive subtype of depression: conceptualizing models and moving towards etiology . Harv Rev Psychiatry 2009; 17(2):72-86 .

74 Alec J. Megibow, MD, MPH, FACH Lori J. Mosca, MD, MPH, PhD Berland LL, Silverman SG, Gore RM, et al . Managing incidental findings on American Heart Association . Heart Disease and Stroke Statistics – 2011 abdominal CT: white paper of the ACR incidental findings committee . J Am Update . Dallas, Texas: American Heart Association; 2011 . Coll Radiol 2010;7:754-773 . Mosca L, et al . Twelve-Year Follow up of American Women’s Awareness of Berland LL . The American College of Radiology strategy for managing Cardiovascular Disease (CVD) Risk and Barriers to Heart Health . Circ Cardiovasc incidental findings on abdominal computed tomography . Radiol Clin North Qual Outcomes 2010;3:120127 . Am 2010;49:237-243 . Mosca L, et al . Effectiveness-Based Guidelines for the Prevention of Berlin L . The incidentaloma: a medicolegal dilemma . Radiol Clin North Am Cardiovascular Disease in Women -- 2011 Update: A Guideline From the 2011;49:245-255 . American Heart Association . Circulation, 2011;123(11):1243-62 Megibow AJ . Preface imaging of incidentalomas . Radiol Clin North Am Thomas H. Murray, PhD 2011;49:xi-xii . NIH-DOE Working Group on Ethical, Legal and Social Implications of Human Genome Research . Genetic Information and Health Insurance Report of the Task Mary Jane Minkin, MD, FACOG, NCMP Force on Genetic Information and Insurance . Bethesda, MD: Department of Loprinzi CI, Wolf SL, Barton DI, Laack NN . Symptom management in Health and Human Services, 1993 . premenopausal patients with breast cancer . Lancet 2008; 9:993-1001 . Murray TH. Genetic exceptionalism and “future diaries”: Is genetic information Low Dog T . Menopause: a review of botanical dietary supplements . Am J Med different from other medical information? In Rothstein M, ed . Genetic Secrets . 2005;118 Suppl 12B:98-108 . New Haven: Yale University Press, 1997:71 . Nelson HD, Vesco KK, Haney E, et al . Nonhormonal therapies for menopausal Annas GJ, Glantz LH, Roche PA . Drafting the genetic privacy act: science, hot flashes: systematic review and meta-analysis. JAMA 2006;295:2057-2071 . policy, and practical considerations . J Law Med Ethics 1995;23:360-366 . Pritchard KI, Khan H, Levine M . Clinical practice guidelines for the care and Murray TH . Genetics and the moral mission of health insurance . Hastings Cent treatment of breast cancer: 14 . The role of hormone replacement therapy in Rep 1992;22:12-17 . women with a previous diagnosis of breast cancer . CMAJ 2002;166:1017-1022 . Sankar P . 2003 . Genetic Privacy . Annual Review of Medicine 54:393–407 . Walji R, Boon H, Guns E, Oneschuk D, Younus J . Black cohosh (Cimicifuga Green MJ, Botkin JR . Genetic exceptionalism in medicine: Clarifying the racemosa): safety and efficacy for cancer patients. Support Care Cancer differences between genetic and nongenetic tests . Ann Intern Med 2007;15:913-921 . 2003;138:571-575 .

Monica Morrow, MD, FACS Suter S . The allure and peril of genetics exceptionalism: Do we need special genetics legislation . Wash Univ Law Q 2001;79:669-748 . Morrow M . Magnetic resonance imaging for screening, diagnosis, eligibility for breast conserving surgery: promises and pitfalls . Surg Oncol Clinics Rothstein MA . Genetic exceptionalism and legislative pragmatism . J Law Med NA 2010;19:475-492 . Ethics . 2007;35:59-65 .

Houssani N, Ciatto S, Macaskill P, et al . Accuracy and surgical impact of magnetic Teri B. Pearlstein, MD resonance imaging in breast cancer staging: systemic review and meta-analysis in detection of multifocal and multi-centric cancer . J Clin Oncol Soares CN, Frey BN . Challenges and opportunities to manage depression 2008;26:3248-3258 . during the menopausal transition and beyond . Psychiatr Clin North Am 2010;33:295-308 . Turnbull L, Brown S, Harvey I, et al . Comparative effectiveness of MRI in breast cancer (COMICE) trial: a randomized controlled trial . Lancet 2010;375:563-571 . Clayton AH, Ninan PT . Depression or menopause? Presentation and management of major depressive disorder in perimenopausal and Warner E, Messersmith H, Causer P, et al . Systemic review: using magnetic postmenopausal women . Prim Care Companion J Clin Psychiatry resonance imaging to screen women at high risk for breast cancer . Ann Int Med 2010;12:PCC .08r00747 . 2008;148:671-679 . Parry BL . Optimal management of perimenopausal depression . Int J Womens Nichols HB, de Gonzalez AB, Lacey JV Jr . Declining incidence of Health 2010;2:143-151 . contralateral breast cancer in the United States from 1975 to 2006 . J Clin Oncol 2011;29:1564-1569 . Dupuy JM, Ostacher MJ, Huffman J, Perlis RH, Nierenberg AA . A critical review of pharmacotherapy for major depressive disorder . Int J Neuropsychopharmacol 2011 Feb 24:1-15 [Epub ahead of print] . Joffe H, Petrillo LF, Koukopoulos A, et al . Increased estradiol and improved sleep, but not hot flashes, predict enhanced mood during the menopausal transition . J Clin Endocrinol Metab 2011;96:E1044-1054 .

75 Invited Speakers’ Recommended Reading (continued)

William E. Reichman, MD Reichman WE, Fiocco AJ, Rose NS . Exercising the brain to avoid cognitive decline: examining the evidence . Aging Health 2010;6:565-584 . Jack CR, Jr, Albert MS, Knopman DS, et al . Introduction to the recommendations from the National Institute on Aging and the Alzheimer’s Association workgroup on diagnostic guidelines for Alzheimer’s disease . Alzheimers Dement 2011;7:257-262 . Valenzuela M, Sachdev P . Can cognitivie exercise prevent the onset of dementia? Systematic review of randomized clinical trials with longitudinal follow-up . Am J Geriatr Psychiatry 2009;17:179-187 . Sitzer DI, Twamley EW, Jest DV . Cognitive training in Alzheimer’s disease: a meta-analysis of the literature . Acta Psychiatr Scand 2006;114:75-90 . Verghese J, Lipton RB, Katz MJ, et al . Leisure activities and the risk of dementia in the elderly . N Engl J Med 2003;348:2508-2516 Not. submitted in time for

Patricia J. Sulak, MD AHA/ACCF 2009 performance measures for primary prevention of cardiovascular disease in adults: a report of the American College of Cardiology Foundation/American Heart Association task force on performance measures (writing committee to develop performance measures for primary prevention of cardiovascular disease): developed in collaboration with the American Academy of Family Physicians; American Association of Cardiovascular and Pulmonary Rehabilitation; and Preventive Cardiovascular Nurses Association: endorsed by the American College of Preventive Medicine, American College of Sports Medicine, and Society for Women’s Health Research . Circulation 2009;120:1296-1336 . Sofi F, Cesari F, Abbate R, Gensini GF, Casini A . Adherence to a Mediterranean diet and health status: meta-analysis . BMJ 2008;337:1344-1336 . Villareal DT, Chode S, Parimi N, et al . Weight loss, exercise, or both and physical function in obese older adults . N Engl J Med 2011;364:1218-1229 .

Jonathan L. Tilly, PhD Perez GI, Robles R, Knudson CM, Flaws JA, Korsmeyer SJ, Tilly JL . Prolongation of ovarian lifespan into advanced chronological age by Bax deficiency . Nat Genet 1999;21:200-203 . Tilly JL . Commuting the death sentence: how oocytes strive to survive . Nat Rev Mol Cell Bio 2001;2:838-848 . Johnson J, Canning J, Kaneko T, Pru JK, Tilly JL . Germline stem cells and follicular renewal in the postnatal mammalian ovary . Nature 2004;428:145-150 . Perez GI, Jurisicova A, Wise L, Lipina T, Kanisek M, Bechard A, Takai Y, Hunt P, Roder J, Grynpas M, Tilly JL . Absence of the pro-apoptotic Bax protein extends fertility and alleviates age-related health complications in female mice . Proceedings of the National Academy of Sciences USA 2007;104:5229-5234 . Selesniemi K, Lee H-J, Muhlhauser A, Tilly JL . Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies . Proceedings of the National Academy of Sciences USA 2011;(in press) .

76 Demonstrate your interest & expertise… Become a NAMS Certified Menopause Practitioner (NCMP)

As the definitive menopause resource, The North American Menopause Society (NAMS) developed this competency examination for healthcare providers who want to demonstrate their expertise in the field of menopause management. Passing the exam leads to the prestigious NAMS Certified Menopause Practitioner credential. Benefits include:

• Validation by the preeminent menopause organization that you are a menopause expert “With • Possibility of more patient referrals, job promotion, and higher salaries new menopause- related information emerging and confusion about • Enhanced credibility with your peers and the personal satisfaction of hormone therapy, our patients and providing your patients with the best possible care colleagues are looking for providers who can guide them with the latest, • A certificate suitable for framing up-to-date recommendations. The NCMP credential is a great way to let them know about your expertise.” • Annual lapel pins, which help promote your achievement to patients and colleagues – Peter F. Schnatz, DO, FACOG, NCMP, “By Reading, PA • Pride of using “NCMP” alongside your other credentials taking the NAMS competency Move your career forward and validate your level of exam and maintaining my credential, I have proved that knowledge to your patients and peers! I am continuing to keep up with the latest menopause information. I am the go-to physician in my “As organization as a result.” one of the first Canadian nurses to – Robyn B. Faye, MD, NCMP, hold the NAMS Menopause Ft. Washington, PA Practitioner credential, I feel I am empowered and have increased autonomy, accountability, and job satisfaction.”

– Sally J. Payette, RN, CME, NCMP, Ottawa, ON, Canada

To learn more about how to earn this prestigious certification, or to apply for an upcoming exam date, visit the NAMS website: www.menopause.org/compexam.aspx 268

CompExamAd2011a.indd 1 8/19/11 11:22 AM Menopause Practice: A Clinician’s Guide

New Print & Digital Format

The North American Menopause Society is proud to offer the fully updated and referenced fourth edition of its leading professional resource. Edited by dozens of experts in the field, this comprehensive clinical practice textbook is available in both print and digital formats.

Featuring: • Digital format updated as important new information is available • CME credit available through 2013 • Low pricing: For members: – $89 for either print or digital edition – $110 for print/digital bundle For nonmembers: – $99 for either print or digital edition – $120 for print/digital bundle

To order, go to www.menopause.org or call for an order form at 440-442-7550

“This current, annotated resource is for all clinicians caring for menopausal women. It is also an invaluable tool for teaching medical students and staff.”

Risa Kagan, MD, FACOG, CCD, NCMP Berkeley, CA

265

NAMS_Ad265.indd 1 12/15/10 10:41:15 AM Submit your abstracts to NAMS for presentation at the 23rd Annual Meeting

Gaylord Palms Hotel Orlando, Florida October 3–6, 2012

Submit your abstract through the NAMS website: www.menopause.org

• The abstract submission site will open in January 2012

• Abstract submission deadline is April 30, 2012

• Top abstracts will be accepted for oral presentation and up to four poster prizes will be awarded (top prize: $1,000)

• Accepted abstracts will be published in the NAMS journal, Menopause

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