ABSTRACT PRESENTATIONS

THURSDAY CONCURRENT SESSION #1 adjusted for age, marital status, family income, race/ethnicity, education level, type of employment, physical activity, self-rated health, Selective Serotonin Reuptake Inhibitor (SSRI) use, depression, hysterectomy, chronic disease (hypertension, cardiovascular S-1. disease, rheumatoid arthritis, congestive heart failure, breast cancer, ovarian cancer, Influence of Reproductive Hormones and Nighttime Hot Flashes on Mood cervical cancer), menopausal hormone therapy, exercise, smoking, body mass index, in Depressed Perimenopausal Women reporting Stressful Life Events and alcohol use. Results: 48,396 (52%) participants reported sexual activity with a Hadine Joffe, MD, MSc2,1, Sybil Crawford, PhD3, Marlene P. Freeman, M.D.1, Geena partner within the last year and 52,250 (56%) reported being somewhat or very satisfied Athappilly, M.D.2, Wolfe David, MD, MPH2, Semmie Kim2, Thania Galvan2, Julia with their current sexual activity. Problematic insomnia was reported by 28,546 (30%). Camuso2, Freid Cathryn2, Lee S. Cohen, MD1, Janet Hall4. 1Psychiatry - Center for Participants with problematic insomnia were less sexually active than those not reporting Women’s Mental Health, Massachusetts General Hospital, Boston, MA; 2Psychiatry - problematic insomnia (49.7% vs. 53.3%, p-value <0.0001), and more were unsatisfied Women’s Hormones and Aging Research Program, Brigham and Women’s Hospital, with their sexual activity (35.9% vs 29.7%, p-value <0.0001). The odds of sexual activity Boston, MA; 3School of Medicine, University of Massachusetts, Worcester, MA; and sexual satisfaction were higher in women reporting no problematic insomnia vs. 4Reproductive Endocrine Unit, Massachusetts General Hospital, Boston, MA problematic insomnia (OR 1.20, 95% CI 1.05 – 1.37 and OR 1.19, 95% CI 1.07 -1.33). Objective: The perimenopause is a period of increased risk for depression. Estradiol Conclusion: Our results indicate an association between problematic insomnia as defined variability, hot flashes, and stressful life events each increase the risk for depressive by the WHIIRS and self-reported partnered sexual activity and sexual satisfaction. symptoms during this time period. However, the relative contribution of these factors to Longitudinal investigation of sleep and its impact on sexual function during menopause depressive symptom severity in depressed perimenopausal women is not well understood. would help clarify this relationship further. We hypothesized that estradiol variability and nighttime hot flashes would independently predict worse mood in depressed perimenopausal women. Design: Perimenopausal women with mild depression (Montgomery-Åsberg Depression Rating Scale [MADRS] S-3. score 10–24) completed assessments of mood, serum estradiol and progesterone weekly The Prevalence of Insomnia in Perimenopausal Women Transitioning for 9 weeks, as well as a stressful life event survey and a daily hot flash diary. Repeated- to Menopause measure regression was used to examine independent associations of mood with the Colleen L. Ciano, PhD1, Tonya King, PhD3, Judith Hupcey, Ed.D2, Kristen Kjerulff, coefficient of variability in estradiol, the number of distinct progesterone elevations PhD3, Robin Redmon Wright, PhD4, Amy Sawyer, PhD2. 1School of Nursing, University exceeding 6 nl/dl, and hot flashes, while accounting for recent stressful life events. of Pennsylvania, Lancaster, PA; 2College of Nursing, The Pennsylvania State University, Results: Among 51 perimenopausal participants with a mean age of 48.2yrs, menopause State College, PA; 3Public Health Sciences, The Pennsylvania State University, Hershey, status was evenly divided between the early and late menopause transition. The mean PA; 4School of Behavioral Science and Education, The Pennsylvania State University, baseline MADRS score was 15.4 reflecting mild-to-moderate depressive symptom levels, Harrisburg, PA 84% of women reported experiencing hot flashes, and 88% reported recent stressful life Objective: Background/Significance: Insomnia in adults contributes to poor health events. During the study period, 90% had variable but detectable estradiol levels while outcomes such as myocardial infarction and obesity. Empiric evidence consistently 10% were persistently hypo-estrogenic; 61% never had a progesterone elevation, while suggests a predisposition to insomnia in women; yet, there is a paucity of research that the remaining 39% had at least one distinct elevation. Fewer progesterone elevations addresses the insomnia trajectory in a high-risk group of women – perimenopausal (p<0.001), greater variability in estradiol (p=0.049), and stressful life events (p=0.06) women transitioning to menopause. Perimenopause will affect 500 million women were associated with higher depression scores in univariate models. In adjusted models, within the next decade. Quantitative studies related to perimenopause and individual MADRS scores were lower in women who had episodic elevations of progesterone sleep symptoms are abundant yet scientists have yet to frame the insomnia trajectory (p<0.001), while greater variability in estradiol increased MADRS scores in the in perimenopausal women transitioning to menopause. The study purpose was to absence (p<0.001), but not the presence (p=0.80), of episodic progesterone elevation. describe the prevalence of insomnia in all perimenopausal women progressing naturally Nighttime (but not daytime) hot flashes were associated with higher MADRS scores to menopause. Design: Theoretical Framework: An adaptation of the Spielman 3 in women with persistent hypo-estrogenism (p=0.001), but were not associated with P Model of Insomnia and the Symptom Management Theory were used to guide this depressive symptom severity in those with detectable estradiol levels (p=0.22). Stressful study. The SMT and 3 P Model of Insomnia, when combined, address the essence of life events were not associated with depression symptom severity in adjusted models. the subjective and objective experience of sleep complaints among perimenopausal Conclusion: In perimenopausal depressed women, increasing dysregulation of ovarian women. Methods: A secondary analysis of publically-available data from the Study hormones with greater estradiol variability and loss of ovulation indicated by absence of Women’s Health Across the Nation (SWAN), a multisite, longitudinal study of the of progesterone production is associated with worse mood. In addition, nighttime hot natural history of menopause (n=3302) was conducted. Baseline and 13 annual data flashes are associated with higher depression scores among those who are persistently collection points inclusive of survey and biophysical data were completed. Survey data hypo-estrogenic. These menopause-specific correlates of depression are strongly linked from perimenopausal women, including perimenopausal stages and sleep symptoms, with worse mood after accounting for stressful life events. were used to examine the insomnia trajectory, defined by American Academy of Sleep Medicine (AASM) insomnia criteria. The primary outcome variables were four sleep complaints: difficulty falling asleep, sleep latency [SL], awakenings from sleep [A], S-2. wake after sleep onset [WASO], and sleep quality [SQ]. Descriptive analysis of all Association of Sleep and Sexual Function in Postmenopausal Women variables for each study interval was completed. Repeated measures logistic regression Juliana M. Kling, MD, MPH10, JoAnn E. Manson, MD, DrPh8, Michelle J. Naughton, was used to identify if insomnia symptoms (SL, WASO, A, SQ) change over time by Ph.D., MPH1, M’hamed Temkit, Ph.D.2, Shannon D. Sullivan, MD, PhD3, Emily W. perimenopausal stage (Table 1). Multivariable logistic regression models were used Gower, Ph.D.4, Lauren Hale, Ph.D.5, Julie C. Weitlauf, Ph.D.6, Sara Nowakowski, Ph.D.9, to identify predictors of influence on chronic insomnia. Results: Results: The sample Carolyn J. Crandall, MD, MS7. 1Department of Internal Medicine, Ohio State University, (n=3302) were middle aged (45.9 + 2.69) women at baseline survey. Insomnia was Columbus, OH; 2Division of Health Sciences Research, Mayo Clinic, Scottsdale, AZ; present in a third or more of perimenopausal women at any point in the transition period 3Division of Endocrinology, Medstar Washington Hospital Center and Georgetown (31%-42%). Awakenings (A) were the most frequently reported insomnia symptom University, District of Columbia, DC; 4Department of Epidemiology and Opthalmology, (31%); SL was least frequently reported (14%); and WASO (15%) was reported half as Wake Forest School of Medicine, Winston-Salem, NC; 5Program in Public Health, Stony often as A. SQ (restless or very restless sleep) did not significantly worsen by self-report Brook University, Stony Brook, NY; 6Department of Medicine, Stanford University over the ten year study period. Insomnia symptoms were worse and more prevalent in School of Medicine, Palo Alto, CA; 7Department of Medicine, David Geffen School the late stage of perimenopause. The odds of having any one symptom of insomnia were of Medicine at University of California, Los Angeles, Los Angeles, CA; 8Department 1.3 times greater for those in late stage versus early stage of perimenopause (95% CI of Medicine, Brigham and Women’s Hospital, Harvard, Boston, MA; 9Department (1.2, 1.5); p<0.001). The odds of developing chronic insomnia were 1.5 times greater for of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX; those in perimenopause than pre-perimenopausal status at baseline (95% CI (1.3, 1.8); 10Department of Medicine, Mayo Clinic, Scottsdale, AZ p<0.001). Conclusion: Conclusions & Implications: Perimenopausal women are at risk Objective: During the menopausal transition, women may report sleep disturbance for developing chronic insomnia when compared to pre-perimenopausal women. The and decreased sexual function and satisfaction. However, associations between sleep results of this study provide research and clinical implications that offer insight to design quality and sexual function in postmenopausal women have not been fully explored. interventions to improve the sleep and long-term health of perimenopausal women. The aim of this cross-sectional study was to determine whether insomnia and sleep Table 1. Summary Of Insomnia/Insomnia Symptoms by Groups for 10 Year Study duration using a validated, clinically relevant scale are associated with sexual activity Interval and sexual satisfaction in the Women’s Health Initiative (WHI) Observational Study (OS) cohort. Design: Sexual activity questions and self-reported sleep in the past 4 weeks were assessed at baseline for 93,668 women age 50 to 79 years enrolled in the WHI OS. Insomnia was measured using the validated WHI Insomnia Rating Scale (WHIIRS), which includes questions on whether participants had trouble falling asleep, woke up several times at night, woke up too early, had trouble getting back to sleep after awakening early, and overall sleep quality (very sound/restful to very restless). Typical sleep duration (5 hrs or less, 6 h, 7 h, 8 h, 9 h or more) was also recorded. Scores on the WHIIRS range from 0 – 20, with a score > 9 indicative of problematic insomnia. We examined cross-sectional associations between sleep measures (hours of sleep and insomnia) and two indicators of sexual function: sexual activity with a partner (yes/no) and sexual satisfaction (very satisfied and somewhat satisfied vs. very unsatisfied and a little unsatisfied) within the last year. The association between each risk factor and outcome was evaluated by fitting a multivariate logistic model that

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S-4. the recording with lower estradiol levels (23.3 ± 25.2 pg.mol-1) and the recording with Prominent sleep disturbance confirmed with objective polysomnographic higher estradiol levels (54.9 ± 35.8 pg.mol-1) showed that women had more hot flashes recordings in women who develop insomnia in the approach to menopause (Wilcoxin signed rank test, Z = 2.1, p = 0.036) and tended to have a greater percentage Fiona C. Baker, PhD1,2, Massimiliano de Zambotti, PhD1, Adrian R. Willoughby, PhD1, of hot flash-associated wake (Wilcoxin signed rank test, Z = 1.78, p = 0.07) on the night Stephanie A. Sassoon, Ph.D.1, Stephanie Claudatos1, Sarah Inkelis1, Lena Kardos1, David with lower estradiol levels. Conclusion: Lower estradiol levels are associated with a Dresser1, David Sugarbaker1, Ian M. Colrain, PhD1,3. 1SRI International, Menlo Park, CA; greater impact of hot flashes on sleep, as determined from an objective measure of hot 2Brain Function Research Group, University of the Witwatersrand, Johannesburg, South flash-associated wake time, in women in the menopausal transition. Longitudinal data Africa; 3Melbourne School of Psychological Sciences, The University of Melbourne, are required to confirm whether hot flashes have an increasingly greater negative impact Melbourne, VIC, Australia on sleep as women transition menopause and estradiol levels decline. Objective: The majority of women experience sleep difficulties, particularly night- time awakenings, as they approach menopause, and for about 25% of women, sleep disturbances are severe, causing significant distress and impacting functioning, THURSDAY CONCURRENT SESSION #2 qualifying them for a diagnosis of insomnia disorder. However, it is unclear whether these perceived sleep disturbances are matched with polysomnographic (PSG) S-6. evidence of poor sleep quality, leading to a lack of clarity about the nature of severe Childhood Physical and Sexual Abuse Predict Menopausal Symptoms sleep problems in midlife women and how to treat them most effectively. We aimed to determine whether there is physiological evidence of disturbed sleep, based on PSG and among Sexual Minority Women Bethany Everett, PhD1, Pauline Maki, Ph.D.2, Tonda Hughes, PhD3. 1Sociology, spectral electroencephalographic analysis, in women who developed DSM-IV insomnia University of Illinois at Chicago, Chicago, IL; 2Psychiatry & Psychology, University in the context of the menopause transition (with no past history of insomnia disorder) of Illinois, Chicago, IL; 3Health System Sciences, University of Illinois, Chicago, IL compared with age-matched women in the menopause transition without insomnia. Objective: Studies of menopause have focused almost exclusively on heterosexual Design: Participants were seventy-two women (age range: 43-57 years; 38 meeting women, depsite evidence that sexual minority women report mutliple risk factors for DSM-IV criteria for insomnia with an onset proximate to the menopause transition, and more severe menopausal symptoms including childhood physical and sexual abuse. 34 controls with no/mild sleep difficulties). They completed sleep diaries for two weeks Our obejctive is to examine the association between a history of abuse (i.e., childhood and came to the laboratory for a clinical PSG screening/adaptation night to confirm physical and sexual) and menopausal symptoms in a sample of sexual minority women. absence of breathing-related or limb movement sleep disorders. They then returned for Design: Data are from the Chicago Health and Life Experiences of Women (CHLEW) an additional PSG recording night. Sternal skin conductance was measured throughout Study, a longitudinal study of sexual minority women in the Chicago area. Participants the night to quantify hot flashes. Results: On their sleep diaries, women with insomnia were initially recruited in 2000-2001, and the third and most recent wave of data was reported a shorter sleep duration (p=0.04), more wake after sleep onset (p=0.002), more collected in 2010-2012. The sample for this study is restricted to women who reported nocturnal awakenings (p=0.050), and more hot flashes (p=0.012) than controls. On the transitioning through menopause between those two waves (N=112). The mean age of the PSG recording night, women with insomnia had a shorter sleep duration (364.3 ± 37.4 sample is 59.3. Logistic regression models were used to assess the association between min) than controls (406.8 ± 37.2 min, p<0.001), due to a shorter time in bed (p < 0.05) childhood abuse and self-reported menopausal symptoms including vaginal dryness, and a higher percentage of PSG-defined wake after sleep onset (p < 0.01). Women with hot flashes, and psychological symptoms. All models adjust for age, race/ethnicity, insomnia also had a lower percentage of N2 sleep (insomnia: 46.2 ± 6.7 %, control: education, alcohol and tobacco use, anxiety, and BMI. Results: Eighty percent of the 49.8 ± 6.6 %, p=0.024) and a lower sleep efficiency (insomnia: 85.6 ± 7.5, control: sample reported hot flashes, 33% reported vaginal dryness, and 55% reported nervousness 90.1 ± 4.7, p=0.004). More insomniacs (18 of 38) than controls (3 of 34) had a short and depression during menopause. Twenty percent of the sample reported childhood sleep duration (< 6h) (χ2=12.90, p<0.001). Measures of electroencephalographic activity during sleep did not reveal any group differences although insomniacs tended to have physical abuse and 36% reported childhood sexual abuse. Fully adjusted models reveal lower delta power during deep sleep than controls (p=0.055). Insomniacs were more no significant relationship between childhood abuse and hot flashes, however, women likely than controls to have at least one objective hot flash during the PSG recording who reported childhood physical abuse were almost 10 times as likely to report vaginal (χ2=11.07, p<0.001). Conclusion: Women with first-onset insomnia in the approach to dryness (OR=9.77, p<.001) and women who reported childhood sexual abuse were four menopause have a measurable sleep deficit, with shorter sleep duration, more wake after times as likely to report nervousness and depression (OR=4.12, p<.01) during menopause sleep onset, poorer sleep efficiency, and less stable sleep, compared to women in the compared to women who did not report abuse (See Table). Conclusion: Rates of hot menopause transition without insomnia. Nocturnal physiological hot flashes are more flashes, vaginal symptoms, and psychological symptoms among sexual minority women common in insomniacs and are likely an important contributor to nocturnal wakefulness were similar to rates observed in epidemiological studies of the menopause, though in this population. Insomnia in the context of menopause has unique etiological features, rates of childhood physical and sexual abuse were higher. Results show an association such as hot flashes, which should be considered when treating women with menopause- between childhood sexual and physical abuse and women’s health at midlife. The onset insomnia. association between childhood physical abuse and vaginal dryness in postmenopausal women was particularly strong while the association between childhood sexual abuse and vaginal dryness was not significant. Although link between childhood sexual abuse S-5. and sexual function in adulthood is well established, the current findings did not suggest Lower estradiol levels are associated with greater hot flash-related sleep that this association is particularly pronounced during the postmenopausal period. The disturbance in women in the menopausal transition menopausal transition is associated with an elevated risk of depression and anxiety Massimiliano de Zambotti, PhD1, Sarah Inkelis1, Stephanie Claudatos1, David Dresser1, disorders, and our findings suggest that a history of childhood sexual abuse contributes Lena Kardos1, David Sugarbaker1, Ian M. Colrain, PhD1,3, Fiona C. Baker, PhD1,2. to a worsening of those symptoms in the postmenopause. Future research should continue 1SRI International, Menlo Park, CA; 2Brain Function Research Group, University of to investigate predictors of menopausal symptoms among sexual minority women and the Witwatersrand, Joahnnesburg, South Africa; 3Melbourne School of Psychological their effect on sexual minority women’s health later in life. Sciences, University of Melbourne, Melbourne, VIC, Australia Table 1: Odds Ratios for effects of childhood abuse on menopausal symptoms among Objective: Hot flashes, defined as transient periods of heat, sweating, anxiety, and sexual minority women. chills, are reported by about 80% of women in natural menopause. Hot flashes emerge in association with declining estradiol levels and impact quality of life, affecting productivity, mood, social activities, and sleep. We recently showed that a calculation of the amount of time spent awake in association with hot flashes (hot flash-associated wake time) goes beyond hot flash frequency in providing a useful index of the impact of hot flashes on sleep in perimenopausal women (de Zambotti et al., Fertil Steril, 2014 102:1708-15). Hot flash-associated wake time contributes a variable percentage to total in-bed wakefulness, ranging between 0-89%. Reasons for this variable impact of hot flashes on sleep are unknown. Here, we aimed to investigate whether the impact of hot flashes on sleep is associated with circulating reproductive hormones, specifically estradiol and follicle stimulating hormone (FSH). Design: Participants were twenty- Notes: N=112; OR=Odds Ratio; CI=Confidence Interval; Adjusted models control -2 seven women (age: 50.3 ± 3.04 years, BMI: 23.5 ± 2.9 Kg.m ) in the menopause for age, race/ethnicity, education, BMI, anxiety, tobacco and alcohol use transition. They completed a clinical polysomnographic (PSG) screening night to confirm the absence of breathing-related or periodic limb movement sleep disorders and then returned for at least one recording PSG night. Sternal skin conductance was measured S-7. throughout the night to quantify hot flashes. A blood sample was drawn at their PSG Women’s Attitudes and Behaviors towards Vulvar and Vaginal Atrophy recording and serum was analyzed for FSH and estradiol using standard immunoassay (VVA) kits. A stepwise multiple regression model was used to predict the percentage of hot Sheryl Kingsberg, PhD1, Julia M. Amadio, MBA2, Shelli Graham, PhD2. 1Department flash-associated wake time using estradiol and FSH levels, age, and BMI as dependent of OB/GYN, Case Western Reserve University School of Medicine, Cleveland, OH; variables. Results: Women had between one and eight physiological hot flashes during 2TherapeuticsMD, Boca Raton, FL their overnight recordings and hot flash-associated wake time contributed between 0 and Objective: To improve understanding of the reasons why women do or do not use 89% to the total amount of wakefulness. Estradiol (Beta = -0.49) was the only significant prescription (Rx) therapies for VVA and to identify women’s perceptions of VVA. factor in the model for predicting the percentage of hot flash-associated wake time Design: Six in-person focus groups of postmenopausal women diagnosed with VVA and (F(1,25) = 7.96, p=0.009) and explained 21% of the variance, with lower estradiol levels experiencing moderate to severe dyspareunia were held in 3 cities (Tampa, Philadelphia predicting a greater percentage of hot flash-associated wake. Nine of the women had two and Chicago) from February to March, 2015. A total of 38 women participated in the PSG recordings and an exploratory analysis of differences in hot flash measures between

43 ABSTRACT PRESENTATIONS focus groups (FG) with a mean age of 62.9 years (range: 49 - 74 years); 58% were vaginal estrogen. Nearly 1 in 3 clinicians identified the HEDIS/Medicare designation 60-69 years of age. The 6 groups were comprised of: a) women currently taking of estrogen as a high-risk medication for the elderly as a barrier to vaginal estrogen use. prescription VVA medications (Rx user; FG=1, n=6); b) women not taking prescription Conclusion: Perceived barriers to patient care and knowledge gaps among clinicians VVA medications (Rx non-user; FG=3, n=20), and c) a mix of Rx users and Rx non- may explain why GSM is frequently underdiagnosed and undertreated. PC clinicians users (FG=2, n=12). Facilitated discussion topics included: general health, menopause demonstrated more knowledge deficit, lack of confidence, and misconceptions in GSM experience, VVA awareness and knowledge, VVA symptoms and HCP diagnosis or diagnosis and treatment. Efforts to help improve postmenopausal symptoms of GSM not, impact of dyspareunia, treatment experiences (Rx and OTC), and risk/benefit of Rx should include PC clinicians as they provide a large proportion of routine health care treatments. Results: Women who were not using Rx therapy reported significant pain, visits for postmenopausal women. Further, health system interventions need to focus on loss of sexual function, emotional trauma, lower self-esteem, and damage to marital providing tools and education to overcome perceived barriers. and partner relationships. Statements regarding dyspareunia included: “way more than Table. Clinician-reported Barriers to GSM Diagnosis and Treatment bothersome, this is severe pain, this is defeating and life changing – in this day and age, there should be a solution”; “it felt like someone was stabbing me with a knife”; “it’s sharp - on a 10-point scale, a 10”. Women also reported that the pain can be enduring: “soreness lasts for days after intercourse”; “can’t wipe, it’s irritated and not natural”. Some also reported being frightened by vaginal bleeding and noted that VVA had a negative impact on other daily activities including exercise (jogging and biking). Most non Rx users reported that the experience of sex itself is frustrating with a loss of spontaneity and pleasure. Many do not discuss their symptoms with others stating it is too personal and embarrassing and when they raised the issue with their doctor they reported they did not listen to them. Treatment options are not adequately discussed by providers. Some non-users simply refused to consider an Rx therapy and actively sought other options. OTC products helped with milder symptoms but not moderate to severe pain. Attitudes were very different between Rx users and Rx non-users. Rx Users Recognize physical and emotional benefits of estrogen Strong anti-aging beliefs (fight to stay young; reverse aging) Search-out medical advice (switch doctors; demand Rx) Empowered personality Optimistic and sexually active Rx Non-Users Accept aging and symptoms as inevitable Less likely to talk with doctor, embarrassed Lack of knowledge, fears and confusion dominate thinking Depressed about the future Not in an active sexual S-9. relationship When asked about the medications they were currently taking, none of the Efficacy of intravaginal dehydroepiandrosterone (DHEA) on dyspareunia Rx users mentioned their VVA product. Upon follow-up, as to why, they replied that and on the FSFI questionnaire in vulvovaginal atrophy due to menopause it was not for a “real” medical condition but a sexual condition. There was a lack of Fernand Labrie1, David F. Archer, MD, NCMP2, David J. Portman, MD3, Marlene knowledge/understanding about estrogen, how it works and differences between local Montesino1, Isabelle Côté1, Lyne Lavoie1, Celine Martel1, John Balser5, Érick Moyneur4. and systemic estrogen, which led to negative perceptions and generalized fears of side 1EndoCeutics Inc., Quebec, QC, Canada; 2CONRAD Clinical Research Center, Nortfolk, effects (cancer and blood clots). The women noted that current Rx options were costly, VA; 3Columbus Center for Women’s Health Research, Columbus, OH; 4StatLog interfered with spontaneity, were messy or inconvenient, and may cause pain by using Consulting Inc, Ottawa, ON, Canada; 5Veristat, Holliston, ME an applicator. Most stated that they would like to take estrogen to treat their VVA if it Objective: The aim of this study was to confirm the beneficial effects of intravaginal was safe and had no systemic absorption. The mixed groups generated a lot of discussion dehydroepiandrosterone (DHEA, prasterone) on moderate to severe dyspareunia or pain about user product experience. Conclusion: Based on this sampling of VVA patients, at sexual activity, the most frequent symptom of vulvovaginal atrophy (VVA) or of the there is a segment of highly motivated patients interested in solutions to the problem of genitourinary syndrome of menopause (GSM). Design: In a prospective, randomized, postmenopausal pain with penetration and the underlying condition. However, most of double-blind and placebo-controlled phase III clinical trial, the effect of daily intravaginal these women do not understand VVA, nor are they treating it. Non-treating women are 0.50% DHEA (6.5 mg) (prasterone, EndoCeutics) was examined on four co-primary not motivated to take action to find help and are not being heard by physicians when objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal they do raise it. Women’s perceptions of estrogen are both a barrier to treatment and pH and moderate to severe pain at sexual activity (dyspareunia) identified by the women an opportunity for education about the risks/benefits of currently approved prescription as their most bothersome VVA symptom. The Intent-to-treat (ITT) population included therapies. Women felt that a new treatment alternative is warranted to address their needs. 157 and 325 women in the placebo and DHEA-treated groups, respectively. Results: After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the ANCOVA test, the percentage of parabasal cells decreased by 27.7% S-8. over placebo (p<0.0001) while the percentage of superficial cells increased by 8.44% Clinician Knowledge, Attitudes, and Barriers to Diagnosis and Treatment over placebo (p<0.0001), vaginal pH decreased by 0.66 pH unit over placebo (p<0.0001) of Genitourinary Syndrome of Menopause: Variations in Primary Care and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 and Gynecology unit over placebo (p=0.0002). On the other hand, moderate to severe vaginal dryness Kimberly Vesco, MD, MPH1,2, Kate Beadle, NP2, Amanda Clark, MD, MCR2, Joanna present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared Bulkley, PhD1, Ashley Stoneburner, MPH1, Michael Leo, PhD1. 1Center for Health to baseline or 0.27 unit over placebo (p=0.004). At gynecological evaluation, vaginal Research, Kaiser Permanente Northwest, Portland, OR; 2Department of Obstetrics and secretions, epithelial integrity, epithelial surface thickness and color all improved by 86 Gynecology, Kaiser Permanente Northwest, Portland, OR to 121% over the placebo effect (p<0.0001 for all comparisons with placebo). A 33.0% Objective: Nearly 50% of postmenopausal women experience symptoms related to (orgasm, p=0.047) to 56.8% (arousal, p=0.0022) increase over placebo in all the six genitourinary syndrome of menopause (GSM); however, few seek treatment and few domains of the FSFI was observed, thus confirming the previous benefits of intravaginal clinicians ask about GSM symptoms. In preparation for a health-system based, cluster DHEA on female sexual function by an action exerted exclusively at the level of the randomized trial of an intervention to improve the diagnosis and management of the vagina. Serum steroid levels remained well within the normal postmenopausal values GSM, we assessed clinician knowledge, attitudes, and barriers regarding its diagnosis and according to the mechanisms of intracrinology responsible for intravaginal DHEA management. Design: We developed a survey that included 3 content areas; Knowledge: transformation into the cell-specific intracellular sex steroid formation and their local 8 multiple-choice questions about GSM prevalence, diagnosis and treatment; Attitudes: 3 inactivation. The only side effect reasonably related to treatment is vaginal discharge Likert-scale questions asking clinicians to report their likelihood of assessing for GSM at due to melting of the vehicle at body temperature and reported in about 5% of subjects. a routine visit and confidence in ability to counsel patients about GSM; and Barriers: a 12- Conclusion: The daily intravaginal administration of 0.50% (6.5 mg DHEA) prasterone item list with instructions to check all that apply. We conducted the survey on-line using has shown clinically and highly statistically significant effects on the four co-primary Survey Monkey. Our health system data showed that most well-care visits for women ≥ parameters suggested by the US Food and Drug Administration. The strictly local 55 years (82%) are conducted in Primary Care (PC: Family Practice/Internal Medicine); action of prasterone in the vagina at its site of application is in line with the absence of our planned intervention targets both PC and Gynecology (Gyn) clinics. Therefore, we significant systemic drug-related adverse events, thus showing the high benefit/risk ratio emailed invitations to all PC and Gyn clinicians in our health system with valid addresses of this treatment essentially based upon the novel understanding of the physiology of sex (363 of 368). We allowed 4 weeks for a response and sent 2 reminder emails. Results: steroids in postmenopausal women when all sex steroids are made locally in peripheral The survey response rate was 33% (120/363). The respondents were representative of the tissues from circulating but decreasing DHEA activity. overall PC and Gyn clinician population in age (mean 47.8 years), gender (71% female), and clinician type (76% PC). Overall, 67% of knowledge questions were answered correctly, with some variability between Gyn (78% correct, range 37%-97%) and PC S-10. clinicians (64% correct, range 18%-97%). Compared to PC, more Gyn clinicians reported Local Estrogens for Genitourinary Symptoms of Menopause. Does the being highly likely or likely to assess for GSM during a routine visit (73% vs 28%), Method of Treatment (Tablets or Cream) Change the Compliance and and reported being highly or very highly confident in counseling about GSM symptoms Adherence to Treatment? (73% vs. 33%) and in advising on risks/benefits of vaginal estrogen (77% vs. 30%). Israel Yoles, MD1, Tuvia Bayevsky, MD1, Alina Weissmann-Brenner, MD2. 1Clalit Lack of time was the most commonly reported barrier to GSM diagnosis and treatment Health Services, Central District, Israel; 2The Sheba Medical Center, Ramat Gan, Israel (Table). Both PC and Gyn clinicians indicated that patient discomfort discussing GSM Objective: Prior studies have showed that local estrogens for the treatment of was a barrier. Gyn clinicians identified three barriers more often than PC: 1) FDA black genitourinary symptoms of menopause are underutilized. It has also been established box warning for vaginal estrogen prescriptions; 2) patient dissatisfaction with options that the efficacy and adverse effects of both estrogen- containing vaginal tablets (VT) for vaginal estrogen, and 3) cost of vaginal estrogen. However, PC clinicians were and creams(VC) are comparable. In this study, we gathered real world data of vaginal twice as likely to report concern about increasing risk of breast cancer by prescribing estrogen treatment in a large cohort of Israeli women, and compared the compliance

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and adherence to treatment with VT vs.VC. Design: This study includes data from a National Institutes of Health, U.S. Department of Health and Human Services through large population in the Central District of “Clalit Health Services”, the largest HMO contracts HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, in Israel. All demographic data, as well as treatment utilization, were electronically HHSN268201100003C, HHSN268201100004C, and HHSN271201100004C) recorded. Following the approval by the Clalit IRB, we analyzed data on the use of VT and VC over a nine-year period, from January 2006 to December 2014. During the study period, 87,184 women aged 40 and older were registered in this district. Patient age ranged between 40-89 years at entry. “Sporadic” users (patients filling fewer than 4 prescriptions) were not included in the analysis. We defined patients as compliant to treatment if the average interval between prescriptions was less than 4 months. Patients were defined as adherent if they followed the treatment regimen over the entire period of estrogen treatment. Student’s t-test was used to compare between treatments. Results: 21,674 patients,i.e.25% of the age-matched women, received at least one local estrogen prescription during the study period, of which 252 were lost to follow-up. Of the remaining 21,422 patients, 17648 (82%) were sporadic users and were therefore excluded from the study. In total, 3,774 women were eligible for analysis, of which 2,269 (60%) used only one type of treatment (monotherapy), while 1,505 (40%) switched between treatments (switchers). The switchers were not analyzed in the current study. The mean age was 59±9 yrs. In the monotherapy group, 487 (21%) used VT and 1782 S-12. (79%) used VC. In the VT group 314/487 (64%) were found to be compliant, as opposed Physiologically monitored hot flashes and subclinical cardiovascular to only 699/1782 (39%) in the VC group. Compliant patients in the VT group adhered disease among midlife women to treatment for 1002±38 days as compared to adherence of only 787±25 days in the VC Rebecca C. Thurston, PhD1,2, Emma Barinas-Mitchell, PhD2, J. Richard Jennings, PhD1, group (significant difference, t-test p<6x10-7, Fig.1). Conclusion: In the monotherapy Nanette Santoro, MD3, Roland von Känel, PhD4, Yuefang Chang5, Doug Landsittel, group, compliance with vaginal estrogen tablets therapy was higher than with vaginal PhD6, Karen A. Matthews, PhD1,2. 1Department of Psychiatry, University of Pittsburgh, cream. Additionally, the mean duration of VT usage was significantly longer than with Pittsburgh, PA; 2Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA; VC. Since the efficacy of VT and VC are considered similar, one possible explanation of 3Department of Obstetrics and Gynecology, University of Colorado at Denver, Denver, these findings may be the difference in the ease of usage between locally applied creams CO; 4Department of Neurology, Inselspital, Bern University Hospital, and University and tablets.In addition, utilization of local estrogens, in general, by postmenopausal of Bern, Bern, Switzerland; 5Department of Neurosurgery, University of Pittsburgh, women, was extremely low: only one quarter of the population ever used local estrogens, Pittsburgh, PA; 6Department of Medicine, University of Pittsburgh, Pittsburgh, PA 82% of patients filled prescriptions sporadically and only 5% of the women over 50 years Objective: Emerging research suggests relations between menopausal hot flashes and of age,repeatedly applied any kind of local estrogen. Since, in some degree, genitourinary subclinical cardiovascular disease (CVD) among midlife women. However, findings have symptoms affect most menopausal women, these findings are a loud call for action. largely been derived from post hoc analyses of studies of brief self-report measures of hot flashes subject to memory and reporting biases. Here we present data on the first large- scale study designed to test whether physiologically-assessed hot flashes are associated with elevated carotid intima media thickness (IMT), a widely used measure of subclinical CVD, over and above standard CVD risk factors. Design: 255 nonsmoking midlife (aged 40-60) women free of clinical CVD, 134 who reported having daily hot flashes and 121 who reported no current hot flashes were recruited. No women were taking beta blockers, calcium channel blockers, insulin, or medications known to impact hot flashes. Women underwent 24 hours of physiologic hot flash monitoring to quantify the physiologic frequency of hot flashes and 3 days of electronic diary hot flash monitoring completed at the time of the hot flash to quantify the self-reported frequency, severity, and bother associated with hot flashes. Women also underwent anthropometric measures; a blood draw for assessment of lipids, glucose, insulin, and estradiol (quantified via liquid chromatography-tandem mass spectrometry); and a carotid ultrasound for assessment of IMT. Relations between hot flashes and subclinical CVD indices were examined controlling for age, race, body mass index (BMI), systolic blood pressure (SBP), lipids, the homeostatic model assessment (HOMA), and use of lipid-lowering, anti-hypertensive, and anti-diabetic medications. Estradiol and menopausal stage were C vs T, **p<6x10-7 also considered as covariates. Results: Women were on average 54 years old, overweight (BMI=29), and postmenopausal (83%). 29% were nonwhite. Almost half (n=57, 47%) of the 121 women reporting not having hot flashes at enrollment showed physiologic TOP SCORING ABSTRACT PRESENTATIONS hot flashes on ambulatory monitoring. Women with and without hot flashes (either self- reported or physiologically detected) did not differ on IMT. However, controlling for standard CVD risk factors, a greater frequency of waking physiologically-assessed hot S-11. flashes, particularly among women showing physiologic hot flashes, was associated Genome-wide Association Study of Hot Flashes in the Women’s Health with significantly higher mean IMT [b(SE)=.003 (.001), p=.004] and maximal IMT Initiative Study [b(SE)=.004 (.001), p=.003] as well as individual segments bulb IMT [b(SE)=.005(.002), Carolyn J. Crandall, MD, MS1, Chancellor Hohensee2, Steve Horvath1, JoAnn E. p=.009] and internal carotid artery IMT [b(SE)=.003(.001), p=.03]. Findings persisted Manson, MD, DrPh3, Erin LeBlanc4, Mara Vitolins5, Rami Nassir6, Jean Wactawski- after controlling for estradiol and menopausal stage, neither of which was related to IMT. Wende7, Janet Sinsheimer1. 1University of California, Los Angeles, Los Angeles, CA; Greater diary-reported frequency [b(SE)=.006 (.003), p=.03), severity [b(SE)=.03(.009), 2Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, p=.002], and bother [b(SE)=.03(.009), p=.002] of hot flashes were also associated with WA; 3Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard higher mean IMT in women reporting hot flashes in multivariable models. Notably, Medical School, Boston, MA; 4Kaiser Permanente, Portland, OR; 5Wake Forest School physiologic hot flashes accounted for a comparable or greater amount of variance in IMT of Medicine, Winston-Salem, NC; 6University of California-Davis, Davis, CA; 7State in women with hot flashes than standard CVD risk factors including BMI, lipids, HOMA, University of NY at Buffalo, Buffalo, NY or SBP. Conclusion: This is the first study to date to test whether physiologically- Objective: To identify single-nucleotide polymorphisms (SNPs), assessed by genome- assessed hot flashes were associated with higher IMT. More frequent, severe, or wide association studies (GWAS), associated with vasomotor symptoms (VMS, i.e. hot bothersome hot flashes were robustly associated with higher IMT, particularly among flashes and/or night sweats). Design: 18,215 European American, African American, women with hot flashes. These associations were not accounted for by traditional CVD and Hispanic American postmenopausal women aged 50-79 years at baseline who risk factors or by endogenous estradiol and were strongest for physiologically-measured were enrolled in the Women’s Health Initiative Observational Study and Clinical hot flashes. The magnitude of the association between physiologic hot flashes and IMT Trials underwent GWAS assessment and provided information regarding VMS during was at least as strong as that of standard CVD risk factors. Study findings further support the previous 4 weeks (any vs. none). We excluded data from samples with call rates links between hot flashes and CVD risk. <97%, SNP assays with call rates <98%, and SNPs with Hardy-Weinberg p-values < 1x10-4. Results: After adjustment for bilateral oophorectomy, age, smoking, alcohol intake, physical activity, population structure, body mass index, education, income, and S-13. menopausal estrogen therapy use, and combining across substudies by meta-analysis, we Effect of Postmenopausal Hormone Therapy on the Severity of identified 3 SNPs that were associated with VMS <5x10-8. All 3 of these SNPs are located Myocardial Infarction within the same region of chromosome 4 (Table 1). Conclusion: Genetic variation at the Pauliina Tuomikoski, Adjunct Professor1, Aki Havulinna3, Veikko Salomaa3, Tomi loci identified on chromosome 4 may account for some of the heritability of VMS. To Mikkola1,2. 1Department of Obstetrics and Gynecology, Helsinki University Hospital, our knowledge, this is the first published GWAS to examine SNPs associated with VMS. HUS Helsinki, Finland; 2Folkhälsan Research Center, Helsinki, Finland; 3THL-National If our results are replicated in an independent population, elucidation of these variants Institute for Health and Welfare, Helsinki, Finland may lead to new insights into the biological pathways involved in VMS, which are poorly Objective: Acute myocardial infarction (MI) is still the leading cause of death in women. understood. (The WHI program is funded by the National Heart, Lung, and Blood Institute, In general, pre-hospital case-fatality in women is 25-30%, and 1-year case fatality as high as 50%. Luckily total mortality to coronary heart disease is declining due to an increase in

45 ABSTRACT PRESENTATIONS survival after MI. Postmenopausal hormone therapy (HT) confers cardiovascular benefits FRIDAY CONCURRENT SESSION #1 in terms of reduced coronary heart disease, if treatment is initiated to a healthy woman who is younger than 60 years, or less than ten years postmenopausal. Less is known about the outcomes of myocardial infarction (MI) in HT users. Design: Register-based cohort S-15. study. All Finnish women aged ≥40 years who buy HT are registered in a nationwide Objective and subjective hot flashes in the city of Campeche, Mexico Reimbursement Database. Data on HT purchases are available from 1994 onwards. In Lynnette L. Sievert, PhD1, Laura Huicochea Gomez, PhD2, Diana Cahuich Campos, Finland HT regimens require a doctor’s prescription and they can be bought only for a PhD2, Daniel E. Brown, PhD3. 1Anthropology, Univ. of Mass. Amherst, Amherst, MA; 3-months need at time. Therefore repeat entries into the Reimbursement register confirm 2Area de Sociedad, Cultura y Salud, El Colegio de la Frontera Sur, Campeche, Mexico; that a woman is truly using the HT once prescribed. FINAMI is a register that comprises 3Anthropology, University of Hawaii Hilo, Hilo, HI data on all acute coronary events on four regions in Finland. The FINAMI data also Objective: Hot flashes associated with the hormonal changes of menopause can cause include information about the patients previous MIs, smoking status, levels of lipids considerable discomfort, and can last for 10 years or longer. Human biologists have and cardiac enzymes, treatment of the coronary event in question and case fatality. By shown population differences in heat dissipation responses, e.g., the number and location combining these two register databases we studied the association between HT use and of sweat glands, and the quantity of sweat produced. These findings may pertain to the the severity of MI and the possible impact of continued /discontinued HT use and the study of hot flashes. Previous research found that women in Mexico described hot flashes risk of reinfarction. Results: We acquired data on MIs in 12 483 women during 1995 on the back of the neck, in addition to the more common U.S. pattern of hot flashes on the to 2009. Overall, in women with acute MI, the use of HT was associated with a 31% face and upper chest. The purpose of this study was to document the experience of hot (p<0.001) reduced risk of death within 28 days from the MI, as compared with non-users. flashes in Campeche, Mexico, and whether ambulatory hot flashes measured across the The use of systemic HT was associated with a 44% (p<0.001) lower risk of 28-day case- sternum and back of the neck correspond with subjective report. Ethnicity was examined fatality, whereas the use of vaginal estrogen use did not confer a significant reduction in in relation to hot flashes, with the expectation that Mayan women would be less likely this mortality risk (OR 0.80, p=0.053). Conclusion: Our preliminary data imply that to report and demonstrate hot flashes. Design: Women aged 40 to 55 were recruited systemic HT use is associated with a decreased risk of death due to MI. Further analyses throughout the city of Campeche by opportunity sampling and snowball techniques. on the association between various lengths of HT use and the severity of MI, immediate, Mayan and non-Mayan ancestry was defined by birth place, last names, and language 28-day, and 1-year case-fatality, will be completed in the coming months. Interesting spoken by the participant, her parents, and her grandparents. Women participated in data on the possible impact of HT discontinuation on the risk of reinfarction will also face-to-face interviews with structured questionnaires that queried symptom frequencies be investigated. during the past 2 weeks. A body diagram was used to show where women felt the heat of hot flashes and the sweating associated with hot flashes. Women who were peri- menopausal (with irregular periods) or early post-menopausal (up to 2 years after the S-14. final menstrual period) were invited to wear a 2-channel Biolog ambulatory hot flash Endometrial effects of lasofoxifene: Results from two phase 3 osteoporosis monitor for 24 hours. Electrodes were placed 4” apart on the upper chest and 4” apart prevention trials on the back of the neck. To date, 187 women have participated in interviews. Of those, Steven R. Goldstein, MD1, David Portman, MD2, James Symons, MS, PhD2. 1NYU 53 women wore a hot flash monitor. Results: The sample consists of women of Mayan School of Medicine, New York, NY; 2Sermonix Pharmaceuticals, Columbus, OH ancestry (n=95), non-Mayan ancestry (n=55), and women for whom we were unable to Objective: Unopposed estrogens and tamoxifen have been found to increase the incidence classify ancestry (n=21). Forty-eight percent of women reported hot flashes (calores, of endometrial hyperplasia and endometrial cancer in a dose- and duration-dependent n=180), and 48% reported night sweats (n=172) with no significant difference in manner. Several selective estrogen receptor modulators (SERMs) halted in development frequency of vasomotor symptoms by ethnicity. Hot flashes were reported by 46% of have also been associated with similar unfavorable endometrial effects. An extensive women with Mayan ancestry, 53% of women without Mayan ancestry, and 50% of the endometrial safety evaluation of the SERM lasofoxifene was therefore conducted as part unclassified. On body diagrams (n=105), hot flashes were described most frequently as of two identical 24-month phase 3 studies of postmenopausal osteoporosis prevention. occurring on the upper chest (73%), face (69%), front of neck (69%), and back of neck Design: Gynecologic safety was assessed based on endometrial histopathology. Subjects (58%). Sweating was described most often on the face (56%), upper chest (49%), front with an intact uterus and a uniform endometrial thickness of <8 mm on transvaginal of neck (38%), back (40%), and back of neck (33%). Mayan women and women not ultrasound (TVU) were included. Subjects with endometrial thickness of >8 mm found classified were most likely to report hot flashes on the face (76% and 91%) compared during the study underwent saline infusion sonography, hysteroscopy, and/or endometrial to non-Mayan women (50%, p<0.01). The same pattern was true for the front of the biopsy. At the end-of-study visit, endometrial tissue was evaluated from all subjects neck (p=0.06), with no other significant differences in where hot flashes occurred. Hot with an intact uterus. Endometrial histology was categorized as: no sample obtained flash monitors were worn for an average of 21.0 hours (s.d., 4.0 hours). Among the first or no interpretable endometrium present, atrophic/inactive endometrium, secretory 27 women who wore the monitors, the number of objective sternal hot flashes ranged endometrium, menstrual type, proliferative endometrium, hyperplastic endometrium, from 0 to 22, with a mean of 5.2 (s.d., 5.3), and nuchal hot flashes ranged from 0 to 14, or carcinoma. Endometrial thickness at Month 24 was analyzed by means of a linear with a mean of 5.9 (s.d., 4.0). The number of subjective hot flashes ranged from 0 to model. Tests were done on least squares means. Two-sided 95% confidence intervals 6 with a mean of 1.3 (s.d., 1.6). There was no significant difference between Mayan for the difference from placebo were calculated. Results: Age, weight, height, and and non-Mayan women in the number of objective or subjective hot flashes. Among years postmenopausal were comparable for subjects across the 2 identical studies. The women who reported at least one subjective hot flash, frequency of concordance was very endometrial effect analyses included postmenopausal women without prior hysterectomy similar between sternal (1.1, s.d. 1.9, range 0 to 3) and nuchal (1.2, s.d. 1.2, range 0 to 4) randomized to one of 4 groups: 0.025 mg/day, 0.25 mg/day, or 0.5 mg/day lasofoxifene, hot flashes. Frequency of subjective/objective concordance did not differ by ethnicity. or placebo. At Month 24 the incidence of atrophic/inactive endometrium in the Conclusion: About half of women experienced vasomotor symptoms around the time of lasofoxifene treatment groups (n=773) ranged from 55.0% to 58.5% compared with menopause, without variation by ethnicity. Subjective, but not objective, patterns of heat 56.0% in the placebo group (n=243). The incidence of weakly/marginal proliferative dissipation differed by ethnicity. Rates of concordance were similar between subjective endometrium in the lasofoxifene treatment groups ranged from 4.4% to 6.5% compared and objective sternal vs. nuchal measures. This study is on-going, with data collection in with 0.4% in the placebo group. Two lasofoxifene subjects, 1 in the 0.025 mg/day group rural communities as well as the city of Campeche. Funding: NSF Grant #BCS-1156368 (0.4%) and 1 in the 0.5 mg/day group (0.4%), and 1 placebo subject (0.4%) were found to have endometrial hyperplasia. Two cases of endometrial carcinoma occurred, one in the 0.025 mg/day lasofoxifene group (0.4%) and one in the placebo group (0.4%). At S-16. Month 24, for lasofoxifene-treated subjects (n=896) mean endometrial thickness ranged Baseline Anti-Mullerian hormone (AMH) is associated with incident from approximately 3.8 to 4.1 mm compared with approximately 2.9 mm for placebo natural menopause in the CARDIA Women’s Study (CWS) subjects (n=305). Overall, endometrial thickness ≥8 mm occurred in approximately Sangeeta Nair1, James Terry1, Chris Slaughter1, Duke Appiah2, Imo Ebong3, Cora Lewis4, 10% of lasofoxifene subjects in a non-dose dependent manner and approximately 3% of Pamela Schreiner2, David Siscovick5, Erica Wang6, Edmond Kabagambe1, Melissa placebo subjects. All histopathological assessments from these subjects were benign. The Wellons, MD, MHS1. 1Vanderbilt University, Nashville, TN; 2University of Minnesota, incidence of vaginal bleeding (preferred term: vaginal hemorrhage) in the lasofoxifene Minneapolis, MN; 3Loma Linda University, Loma Linda, CA; 4University of Alabama treatment groups (n=1419) ranged from 1.5% to 1.7% compared with 1.9% in the placebo Birmingham, Birmingham, AL; 5The New York Academy of Medicine, New York, NY; group (n=475). Conclusion: Lasofoxifene in postmenopausal non-hysterectomized 6Cedars-Sinai, Los Angeles, CA women was not associated with an increase in endometrial hyperplasia or carcinoma. Objective: The timing of menopause is associated with future risk of cardiovascular After 24 months, the incidence of endometrial hyperplasia or carcinoma was 0.4% disease, cancer and osteoporosis. Previously in CWS, we have shown that ultrasound- (3/773) for all lasofoxifene-treated subjects compared with 0.8% (2/243) in placebo- measured antral follicle count (AFC) can predict incident menopause up to 7 years later, treated subjects which was well below the FDA requirement of <1% and no different than supporting AFC’s potential as a useful biomarker of the timing of menopause. Anti- placebo. For all lasofoxifene treatment groups after 24 months, endometrial thickness Mullerian Hormone (AMH) is a more readily obtained serum biomarker of incident had increased from baseline in a non-dose dependent manner. Sub-endometrial cystic menopause. In cross-sectional studies, AMH appears to peak in women around 25 years echotexture and cystic atrophy appeared to account for these TVU changes; the majority of age and then gradually declines, disappearing by age 50, near the average age for of biopsies were atrophic or inactive on histology (55.0% to 58.5% for lasofoxifene menopause in the US. In longitudinal studies that have included Iranian, Dutch, and US groups; 56.0% for placebo). The incidence of vaginal bleeding was comparable between women, AMH is associated with the timing of menopause. In one Dutch study (n=257) the lasofoxifene groups and the placebo group. Lasofoxifene for the prevention of that also investigated AFC, AMH was the only biomarker associated with menopause osteoporosis has a safe endometrial profile out to 24 months. Published gynecologic after adjustment for age. Our aim here is to establish AMH’s age-independent association effects in the PEARL fracture trial also did not demonstrate any increase in endometrial with incident natural menopause in the longitudinal CARDIA study. Design: The hyperplasia or carcinoma out to 5 years with lasofoxifene 0.25 mg/day and 0.5 mg/day Coronary Artery Risk Development in Young Adults Study (CARDIA) is a longitudinal so supports the conclusion that lasofoxifene is safe at the endometrium. There was no population-based study (Chicago, IL; Birmingham, AL; Minneapolis, MN; and apparent dose-response effect on endometrial thickness or histology. Oakland, CA) that recruited 18-30 year olds when it began in 1985-86. In 2002-2003, a subset of CARDIA women, the CARDIA Women’s Study (CWS), had transvaginal

46

ultrasonography performed with AFC measured (2-10 mm follicles on both ovaries) and serum collected and stored for potential future use. In 2014, we measured AMH in stored samples from all CWS women with serum available. AMH was measured using the Ansh ultrasensitive method ELISA kit [ReproSource Laboratory (Boston, MA)] with a detection limit of 0.08 ng/ml. Follicle stimulating hormone (FSH) and estradiol were also measured. Demographic information, smoking history, and reproductive characteristics were obtained from self-report. BMI was calculated from measured height and weight in kg/m2. Incident natural menopause was determined by self-report through the Year 25 CARDIA exam (2010-2011). We analyzed the crude and adjusted associations of serum AMH with incident natural menopause using logistic regression analysis. Women self-reporting prevalent natural menopause, prevalent hysterectomy, or incident hysterectomy were excluded from analyses. Models included age (years), race (black vs. white), CARDIA site, smoking history (never vs. current, past), education (≤high school vs. >high school), menstrual cycle characteristics (stable menses vs. all other answers), FSH (ng/dL), estradiol (ng/dL) and BMI. Results: In our sample of initially premenopausal women with measured AMH (at ages 34-49) who completed the Year 25 CARDIA survey on menopause and denied hysterectomy (n=703), 193 women reported natural menopause, 9 years after initial AMH measurement. Among all women in our sample, the median AMH was 0.76 ng/dL and the 25% to 75% interquartile range/IQR was 0.22-1.98 ng/dL. Fifteen-percent (n=105/703) had AMH below the limit of detection of the assay (<0.08 ng/dL). Among those with and without natural menopause at Year 25 (2010-11), the median baseline AMH was 0.14 (IQR 0.09-0.41) and 1.27 (IQR 0.53- S-18. 2.75) ng/dL, respectively at a baseline (2002-2004) median age of 45 (IQR 44-47) and Increases in High Density Lipoprotein-Cholesterol Levels are Associated 41 (IQR 38-43) years. In logistic regression models, baseline AMH, age, and race were with Greater Intima-Media Thickness Progression over The Menopausal independently associated with incident natural menopause over 9 years. Women with Transition: The Study of Women’s Health Across the Nation (SWAN) a 0.5 ng/dL lower AMH had a 3-fold higher crude odds of experiencing menopause Samar R. El Khoudary, PhD, MPH1, Lin Wang1, Maria M. Brooks1, Rebecca C. Thurston, over 9 years of follow-up (OR 3.19; 95% CI, 2.49-4.10) and 2-fold higher odds after PhD1, Carol Derby2, Karen A. Matthews1. 1University of Pittsburgh, Pittsburgh, PA; adjustment for all covariates (OR 2.22; 95% CI, 1.76-2.86). Conclusion: Baseline AMH 2Albert Einstein College of Medicine, Bronx, NY is independently associated with natural menopause over 9 years of follow-up after Objective: Experimental and observational evidence demonstrates that high density controlling for demographic information and clinical markers of ovarian aging. We are lipoprotein (HDL) can lose its well-documented atheroprotective functions and currently comparing the utility of AMH, AFC, and FSH as biomarkers of the timing even adopt a paradoxically proinflammatory nature in certain conditions. Hormonal of future natural menopause. These analyses are needed to establish the most useful alterations, especially estradiol reduction, influence the accumulation of risk factors that biomarker, or combination of biomarkers, to predict the timing of natural menopause could potentially impair the quality of HDL as women transitioning through menopause. in CARDIA women. Limited data exist to evaluate the relationship between changes in high density lipoprotein cholesterol (HDL-C) over the menopausal transition and the development of S-17. atherosclerosis in women. We evaluated the association between changes in HDL-C and The association between menopausal hormone therapy and coronary progression of carotid intima-media thickness (cIMT) since the final menstrual period heart disease depends on timing of initiation in relation to menopause (FMP) in a sample of midlife women. Design: Participants were from the Study of Women’s Health Across the Nation (SWAN) Pittsburgh site, who had up to 5 measures onset. Results based on pooled individual participant data from The of cIMT over a maximum of 9 years of follow-up. Women were free of cardiovascular Combined Cohorts of Menopausal Women – Studies of Register Based disease (CVD) at the baseline scan. Time points at which women were on hormone Health Outcomes in Relation to Hormonal Drugs (COMPREHEND) therapy or lipid lowering medications were excluded. Linear mixed effects models with a study. random intercept were used to model longitudinal measures of cIMT. Repeated measures German D. Carrasquilla, PhD student1, Chiara Chiavenna1, Matteo Bottai1, Patrik K. of HDL-C were coded using separate interactions between time since FMP and HDL-C at Magnusson2, Michele Santacatterina1, Alicja Wolk1, Göran Hallmans3, Jan-Håkan baseline, and between time since FMP and change in HDL-C since baseline to assess the Jansson4, Gunnar Engström5, Christer Borgfeldt5, Nancy L. Pedersen2, Mats Eliasson4, cross-sectional and the longitudinal effects of HDL-C on cIMT progression, respectively. Anita Berglund1, Karin Leander1. 1Inst. of Environmental Medicine, Karolinska Institutet, Final models included age at baseline, time since FMP, race, education, and time- Stockholm, Sweden; 2Dept. of Medical Epidemiology and Biostatistics, Karolinska varying covariates: systolic blood pressure (SBP), body mass index (BMI), low density Institutet, Stockholm, Sweden; 3Dept. of Biobank Research, Umeå University, Umeå, lipoprotein cholesterol (LDL-C), menopausal status, and use of CVD medications. Sweden; 4Dept. of Public Health and Clinical Medicine, Umeå University, Umeå, Results: The study included 225 women (28% Black, 72% White; 95% pre- or early Sweden; 5Dept. of Clinical Sciences, Lund University, Lund, Sweden peri-menopausal) aged (mean (SD)): 45.7(2.5) years at the baseline scan. In a minimally Objective: Menopausal hormone therapy (MHT) use has been intensely debated adjusted model for age at baseline, time since FMP, race and education, a higher baseline during the last decade. Discrepant results have been reported from observational cohort level of HDL-C was significantly associated with a slower cIMT progression [-0.002 studies and randomized control trials regarding the association between MHT and risk mm/year per 1 SD (11.80 mg/dL) increase in baseline HDL-C, p=0.02], while a larger of coronary heart disease (CHD). It has been suggested that lack of consideration of increase in HDL-C since baseline was significantly associated with a faster cIMT timing of MHT initiation in relation to menopause onset may partly explain discrepancies progression [0.002 mm/year per 1 SD (6.06 mg/dL) increase in HDL-C since baseline, between study results. This study aims to assess if early and late initiation of MHT, p = 0.009]. Additional adjustment for SBP, BMI, LDL-C, menopausal status, and use respectively, associates with the development of CHD. Design: Individual participant of CVD medication attenuated the association between baseline HDL-C level and cIMT data on MHT use and other relevant data collected at baseline investigations (1991-2006) progression (p= 0.09); while the association between HDL-C change since baseline and of menopausal female participants of 5 population-based Swedish cohort studies (total cIMT progression remained significant (p= 0.009). Conclusion: As women transition n=74,352) were pooled. Prospective surveillance data on CHD diagnoses and causes of through menopause, increases in HDL-C levels, known as the good cholesterol, are death were obtained by record linkage to the National Patient Register and the Cause of associated with greater cIMT progression, independent of traditional CVD risk factors. Death Register. Using Laplace regression, we analyzed associations between MHT and These findings suggest that the quality of HDL may be altered over the menopausal CHD risk by estimating the first and fifth survival percentile differences (PD) with 95% transition rendering HDL dysfunctional and not providing the expected cardioprotective confidence intervals (CI). The PD indicates the differences in the number of event-free effect. Acknowledgments: The Study of Women’s Health Across the Nation (SWAN) years between the exposed group and the unexposed group. Adjustments were made for has grant support from the National Institutes of Health (NIH), DHHS, through the age, age at menopause onset, educational level, smoking status, body mass index, type National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) of menopause, diabetes, hypertension and dyslipidemia. Results: During a maximum of and the NIH Office of Research on Women’s Health (ORWH) (Grants NR004061; 22.7 years of follow up (average of 13.4 years) we recorded 4,714 first-time CHD events. AG012505, AG012535, AG012531, AG012539, AG012546, AG012553, AG012554, Compared with never use, the early initiation of MHT (within 5 years from menopause AG012495). The Study of Women’s Health Across the Nation Heart is supported by the onset) was associated with a longer time period free from CHD events, after adjusting National Heart, Lung, and Blood Institute (Grants HL065581, HL065591). for confounders: 1st PD of 0.31 years (95% CI -0.41, 1.04) and 5th PD of 1.34 years (95% CI 0.47, 2.21). Compared with never use, the late initiation of MHT (more than 5 years since menopause onset) was associated with a shorter time period free from CHD events: S-19. 1st PD of -1.02 years (95% CI -1.82, -0.22) and 5th PD of 0.05 years (95% CI -0.93, 1.03). Gamma-oryzanol increases NO production of carotid artery in Conclusion: Early initiation of MHT with respect to menopause onset was associated ovariectomized rats with a decreased risk of future incident CHD, while late initiation was associated with Makoto Iizuka, M.D.1,2, Satoshi Obayashi, M.D., Ph.D.1, Ayumi Yamaguchi, M.S.1, an increased risk. Yoshinori Ohkura, M.D., Ph.D.1, Shuichi Sakamoto, M.D., Ph.D.2, Toshiro Kubota, M.D., Ph.D.1. 1Department of Comprehensive Reproductive Medicine, Tokyo Medical & Dental University, Bunkyo-ku, Japan; 2Obstetrics and Gynecology, Dokkyo Medical University Koshigaya Hospital, Koshigaya, Japan Objective: Loss of ovarian hormone has impairment on endothelial function and results in cardiovascular disease. In Japanese traditional foods, rice bran oil has been used to improve the effect of menopausal symptom and to prevent cardiovascular diseases, but

47 ABSTRACT PRESENTATIONS its precise mechanism was not clarified. Gamma-oryzanol (gamma-ORZ) is a mixture of total hip BMD by 1.4%, 2.0%, and 2.1% in the 0.025mg, 0.25mg and 0.5mg doses phytosteryl ferulates purified from rice bran oil and we examined whether gamma-ORZ respectively, compared to a 0.3% loss in the placebo group. The 0.25mg and 0.5mg doses represents some direct effects on the endothelial function including nitric oxide (NO) produced significantly superior BMD responses as early as 6 months when compared to production. The aim of this study was to determine the bioavailability of gamma-ORZ the 0.025mg dose. Lasofoxifene at all doses showed significant improvement (p<0.021) and possible involvements in arterial function. Design: Twelve weeks female Sprague- in all sub-components of the total hip (femoral neck, greater trochanter, intertrochanteric Dawley rats underwent abdominal overiectomy and fed by soy-bean free diet, AIN-93G area, Ward’s triangle) at all time points. Lasofoxifene at all doses and all time points for 2 months in order to eliminate the effect of endogenous estrogen and phytoestrogens. significantly (p<0.001) decreased osteocalcin and CTX at 6 and 24 months when After 16th week, rat were divided into 3 groups and given the following diets: Group1 compared to placebo. Conclusion: Lasofoxifene, an estrogen agonist-antagonist, (n=6), AIN-93G; Group2 (n=8), AIN-93G mixed with 1% gamma-ORZ; Group3 (n=6), demonstrates estrogen-like anti-resorptive properties on bone, as well as estrogenic AIN-93G mixed with 3% gamma-ORZ. At 18th weeks, the left carotid arteries were effects on the vagina, and antagonistic effects on breast. At doses ranging from 0.025mg denuded with 2 Fr forgaty balloon catheter to induce intimal hyperplasia and all rats were to 0.5mg, bone turnover markers and bone density measurements confirm beneficial sacrificed at 20th week. The effect of gamma-ORZ (1% or 3%) on formation of intimal effects in protecting against postmenopausal bone loss. Additionally, the published hyperplasia were evaluated with microscopic findings, and the effects on endothelial PEARL 5-year lasofoxifene fracture prevention trial demonstrated reduction in vertebral function including endothelial NO release in carotid artery were evaluated with isometric fractures at 3 years with the 0.25mg and 0.5mg doses and non-vertebral fracture reduction tension change. Acetylcholine (ACh: 10(-9) to 3x10(-6) M) was used as a receptor- at 5 years with 0.5mg. The present pivotal phase 3 studies identify lasofoxifene in doses mediated endothelium-dependent agonist and A23187 (10 (-6) to 3×10(-3) M) was of 0.25mg and 0.5mg as an effective option for the prevention of osteoporosis in women used as a receptor-non-mediated, endothelium-dependent agonist. These two agonists seeking the tissue selective benefits of the SERM lasofoxifene. induced relaxation with or without NO synthase inhibitor (NG nitro L-arginine: LNA: 10(-4) M) under U46619 (10(-7) M) evoked contraction, was recognized as NO release marker. Sodium nitroprusside (SNP; 10(-10) to 3×10(-5) M) as an NO donor was used to S-21. evaluateNO sensitivity of smooth muscle. The plasma ferulate acid (FA) concentration Lasofoxifene, an estrogen agonist/antagonist favorably impacts lipid as the metabolite of gamma-ORZ was also assessed by high performance liquid parameters: Results from the Osteoporosis and Lipid Lowering (OPAL) chromatography (HPLC). All results are expressed as mean ± S.D. Statistical analysis Study were performed with t-test or two-way ANOVA with Stat View J 5.0 program and David J. Portman, MD1, James A. Simon, MD, CCD, NCMP, FACOG2, James values of p<0.05 were considered as statistically significant. All studies complied with Symons, MS, PhD1. 1Sermonix Pharmaceuticals, Columbus, OH; 2George Washington, the Animal Welfare Regulations of the Tokyo Medical and Dental University. Results: Washington, DC There were no significant differences in body weights among 3 groups. In gamma-ORZ Objective: Some of the beneficial effects of estrogen on the cardiovascular system groups, the plasma concentration of FA were significantly higher (1% group, 70.1±11.9 in early menopause may be attributable to a favorable impact on lipids, however the (ng/ml) ; 3% group, 70.9±10.2) compared with control group (CON: 53.3±3.0 and increase in cardiovascular-related adverse events[JS1] in women initiating oral hormone gamma-ORZ groups indicated higher reduction in intima:media ratio (0.63±0.59 and therapy later in menopause may be associated with plaque instability and an increase in 0.66±0.53, respectively) than control group (1.30±0.61). The relaxation response induced inflammatory markers, most notably C-Reactive Protein (CRP). Additionally, estrogen/ by ACh (3×10(-6) M) was significantly higher in 3% group (71.6±5.1 (%) ) than control progestin therapy has been linked to an increase in breast cancer incidence with longer- group (46.4±13.2 (%) ),however, no significant differences were observed compared term use. Lasofoxifene, a third-generation selective estrogen receptor modulator (SERM), with 1% group (57.9±8.4 (%) ). And these relaxations were significantly inhibited by has estrogen-agonist effects on the vagina and bone, as well as estrogen-antagonist LNA pretreatment (CON:9.3±5.9(%); 1% group, 8.4±6.0; 3% group,5.1±3.5). On the effects at the breast. The OPAL (Osteoporosis Prevention and Lipid Lowering) study other hand, no significant differences were observed in both A23187 (3×10(-6) M) and was conducted to evaluate the impact of lasofoxifene on lipid parameters in a subgroup SNP (10(-6) M) induced relaxation responses among 3 groups which suggested the of women with elevated cholesterol at baseline as well as an overall cohort of women remaining post receptor signal transduction in these groups. Conclusion: In isoflavone seeking osteoporosis prevention. Design: The 24 month OPAL trial randomized 1,907 free condition, gamma-ORZ administration enhanced Ach stimulated vasodilation women (mean age 58.6 years). Approximately 575 were assigned to one of four treatment through Ach membrane receptor level or post rereceptor level modification. Gamma- arms: lasofoxifene 0.025, 0.25, or 0.5mg, or placebo. The two co-primary endpoints of ORZ may have a beneficial effect for intimal hyperplasia and cardiovascular disease the study were percent change in lumbar spine BMD at 24 months and percent change through increased endothelial NO release. in serum LDL-C (baseline to 6 months, measured by direct assay) in a pre-specified subgroup. This designated Lipid Analysis Subgroup of 575 women required a stable baseline serum LDL-C between 130 and 190 mg/dl after a 6 week, low-fat diet, run-in FRIDAY CONCURRENT SESSION #2 period and who did not use lipid-lowering medications during the 90 days preceding the trial. The study population at large was also evaluated for lipid effects and safety. Rank- transformed percent change from baseline in LDL-C was analyzed by means of linear S-20. models and tests were done on least square means. Results: Lasofoxifene in the Lipid Lasofoxifene prevents postmenopausal bone loss: Pooled data from two Analysis Subgroup, at all doses, and at all timepoints (1.5, 3 and 6 months) significantly pivotal 24 month osteoporosis prevention trials (p<0.001) reduced serum LDL-C compared to placebo. Lasofoxifene at 0.25mg and Risa Kagan, MD1, James Symons, MS, PhD2, David Portman, MD2. 1University of 0.5mg decreased LDL-C by 16% and 17% respectively, compared to a 9% reduction California,San Francisco and Sutter East Bay Medical Foundation, Berkeley, CA; with 0.025mg. The difference between 0.025 mg lasofoxifene and the two higher doses 2Sermonix Pharmaceuticals, Columbus, OH was statistically significant (p<0.001). LDL-C was unchanged at all time points in the Objective: Rapid onset of bone loss in menopause predisposes women to lower bone placebo group. In the overall OPAL cohort, multiple lipid parameters were also evaluated mass and to an ultimate 50% lifetime risk of fragility fracture. Early intervention may at 12 months. Lasofoxifene at all doses showed significant (p<0.001) reductions in total help women maintain peak bone mass and treatments for symptomatic conditions in cholesterol, LDL-C, Apo B-100 and Lp(a). Similar LDL-C reductions of approximately menopause may confer multiple benefits and encourage compliance with therapy. 18% were observed in both this general study population (median at 12 months) and Lasofoxifene,a naphthalene-derivative, third generation tissue-selective estrogen the lipid subgroup (mean at 6 months) for the 0.25mg and 0.5mg lasofoxifene doses. receptor modulator (SERM), has favorable estrogenic effects on vulvovaginal atrophy Conclusion: In the placebo-controlled OPAL study of women with elevated baseline (VVA) and bone remodeling, and estrogen antagonistic effects on breast tissue. The LDL-C as well as in the larger osteoporosis prevention cohort, lasofoxifene had impact of lasofoxifene on bone mineral density(BMD) and bone turnover markers significant beneficial lipid-lowering effects. Additionally, in the lasofoxifene Phase 3 (BTMs)were the subject of 2 randomized placebo controlled studies in postmenopausal program, CRP was lowered by 13-16%. Of note, in the published 5 year PEARL study women. Design: Screened postmenopausal women 40-74 years of age with normal or of over 8,500 women 67 years of age on average, lasofoxifene was associated with a low spinal bone mass were given 1000 mg calcium and 200–500 IU of vitamin D daily reduction in coronary heart disease and stroke. The 0.5mg dose statistically reduced during a 6 to 8-week pre-randomization period. A total of 1,907 women (mean age 58.6) major coronary heart events by 32% (primarily coronary revascularization). This differs were randomized in two trials, approximately 475 each to one of 4 treatment groups: from the increase in early harm cardiovascular events seen in the Women’s Health lasofoxifene 0.025mg, 0.25mg, 0.5mg, or placebo. At baseline, the subjects were a mean Initiative when estrogen-progestin was initiated later in menopause. The favorable 10.1 years postmenopausal with an average BMD T-score -1.36 at the lumbar spine impact of lasofoxifene on lipid parameters and inflammatory markers may help explain (LS: L1–L4) with no significant baseline demographic differences between treatment its beneficial impact on coronary heart disease reduction in postmenopausal women with groups. 88% remained in the trial for the planned 24 months. 90% had a baseline and osteoporosis. Lasofoxifene offers women a SERM alternative to estrogen, with extra- at least one on-study lumbar spine BMD and were analyzed for the primary endpoint skeletal benefits on the cardiovascular system in addition to its demonstrated favorable of percent change from baseline to two years in BMD of the LS. Secondary endpoints effects on breast and vulvo-vaginal health. included percent change from baseline to months 6, 12, and 24, in BMD for total hip, femoral neck, intertrochanteric area, greater trochanter, and Ward’s triangle and percent change from baseline in BTMs osteocalcin and C-telopeptide (CTX)at Months 6 and S-22. 24 between lasofoxifene and placebo. The linear model used for analyzing percent Effects of Ospemifene on Lipid and Coagulation Parameters in change from baseline in LS and non-lumbar BMD included treatment group and Postmenopausal Women baseline BMD as covariates. Serum BTMs were rank-transformed and analyzed using David F. Archer1, Corrado Altomare, MD2, Wei Jiang2, Susannah Cort2. 1Eastern Virginia linear models. Results: Lasofoxifene, at all doses, and at all time points significantly Medical School, Norfolk, VA; 2Shionogi Inc., Florham Park, NJ (p<0.001) increased lumbar spine BMD compared to placebo. At 24 months, lasofoxifene Objective: Ospemifene is the first FDA-approved, oral treatment option for moderate increased mean lumbar spine BMD by 1.5%, 2.3%, and 2.3% for the 0.025mg, 0.25mg, to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), a component and 0.5mg doses respectively, compared to a 0.7% loss in placebo. The 0.25mg and of the newly recognized genitourinary syndrome of menopause. This post-hoc, pooled 0.5mg lasofoxifene groups produced significantly superior BMD responses as early as analysis evaluated the effect of ospemifene 60 mg/day on lipid and coagulation 6 months when compared to the 0.025mg dose. At 24 months, lasofoxifene increased parameters in postmenopausal women. Design: Six phase 2 or 3 randomized, placebo-

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controlled clinical trials of ospemifene in postmenopausal women were included. Lipid Median time to a stable 50% reduction was 9, 10, and 38 d respectively. Median time to and coagulation parameters were measured at baseline, and at 12 weeks, 6 months, and a transient 90% reduction was 32 d for CE0.45mg/BZA20mg and 22.5 d for CE0.625mg/ 12 months. Lipid parameters included total cholesterol (TC), high density lipoproteins BZA20mg vs >12 wk (not reached) for PBO. Median time to a stable 90% reduction was (HDL), low density lipoproteins (LDL), and triglycerides (TG). Coagulation parameters 83 and 29 d, vs >12 wk (not reached). Conclusion: Although women using CE/BZA may included activated partial thromboplastin time (aPTT), fibrinogen, antithrombin antigen, not achieve permanent elimination of HFs, HF frequency is likely to be substantively protein C Ag, and protein S Ag free. Mean±SD percent changes from baseline were reduced during the first week to month of use. Women can expect ~50% reduction in HF calculated. Welch’s t-test was used to compare ospemifene 60 mg/day versus placebo. frequency after about 8–10 d; once achieved, this improvement is likely to be sustained Subgroup analyses based on age, BMI, and baseline TG level were also conducted. quickly with continued treatment. Improvement may vary for individual women. Women Results: A total of 2,166 participants were randomized in the 6 trials to receive oral should be encouraged on the rapidity of response but cautioned against discontinuing daily ospemifene 60 mg (N=1,242) or placebo (N=924). Similar percentages of women CE/BZA prematurely as greater reductions in HF frequency are expected as treatment completed the studies in the ospemifene (85.4%) and placebo groups (86.8%). Baseline continues. characteristics (age, race, BMI, gynecological history) were similar between groups; the majority of the women were Caucasian with mean age 59 years and mean BMI 26 kg/ m2. Ospemifene significantly increased HDL and decreased LDL levels, compared with placebo, at 12 weeks, 6 months, and 12 months (Table 1). TG and TC levels were not significantly different between the ospemifene and placebo groups, except for TC at 6 months (Table 1). Similar effects on the lipid factors were observed across subgroups based on age, BMI, and baseline TG level. The coagulation parameters, fibrinogen and protein C Ag, significantly decreased from baseline with ospemifene versus placebo at all time points (Table 2). The post-baseline levels of those two factors remained within the normal range in more than 90% of women throughout the study. Conclusion: In this pooled, post-hoc analysis, ospemifene 60 mg/day significantly increased HDL and decreased LDL levels, while having little effect on TG levels, compared with placebo. Such effect of ospemifene on lipids appears to be similar to that of other SERMs. The decreases in fibrinogen and protein C Ag levels in ospemifene-treated women are considered unlikely to have clinical consequences. Table 1. Changes in serum lipid levels from baseline to 12 weeks, 6 months, and 12 months with ospemifene 60 mg.

Table 2. Changes in coagulation parameters from baseline to 12 weeks, 6 months, and 12 months with ospemifene 60 mg.

Fig. Time to (A) Transient and (B) Stable Events

S-24. Time to First Occurrence of Breast Pain/Tenderness and Vaginal Bleeding in Phase 3 Trials of CE/BZA JoAnn V. Pinkerton, MD1, Andrew Bushmakin, MS2, Joel Bobula, MA3, Joanne Lavenberg, BS3, Barry Komm, PhD3, Lucy Abraham, MSc, CPsychol4. 1University of Virginia Health System, Charlottesville, VA; 2Pfizer Inc, Groton, CT; 3Pfizer Inc, Collegeville, PA; 4Pfizer Ltd, Tadworth, United Kingdom Objective: Estrogen-progestin therapy increases breast pain/tenderness (BP/T) and vaginal bleeding. In clinical trials of a menopausal therapy combining conjugated S-23. estrogens (CE) with the selective estrogen receptor modulator bazedoxifene Time to Transient and Stable Reductions in Hot Flush (HF) Frequency (BZA), BP/T and vaginal bleeding rates were comparable to PBO and lower vs CE/ in Postmenopausal Women Using CE/BZA medroxyprogesterone acetate (CE/MPA). This post hoc analysis determined median time JoAnn V. Pinkerton, MD2, Andrew Bushmakin, MS3, Lucy Abraham, MSc, CPsychol1, to first occurrence of BP/T and vaginal bleeding with CE/BZA, PBO, and CE/MPA. Barry Komm, PhD4, Joel Bobula, MA4. 1PRO Center of Excellence, Pfizer Ltd, Tadworth, Design: In phase 3 CE/BZA trials, postmenopausal women recorded the presence of United Kingdom; 2University of Virginia Health System, Charlottesville, VA; 3Pfizer Inc, BP/T (SMART-1, -2, -5) and vaginal bleeding (SMART-1, -5) in diaries. Median time Groton, CT; 4Pfizer Inc, Collegeville, PA to first incident was determined in women taking CE0.45mg/BZA20 mg, CE0.625mg/ Objective: Phase 3 trials of conjugated estrogens/bazedoxifene (CE/BZA) reported BZA20 mg, and PBO (SMART-1, -2, -5), and CE0.45mg/MPA1.5mg (active control, reductions in HF frequency at 12 wk and beyond, but time to various degrees of SMART-5). We included on-treatment data in healthy postmenopausal women improvement is unknown. To help clinicians set patient expectations regarding onset of (SMART-1: 2 y; SMART-5: 1 y), and postmenopausal women with moderate/severe benefit, this post hoc analysis estimates median time to transient and stable reductions in VMS (SMART-2: 12 wk; SMART-1 subgroup: 2 y). Analyses used SAS Proc Lifetest. HF frequency in postmenopausal women using CE/BZA. Design: In the 12-wk SMART-2 Results: In SMART-5, median time to onset of breast tenderness was 299 d for CE/ trial of CE0.45mg/BZA20mg and CE0.625mg/BZA20mg, women with ≥7 moderate/ MPA, 353 for PBO, and >365 (median not reached) for CE0.45mg/BZA20mg and severe HF/d or 50/wk at screening recorded frequency of moderate/severe HF in diaries. CE0.625mg/BZA20mg. Median time to vaginal bleeding was 314, 341, 357, and 362 We used nonparametric models to estimate median times to transient improvement (first d respectively. Survival curves (Fig) were not significantly different for CE/BZA and postbaseline day with improvement) and stable improvement (first postbaseline day PBO (P>.05), but were (P<.0001) when CE/MPA was added to the sample. Breast pain with improvement maintained for the remainder of the study). Improvement was defined survival curves in SMART-1 and -2 were not significantly different for CE/BZA and based on reduction in HF frequency. The SAS Proc Lifetest was used. Results: CE/ PBO. Breast pain occurred at a median of >730 d with CE/BZA and PBO in SMART-1 or BZA produced transient HF frequency reductions of 40%–100% and stable reductions of >84 d in SMART-2 (medians not reached at 2-y and 12-wk, respectively). Results were 30%–100% significantly faster than PBO (Fig). Median time to a transient 50% reduction similar for vaginal bleeding (SMART-1), with a median of >730 d for CE/BZA or PBO. was 8 d for CE0.45mg/BZA20 mg, 9.5 for CE0.625 mg/BZA20mg, and 10 for PBO.

49 POSTER PRESENTATIONS

Conclusion: Median times to BP/T and vaginal bleeding were not reached for up to 2 y withdrawal-induced osteocytes apoptosis may be related to changes in the HMGB1 with CE/BZA and were no sooner with CE/BZA vs PBO. Events occurred significantly immunoexpression pattern in these cells. These findings point to a possible role of earlier with CE/MPA vs CE/BZA or PBO. HMGB1 in the recruitment of osteoclasts culminating in bone resorption in estrogen deficient female rats.

P-2. Altered short-term in vitro proliferative activity of human endometrial stromal cells by high-concentration gonadotropins Yoon Young Kim, PhD, Hye Min Kim, Seung-Yup Ku, MD,PhD, Chang Suk Suh, MD, PhD, Seok Hyun Kim, Young Min Choi. OB/GYN, Seoul Natl Univ Hospital, Seoul, Korea (the Republic of) Objective: Menopause is accompanied by high FSH and LH levels. Recently, FSH receptors as well as LH receptors were found on the endometrium. However, direct effects of gonadotropins on the endometrium is rarely elucidated to date. We tried to evaluate the effects of FSH, LH and hMG on the in vitro proliferative activity of human endometrial stromal cells. Design: A human endometrial stromal cell (HESC) line was purchased from ATCC. Cells were plated at a concentration of 1.5 x 105 cells/plate, and treated with 0, 15, 30, 150 mIU/mL of urinary and recombinant FSH, LH and hMG for up to 72 hrs. Proliferative activity was measured by BrdU assay. Expression of cell cycle- related genes, cyclin A1, cyclin D1 and cyclin E1 was evaluated using qRT-PCR from 24, 48, 72 hrs groups. Results: In vitro proliferative activity of HESCs was decreased in response to gonadotropin treatment, however, significant dose dependent response was not observed. Expression of cell cycle-related gene expression was altered in all treated groups. Conclusion: Taken together, gonadotropin-induced suppression of endometrium in addition to depletion of estrogen may explain the atrophy of postmenopausal endometrium. (HI14C2289 and HI14C2259).

P-3. Imbalance between the apoptotic cell death (caspase-3 cleaved) and the cellular proliferation (PCNA) in lacrimal gland of female mice of hyperprolactinemic female mice Ariadne S. Leal, Ms3,1, Manuel J. Simões, PhD1, José M. Soares Júnior, MD, Ph.D4, Carina Verna, Dr3,1, Regina C. Teixeira Gomes, PhD2,1. 1Department of Morphology, Federal University of São Paulo, São Paulo, Brazil; 2Gynecology, Federal University of São Paulo, São Paulo, Brazil; 3Ophthalmology, Federal University of São Paulo, São Paulo, Brazil; 4Obstetrics and Gynecology, Faculty of Medicine University of São Paulo, São Paulo, Brazil Objective: To investigate expression of cleaved caspase-3 and PCNA in the in the lacrimal gland of female mice of hyperprolactinemic mice female. Design: 20 female/groups: control group (non pregnant, Ctr1): 0.2 mL of saline (vehicle) and the experimental group (non pregnant, HPrl1): 200 μg/day of metoclopramide, dissolved in vehicle. After 50 days 10 females of each group were placed for mating with males and continued to receive treatment. The females non pregnant was euthanasia on 50th day (experimental I) and the females pregnant were euthanasia on 5.5th to 6.5th post-coital day (Ctr2: control group and HPrl2: experimental group). The blood samples were collected for hormone measurements. The uterus was processed for immunohistochemistry. The results were subjected to statistical test (p <0.05). Results: The decreased immunoexpression of caspase 3 in the non pregnant controls compared to non-experimental group (p <0.05). And increased cell proliferation (PCNA) in the pregnant control group compared to pregnant experimental group (p <0.05). Serum prolactin levels were higher whereas the levels of estradiol and progesterone were lower in the animals that received metoclopramide compared to controls. Conclusion: The Fig. Kaplan-Meier survival analysis for onset time of breast tenderness (A) and vaginal metoclopramide-induced hyperprolactinemia altered the cellular activity in lacrimal bleeding (B), SMART-5 glands in non pregnancy and pregnancy as a consequence of the imbalance between the apoptotic cell death (caspase-3 cleaved) and the cellular proliferation (PCNA). It is hypothesized that this effect might be related with decrease in the hormonal production BASIC SCIENCE POSTER PRESENTATIONS of estrogen and progesterone.

P-1. P-4. A possible participation of HMGB1 in the recruitment of osteoclasts in Expression and influence ovarian function by the upregulation the alveolar bone of estrogen deficient female rats. and downregulation of steroidogenesis related genes in ovary of Rinaldo Florencio-Silva, Dr1, Gisela R. Sasso1, Estela Sasso-Cerri, Dr2, Manuel J. pinealectomized rats in proestrous phase: Folistatin and Inhibin-βA Simões, PhD1, Paulo Cerri, Dr2. 1Morfologia e Genética, Universidade Federal de São Carla C. Maganhin, post doctoral1, Luiz F. Fuchs1, Ricardo S. Simões, Dr1, Gisela Paulo, São Paulo, Brazil; 2Unesp-Araraquara, Araraquara, Brazil R. Sasso2, Edmund C. Baracat1, José Maria Soares- Jr1. 1Obstetrics and Gynecology, Objective: To evaluate the HMGB1 (a chromatin nuclear associated protein) University São Paulo, FMUSP/USP, São Paulo, Brazil; 2Morphology and Genetics, immunoexpression pattern in osteocytes and a possible association with alveolar bone Federal University of São Paulo, São Paulo, Brazil resorption in ovariectomized rats Design: Eighteen adult female rats were sham- Objective: To analyze the immunoexpression of estrogen receptors in ovaries of operated (SHAMG) or ovariectomized (OVXG). After 21 days, the rats received daily pinealectomized or melatonin-treated pinealectomized rats. Design: Thirty adult female subcutaneous injection of 30μg/Kg of body weight of estrogen (OVXEG) or vehicle rats were randomly divided into three groups of 10 animals each: Group I – Control; solution (OVXG) for 30 days. The rats were euthanized and the fragments of maxilla Group II - pinealectomized (Px), and Group III - Px treated with melatonin (10μg/ containing the alveolar bone of the first molars were fixed and embedded in paraffin. night, per animal). After two months’ treatment, the ovaries were collected, fixed in Sections were subjected to the TRAP method (osteoclast marker) for osteoclast 10% buffered formaldehyde and processed for paraffin embedding. Sections were quantification and TUNEL method for apoptosis detection. Sections were also subjected then subjected to immunohistochemical detection of estrogen receptors. Under 400x to immunhistochemistry for detection of HMGB1. The number of TUNEL-positive of magnification, the analyses were carried out according to the color intensity, which osteocytes and the percentage of HMGB1 immunolabeled cytoplasm and nuclei in varied from weak to strong immunoreactivity. Results: The Px (GII) group showed a osteocytes were computed. Statistical analyses were performed using Tukey test and the higher immunoreactivity of estrogen receptors in the granulosa and interstitial cells, as significance level was 5%. Results: OVXG group showed a singnificant increase in the compared to the control (GI) and melatonin treated (GIII) groups, whereas a similar weak number of osteoclasts and TUNEL-positive osteocytes in comparison to SHAMG and immunostaining was found in the outer and inner theca cells in all groups. Conclusion: OVXEG groups. In addition, a high percentage of HMGB1-citoplasmic immunolabeling Melatonin may decrease estrogen receptors immunoexpression in ovarian follicles of and a low percentage of HMGB1-positive nuclei in osteocytes were seen in the OVXG pinealectomized rats. group in comparison with the SHAMG and OVXEG groups. Conclusion: The estrogen

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P-5. as compared to SC progesterone. In addition, Ki67 staining was the greatest in in the Imnunoexpression of estrogen receptors may decrease produce melatonin group receiving unopposed estradiol and significantly less in the group treated with in ovaries of pinealectomized female rats progesterone, SC. The group treated with topical progesterone had numerically less Ki67 Carla C. Maganhin, post doctoral1, Luiz F. Fuchs1, Gisela R. Sasso2, Ricardo S. Simões, staining. Conclusion: Topically-applied progesterone successfully penetrates the skin of Dr1, Edmund C. Baracat1, José M. Soares Júnior, MD, Ph.D1. 1Obstetrics and Gynecology, the rat and opposes the effects of 17-beta estradiol to a similar degree as SC progesterone University of Sao Paulo,FMUSP, São Paulo, Brazil; 2Morphology and Genetics, Federal in a model of estradiol-induced endometrial hypertrophy and proliferation. University of Sao Paulo, São Paulo, Brazil Objective: To analyze the immunoexpression of estrogen receptors in ovaries of P-8. pinealectomized or melatonin-treated pinealectomized rats. Design: Thirty adult female Exposure, Tissue Distribution, and Metabolite Profile of Transdermal rats were randomly divided into three groups of 10 animals each: Group I – Control; Group II - pinealectomized (Px), and Group III - Px treated with melatonin (10μg/ Progesterone in the Female Rat Ginger D. Constantine, MD2, Philip Inskeep, PhD3, Richard Winneker, PhD4, Lawrence night, per animal). After two months’ treatment, the ovaries were collected, fixed in de Garavilla, PhD5, Brian Bernick1, James H. Pickar6, Annette M. Shadiack, PhD1. 10% buffered formaldehyde and processed for paraffin embedding. Sections were 1TherapeuticsMD, Boca Raton, FL; 2EndoRheum Consulting LLC, Makvern, PA; then subjected to immunohistochemical detection of estrogen receptors. Under 400x 3InskeepDMPK, LLC, East Lyme, CT; 4RC Winneker Consulting, LLC, Penllyn, PA; of magnification, the analyses were carried out according to the color intensity, which 5GDL Consulting and Contracting, Doylestown, PA; 6Columbia University Medical varied from weak to strong immunoreactivity Results: The Px (GII) group showed a School, New York, NY higher immunoreactivity of estrogen receptors in the granulosa and interstitial cells, as Objective: To compare plasma, uterine, and salivary gland levels of progesterone, compared to the control (GI) and melatonin treated (GIII) groups, whereas a similar weak allopregnanolone (ALLO), and ALLO-sulfate in the rat following either transdermal or immunostaining was found in the outer and inner theca cells in all groups. Conclusion: subcutaneous delivery of progesterone. Design: Thirty-two 8-week-old, female, Crl:CD® Melatonin may decrease estrogen receptors immunoexpression in ovarian follicles of rats underwent oophorectomy 2 weeks prior to study start. Rats were randomly assigned pinealectomized rats to 4 groups of 8 rats each. Three of the groups received 3 mcg/kg/day 17 beta-estradiol, subcutaneously (SC), for 8 days as well as one of the following: (a) placebo cream, (b) P-6. 10 mg/kg/day (~2.5 mg/rat/day) progesterone, SC, or (c) 3.13 mg/rat/day progesterone Preventive application of high-frequency mechanical vibration is better transdermally beginning on Day 4. An additional group received vehicle, SC, for 8 days than its treatment in bone of osteopenic rats and placebo cream beginning on Day 4. Two hours post the final dose (Day 8), the Gisela R. Sasso, Rinaldo Florencio-Silva, Miriam A. Santos, Cristiane D. Teixeira, Dr, rats were humanely euthanized and plasma, salivary glands, and medial portions of the Manuel J. Simões, PhD. Federal University of São Paulo, São Paulo, Brazil uterine horns were frozen for bioanalysis. Plasma and tissue homogenates were analyzed Objective: Low-intensity, high-frequency mechanical vibration (LHMV) has shown to for progesterone, ALLO, and ALLO-sulfate using LC-MS/MS. Results: Mean (± SD) increase bone formation. However, studies comparing the effectiveness of preventive progesterone levels in the plasma following topical administration were 2.0 ± 0.65 ng/ and late-treatments of LHMV to counteract bone loss have not been documented. This mL/mg dose as compared to 5.4 ± 1.9 ng/mL/mg dose when administered SC. Mean (± study was designed to compare the effects of preventive and late-treatments of LHMV SD) progesterone levels in the salivary glands and log-transformed means (lower, upper (at 30 Hz/0.6g, 20 min per day/five days per week, for 12 weeks) on bone parameters SD) in the uterus following topical administration were 10 ± 15 and 24 (9.3, 63) ng/ in ovariectomized (Ovx) rats. Design: Thirty days after ovariectomy, 40 adult rats were mL/mg dose, respectively as compared to 5.9 ± 9.4 and 39 (11, 140) ng/mL/mg dose, divided into four groups: GI (preventive control group); GII treated with LHMV three respectively, when administered SC. The ratios of progesterone levels in the uterus to weeks after Ovx (preventive treatment); GIII (late control group) and GIV treated with plasma was 12 when given transdermally and 7.3 when given SC. Additionally, although LHMV twelve weeks after Ovx (late treatment). Bone mineral density (BMD) was the levels of ALLO in plasma were similar with both routes of administration, the levels analyzed before Ovx and after treatments. Animals were killed, the femurs collected and of ALLO-sulfate in plasma were ~12-times higher with SC administration compared to their length and diaphysis diameter were measured; the distal femurs were processed topical (7.8 ± 6.8 and 0.60 ± 0.25 ng/mL/mg dose, respectively). In all instances, the for histomorphometry and polarized light microscopy for collagen fibers analysis or mean tissue levels of both ALLO and ALLO-sulfate were higher with SC administration subjected to immunohistochemistry of cleaved caspase-3 in osteocytes. Statistical compared to topical. Furthermore, the sum of the levels of these metabolites in the plasma analysis: ANOVA and Bonferroni post hoc test (P<0.05). Results: BMD was similar was 2-times the levels of progesterone after SC dosing as compared to equivalent levels among the groups before Ovx, but after treatments, it was significantly higher in GII after topical dosing. Conclusion: Transdermal delivery of progesterone cream resulted and GIV compared with their control groups (P<0.05). Femur length and cortical bone in similar progesterone levels in the uterus compared with SC delivery; however, lower thickness was similar among the groups, but the diaphysis diameter of GII was higher plasma levels of progesterone and ALLO were reported. These data suggest that this compared to GI. Trabecular bone area was higher in the vibrated groups, but was greater formulation of topical progesterone may provide protective endometrial effects from in GII (P<0.05). Also, GII showed the higher presence of mature collagen fibers and estradiol while limiting systemic exposure. lower percentage of apoptotic osteocytes (positive caspase-3 immunoreactivity) when compared to the other groups (P<0.05). Conclusion: These results suggest that both P-9. preventive- and late-treatments with LHMV counteract bone loss and improve bone High Serum Enzyme Catalase Level In Menopausal Paramedics As A parameters in Ovx rats, being the preventive treatment was more effective than the late treatment. Marker Of Oxidative Stress; A Study Based In Indonesia Muhammad Fidel G. Siregar, Ph.D, M.Ked ( OG ), Pantas S. Siburian, Yostoto B. Kaban, Henry S. Siregar, Iman H. Effendi, Riza Rivany. Obstetric and Gynaecology, Universitas P-7. Sumatera Utara, Medan, Indonesia Transdermal Progesterone Opposes the Effects of 17-beta Estradiol on Objective: A recent estimation stated that 25 million women will reach menopausal the Uterus of the Female Rat age each year. Based on survey conducted by Indonesian Menopause Society (PERMI/ Ginger D. Constantine, MD2, Richard Winneker, PhD3, Lawrence de Garavilla, Perkumpulan Menopause Indonesia) on 2005, the average age of menopause among PhD4, Brian Bernick, MD1, James H. Pickar, MD5, Annette M. Shadiack, PhD1. Indonesian women is 49 ± 0.20 years old. Data from Indonesian Statistical Bureau 1TherapeuticsMD, Boca Raton, FL; 2EndoRheum Consulting LLC, Makvern, PA; (BPS/Biro Pusat Statistik) stated that the number of menopausal women in Indonesia 3RC Winneker Consulting, LLC, Penllyn, PA; 4GDL Consulting and Contracting, is 5,320,000 on 2008. In Province of Sumatera Utara Indonesia, especially in its capital Doylestown, PA; 5Columbia University Medical School, New York, NY city, Medan, the average life expectancy for women increase each year, with data Objective: To demonstrate that transdermally delivered progesterone can inhibit from 2008 shows the average age of 72.7 years old. These facts are important because estrogenic effects on the endometrium and vagina in oophorectomized rats. Design: that means one third of women’s life will be spent in menopausal age. Menopause Thirty-two 8-week-old, female, Crl:CD® rats underwent oophorectomy 2 weeks prior to is a predisposing factor for the development of oxidative stress, marked by estrogen study start. Rats were randomly assigned to 4 groups of 8 rats each. Three of the groups deficiency, which also has a role as an antioxidant. Oxidative stress is defined as an received 3 mcg/kg/day 17 beta-estradiol,(E2) subcutaneously (SC), for 8 days as well imbalance of oxidants and antioxidants which have an important role in the aging process as one of the following: (a) placebo cream, or (b)10 mg/kg/day progesterone, SC, or (c) . Oxidative stress considered to be involved in the pathogenesis of several diseases, such 3.125 mg/day progesterone transdermally beginning on Day 4. A fourth group received as aging acceleration and degenerative process including heart disease, and pathological the E2 vehicle (corn oil), SC for 8 days and placebo cream beginning on Day 4. Two process in the female reproductive system . Assessment of oxidative stress can be done hours post the final dose (Day 8), the rats were humanely euthanized and the vagina and using catalase enzyme. Catalase has a role in catalysis of peroxides and free radicals into distal portions of the uterine horns were fixed and processed for histology and computer- oxygen and water, and is able to inhibit the formation of free radicals. One profession aided morphometry. Uterine immunohistochemistry for the proliferation marker, Ki67, that is a subject of high oxidative stress is paramedic. Paramedic needs professionalism was also performed. Results: As expected with this model, oophorectomy without in patient management, clinical skill, and drug administration. Deteriorating health in hormone replacement resulted in significant atrophy of the uterus while unopposed E2 paramedic, affected by changes in menopause period will influence their quality of treatment led to uterine (including endometrial) hypertrophy as demonstrated by organ patient’s care. Design: This is an analytic study with case control design, conducted in weight measurements and histology. Significantly reduced uterine weight was observed Adam Malik General Hospital on September 2014, with all study subjects consists of in both groups receiving progesterone. In addition, several estrogen-induced histological paramedics. Consecutive sampling was used. 32 subjects were obtained for each sample changes seen in the uterus (e.g. columnar luminal epithelium) and vagina (e.g. keratinized and control group. The inclusion criteria were : never had a hysterectomy or bilateral epithelium, rete pegs) were not detected in the groups receiving progesterone SC or oophorectomy, not receiving Hormone Replacement Therapy (HRT), not suffering from transdermally. Dosing with progesterone, both SC and transdermally, resulted in a a malignant process, no history of cardiovascular disease, diabetes mellitus, hypertension significant reduction of luminal epithelial cell height compared to unopposed estradiol. or osteoporosis, not consuming alcohol, not smoking, no history of mental disorder and A significant increase in endometrial gland density was observed for both progesterone- willing to participate in the study. Subjects from Menopause group were given L-MMPI dosed groups compared to unopposed estradiol and a greater increase with transdermal (Lie-Minnesota Multiphasic Personality Inventory) Test and MENQOL (Menopause

51 POSTER PRESENTATIONS

Specific Quality Of Life) questionnaire to be filled. This study use MENQOL as an the gene expression and the immunolocalization of the small leucine-rich proteoglycans instrument to confirm that the patients is in menopause period. To confirm the validity (SLRPs) in the extracellular matrix of the endometrium of pregnant and non pregnant. of MENQOL, L-MMPI scale was used because the examination instrument in this study That fact could lead to a failure in embryo implantation. are subjective and influenced by the respondents honesty. Blood sample then withdrawn from subjects in both group to analyze their catalase enzyme serum level. Data then analyzed descriptively to determine the frequency distribution of subjects characteristic, P-12. mean, standard deviation and numeric data. To analyze the differences between variables, Evaluation of the hyaluronic acid and sulfated glycosaminoglycan on rats t-independent test was performed with confidence interval of 95% (p < 0,05) Results: breasts after treatment with steroid hormones Majority of subjects from menopause group were from age group of 50-54 years old Sueli P. Torres, Ms1, Manuel J. Simões, PhD1, Edmund C. Baracat3, José M. Soares (56,2%), while the majority of subjects from the control group were from the age group of Júnior, MD, Ph.D3, Regina C. Teixeira Gomes, PhD1,2. 1Department of Morphology, 31-40 years old (50%). Mean level of serum catalase enzyme in control and menopause Federal University of São Paulo, São Paulo, Brazil; 2Gynecology, Federal University group were 105,94 ± 22,37 mU/ml and 155,53 ± 12,24 mU/ml respectively (CI : 95%; p < of São Paulo, São Paulo, Brazil; 3Obstetrics and Gynecology, Faculty of Medicine 0,05). From 29 MENQOL questions, the highest score came from sexual complaint with University of São Paulo, São Paulo, Brazil 3,89 ± 1,65, followed by physical complaint 2,74 ± 1,9, vasomotor complaint 2,39 ± 1,34, Objective: To evaluate the hyaluronic acid and sulfated glycosaminoglycan on and psychosocial complaint 2,36 ± 1,12. Conclusion: There is a significant difference of breasts of female rats ovariectomized (OVX) after hormonal treatment. Design: serum catalase enzyme level between menopause and reproductive aged women. Serum 40 adult rats were initially ovariectomized and after 21 days randomly divided into catalase enzyme level in menopausal women is higher than its level in reproductive aged four groups, each containing 10 animals, namely: CG - received saline solution, EG) women. This finding means that women in menopause is subjected to higher level of - received estradiol benzoate (37.6 μg per animal/day) for 7 consecutive days, PG - oxidative stress, especially in paramedic. received medroxyprogesterone acetate (11.28 mg per animal/day) for 23 consecutive days, EPG - received estradiol benzoate (37.6 μg, for 7 consecutive days followed by medroxyprogesterone acetate (11.28 mg, for 23 consecutive days). Results: Dermatan P-10. sulfate in breast tissue of hormonal-treated animals showed a lower concentration in Imunoexpression of BCL-2 and BAX in ovarian follicles of all groups compared to CG, p<0.05. Heparan sulfate and Hyaluronic acid in breast of pinealectomized or melatonin-treated pinealectomized rats P-treated animals showed a lower concentration compared to others groups (CG, EG and Luiz F. Fuchs1, Carla C. Maganhin, post doctoral1, Gisela R. Sasso2, Ricardo S. Simões, EPG), p<0.05. There were no differences among the other groups analyzed. Conclusion: Dr1, Edmund C. Baracat1, José Maria Soares- Jr1. 1Obstetrics and Gynecology, University The results showed that the treatment with estrogen in their composition were able to of Sao Paulo, FMUSP, São Paulo, Brazil; 2Morphology and Genetics, Federal University stimulate the production the sulphated glycosaminoglycans (heparan and dermatan) of Sao Paulo, São Paulo, Brazil and non-sulphated glycosaminoglycans (hyaluronic acid) in breast tissue compared to Objective: to evaluate the expression of Bcl-2 and Bax in ovarian follicles of progesterone treatment. Although the concentration of GAGs analyzed was higher in the pinealectomized or melatonin-treated pinealectomized rats. Design: Thirty adult rats breast of the control group animals. were randomly divided into three groups of 10 animals: Group I – Control; Group II - pinealectomized (Px), and Group III - Px treated with melatonin (10μg/night, per animal). After two months’ treatment, on the night of proestrous, the animals were P-13. placed in metabolic cages for night urine collection and subsequent measurement of The Accuracy of Self-Reported Glaucoma in the Women’s Health 6-sulfatoxymelatonin (6-SMT). The rats were anesthetized, blood samples were taken Initiative for estrogen and progesterone determinations, and they were then euthanized. The Thasarat S. Vajaranant, MD1, Pauline Maki, Ph.D.2, Louis R. Pasquale3, Farqan Khan1, ovaries were collected, fixed in 10% buffered formaldehyde and processed for paraffin Julie Mares3, Kristin J. Meyer4, Mary N. Haan5. 1Ophthalmology and Visual Sciences, embedding. From the paraffin blocks, 5μm thick sections were collected to silanized University of Illinois at Chicago, Chicago, IL; 2Psychiatry, University of Illinois, Chicago, slides and submitted immunohistochemical methods for the detection of Bcl2 (Spring IL; 3Ophthalmology, Harvard Medical School, Boston, MA; 4Ophthalmology and Visual Bioscience Corp. US) and Bax (Spring Bioscience Corp. US). Images were obtained Sciences, University of Wisconsin, Madison, WI; 55Department of Epidemiology and using a light microscope (Axiolab Standard 2.0 - Carl Zeiss) attached to a high definition Biostatistics, University of California at San Francisco, San Franscisco, CA camera (AxioCam MRC - Carl Zeiss) and by the image analyzing image (AxioVision Objective: Women comprise the majority of individuals affected by glaucoma, a leading Rel. 4.8.2 - Carl Zeiss). Reaction expression was analyzed and quantified according with cause of irreversible blindness worldwide. Previous studies suggest that early menopause the color intensity with the aid of the Image J Pro Plus, having photographed 5 fields increases the risk for glaucoma. Epidemiologic studies of large national health cohorts each slide, with the 40x objective. Obtained data was submitted to statistical analysis sometimes rely on self-reported eye disease without validation of self-reports against using ANOVA test complemented by the Tukey-Kramer test (p<0.05). Results: The medical records. We determined the accuracy of self-reported vs. medically diagnosed urinary levels of 6-SMT and serum progesterone were lower in the Px group (GII). glaucoma in a subset of the Women’s Health Initiative (WHI), a large NIH-funded cohort Exogenous melatonin treatment restored both blood melatonin and 6-SMT urinary study involving 161,808 post-menopausal women. Design: We recruited women who levels. The Bax/Bcl-2 ratio was highly immunoexpressed in the GIII - Px treated with reported glaucoma either at WHI enrollment (1994–1998) or in annual health update melatonin (GIII = 60.93±3.95) when compared with the Control (GI = 40.39±3.05) and questionnaires through 2005. Eligible women were selected from two ancillary eye GII - Pinealectomized (Px) (GII = 51.09±2.85) (p<0.05) Conclusion: Our data showed studies: the WHI Sight Exam (WHISE) study and the Carotenoids in Age-Related that melatonin enhances apoptosis in the ovary of pinealectomized rats. Eye Disease Study (CAREDS). In a follow-up phone interview for this pilot study, the selected women were asked if eye care providers told them that they had glaucoma. Additionally, they were asked to release their medical records to verify the diagnoses. P-11. We used a method described in the Nurses’ Health Study (NHS) to confirm the diagnosis Gene expression of small leucine-rich proteoglycans (SLRPS) on the of primary open-angle glaucoma (POAG). POAG was defined as glaucoma without murine uterus non pregnant and pregnant with hyperprolactinemia secondary causes and open-angle was confirmed by gonioscopy or absence of adverse induced metoclopramide effects after dilated exams. Reliable characteristic glaucomatous visual field defects were Regina C. Teixeira Gomes, PhD1,2, Carina Verna, Dr3, Ariadne S. Leal, Ms3, Helena B. used as a main diagnostic criterion (perimetric POAG). Results: A total of 276 women Nader, PhD4, Edmund C. Baracat5, Ricardo S. Simões, Dr5, José M. Soares Júnior, MD, were contacted and 200 (72.5%) consented to a phone interview (15.9% declined, 2.5% Ph.D5. 1Department of Morphology, Federal University of São Paulo, São Paulo, Brazil; were deceased, and 9.1% were non-responders). Medical records were obtained on 186 2Gynecology, Federal University of São Paulo, São Paulo, Brazil; 3Ophthalmology, of the 200 consented (93.0%). Of the 186, 52.7% (98/186) had no available or insufficient Federal University of São Paulo, São Paulo, Brazil; 4Biochemistry, Federal University visual field data. POAG was verified in 29.3% (55/186). Limiting to the 88 women with of São Paulo, São Paulo, Brazil; 5Obstetrics and Gynecology, Faculty of Medicine sufficient visual field data, POAG was verified in 62.5% (55/88). Although all women University of São Paulo, São Paulo, Brazil reported glaucoma in sometime between 1994 and 2005, only 46.5% (86/185) confirmed Objective: This report aims to assess gene expression and immunolocalization of small during phone interviews during 2013. Of those who reported glaucoma twice, POAG was leucine-rich proteoglycans, SLRPs, (class I: biglycan and decorin) and (class II: lumican verified in 50.0% (43/86). Of these 86 women, 63 had sufficient visual fields and POAG and fibromodulin). Design: 20 female/groups: control group (non pregnant Ctr): 0.2 was verified in 68.3% (43/63). Conclusion: We were able to verify 29% of self-reports mL of saline (vehicle) and the experimental group (non pregnant HPrl): 200 μg/day of of perimetric POAG in the WHI, which is similar to that of the NHS (35%). The accuracy metoclopramide, dissolved in vehicle. After 50 days 10 females of each group were placed of self-reported glaucoma increased from 29% to 50% if glaucoma was reported twice. for mating with males and continued to receive treatment. The females non pregnant were This information is essential as it helps assess the validity of epidemiologic analyses euthanasia on 50th day (experimental I) and the females pregnant were euthanasia on 5.5th using self-reported glaucoma and/or plan future nested case-control study of POAG in to 6.5th post-coital day (experimental II). The blood samples were collected for hormone the WHI. measurements. The uterus was processed for immunohistochemistry and gene expression by RT-qPCR. The results were subjected to statistical test (p <0.05). Results: Gene expression and immunolocalization showed increase of the biglycan in non pregnant HPrl compared to non pregnant Ctr, p < 0.05, and decrease pregnant HPrl compared to pregnant Ctr, p < 0.05. Gene expression of the decorin, lumican and fibromodulin showed decrease in non pregnant/pregnant HPrl compared to non pregnant/pregnant Ctr, p < 0.05. Serum prolactin levels were higher in all the groups, while the levels of estradiol and progesterone were lower only in non pregnant group compared to non pregnant group. Conclusion: Our data suggest that the state of hyperprolactinemia changed differently

52

MENOPAUSE SYMPTOMS POSTER PRESENTATIONS P-16. Diagnostic frequency of the vasomotor syndrome (Greene’s scale vs. P-14. Garrie Gast’s scale) Perla Aldama, Imelda Hernández. Hospital Juárez de Mexico, México D. F., Mexico Knowledge Deficits Related to Menopause: Objective: The vasomotor syndrome is the main reason of consultation in menopause. A Focused Review and Thematic Analysis of the Literature Additionally, it has been associated with cardiovascular risk increase. Thus, the 1 2 Patricia Camillo, PhD. Nursing Professor LLC, Bloomington, MN; Carmenta Health importance of its diagnosis. However the assessment scale used in our country (Greene’s Innovations PLC, Minneapolis, MN scale) is inadequate to assess this syndrome. The scale proposed by Garrie Gast et al Objective: Objective: Menopause is a lived experience that is difficult to quantify in 2008 assesses vasomotor syndromes specifically. The objective of this study is to due to various socio-cultural and environmental factors. This can be problematic when determine the diagnostic frequency of the vasomotor syndrome using the Greene’s designing education programs to meet the needs of this population. A focused literature scale vs. the Garrie Gast’s scale in patients in transition stage to menopause and post- review and thematic analysis was conducted to gain a better understanding of current menopause, seeking to apply it in our population and improve the diagnosis and treatment knowledge deficits, both among midlife women as well as their healthcare providers, of the vasomotor syndrome. Design: Comparative, observational, descriptive, cross- related to this transition. Design: Design: A search of PubMed was conducted using the sectional and prospective trial of a group using different measurement scales, with a key word “menopause” in combination with each of the following three words: education, qualitative approach. Inclusion criteria: patients who went to the Climacteric Clinic of knowledge and information. Publications were limited to the time period from January the Juárez Hospital of Mexico, in stage STRAW +10: -2, -1, +1, +2 (transition to early 2010 through June 2015. A total of 182 articles were retrieved. These articles were all and late menopause; early and late post-menopause); patients who are assessed with the peer reviewed and limited to English. Of these, 127 were eliminated, primarily related to Greene’s scale and the Garrie Gast’s scale. Exclusion criteria: patients under treatment the word “education” used as a demographic variable within studies that did not address (hormonal treatment, non-hormonal treatment, natural treatment, phytoestrogens). A knowledge of menopause. Thematic analysis was conducted for the remaining 55 studies statistic analysis was made of the differences using the t student test. Results: Two focusing on knowledge deficits related to menopause identified by the researchers. This hundred and one patients were assessed with the Greene’s and Garrie Gast’s scales from was a mixed method approach incorporating the findings from both qualitative as well as June 30, 2014 to January 15, 2015. The average age was 52 years. The most frequent quantitative studies. Thematic analysis was conducted with the goal of being descriptive stage is +2 (late post-menopause) with a total of 73 patients (36 %). The patients assessed rather than critical. Results: Results: The top three knowledge deficit themes identified with the Greene’s scale presented vasomotor symptoms (mild, moderate, and severe) in were: (1) menopause management during and after cancer treatments, (2) options for 74 %; this percentage increased to 86 % when the Garrie Gast scale was applied (mild, hormone therapies, and (3) maintenance of sexual health. Further analysis resulted moderate, and severe) p=0.031. Of the 52 patients without symptoms with the Greene’s in specific content items for each of these three major areas. In addition to women’s scale, 38 patients (73 %) had vasomotor symptoms (mild, moderate and severe) with knowledge deficits, competency in menopause management was identified as a growing the Garrie Gast’s scale. And of the 28 patients without symptoms with the Garrie Gast’s concern for a variety of health professionals. Menopause encompasses multiple body scale, 14 patients presented mild symptoms with the Greene’s scale (due to a higher score systems that are not the focus of ob-gyn curriculums and although internists have that in the somatic, psychological, and sexual scale). Conclusion: The scale proposed by expertise, they lack the knowledge specifically related to menopause management. Garrie Gast presents greater diagnostic frequency of the vasomotor syndrome, because it Similar knowledge deficits were also identified among nursing specialties with midwives has more specific items for assessment of hot flashes and nocturnal sweating. Therefore, focused primarily on the reproductive years. Finally, the provision of culturally sensitive using is in our population is suggested to obtain greater diagnostic accuracy and deliver educational content was a pervasive theme across all content areas in this review. timely vasomotor syndrome treatment. Conclusion: Conclusion: This focused review of the literature provided insight into the Symptom frequency comparing the Green’s scale vs. the Garrie Gast’s scale as current knowledge deficits related to menopause found among midlife women as well as assessment method those providing their care. Although not prescriptive in design, this review provides the basis for further investigation into these educational needs. The most dominant concern for women, identified in this review, was the knowledge deficit experienced during and after treatments for various cancers. There are few educational resources for this population and there are indications from this review that many health professionals would not be prepared to address these specific learning needs. Educators designing programs for either midlife women and/or their healthcare providers need to be vigilant in identifying current knowledge deficits as the population changes and the state of the science continues to evolve.

P-15. MsFLASH Participants’ Priorities for Alleviating Menopausal Symptoms Janet Carpenter1, Nancy F. Woods, PhD, RN, FAAN2, Julie Otte, PhD, RN1, Katherine Guthrie, PhD3, Chancellor Hohensee3, Katherine M. Newton, PhD4, Hadine Joffe, MD, MSc5, Lee Cohen, MD6, Barbara Sternfeld, PhD7, R. Jane Lau8, Susan D. Reed, MD, MPH9, Andrea Z. LaCroix, PhD10. 1Science of Nursing Care, School of Nursing, Indiana University, Indianapolis, IN; 2Biobehavioral Nursing, University of Washington, Seattle, WA; 3Fred Hutchinson Cancer Research Center, Seattle, WA; 4Group Health Research Institute, Seattle, WA; 5Psychiatry, Harvard Medical School, Boston, MA; 6Center for Women’s Mental Health and Perinatal & Reproductive Psychiatry Clinical Research Program, Massachusetts General Hospital, Boston, MA; 7Division of Research, Kaiser Permanente Medical Program of Northern California, Oakland, CA; 8Department of Obstetrics and Gynecology, School of Medicine, Indiana University, Indianapolis, IN; 9Departments of Obstetrics/Gynecology and Epidemiology, University of Washington School of Medicine, Seattle, WA; 10Department of Preventive Medicine, University of California San Diego, San Diego, CA Objective: To describe self-reported menopausal symptom priorities and their P-17. association with demographics and other symptom measures among women randomized Effects of Recent Abuse on Menopausal Symptom Bother: Results from to an intervention trial for vasomotor symptoms (VMS). Design: Cross-sectional study the Data Registry on Experiences of Aging, Menopause and Sexuality embedded in the MsFLASH 02 trial, a three by two factorial design of yoga vs. exercise (DREAMS) vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n=355) Suneela Vegunta, MD1, Carol Kuhle, DO2, Juliana M. Kling, MD, MPH1, Julia Files, completed hot flash diaries, a card sort task to prioritize symptoms they would most MD1, Ekta Kapoor, MBBS2, Paru S. David, MD1, Jordan Rullo, PhD, LP2, Richa Sood, like to eliminate, and standardized symptom questionnaires. Results: The 4 most MD2, Jacqueline Thielen, MN2, Lynne T. Shuster, MD2, Aminah Jatoi, MD3, Darrell common symptom priorities were: VMS (n=322), sleep (n=191), memory (n=140), R. Schroeder, M.Sc2, Stephanie Faubion, MD2. 1Division of Women’s Health Internal and energy (n=116). In multivariate models, (1) women who chose VMS as their top Medicine, Mayo Clinic, Scottsdale, AZ; 2Women’s Health Clinic, Division of General priority symptom (n=210) reported significantly greater VMS severity (p=0.004) and Internal Medicine, Mayo Clinic, Rochester, MN; 3Division of Medical Oncology, never smoking (p=0.03) and (2) women who chose sleep as their top priority symptom Department of Oncology, Mayo Clinic, Rochester, MN (n=100), were more educated (p<0.002) and had worse sleep quality (p<0.001). ROC Objective: Abuse of women in the US is prevalent and associated with adverse health curves identified sleep scale scores that were highly predictive of ranking sleep as a top outcomes. While a history of adverse childhood experiences has been associated with priority symptom. Conclusion: Among women entering an intervention trial for VMS increased reporting of vasomotor symptoms, the relationship between recent abuse and and with relatively low prevalence of depression and anxiety, VMS was the priority menopausal symptoms has not been fully explored. Our objective was to determine symptom for treatment. A card sort may be a valid tool for quickly assessing symptom whether there is an association between menopausal symptom bother (MSB) and priorities in clinical practice and research. a history of abuse (physical, sexual or emotional/verbal) in the last year. Design: All women presenting for menopause consultation in the Women’s Health Clinic (Rochester, MN) complete the Menopause Health Questionnaire (MHQ). MHQ data were collected between January 1, 2006 and October 7, 2014. Menopausal symptom presence and severity were assessed in the MHQ with 33 questions, rated with a score of

53 POSTER PRESENTATIONS

1 to 4 for degree of bother (1 = not at all; 2 = a little bit; 3 = quite a bit; 4 = extremely). Cycle And Hormonal Differences In 20 Year Olds And 40 Year Olds In addition to total score, menopausal symptoms were grouped into 6 domains based on content: vasomotor, sleep, neurocognitive, bowel/bladder function, sexual function, and general. Abuse in the last year was assessed as present/absent (yes/no); menopausal status was self-reported as premenopausal, perimenopausal or postmenopausal; current tobacco use was assessed as present/absent (yes/no). Demographic data (BMI, education, employment status, and race/ethnicity) were obtained from the electronic medical record. Data were summarized using mean (SD) for continuous variables and frequency percentages for nominal variables. The MHQ total and subscale scores were calculated as the mean response of the items included in the given domain. Scores were analyzed as continuous variables; total scores were the primary endpoint and subscale scores the secondary endpoint. MHQ scores were compared between women self-reporting abuse versus not using the two-sample test. Analysis of covariance was used to assess whether *1 pml/l = 0.2724 pg/ ml. Our lowest measureable estradiol is 73.4 pmol/l. abuse was associated with MSB after adjusting for baseline patient characteristics. Therefore, this number is used in calculations when results are given as < 73.4 Two-tailed p-values ≤ 0.05 were considered statistically significant. Results: Of 4,956 even though estradiol levels were lower. women who completed one or more MHQs during the study period, 3740 were included ** Ultrasound structure > 16 mm seen in one of the ovaries and interpreted as a after exclusion of women who did not provide authorization for use of their records, functional cyst. those under 40 years of age and those who did not complete any of the MHQ items assessing MSB or abuse in the last year. Of these 3,740 women, 253 (6.8%) reported experiencing one or more forms of abuse in the last year; 245 of 253 (96.8%) reported P-19. verbal/emotional abuse, 34 (13.4%) reported physical abuse and 10 (3.9%) reported Q-1001: A Phase 1b Study of the Safety and Effect of Q-122 on Vasomotor sexual abuse. Demographic characteristics (age, race/ethnicity, BMI, menstrual status, Symptoms in Females with Breast Cancer education, employment, cigarette smoking, alcohol use, and self-reported history of Elizabeth O. Ofili, MD, MPH, FACC2, April L. Speed, MD2, Alice T. Robertson, PhD1, alcoholism) were similar between groups based on prior abuse, with the exception Earl E. Sands, MD, FACOG3, Wendy P. Painter, MD, MPH1. 1Clinical Development, of employment status (p=0.001). A higher percentage of those reporting abuse in the QUE Oncology, Atlanta, GA; 2Clinical Research Center, Morehouse School of Medicine, last year were classified as work disabled. The prevalence of cigarette smoking was Atlanta, GA; 3Consultant, QUE Oncology, Atlanta, GA higher in those who reported abuse in the last year (p<0.001). The prevalence of current Objective: QUE Oncology is developing Q-122, a novel, orally available small molecule alcohol use was lower in women who reported abuse in the last year (p=0.017), but the with the chemical formula N-(4-((pyrimidin-2-ylamino)methyl)benzyl)-pyrimidin- prevalence of self-reported lifetime alcoholism was higher in those who reported abuse 2-amine, as a treatment for vasomotor symptoms (VMS) commonly associated with (p<0.001). Those reporting abuse in the last year had higher (p<0.001) mean total MSB menopause. The initial target population for the development program is females with a scores, and higher (p<0.001) scores for each of the individual subscales than those who history of breast cancer who are taking tamoxifen or an aromatase inhibitor (AI). The first did not report abuse with the exception of vasomotor (p=0.387). Consistent findings were proof of concept study in this population was Q-1001, a Phase 1b, open-label, two dose, obtained from multivariable analyses adjusting for all demographic and substance use dose-escalation study evaluating the safety, tolerability and preliminary effectiveness of characteristics. Conclusion: In the present study from the Data Registry on Experiences Q-122 therapy. Design: Study Overview: Q-1001 was a single-site study that enrolled of Aging, Menopause and Sexuality (DREAMS), MSB scores were significantly female subjects who were menopausal, age 30 – 70 years, with a history of breast associated with recent abuse, particularly verbal or emotional abuse. On subanalysis of cancer and taking tamoxifen or an AI. To be eligible for the study, subjects had to be menopausal symptoms, individual subscales of symptoms were associated with recent experiencing at least 7 moderate to severe hot flashes (HF) per day or 50 per week. Key abuse, whereas the subscale of vasomotor symptoms was not. exclusion criteria included significant renal or hepatic disease, untreated hyperthyroidism and clinically significant abnormal laboratory findings. Although paroxetine is P-18. approved for treatment of moderate to severe VMS, concurrent therapy with SSRIs or Observing Differences in Spontaneous Monitored Cycles in 20-Year-Olds SNRIs was not an exclusion criterion. The study period consisted of a 2-week drug and 40-Year-Olds To Help Understand Perimenopausal Changes free screening period to establish baseline values of VMS, a 4-week treatment period, and a final 2-week drug-free follow-up period before the final study termination visit. James S. Martin, BSc MD FRCS(C). Southern Ontario Fertility Technologies, London, Subjects were initially enrolled into Group 1 (100 mg Q-122). After Group 1 was fully ON, Canada enrolled, safety parameters were reviewed prior to enrolling subjects into Group 2 (200 Objective: This study examines 100 consecutive, monitored, spontaneous cycles per mg Q-122). Methods: Safety was monitored by reporting of adverse events (AEs) and group, initially performed for intrauterine insemination (IUI), in women aged 20 to 24 serious adverse events (SAEs), and evaluation of treatment emergent adverse changes in compared to women aged 40 to 44. The purpose of the comparison is to gain insight into physical findings and laboratory values. Efficacy was assessed by calculating the mean hormone and cycle differences in potentially perimenopausal women (40-44) compared changes in frequency and severity of moderate to severe HF from baseline to Week 4. For to younger women (20-24). Design: An arbitrary start point for collection of cycles was comparison across treatment weeks, a daily average frequency of HF was calculated for January 2008. The first consecutive 100 monitored cycles for spontaneous IUI for women each treatment week. Severity was assessed by calculating a HF severity score (HFSS) age 20 to 24 and for women 40 to 44 were selected and available measured parameters that was normalized to frequency for each treatment week. Results: Twenty-one subjects were compared. Exclusion criteria were cycles in which any medical intervention took received Q-122 of which 20 were included in the efficacy analysis; 8 subjects in each place (IE: HCG was given to induce ovulation, the luteal phase was supplemented with group completed the study. Safety: A total of 29 AEs with one SAE were reported during progesterone). Limitations of the study were that the older women were not diagnosed the study (10 in 7 of 10 subjects in Grp. 1; 19 (including 1 SAE) in 7 of 11 subjects in as perimenopausal. Also, follicular FSH levels, other than day-3, were not collected and Grp. 2). All the reported AEs were mild (79%) or moderate (21%) in severity. Three symptoms were not documented. Data was retrieved from our clinics Excel ® spread AEs reported by one subject (headaches (2 events), and insomnia) were the only events sheet. Results: The results are presented in the table: Cycle and Hormonal Differences considered possibly related to study drug by the Investigator. There were no remarkable In 20 Year Olds Vs. 40 Year Olds Conclusion: Spontaneous cycles are very different or dose-related changes in adverse events, physical findings or laboratory values. in these two age groups. Although day-3 FSH is not very different (4.7 vs. 6.5 IU), the Efficacy: After 4 weeks of treatment with Q-122, both frequency and normalized severity day-3 estradiol is quite different (99 vs. 298 pmol/L). More residual follicles remain of moderate to severe HF were significantly reduced from baseline values. The reduction visible on day-3 (12 vs. 47), perhaps producing some of the observed increased estradiol was seen in each dose group, in all subjects combined, and in subjects who were taking and perhaps indicating less complete ovulation. Endometrial lining is thicker (4.0 vs. an SSRI or SNRI. Baseline (BSLN) and Change from Baseline (CFB) in moderate and 8.0) perhaps representing a bioassay for estradiol. The leading follicle grows larger (20.3 severe HF frequency and severity is displayed in Table 1. Conclusion: No safety issues vs. 24.8) and the peak estradiol is greater (404 vs. 1044). There is more likely more associated with the use of Q-122 were identified in this study. Further, Q-122 therapy than one developing follicle (4 vs. 12) which is perhaps related to the observed higher resulted in reduction in both frequency and severity of VMS over the 4-week treatment spontaneous twinning rate in older women. The follicular phase (12.8 vs. 10.6 days), the period. These results compare favorably with published results from studies assessing the luteal phase (14.9 vs. 12.1 days) and the cycle length (27.7 vs. 24.7 days) are shortened. ability of other non-hormonal drugs to treat VMS in various populations. The pregnancy rate (especially the ongoing pregnancy rate) is decreased. Some of these Table 1: Change in Frequency and Severity of Moderate to Severe Hot Flashes Following observations may help to explain commonly observed perimenopausal symptoms. Treatment with Q-122

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P-20. and specificity of 80.4% and 93.2% respectively. Conclusion: With cut off point of >5.5, Characteristics and Symptom Severity of Women Referred to an vaginal pH is a feasible, accurate and inexpensive alternative for definitive diagnosis Interdisciplinary Menopause Clinic of menopause. The result of this study could be applied to another region with similar Tami Shandro, MD2, Nese Yuksel, BScPharm, PharmD1, Lori Battochio, RN2, Beate geographical and economical background as Indonesia. Sydora, MSc, PhD3, Sue Ross, BScPharm, PhD, MBA3. 1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; 2Lois 3 P-22. Hole Hospital For Women, Edmonton, AB, Canada; Department of Obstetrics and Vasomotor symptoms are associated with circulating adipocyte-derived Gynecology, University of Alberta, Edmonton, AB, Canada Objective: To describe the characteristics of women, who are referred by their physicians, hormones in postmenopausal women Hung-Ming Wu, MD, PhD1, Wan-Yu Huang1,2. 1Department of neurology, Changhua to an interdisciplinary menopause clinic and to assess the types and severity of self- Christian Hospital, Taichung city, Taiwan; 2Institute of Basic Medical Sciences, National reported symptoms. Design: A retrospective chart review was conducted of women Cheng Kung University, Taina, Taiwan attending the Lois Hole Hospital for Women (LLHW) Menopause Clinic in Edmonton, Objective: Vasomotor symptoms are the main symptoms of menopause. These Alberta, Canada from 2008 - 2013. Women who did not have a completed health profile symptoms have been postulated to play a role in the development of metabolic disorders. were excluded. Data extracted from the patient charts included demographics, medical The research aimed to evaluate the impact of vasomotor symptoms on metabolic risk- conditions, menopause symptoms and treatment recommendations. Menopause symptom related profiles in postmenopausal women. Design: A cross-sectional study conducted severity scores were captured on a scale of 1 – 4 (none, mild, moderate, severe). Symptom at a hospital. Healthy postmenopausal women with or without vasomotor symptoms scores were compared from initial to follow-up visits. A convenience sample of 200 were enrolled. Clinical data, sleep, hot flashes, and fasting blood samples were analyzed. patients was chosen. Summary statistics were used to describe the extracted data. Results: Serum glucose, lipid profile, hs-C-reactive protein, plasma insulin, adipocyte-derived Physicians referred women most commonly for severe vasomotor symptoms (53%), hormones, and IL8 were analyzed Results: There were significant differences between sleep disturbance/fatigue (45%) and mood changes (42%). The women had a mean age both groups in plasma levels of HDL, adiponectin, and resistin. Vasomotor symptoms 52 years (±SD 6.28), presented with a mean BMI of 29 (±SD 7). Thirty five percent were were inversely correlated to adiponectin concentrations, and positively to leptin levels perimenopausal, 52% had experienced a natural menopause and 13% were menopausal Conclusion: The present study found that vasomotor symptoms significantly affected secondary to bilateral salpingo-oophorectomy (BSO). Almost 55% of the women had 4 circulating concentrations of adiponectin, and leptin. Those factors are involved in insulin or more medical conditions – the most prevalent being mood disorder (depression 37%, signal pathways, playing important regulatory roles in insulin sensitivity. The results anxiety 31%), followed by migraines (26%), high blood pressure (20%), high cholesterol suggest that vasomotor symptoms are potential risk factors for development of incident (19%), thyroid disease (18%), and IBS (18%). Mean symptom severity scores at the insulin resistance. first visit were 2.85, 2.63, 2.61 and 2.27 for sleep disturbance, vasomotor, muscle/joint pain and mood symptoms respectively. Women at higher cardiovascular (CV) risk had higher symptom severity scores for each of these symptoms at 3.10, 2.76, 2.88 and 2.38 respectively. Initial treatment recommendations included calcium and vitamin D ESTROGEN THERAPY POSTER PRESENTATIONS supplementation (59%), dietary changes (39%), and exercise (15%), as well as hormone therapy (79%). The majority of women were followed for three visits, approximately 3.5 P-23. months apart, and 75% of the women experienced symptom improvement by their last Compounded Bioidentical Hormone Replacement Therapy (BHRT) visit. Conclusion: Women referred to the interdisciplinary Menopause Clinic at LHHW, Improves Bone Density In Menopausal Women With Low Bone Density had moderate to severe menopausal symptoms, and the highest rated severity score was James S. Martin, BSc MD FRCS(C). Southern Ontario Fertility Technologies, London, sleep disorder. Those with multiple medical concerns, at higher cardiovascular risk, self- ON, Canada reported more severe symptoms. Three quarters of the women experienced symptom Objective: To demonstrate improved bone density in a group of women with low bone improvement after attending the clinic. density taking BHRT for at least 1 year. Design: A consecutive case series of women presenting for consultation to consider use of BHRT for menopausal symptoms who P-21. had a previous bone density performed (Dual-energy X-ray Absorptiometry = DEXA), Vaginal pH As An Alternative Diagnostic Tool For Menopause In Remote which demonstrated low bone density were asked to consider our study. Inclusion criteria Area; A Study Based In Indonesia were: willingness to repeat their bone density after being on BHRT for at least 12 months without other treatments, an initial-visit FSH over 40 pmol/l* confirming menopause, Muhammad Fidel G. Siregar, Ph.D, M.Ked ( OG ), Hotbin Purba, Syamsul A. Nasution, our ability to obtain a copy of their previous bone density study, (completed within a Sarma N. Lumbanraja, Aswar Aboet, Riza Rivany. Obstetrics & Gynaecology, Faculty year of the consultation) confirming low bone density at both the femoral neck and the of Medicine, University of Sumatera Utara, Medan, Indonesia lumbar spine, and not taking pharmaceutical medications effecting bone density except Objective: A recent estimation stated that 25 million women will reach menopausal Calcium and Vitamin D supplements. BHRT included Biest (80% Estriol/ 20% Estradiol) age each year. This number will increase along with development in healthcare, and 3% Progesterone cream in all women and 3% Testosterone cream in some women which in turn will increase the overall life expectancy. Based on survey conducted by (33/94 =35%) prescribed in levels appropriate to relieve their menopausal symptoms. All Indonesian Menopause Society (PERMI/Perkumpulan Menopause Indonesia) on 2005, women were encouraged to take Calcium and Vitamin D supplements and to perform the average age of menopause amongst Indonesian women is 49 ± 0.20 years old. Data moderate weight bearing exercise. Results: 94 women evaluated from Jan. 2003 to Jan. from Indonesian Statistical Bureau (BPS/Biro Pusat Statistik) stated that the number of 2012 met the inclusion criteria and all agreed to take part in the study. Ages ranged from menopausal women in Indonesia is 5,320,000 on 2008. In Province of Sumatera Utara 42 to 69 years with an average of 53.1 years. Initial average bone densities were 0.69 + Indonesia, especially in its capital city, Medan, the average life expectancy for women 0.11 grams per cm. squared at the femoral neck and 0.91 + 0.10 grams per cm. squared increases each year, with data from 2008 shows the average age of 72.7 years old. at the lumbar spine. After at least 12 months (average 15.2 months) of treatment with These facts are important because that means one third of women’s life will be spent in BHRT, bone densities were redone using the original lab facilities and found to be 0.72 + menopausal age. Indonesia is an archipelago country with many remote and rural areas 0.09 grams per cm. squared at the femoral neck and 0.93 + 0.07 grams per cm. squared at which is not covered by medical facilities. Moreover, the average level of education the lumbar spine. Both density measurements demonstrated a strong improved trend but and economy in Indonesia is still low, affecting the availability and affordability of did not reach statistical significance. However, 87/94 measurements at the femoral neck medical examination. Many Indonesian women are still uninformed about menopause improved and 91/94 of the measurements at the lumbar spine improved. Conclusion: and often assumed that they had already experienced menopause even without adequate BHRT appears to be effective, with calcium, vitamin D and exercise, at improving bone serum hormonal examination. Compared with serum hormonal examination,vaginal densities in menopausal women with low bone density. Although the improvements were pH examination is relatively easy to perform, and inexpensive as an alternative method modest, losses in this group of women would probably be more expected. Larger studies to diagnose menopause definitively. Design: This diagnostic study was performed in over longer periods of time are certainly indicated. the gynaecology outpatient clinic of Haji Adam Malik General Hospital Medan and the affiliate hospitals of Universitas Sumatera Utara Medical Faculty on September 2014. This study included menopausal woman as sample and non menopausal women P-24. as control. The inclusion criteria for both groups are : not having sexual intercourse Application of Testosterone Cream to the Clitoral Area Vs. to General for 3 days before the sampling, not suffering from vaginitis or diabetes mellitus, not Skin May Be Beneficial in Bioidentical Hormone Replacement Therapy receiving hormone replacement therapy for 3 months before the sampling, not smoking or consuming alcohol, not currently in treatment with intravaginal medication or douche, (BHRT) James S. Martin, BSc MD FRCS(C). Southern Ontario Fertility Technologies, London, and willing to sign the informed consent of the study. Vaginal pH was measured using ON, Canada pH meter strips and 3 cc of blood were withdrawn from samples and analyzed for FSH Objective: Bioidentical hormone replacement therapy (BHRT) usually includes levels. Statistical analysis was performed using Mann-Whitney test and multivariate replacement of estrogen, progesterone and sometimes testosterone in trans-dermal analysis for sensitivity, specificity, ROC, and vaginal pH cut off point. Results: Majority creams. Testosterone replacement is the most difficult as it is often a balancing act of menopausal group subjects was from the age group of 50-59 years old (80.4%), with between benefit and side effects. Recently we have found that direct application of the parity of 3-4 (47.8%), Body Mass Index indicating obesity (56.5%), and has experienced testosterone to the clitoral area improves benefit. This randomized study investigates the menopause for more than 4 years (67.4%). Whereas the majority of non menopausal blood values, and benefit / risk profiles associated when testosterone cream was applied group subjects was from the age group of 30-39 years old (54.5%), with parity of 3-4 to the clitoral area as apposed to general body surface. Design: 200 consecutive women (38.6%), and normal BMI (43.2%). Mean vaginal ph levels in menopausal and non seen in consultation, diagnosed as menopausal, interested in Bioidentical Hormone menopausal women were 6.11 + 0.71 and 3.70 + 0.85 respectively. Mean FSH level Replacement Therapy, and listing one of their concerning symptoms as decreased in menopausal and non menopausal women were 71.98 +36.07 and 24.29 +32.79 libido were selected for study. All were originally treated with Biest (80% Estriol / respectively. Vaginal pH levels has an optimal diagnostic value as the curve approaches 20% Estradiol) and Progesterone cream and were seen in a review visit 6 months later. 100% with an AUC value of 98.5%. Vaginal pH level cut off point is >5.5 with sensitivity

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199/200 women returned for follow-up and were offered 3% testosterone cream, 0.1 was 52.4 years (SD ±3.9) and mean age at menopause was 48 ±3.7 years. Comparison ml daily. 137 accepted testosterone and were randomized to clitoral area vs. general between groups revealed a statistically significant improvement in somatic (p=0.02) and skin application by alternating the suggested application method. 134 took testosterone urogenital (p=0.04) symptoms in the users of HT and dietary soy supplementation. A and returned for their third visit (64 applying to the clitoral area and 70 applying to significant improvement in QOL was observed in women with a better improvement in the general skin). Efficacy (increased libido) and side effects (predetermined questions) climacteric symptoms, psychological and urogenital symptoms, improvement in vaginal were analyzed at third visit. Improvement in libido was defined by a 50% subjective dryness, with higher schooling and lower age. Urinary incontinence negatively affected improvement and side effects were defined as a positive response from the patient to QOL. Conclusion: Despite HT and soy isoflavones treatment have shown significant any of the predetermined questions about hair growth, acne or voice changes, etc. Serum improvement of symptoms related to menopause, we noticed that the type of treatment testosterone levels were measured using an Immulite 1,000 and recorded in nmol/l.* adopted had no direct impact on multiple domains of QOL. This reinforces the idea that Results: The patients ranged from 48 to 71 years old with an average age of 55.2 years apparently, every effective treatment to reduce menopausal symptoms improves health- old. 129 of the 137 (94%) were continuing testosterone at the third visit. Two women related quality of life. Further studies are still needed to uniformly assess the changes that did not start it, 6 women discontinued it because they saw no benefit or had side effects. diverse forms of menopause therapy can produce in QOL. Of the 64 women applying testosterone to the clitoral area, 60/64 (93.8%) had improved libido and 43/64 (67.2%) had side effects and their average testosterone blood level averaged 146 + 109 nmol/l. Of the 70 women taking testosterone on the general skin P-27. 46/70 (65.7%) had improvement in libido and 40/70 (57.1%) had side effects and their Novel regimen of Hormone Replacement Therapy: Efficacy and Safety of blood levels averaged 72 + 78 nmol/l. Conclusion: Testosterone cream applied to the Transdermal Estrogen plus Intermittent Progesterone clitoral area or to the general skin is very effective at restoring libido but has a high level Hala A. Gomaa, MD, MSc1, Debra Evaniuk1, Shany Klachook2, Wendy L. Wolfman, of side effects in menopausal women. Clitoral application appears to improve benefit MD, FRCSC1. 1Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada; (93% vs. 66%), slightly increase side effects (67% vs. 57%), and significantly increase 2Faculty of Medicine, University of Toronto, Toronto, ON, Canada blood levels (146 vs. 72 nmol/l). This is a preliminary study. It was not previously Objective: Hormone replacement therapy (HRT) is widely used for the successful suspected that absorption would be so improved through application to the clitoral area. relief of moderate to severe menopausal symptoms. Traditional oral regimens of HRT A previous study demonstrated that the average blood level for benefit was 74 nmol/l and are associated with decreased rates of osteoporosis, yet increased rates of vascular for side effects was 139 nmol/l. Perhaps by using a lower concentration of testosterone thrombosis. However, transdermal therapies are associated with lower risk of VTE in the clitoral area, we could maintain or improve benefit, and decrease side effects and and stroke in observational studies. The WHI in the E+P [CEE+ medroxy progesterone blood level. A study comparing 1% testosterone in the clitoral area compared to 3% acetate] arm risk of breast cancer increased by 8/10.0000/y, however it showed in testosterone on the general skin is underway. *1 ng/dl = 0.034 nmol/l and 1 nmol/l = estrogen alone arm for patients after hysterectomy that estrogen alone taken for a 28.2181 ng/dl median 5.9 years significantly lowered the risk of breast cancer in this subgroup (hazard ratio [HR],0.77, p=.02). Also, LaCroix study showed that maintained reduction after 10 years follow up. Therefore we postulate that using intermittent progesterone may P-25. be the preferred preparation of HRT with fewer side effects and maintain endometrial Average Serum Estradiol Levels In Women Switching From safety. The purpose of the study is to determine the efficacy and safety of reducing the Pharmaceutical Hormone Replacement Therapy (HRT) to Bioidentical progesterone dosage of continuous combined hormone therapy to 3-5 days/week with HRT (BHRT) continuous transdermal estrogen 37.5 mcg or 25 mcg in postmenopausal women. The James S. Martin, BSc MD FRCS(C). Southern Ontario Fertility Technologies, London, theoretical goal is to optimize breast safety of HRT while maintaining endometrial safety ON, Canada by minimizing the progesterone dosage. Design: This is a retrospective observational Objective: Our observation has been that many women obtain excellent relief of their study. Following institutional Research Ethics Board approval, we reviewed health vasomotor symptoms using either on HRT and BHRT but usually can do so while records of 155 postmenopausal women in a specialized menopause clinic within our reaching significantly lower serum estradiol levels on BHRT. The purpose of this tertiary health care centre. All women were using transdermal 17-B estradiol 37.5 investigation was to compare the serum estradiol levels in women switching from [117 patients] or 25 microgram [38 patients] either transdermal patches twice a week pharmaceutical HRT to BHRT. Design: Hormonal blood work was determined using or daily transdermal gel, and intermittent progesterone 100mg 3-5 times per week. an Immulite ® 1,000. A consecutive case series of 385 women already on HRT and We analyzed clinical data, including demographic information, significant medical or requesting conversion to BHRT were considered for the study. The estradiol level was family history, age at menopause, duration of HRT use and patient satisfaction. We also measured on the initial consultation visit (while the women were on pharmaceutical reviewed available mammogram results, and transvaginal ultrasounds. Results: We have HRT) and on each visit for review of BHRT. Once the women claimed 80% relief from identified and reviewed medical records of 155 patients, each using HRT consisting of vasomotor symptoms, they were included in the comparison. Pharmaceutical estrogens in 17-B estradiol 25 or 37.5 microgram patches and progesterone 100mg capsules 3-5 times use were, 78 (20%) on Premarin ©, 41 (11%) on conjugated estrogen sulphate (CES) and orally per week . All patients had relief of post menopausal vasomotor symptoms. Follow 137 (36%) were on oral estrogen (estradiol) and 129 (34%) were on a transdermal patch up transvaginal ultrasound was done for 55.48% of patients (86/155) at least 1 year estrogen. BHRT estrogens were Biest (80% estriol/ 20% estradiol) at concentrations of after using our low dose therapy. The average endometrial thickness was 3.9± 2.1mm. 0.625mg/ml, 1.25mg/ml or 2.5mg/ml in Vertabase © cream and using volumes of 0.5 69.76% (60/86) of patients had endometrium measuring less than 5mm in thickness. Only to 1.5 ml each morning titrated over several office visits to obtain therapeutic effect. 5.16% (8/155) of patients had vaginal bleeding or breakthrough bleeding; no abnormal Results: During the initially consultation visit, (therefore on HRT) 309/385 (80%) of the endometrial biopsies. Seventy five patients (48.38%) completed a mammogram; all women on HRT claimed at least 80% relief from their vasomotor symptoms. All patients reports were normal. Conclusion: A combined transdermal 17-B estradiol 25 or 37.5 returned for the first recheck visit on BHRT and 267/385 women (69%) claimed 80% microgram and intermittent administration of micronized progesterone either vaginal or relief. Two patients dropped out by the next recheck visit and 308/383 (84%) obtained oral is a novel approach to providing relief of menopausal symptoms while maintaining 80% relief. 382 patients returned for a third recheck visit and all 382/382 (100%) claimed endometrial safety and a favorable tolerability profile. 80% relief. The average estradiol level on pharmaceutical HRT was 349 + 124 pmol/l*. The average estradiol level on BHRT (once 80% relief of vasomotor symptoms were controlled) was 129 + 65 pmol/l. Conclusion: Women were able to get good control of NON-ESTROGEN THERAPY POSTER PRESENTATIONS their vasomotor symptoms using either HRT or BHRT. Women seeking BHRT are very motivated and compliance rates are excellent with only 3 women dropping out after 4 P-28. visits. Control of vasomotor symptoms was obtained with lower serum estradiol levels with BHRT. However, other hormonal factors (IE: Estriol and Progesterone serum levels) High Soy Protein Consumption Does Not Stimulate Growth of the were not included as part of the study and may be significant. * 1 pmol/l = 0.2724 pg/ml Endometrial Lining in Post-Menopausal Women Caroline Brandon, MD1,2, Christine Derzko, MD2, Amy Strauss, MSc2, Mark Messina, Ph.D., M.Sc.3, Dorothea Faulkner, Ph.D., M.Sc.4, Christopher Ireland, B. Sc.4, David P-26. Jenkins, MD, Ph.D.4. 1Obstetrics and Gynecology, New York University, New York, Hormone therapy or soy isoflavones for a better quality of life after NY; 2Obstetrics and Gynaecology, University of Toronto, Toronto, ON, Canada; 3School menopause: is there a best option? of Public Health, Loma Linda University, Loma Linda, CA; 4Department of Nutritional Adriana O. Pedro, Lucio O. Carmignani, MD, Lucia S. Costa-Paiva, MD, PhD, Aarao Sciences, University of Toronto, Toronto, ON, Canada M. Pinto-Neto, MD, PhD. Departament of Obsterics and Gynecology, State University Objective: Retrospective chart review aimed to evaluate 23 postmenopausal women of Campinas, São Paulo, Brazil who were compliant with the dietary portfolio for varying lengths of time to determine Objective: To identify factors associated with the quality of life (QOL) in symptomatic whether there was a correlation between cumulative soy exposure and thickness of the postmenopausal women according to the type of treatment used for the climacteric endometrial lining. Design: We assessed the endometrial thickness of 23 postmenopausal syndrome. Design: In this double-blind, randomized, placebo-controlled trial, sixty women with varying cumulative soy protein exposures using ultrasonography. We also healthy, symptomatic postmenopausal women, aged 40-60 were randomized into took a cytological sample of the vaginal epithelium to determine the vaginal maturation three groups: a soy dietary supplement group (isoflavone 90mg), a low-dose hormone index (VMI). Results: There was a statistically significant association between increasing therapy (HT) group (estradiol 1mg plus noretisterone 0.5mg) and a placebo group. log cumulative soy consumption and thinner endometrium (r= -0.3655, p=0.0460). There Menopausal symptoms were evaluated through Menopause Rating Scale (MRS). QOL was also a non-significant trend toward an increase in the superficial layer of the VMI, was measured by the abbreviated version of the World Health Organization’s Quality of a marker of hormone response and atrophy. Conclusion: The implication of our finding Life instrument (WHOQOL-BREF) at baseline and at 16 weeks of treatment. Statistical is that soy protein consumption, as part of a balanced diet, is a safe and effective method analysis was performed using the chi-square test, Fisher’s exact test, Kruskal-Wallis for lowering serum cholesterol levels without adverse effects on the endometrial lining nonparametric test and analysis of variance (ANOVA). Multiple linear regression of postmenopausal women. performed used to identify QOL related factors. Results: The mean age of the patients

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P-29. in a dose-dependent manner with an EC50 value of 60 μg/ml, a level considered to be A SERM (Selective Estrogen Receptor Modulator) Treatment Based physiologically achievable. Conclusion: This study suggests that Relizen’s positive Approach to Menopause. effects on menopausal symptoms may be mediated by some inhibition of serotonin Heather D. Foreman, Holly Thacker. Women’s Health, Cleveland Clinic, Cleveland, OH reuptake at synaptosomal junctions. Further study in preclinical and clinical models to Objective: A SERM (selective estrogen receptor modulator) is compound that acts confirm these results is warranted. directly on the estrogen receptor. Their action is different in various tissues, allowing for the possibility to selectively inhibit or stimulate estrogen-like action in those targeted P-31. tissues. In the treatment of menopause, an ideal SERM would stimulate bone but inhibit Incidence of Bleeding or Spotting with a Conjugated Estrogen/ actions in breast and uterine tissue, and most recently has been used in conjugation with estrogen for the treatment of menopausal symptoms. This narrative review research Bazedoxifene Compound Compared to Conjugated Estrogen/Progestogen data highlights the convenient utilization of selective SERMs, including raloxifene, to Placebo 1 2,3 1 tamoxifen, ospemifene, and bazedoxifine for the treatment of menopausal vasomotor Steven R. Goldstein, MD , Risa Kagan, MD . NYU School of Medicine, New York, 2 3 symptoms (VSM), genitourinary syndrome of menopause (GSM), osteoporosis and NY; University of California, San Francisco, San Francisco, CA; Sutter East Bay other uniquely midlife concerns. Design: This study is a narrative review that uses Medical Foundation, Berkeley, CA current literature to summarize clinical findings in the use of SERMs in the treatment of Objective: It is well known that any postmenopausal bleeding, on a drug or no drug is menopausal symptoms. It also provides the women’s health physician or the primary care “endometrial cancer until proven otherwise” and so endometrial evaluation is indicated. physician with quick notes in order to determine which patients are ideal candidates for This has usually involved invasive procedures (endometrial biopsy, sonohysterography, the different SERMs features in this review. Results: SERMs should be considered as a hysteroscopy) although more recently, in some women, transvaginal ultrasound alone viable treatment options for pre- and postmenopausal women depending on their clinical will be sufficient. However, discomfort with having to deal with any bleeding or spotting condition. Raloxifene has been shown to reduce the risk of new vertebral fractures and has in such patients has been one of the major deterrents causing clinicians, especially non- also been shown to decrease the incidence of invasive breast cancer in postmenopausal gynecologic clinicians, not to prescribe hormone therapy even in women who might women with osteoporosis. Raloxifene has a slightly lower risk of endometrial cancer benefit from it. Furthermore, a significant number of women discontinue hormone compared to tamoxifen. Its major adverse reaction is hot flashes and has not been shown therapy due to bleeding in the first year of treatment. In fact, in one large observational to improve GSM over placebo. Tamoxifen has been shown to be an antagonist in the study, unexpected bleeding resulted in 41% of patients to have one or more office visit breast, and is used for ER + breast cancer treatment and prevention. Recent research and 20% to have one or more endometrial biopsy. A treatment for moderate to severe shows that the use of tamoxifen for ten years for ER positive breast cancer was more vasomotor symptoms (VMS) and prevention of osteoporosis utilizing 0.45 mg conjugated effective than with treatment for 5 years. Tamoxifen has showen positive effects on the estrogen (CE) and 20 mg Bazedoxifene (BZA) instead of a progestogen is now available. bone, though not FDA approved for this indication, and is limited by its increased risk of Previously, cumulative amenorrhea rates have been shown to be significantly higher with endometrial hyperplasia and adverse effects on vaginal tissue. Three randomized double this combination than with CE 0.45 mg/medroxy progesterone acetate (MPA) 1.5 mg, blinded clinical trials have demonstrated superiority with use of osphemifene 60 mg while still being similar to placebo. Nomenclature of cumulative amenorrhea is somewhat vs. placebo in the treatment of GSM. In terms of its agonistic effects on the bone, the confusing to clinicians and, therefore, this study was undertaken to report actual rates of use of osphemifene does show a decrease in bone turnover makers in postmenopausal bleeding or spotting at four-week intervals during one year of therapy. Design: SMART women, yet it does not carry and FDA approval for treating osteoporosis. Bazedoxifine V was a Phase III randomized placebo controlled trial of postmenopausal women aged in combination with estrogen has shown great promise in the reduction of VMS and of 40-65 with a uterus seeking treatment for VMS. It was conducted over a one year period. GSM. In several randomized placebo controlled trials (the SMART trials) bazedozifine 455 women received 0.45 mg CE/20 mg BZA, 474 women received placebo and 220 has overall demonstrated a significant reduction in the number and severity of hot flashes women received 0.45 mg CE/1.5 mg MPA (2:2:1 randomization). Of these, 357 (78%) compared to placebo and proved to have a good safety profile. It also shows antagonist of CE/BZA, 383 (81%) of placebo, and 159 (72%) of CE/MPA, completed the trial. Any effects on the endometrium, and acts as an agonist on the bone. It also increased the bleeding or spotting was captured in daily diaries kept by each patient. Results: In the rates of amenorrhea and decreases breast tenderness. Conclusion: The pharmacologic first month of therapy, the incidence of bleeding or spotting was 20.8%, 3.9% and 4.7% aim of SERMS as treatment for menopause is to have specific positive effects on certain in the CE/MPA, CE/BZA and placebo groups, respectively. In the last month of therapy, target tissue such as bone, heart, and brain with neutral or antagonist effects on other the incidence of bleeding or spotting was 8.8%, 1.7%, 1.6% in each of these groups, tissues such as breast and endometrium. Several SERMS are used and ideal candidates respectively. The highest rate of any bleeding or any spotting in any single month was should be noted by physicians. An ideal candidate for treatment with Raloxifene is in 25.6% CE/MPA (month 3), 4.4% CE/BZA (month 2), and 4.8% placebo (month 10) a postemenopausal woman with osteoporosis, with an increased risk of breast cancer. (p <0.001 for all values vs. CE/MPA). Conclusion: Concerns about vaginal bleeding An ideal candidate for tamoxifine is the prevention or treatment of ER positive breast or spotting in patients on continuous combined HT is a deterrent to prescribing HT, cancer patient who does not have bothersome VSM or GSM, as it may worsen these especially by non-gynecologists; as well as a major reason for patients discontinuing HT, conditions. An ideal candidate for osphemifene would be a postmenopausal woman and often results in office visits including invasive endometrial evaluation. Treatment suffering from GSM or severe dyspaurenia who does not want to take hormone therapy with CE 0.45 mg/BZA 20 mg results in significantly less bleeding or spotting than CE and prefers an oral treatment. An ideal candidate bazedoxifene conjugated with estrogen 0.45 mg/MPA 1.5 mg and is similar to placebo. is in a postmenopausal woman with an intact uterus suffering with severe VMS and GSM who cannot tolerate the side effects of HT or who prefer not to take an estrogen P-32. and a progestin. A Phase 1, Open-Label, Parallel-Group Study of the Single-Dose Pharmacokinetics of CE/BZA in Non-Obese and Obese Postmenopausal P-30. Women Does Relizen, a non-hormonal treatment for the relief of menopausal hot William McKeand, MS1, Anna Plotka, MSc1, Kelly Ryan, MS, BSN1, Joanne Salageanu, flashes, work through a serotonergic mechanism of action? BS2, Carol Cronenberger, PhD1. 1Pfizer Inc, Collegeville, PA; 2Pfizer Inc, Groton, CT Steven R. Goldstein, MD1, David Mischoulon2,3. 1NYU School of Medicine, New York, Objective: Duavee® pairs conjugated estrogens (CE) with the selective estrogen receptor NY; 2Massachusetts General Hospital, Boston, MA; 3Harvard Medical School, Boston, modulator bazedoxifene (BZA), and is approved for the treatment of moderate-to- MA severe vasomotor symptoms and for the prevention of osteoporosis in postmenopausal Objective: This in vitro study was designed to determine whether Relizen’s mechanism women. BZA acts as an estrogen antagonist in endometrial tissue and decreases the of action is serotonergic. Relizen® (also known as Sérélys® / Femal® / Femalen®) risk of endometrial hyperplasia when administered with CE. A PK analysis conducted has been shown to reduce symptoms associated with menopause. A double-blind, by the US FDA predicted that oral clearance of the BZA component of Duavee would placebo-controlled study (Winther et al, 2005) showed that Relizen reduced hot flashes increase with increasing BMI, potentially increasing the risk of endometrial hyperplasia. associated with menopause, and alleviated mood swings and tiredness. While other However, the FDA analysis did not incorporate any of the CE components; therefore, herbal products have been shown to reduce menopause symptoms, their activity appears the relationship between CE and BZA with respect to BMI was not evaluated. This study to be due to an estrogenic effect from phytoestrogens. In the above study, measurements characterized the impact of BMI on the PK of BZA and CE following administration of of follicle-stimulating hormone (FSH), estrogen, testosterone and sex hormone binding CE/BZA in obese and non-obese postmenopausal women. Design: In this open-label, globulin (SHBG) did not suggest any hormonal effects from Relizen. Further testing of parallel-group study, generally healthy obese (BMI ≥30 kg/m2) and non-obese (BMI Relizen has confirmed its mechanism of action is not hormonal. Samples of Relizen’s <30 kg/m2) postmenopausal women received a single dose of CE 0.45 mg/BZA 20 mg active ingredient, a Swedish flower pollen extract, were analyzed by high-performance during Period 1. This study also included a second period that investigated the impact liquid chromatography (HPLC) and found to contain subpharmacologic levels of of coadministration of 200 mg itraconazole, a strong cytochrome P450 (CYP450) 3A4 phytoestrogens. Additionally, the flower pollen extract was tested for estrogenic activity inhibitor, on the PK of CE 0.45 mg/BZA 20 mg; these results will be reported elsewhere. in an immature rat uterotropic bioassay. Treatment of immature female rats with high Blood samples were drawn throughout a 5-day, 4-night inpatient stay. Natural log doses of Relizen did not promote uterine growth, suggesting a non-hormonal mechanism transformed AUCinf, AUC0-72, and Cmax for BZA, total estrone and equilin, unconjugated of action. Additionally, in an in vitro study, Relizen produced no proliferation of MCF-7 estrone and equilin, total estrone adjusted for baseline, and unconjugated estrone adjusted breast cancer cells, an effect that depends on interaction with cellular estrogen receptors, for baseline were analyzed using a mixed effect model with treatment, BMI, and treatment in contrast to an active control, 17-beta estradiol, which produced proliferation. Since by BMI interaction as fixed effects and subject as a random effect. Results: Twenty-four Relizen does not work through any estrogenic mechanism, we sought to determine women participated in the study (mean age 54.8 years; 96% White). Mean (range) BMI whether its activity might be mediated by a serotonergic pathway. Design: Relizen, as a was 32.7 (30.0–36.7) kg/m2 in the obese group (n=12) and 25.3 (20.9–28.6) kg/m2 in powder mixture of 75% pollen/pistil extract P182 and 25% pollen extract GC Fem, was the non-obese group (n=12). Obesity was associated with decreased systemic exposures tested for serotonergic effects. Synaptosomes were isolated from the cortex of Wistar to BZA (AUCinf: 13%), total equilin (Cmax: 25%, AUCinf: 32%), baseline-adjusted total rats and incubated with tritium-labeled serotonin and 9 concentrations of Relizen ranging estrone (Cmax: 31%), and baseline-adjusted unconjugated estrone (Cmax: 33%, AUC0-72: from 0.1 μg/ml to 1000 μg/ml. Results: Relizen inhibited the uptake of [3H]-serotonin 34%) (Table). No adverse events occurred in either group during Period 1. Conclusion:

57 POSTER PRESENTATIONS

Although obesity was associated with decreased systemic exposures to BZA and CE, the Table: Comparison of Equol group versus Hormone Replacement Therapy in the relative systemic exposures for each component were not altered in a manner that would Improvement of Vasomotor Symptoms and Secondary Vascular Actions be expected to compromise the endometrial protection provided by the BZA component. PK Parameters in Postmenopausal Women Following Single-Dose Administration of CE 0.45 mg/BZA 20 mg

Baseline and after three months values show means and their standard deviations. Mean change show mean of change and 95% Confidence Intervals. P values refer to comparison between baseline and after three months by paired t-test. Statistically significant at *** p <0.001;** p <0.01; *p <0.05 SBP = Systolic Blood Pressure, DBP = Diastolic Blood Pressure, baPWV = Branchial Ankle Pulse Wave Velocity

P-34. Relationship between Equol Producer Status and Metabolic Parameters in 743 Healthy Women Remi Yoshikata, MD, PhD1,2, Hiroaki Ohta, MD, PhD2,3, Khin Z. Myint, MBBS, MHS2. 1Hamasite Clinic, Minato-ku, Japan; 2Tokyo Midtown Medical Center, Minato-ku, Japan; 3Women Health Center, Sanno Medical Center, Minato-ku, Japan Objective: Equol is an active metabolite produced by the action of intestinal flora on soy isoflavones and possesses the estrogen-like actions. It could be produced naturally from the consumption of soybean isoflavones in about 50% of Japanese female population. AUCinf, area under plasma concentration-time profile from time 0 extrapolated There is increasing evidence on its efficacy in the relief of menopausal symptoms, to infinite time; AUC0-72, area under concentration-time curve from time 0 to suppression of decreased bone mineral density, improving lipid profiles, and decreasing 72 hours post dose; Cmax, maximum plasma concentration; NR, could not be reported. the risk for breast and prostate cancer. This study aimed to examine the relationship between equol producer status and the parameters related to life style related diseases in women in their twenties to eighties. Design: This cross-sectional study was conducted P-33. among 743 healthy women (21 – 89 years; average age: 52.5±11.8 years) who have Comparison of Equol Containing Dietary Supplement with Hormone undergone health screening at Tokyo Midtown Medical Center and given consent to Replacement Therapy in the Improvement of Vasomotor Symptoms and participate in the study. The equol production status was defined by detection of urinary Secondary Vascular Actions in Women with Climacteric Symptoms equol more than 1.0 μM. The metabolic parameters include anthropometric measures, Remi Yoshikata, MD, PhD1,2, Hiroaki Ohta, MD, PhD3, Khin Z. Myint, MBBS, MHS2. lipid profiles and atherosclerosis related biomarkers. The relationship between equol 1Hamasite Clinic, Minato-ku, Japan; 2Tokyo Midtown Medical Center, Minato-ku, Japan; production status and parameters were assessed using Mann-Whitney test and associations 3Sanno Medical Center, Minato-ku, Japan were further confirmed on logistic regression analysis. Results: In our study 236 women Objective: Equol is an active metabolite produced by the action of intestinal flora on (32%) are equol producers. Equol producer proportion is the highest in women in their soy isoflavones. Evidence supports its estrogenic activities such as relief of climacteric twenties (n =18, 39%), lowest in women in their eighties (n=9, 22%), and the proportions symptoms, suppression of decreased bone mineral density and anti-atherosclerotic in the remaining age populations are 32% (30’s: n=79), 31% (40’s: n=222), 31% (50’s: actions. Alternative therapies for HRT have drawn great attention recently. This study n=214), 32% (60’s: n=123), 37% (70’s: n=78). Overall, there is no significant difference aimed to compare the effectiveness of equol dietary supplement to hormone replacement in BMI, blood pressure, lipid profile (triglycerides, HDL cholesterol), HbA1c and bone therapy in women with climacteric symptoms. Design: This was an open, non- mineral density between producer and non-producers of equol. However, when stratified randomized, single-center clinical trial comparing equol to estrogen-progestin therapy. by age, women in their fifties who are equol producers show significantly lower body The investigation included 46 women (4563 years, average age: 51.3±2.7 years), who fat level (25.7 ± 6.4 V.S. 27.8±6.8 %, p<0.5 ), visceral fat CT scan (41.8 ± 20.0 V.S. were enrolled into two groups in a nonrandom fashion. The first group of 24 women 54.0 ± 26.8 cm2 , p<0.01), PWV (1289 ± 89 V.S. 1375 ± 251 cm/s, p<0.05 ). In addition, received equol containing supplement 10mg per day and the second group of 22 women homocysteine levels tend to be lower in women in their sixties who are producers of received combined therapy for estradiol 0.62 mg and norestrone 2.7 mg patch every equol (7.9 ±1.8 V.S. 8.8 ± 2.2, p=0.068). In multivariate logistic regression, increased two weeks. Before intervention and at monthly follow-ups, vasomotor symptoms (hot EPA/AA ratio was significantly associated with higher odds for equol producer status flushes and sweating) in both groups were assessed with the use of four point likert (AOR= 6.778, 95% CI: 1.431 – 32.098, p<0.05) whereas elevated uric acid and pulse scale (No=0, mild=1, moderate=2, severe=3). Also, equol production status is evaluated wave velocity were associated with lower odds (AOR=0.660, 95% CI: 0.452 - 0.962, before intervention. Blood pressure and branchial ankle pulse wave velocity (baPWV) p<0.05 and AOR: 0.998, CI: 0.996 – 1.000, p<0.05 respectively) in women in their measurements were taken before intervention and after three months of follow-up. fifties. On the other hand, equol producers are less likely to be associated with high Results: Fifteen out of 46 women were equol producers (7 in equol group and 8 in homocysteine (AOR: 0.736, 95% CI: 0.546 – 0.992, p<0.05) and urinary NTx (AOR: HRT group). At one month after intervention, more significant improvements in scale of 0.967, 95% CI: 0.940 - 0.994, p<0.05) levels in women in their sixties. Conclusion: vasomotor symptoms were observed in HRT group than in equol group [HRT (hot flush): Equol producer status is associated with favorable metabolic parameters, especially −1.2 ± 0.48, p<0.001; HRT (sweating): −1.0 ± 0.43, p<0.001; Equol (hot flush): -0.38 anti-atherosclerotic conditions, in women of postmenopausal age. This study provides ± 0.36, p<0.05; Equol (sweating): −0.1 ± 0.35, p=0.58)]. After three months both group additional literature on the examination of the relationship between equol and life style showed significant improvement in vasomotor symptoms. Only equol group showed related risk factors among postmenopausal women with declining intrinsic estrogen. significant reduction in both systolic and diastolic blood pressures (SBP, DBP) and pulse Based on these preliminary results, future research should test the influence of equol pressure (baPWV) after three months (See Table). Conclusion: Although inferior to HRT producer status on these parameters, including the assessment of daily consumption in improving vasomotor symptoms such as hot flushes, significant improvements were habits of soy and other phytoestrogen compounds, smoking habit, omega-3 supplement observed with equol dietary supplements. Equol showed more significant improvements consumption and current medication for dyslipidemia or osteoporosis. in vascular health than HRT in this study. These results suggest that equol could be a potential alternative agent for the wellbeing of postmenopausal women.

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P-35. primary endpoints were analyzed using analysis of covariance (ANCOVA). Results: Hot Flush (HF) Frequency and Severity at Baseline (BL) as Predictors VVA efficacy measurements were collected at 2, 4, 8 and 12 weeks with primary efficacy of Time to Transient and Stable Treatment Success: Pooled Analysis of assessed at 12 weeks. Treatment groups were similar with respect to mean baseline 2 CE/BZA Studies measures for the co-primary endpoints. Average subject age was 59. The moderate to severe baseline symptom most commonly chosen as most bothersome was dyspareunia, JoAnn V. Pinkerton, MD2, Andrew Bushmakin, MS3, Joel Bobula, MA4, Joanne followed by vaginal dryness, dysuria, and vulvar and vaginal itching. The adjusted mean Lavenberg, BS4, Barry Komm, PhD4, Lucy Abraham, MSc, CPsychol1. 1PRO Center decreases in MBS were 1.4 in both lasofoxifene treatment groups, compared with a of Excellence, Pfizer Ltd, Tadworth, United Kingdom; 2University of Virginia Health decrease of 1.0 in the placebo group, where a score of 0 corresponds to absence of the System, Charlottesville, VA; 3Pfizer Inc, Groton, CT; 4Pfizer Inc, Collegeville, PA symptom, and a score of 3 corresponds to a rating of “severe.” Both comparisons between Objective: Conjugated estrogens/bazedoxifene (CE/BZA) reduces HF frequency/ lasofoxifene treatment groups and the placebo were statistically significant with p-values severity in postmenopausal women. This post hoc analysis was conducted to determine ≤0.00001. A greater decrease in vaginal pH was reported in both lasofoxifene treatment the impact of BL HF frequency/severity on the time to achieve transient and stable groups relative to placebo-treated subjects at 12 weeks of treatment in the pooled treatment effects with the approved CE 0.45 mg/BZA 20 mg dose, to provide clinicians analysis. The adjusted mean decreases in pH were 0.81 and 0.83 in the lasofoxifene an estimated time for patients to expect improvement. Design: In the randomized, treatment groups compared with a decrease of 0.20 in the placebo group. Comparisons placebo-controlled, phase 3, 2-y SMART-1 and 12-wk SMART-2 trials of CE/BZA, between lasofoxifene treatment groups and placebo were statistically significant with nonhysterectomized postmenopausal women recorded the frequency of moderate/severe p-values <0.00001. A greater mean decrease in the percentage of vaginal parabasal cells HFs in daily diaries. SMART-2 restricted enrollment to women with ≥7 moderate/severe was observed in both lasofoxifene treatment groups relative to placebo-treated subjects at HFs/d or ≥50/wk at screening; SMART-1 did not, but only women with HFs at screening 12 weeks of treatment in the pooled analysis. The adjusted mean decreases were 40.1% were included here. This analysis used nonparametric models to estimate median times to and 40.4% in both lasofoxifene treatment groups compared with a decrease of 6.2% in the transient treatment success (first day that ≥50% improvement in HF frequency/severity placebo group. Both comparisons between a lasofoxifene treatment group and placebo was attained) and stable success (day that was achieved and sustained for remainder of were statistically significant with p-values <0.00001. The mean increases in superficial the study) based on daily frequency/severity of HFs at BL. Daily severity was calculated cells were 6.5% and 5.9% in both lasofoxifene treatment groups compared with an as (# mild HFs) • 1 + (# moderate HFs) • 2 + (# severe HFs) • 3/total HFs that day. Pooled increase of 2.1% in the placebo group in the pooled analysis. Both comparisons between data from women treated with CE 0.45 mg/BZA 20 mg or CE 0.625 mg/BZA 20 mg a lasofoxifene treatment group and placebo were statistically significant with p-values through wk 12 were analyzed using the SAS Proc Lifetest. Women not achieving ≥50% <0.00001. Results of all pooled analyses for all the co-primary endpoints were similar to improvement within 12 wk were censored. Results: Results for CE 0.45 mg/BZA 20 mg those of the individual studies. The most common side effects occurring in the treatment are shown in the figure. Women with fewer BL HFs achieved a transient ≥50% reduction group were vaginal discharge, hot flashes and leg cramps. Conclusion: Lasofoxifene in HF frequency sooner than women with more BL HFs. Similarly, women with less 0.25mg and 0.5mg daily, in each of the individual and pooled studies, demonstrated a severe vs more severe BL HFs achieved a transient ≥50% reduction in severity sooner. statistically and clinically meaningful improvement in the 4 co-primary endpoints, with The same pattern was seen for stable success, which was typically achieved within a few several demonstrating beneficial effect as early as 2 weeks. Lasofoxifene is an effective days after the first ≥50% reduction, but these results were not statistically significantly and well-tolerated treatment of moderate to severe symptoms of VVA and offers women different across BL frequency/severity subgroups. Findings with CE 0.625 mg/BZA 20 an alternative to vaginal and oral estrogens that provide a meaningful benefit for the mg were comparable. Conclusion: Women with more frequent or severe HFs take longer relief of bothersome symptoms of GSM/VVA while conferring extra-genital benefits to to achieve treatment success with CE/BZA, but stable improvement is less influenced bone and breast health. by BL status. These findings allow for an estimate of how long it will take an individual patient to achieve ≥50% improvement in HF frequency/severity based on pretreatment HF frequency/severity. For example, a woman who has an average of 5 HFs/d that are, on P-37. average, moderate in severity can expect to see transient improvement in HF frequency/ Pharmacokinetics of S-equol after administration of a fermented soy severity after about a week of CE 0.45 mg/BZA 20 mg therapy. Stable improvements germ in equol producing and non-producing postmenopausal women of ≥50% are achieved quickly thereafter, regardless of HF frequency/severity at BL. Shigeto Uchiyama1, Soh Iwashita2, Tomomi Ueno1, Belinda H. Jenks3, James Brooks3. Women with frequent/severe HFs should be encouraged to stay with treatment, as it may 1Otsuka Pharmaceutical Co.Ltd,., Saga Nutrceuticals Research Institute, Saga, Japan; take a few weeks to achieve a significant improvement. 2Otsuka Pharmaceutical Co.Ltd.,, Nutraceuticals Division, Tokyo, Japan; 3Pharmavite LLC, Scientific Affairs, Northrige, CA Objective: S-equol, a metabolite of soy isoflavone daidzein, is suggested to have multiple menopausal health benefits including menopausal symptom relief. We found an equol producing lactic acid bacterium Lactococus 20-92 and first developed a fermented soy germ ingredient with S-equol, SE5-OH. Pharmacokinetics of S-equol after administration of SE5-OH was investigated in human including climacteric women. S-equol in plasma exists in both conjugated and unconjugated (free) forms. Not only free form but sulfate conjugates are recognized as bioactive S-equol form. However, pharmacokinetics of S-equol conjugate/unconjugated form are not well elucidated. Thus, the objective in this study was to investigate the pharmacokinetics of free S-equol and sulfate conjugates in healthy postmenopausal women. Design: Eleven healthy postmenopausal Japanese women aged 43-62 years participated in this study. Oral S-equol administration was accomplished using a fermented soy germ SE5-OH. In a single-center, randomized, open-label study, the subjects ingested a single-bolus of SE5-OH tablet including 10 mg S-equol. Plasma samples were collected before and after 0.5, 1, 2, 4, 6, 8, 12, 16, 24, 36 and 48 hours of the administration and urine was collected over the 48 hours period. In Fig. Median Time (Days) to Transient and Stable ≥50% Improvements in HF the measurement of plasma S-equol, free and sulfate conjugates (equol 7-sulfate, equol Frequency/Severity with CE 0.45 mg/BZA 20 mg by BL HF Frequency/Severity 4’-sulfate, equol 4’,7-disulfate) were determined by LC/MS/MS. Urinary isoflavones levels were measured by HPLC-UV. Total equol of the plasma and urine samples were analyzed then hydrolyzed overnight using a mixed beta-glucuronidase and sulfatase P-36. enzyme. Results: In the 11 subjects, equol producers and non-producers were 6 and Lasofoxifene, an estrogen agonist/antagonist improves symptoms of 5, respectively. Time to reach maximum plasma concentrations (Tmax) in free, sulfate genitourinary syndrome of menopause (GSM) and physiologic markers conjugates and total S-equol were all ~1 hour. The maximum plasma concentrations associated with vulvovaginal atrophy (VVA) in two large Phase 3 studies (Cmax) of S-equol in sum of free and sulfate conjugated forms was 0.85μmol/L and that in total was 2.38μmol/L. The plasma elimination half-life (T ) was 6~9 hours in both David J. Portman, MD1,2, James Symons, MS, PhD1. 1Sermonix Pharmaceuticals, 1/2 forms. The area under the curve during the first 24 hours (AUC ) of plasma S-equol Columbus, OH; 2Columbus Center for Women’s Health Research, Columbus, OH 24hr Objective: Many women suffer from genitourinary symptoms in menopause as a concentrations in sum of free and sulfate conjugated forms was 4,484nmolh/L and that in consequence of falling sex steroid levels. A significant number remain untreated due to total was 10,125nmolh/L. Percentage of sum of plasma free and sulfate conjugated forms versus the total S-equol in the AUC was 43.4%. The majority of sulfate conjugated fears of estrogen-containing products and inconvenience of local vaginal administration. 24h Lasofoxifene is an estrogen agonist-antagonist, or SERM, demonstrating beneficial forms was equol 7-sulfate, then equol 4’-sulfate. Only little equol 4’,7-disulfate was effects on bone density, fracture risk and breast cancer risk in menopausal women in detected. The fraction of dose excreted during the 48 hours into urine was 76 %. All large randomized trials out to five years. Herein, results of 2 phase 3 randomized, placebo pharmacokinetics parameters of S-equol after single-bolus oral administration of controlled studies for the treatmment of VVA are presented. Design: Two identical 12 SE5-OH were not different in equol producing status. Conclusion: This study addressed week randomized placebo-controlled Phase 3 treatment studies evaluated lasofoxifene pharmacokinetics of S-equol after administration of SE5-OH in equol producing and 0.25mg and 0.5mg oral tablets per day vs placebo using 4 co-primary endpoints non-producing postmenopausal women. The data demonstrated the 40% of total plasma (measured as change from baseline to week 12) for the treatment of moderate to severe S-equol was bioactive form, which may involve in potential benefits of S-equol. symptoms of VVA: change in pH, percentage of superficial cells, percentage of parabasal cells, and patient self-assessed most-bothersome symptom (MBS). Women had to have at least one moderate to severe symptom of vaginal dryness, dyspareunia, vaginal/vulvar itching, dysuria and a pH of <5 and percent superficial cells <5%. 889 women age 50-80 were randomized and 810 (91%) completed 12 weeks of treatment. Women were allowed to use non-hormonal lubricant as needed during the trial. Changes from baseline in co-

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VAGINAL HEALTH POSTER PRESENTATIONS P-40. Vaginal Dilation: Current Use and Treatment Practices Vaginal Dilator P-38. Clinician Survey: Preliminary Report Health Care Provider Insight Michael Krychman1, Stephanie Pendergast, MPT2, Mark Juravic3. 1Southern California The Impact of a Women’s Sexual Health Product on Genital Engorgement Center for Sexual Health, Newport Beach, CA; 2Pelvic Floor and Rehab, Los Angeles, as Measured by Thermography: A Proof of Concept Study CA; 3Materna Medical, San Francisco, CA 2 2 1 1 Irwin Goldstein, MD , Sue Goldstein, BA,CCRC , Leah Millheiser, MD . Nuelle, Inc, Objective: Vaginal dilators are recommended and used for many clinical indications 2 Mountain View, CA; San Diego Sexual Medicine, San Diego, CA including but not limited to dyspareunia, pelvic floor hypertonus and vulvar vestibulitis. Objective: Sexual function is a vital component of quality of life for many midlife Although they are commonly used in sexual medicine, there is limited data about its women, with up to 75% reporting that it is moderately to extremely important. The natural clinical utility with respect to treatment paradigms. Online clinician and patient surveys decline in circulating estrogen levels that occurs during perimenopause/menopause has were created to ascertain further information concerning dilators and their practical been shown to negatively affect clitoral arterial blood flow and engorgement as well implications in clinical practice Design: Two online clinical surveys were created in as vibratory perception. This, in turn, can increase latency to achieving genital arousal order to ascertain detailed information concerning practical and clinical information during sexual activity. The primary aim of this study was to determine the degree of with respect to dilator use. Random health care professionals were emailed a 2 page 32 engorgement, as measured by temperature change in the external genitalia, produced questions survey and were asked to complete it on line. Participants received a small by a sexual health product utilizing suction and vibration technology to enhance genital financial remuneration for their time. We present the first 77 respondents who completed blood flow. The secondary aims were to determine the time of onset of self-reported the survey from July 2 to and including July 7, 2015. Further comprehensive clinician and sexual arousal during use of the product as well as development of sexual desire. Design: patient data are scheduled to be gathered and presented. Results: The preliminary report A single-site, prospective, non-blinded study of a women’s sexual health product was consisted of 77 respondents (72 female; 5 male) who were in clinical practice for an conducted in 12 sexually active, postmenopausal women (mean age: 59.2 + 5.4 years; average of 15.9 years. The majority were physical therapists (86%) 60/77; and (13) were time since last menstrual period: 9.5 + 8.3 years) from March 2015 to July 2015. Cohort- medical doctors. The most common indication for prescribing dilators was for painful eligible women must not have experienced a menses for at least 12 months, have a intercourse and vaginismus. Approximately 14% of those surveyed prescribed over 100 Female Sexual Function Index (FSFI) total score > 26.5, and have been sexually active dilators per year whereas 16% prescribed approximately fifty. Health care professionals in the 30 days prior to enrollment. Use of postmenopausal hormone therapy was not estimated their success rate as measure by painless penetration at 71% and that patients an exclusion criteria, however, only 2 of the participants were using systemic therapy achieved success on average 4.7 months after starting their dilator program. Clinicians while none reported the use of local estrogen therapy. Each subject underwent a single- estimated that 80% of their patients had suffered from their medical conditions for 2 visit procedure lasting up to 55 minutes that included the establishment of baseline years or greater before seeking treatment with 20% suffering for 5 years or longer. Most temperature, use of the sexual health product placed over the clitoris, and post-product HCP instruct patients to use dilators every other day and follow up is commonly 2-4 skin temperature assessment. Temperature was measured using Forward Looking weeks with only 8.3 % following up every 3 months. Half are instructed to use dilators InfraRed Thermography. Participants were able to self-record the time to onset of sexual at night and the other half are instructed to use them whenever they feel comfortable arousal during use of the product. At the end of the procedure development of sexual in their scheduling. In 80% of the time patients are taught mindfulness, 57% of the desire was assessed using a Likert scale. Results: A two-sided paired t-test was used time meditation and more than half are instructed to listen to calming music during to assess the statistical significance of the temperature increase from baseline to post- dilator exercises. The most common reasons for non-compliance is perceived to be – product use. The temperature increases for the clitoris and vestibule were statistically lack of privacy, pain during use, fatigue and dilators being cumbersome. HCP report significant at all time points (0,2,4,6,8,10 minutes) following removal of the product. patient commonly expressed emotions are anxiety, hopeful, empowered, embarrassed Temperature increase for the labia was only significant at 0 and 2 minutes. The most and frustration. The most commonly recommended dilators are Soul Source (30%), significant temperature increase was observed at 0 minutes for all sites: clitoris (mean Vaginismus.com (27%) and Syracuse (19.7). Only 38.5% of clinicians sell dilators in 2.43°C + 0.96, p < 0.0001), vestibule (mean 1.63°C + 0.58, p < 0.0001), and labia (mean their office and the remainder advocate on line purchasing. However, 77% of HCP would 0.82°C + 0.48, p = 0.0001). Ten out of the 12 participants developed sexual arousal consider selling dilators through their office. Conclusion: Vaginal dilators are widely during use of the product with the average time to onset being 4.5 + 4.3 minutes. An used in sexual medicine practice for a variety of health care conditions however largely analysis of variance showed statistically significant differences in scores across domains remain an understudied and under appreciated sexual accessory. HCP perception of use of the FSFI with orgasm (mean 5.6 + 0.6), satisfaction (mean 5.7 + 0.5), and arousal and impression of emotional barriers to compliance are important facets to understand. (mean 5.6 + 0.4) scoring the highest. Fifty-eight percent of participants (n=7) strongly Patient educational programs and support are necessary to ensure compliance. Further agreed that they “felt in the mood for sex” after use of the product, 25% (n=3) agreed, data is being collected as well as a comparative analysis of information from dilator and 17% (n=2) somewhat agreed. None of the participants disagreed with the statement. patients will be gathered and presented. No adverse events were reported during the study period. One additional subject is scheduled for enrollment to be included in the final analysis, but no significant variances are expected. Conclusion: To date, there has been limited information quantifying the P-41. degree of genital engorgement produced by products that incorporate either vibration Use of Some Biest Cream Vaginally (As Part of Bioidentical Hormone or suction. The women’s sexual health product used in this study, which employs both, Replacement Therapy (BHRT)) is Effective At Relieving Vaginal Dryness produced statistically significant increases in vulvar temperatures, which is a marker of In Menopause genital blood flow and engorgement. A notable finding that warrants further investigation James S. Martin, BSc MD FRCS(C). Southern Ontario Fertility Technologies, London, is the congruence between genital arousal and development of sexual desire as a result of ON, Canada product use in this cohort of postmenopausal women. Objective: BHRT is often prescribed as creams containing hormones, which are rubbed into skin surfaces of the body. Previously, we had found instructing patients to rub some P-39. of their Biest cream into the vagina, very effective treatment for vaginal dryness. The Common causes of postmenopausal bleeding in Korean women: 10-year purpose of this study was to further investigate the effectiveness of Biest (80% Estriol / 20% Estradiol at concentrations of 0.625, 1.25 or 2.5mg/ml in Veribase ® Cream) used follow-up partially vaginally at relieving vaginal dryness for menopausal women. Design: 565 Min Kyoung Kim, M.D., Yaekyu Koh, M.D, Byungseok Lee, Seok Kyo Seo. Obstetrics consecutive untreated menopausal women who gave one of their complaints as “vaginal and Gynecology, Yonsei University College of Medicine, Seoul, Korea (the Republic of) dryness” and were seen in consultation for consideration of bioidentical hormone Objective: The common causes of postmenopausal bleeding (PMB) according to the data replacement between Jan. 2005 and Dec. 2011 were considered for inclusion in the study. from the western world are vaginal or endometrial atrophy, hormone therapy, endometrial Inclusion criteria also were menopausal status, defined as an FSH level greater than 40 cancer, endometrial or cervical polyps, endometrial hyperplasia, and other miscellaneous IU/l* and at least one year of no menstruation, sexual activity despite vaginal dryness diseases. However, there is no existing data from Asia concerning the PMB’s causes. or a desire to return to sexual activity and an opportunity to do so. Exclusion criteria Therefore, we conducted a retrospective study to compare whether the causes of were the use of any prescribed pharmaceutical products for either vaginal dryness or PMB in Korean menopausal women are similar to the already known data. Design: A hormone replacement therapy. 397 of the 565 (70%) of the women met these criteria. retrospective study using 10-year medical records (March, 2005 to December, 2014) of These women were instructed to use 0.2-0.4ml of their Biest cream vaginally by placing PMB women in Yonsei University Health System, Seoul, South Korea. Total of 980 the cream on their finger, inserting their finger to between the 1st and 2nd knuckle women who stopped menstruating for more than 12 months were enrolled in the study. into the vagina and rubbing the Biest cream vigorously into the vaginal mucosa. First The medical records were thoroughly reviewed and arranged into a few categories; past follow-up visit was at 6 months and they were asked to estimate their compliance and history, diagnosis, the method in which the diagnosis was confirmed, and sonographic the % improvement in their vaginal dryness. Results: 375 of 397 (94%) women accepted data. All data were entered into Excel database (Microsoft, USA) for analysis. Results: and filled a prescription for BHRT and returned for their first recheck visit. 293 of the The most common cause of PMB in Korean women was ‘atrophy’ (39.4%). ‘Endometrial 375 (78%) women claimed at least 80% improvement in their vaginal symptoms. Of the and cervical polyps’ were the second common cause (8.6%), ‘cervix cancer’ was the 82 women who returned but did not claim 80% improvement, 28 (34%) had not started third (7.3%), ‘hormone therapy’ (5.7%), ‘cervicitis’ (5.3%), ‘endometrial cancer’ (4.8%), or had stopped the vaginal component of the prescription and 42 of the 82 (51%) had and other miscellaneous causes were ranked next. Conclusion: Only the most common not resumed sexual intercourse. Many of the remaining 82 had had long duration vaginal cause of PMB was the same as the conventional data and other causes were all ranked dryness and many had been found to have very severe vaginal atrophy (consisting of loss differently in Korean postmenopausal women. Due to high prevalence of cervix cancer of labia minora and/or decreased diameter or length of the vagina) on their initial physical and human papilloma virus infection in Korea, ‘cervix cancer’ was noted as the third examination. Conclusion: Using some part of Biest cream vaginally to treat menopausal common cause of PMB. It seems possible that the etiology of PMB is largely affected by patients complaining of vaginal dryness is very effective. the ethnicity and different cultural backgrounds.

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P-42. should adopt a proactive behavior in surgically menopausal women and those with a The Pre-menopausal vs. Postmenopausal Vagina: A Comprehensive history of genital atrophy to identify and treat OAB, thus contributing to an improved Comparison quality of life and healthier aging. Funding source: FAPESP 2011/14526-9 Kaitlyn H. Mayer, Adrian Balica, Susan Egan, Gloria Bachmann. Department of Obstetrics, Gynecology & Reproductive Sciences, Rutgers Robert Wood Johnson P-44. Medical School, New Brunswick, NJ Menopausal vulvovaginal atrophy:comparative effectiveness of vaginal Objective: Changes to the vagina from the reproductive years through to menopause have been long recognized. It also has been noted that vaginal symptoms reported by therapies Tatiane Fernandes, MD, Adriana O. Pedro, Luiz F. Baccaro, pHD, Lucia S. Costa-Paiva, reproductive aged women are usually different from those of the aging woman due to MD, PhD, Aarao M. Pinto-Neto, MD, PhD. Obstetrics and Gynecology, State University differences in vaginal hormonal milieu and aging. The purpose of this review was to of Campinas, Campinas, Brazil provide a comprehensive comparison of the pre-menopausal to the postmenopausal Objective: Vaginal atrophy is a common chronic condition among postmenopausal vagina from the macro to micro level. Design: A systematic literature review of vaginal women that can affect their quality of life. According to the North American Menopause changes from the reproductive years through menopause was conducted using PubMed/ Society, symptoms related to vulvovaginal atrophy affect approximately 45% of MEDLINE, Cochrane, Google Scholar, and EBSCO databases. Results: The vagina of postmenopausal women, but only 25% of women receive medical treatment. Recent reproductive age women is rich with estrogen and androgen receptors which decline in studies have evaluated new treatment alternatives for vaginal atrophy; however, few density with menopause. Decreasing estrogen levels in the postmenopausal vagina lead therapeutic options have been thoroughly evaluated. This study aimed to compare the to epithelial atrophy and reduced secretions as compared to the pre-menopausal vagina effectiveness and adverse effects of estrogen, testosterone, polyacrylic acid, and placebo that exhibits a thicker epithelium, higher glycogen content and parakeratosis. The pH of lubricant for the treatment of postmenopausal women with vulvovaginal atrophy. Design: the postmenopausal vagina also is significantly higher than that of the pre-menopausal We conducted a randomized clinical trial with 80 postmenopausal women aged between vagina. The pathologic processes that dominate the pre-menopausal vagina include 40 and 70 years who were being followed up at the Menopause Clinic of CAISM, State bacterial vaginosis and yeast infections whereas the postmenopausal vagina has increased University of Campinas, between November 2011 and January 2013. Inclusion criteria diversity of microbial species with less fluctuation in microbiota over time. Blood vessel were as follows: women aged 40–70 years with physiological menopause, history of quantity, blood flow, and transvaginal potential difference are lower in postmenopausal amenorrhea for more than 3 years, and a follicle stimulating hormone (FSH) level of >30 vagina as compared to the pre-menopausal one. The vaginas of both pre- and post- mIU/mL, absence of hormone therapy for menopausal symptoms in the past 6 months, menopausal women are immunocompetent with no noticeable differences in immune normal Papanicolaou smears and mammograms for the past 12 months, and complaints cell levels through the menopause transition. Genes associated with the maintenance compatible with the symptoms of vulvovaginal atrophy. Women were randomly of epithelial function are down regulated whereas genes associated with inflammation assigned to topical vaginal treatment with estrogen, testosterone, polyacrylic acid and are upregulated in the postmenopausal vagina. Conclusion: The postmenopausal placebo lubricant, three times a week for 12 weeks. It was used the vaginal maturation vagina significantly differs from the reproductive-aged vagina in many ways. As more index, vaginal pH, vaginal health score, vaginal flora, laboratory hormonal tests and microbiologic, genetic and imaging advances occur, future assessments of vaginal health transvaginal ultrasound to evaluate changes of vaginal trophism and endometrium at across the life cycle should consider the use of these measures in addition to the standard baseline and after 6 and 12 weeks of treatment. Data were analyzed on an intention-to- ones currently in use. treat basis, including all participants enrolled in each group. Epidemiological and clinical characteristics data were analyzed using chi-squared test, nonparametric Kruskal–Wallis P-43. test and analysis of variance (ANOVA). Analysis of percentages in each group compared Overactive bladder syndrome in climacteric women: a population-based with the control group for vaginal maturation index, pH, vaginal health and presence of study lactobacilli were performed with the chi-squared and Fisher tests. Results: There were Adriana O. Pedro2,1, Cassia T. Juliato, MD, PhD2, Luiz F. Baccaro, pHD2, Jeffrey F. Lui, no significant differences between groups in terms of age, time after menopause, skin MSc2, Lucia S. Costa-Paiva, MD, PhD2, Aarao M. Pinto-Neto, MD, PhD2. 1Gynecology, color, smoking habits, and numbers of pregnancies or socioeconomic status. After a CLINICA LANE, Campinas, Brazil; 2Obstetrics and Gynecology, UNICAMP, 12-week treatment with topical estrogen and testosterone compared with the lubricant, Campinas, Brazil an increased percentage of patients had vaginal pH<5, increased vaginal score and an Objective: Overactive bladder syndrome (OAB) is characterized by the presence of increase in the number of lactobacilli. There were no significant differences in vaginal pH urinary urgency with or without urinary incontinence. Increased urinary frequency is when comparing placebo with polyacrylic acid. The use of polyacrylic acid as compared the most frequently reported symptom of OAB (85%), followed by urinary urgency with placebo showed no clinical improvement of vaginal atrophy. Treatment with topical (54%) and urge incontinence (36%). Diagnosis of OAB is essentially clinical and can be estrogen improved the vaginal maturation index and showed increased levels of estradiol performed through a structured questionnaire. There are few population-based studies in three women, but remained within the normal postmenopausal range. No changes evaluating the epidemiology of OAB in women, especially in the climacteric stage where were observed in the endometrial evaluation of all treatment groups. Conclusion: The there is a decrease in estrogen production, with an effect on the prevalence of OAB. The postmenopausal women who underwent 12 weeks of treatment for vulvovaginal atrophy objective was to assess the prevalence of OAB and associated factors in climacteric with testosterone propionate and estrogen showed significant clinical improvement of Brazilian women. Design: An exploratory, descriptive, cross-sectional, population- vaginal trophism compared with the placebo lubricant and polyacrylic acid. Funding based study was conducted with 749 climacteric women aged 45-60 years. Inclusion source: FAPESP 2011/14775-9 criteria were native Brazilian women, aged 45–60 years, and residing in the metropolitan region of Campinas. Women who were unable to complete an interview for any reason, P-45. such as illness and incompatibility of schedules, were excluded. The dependent Treatment of pain using a non-implanted intra-vaginal electrical variable was OAB, which was considered as present when the participant answered that she had urinary urgency (“urge to urinate and have to run to the bathroom”), with stimulation device compared to sham device in chronic pelvic pain or without urinary incontinence, and when there was no stress urinary incontinence. patients Trained research assistants held home interviews or a phone interview was scheduled. Elim Shih, MD, Mary J. Uy-Kroh, MD. Center for Specialized Women’s Health/ The questionnaire included four sections: sociodemographic information, health habits, Women’s Health Institute, Cleveland Clinic Foundation, Kent, OH health problems, and self-reported health status.Statistical analysis was performed using Objective: Chronic pelvic pain (CPP) is a complex and devastating diagnosis, the chi-square test and multiple Poisson regression model was created to assess which encompassing multiple different conditions and involving many organ systems. This can variables were independently associated with a higher prevalence of OAB. Prevalence result in challenging cases characterized by pain that is refractory to standard treatment. In ratios (PRs) and 95% confidence intervals (95% CIs) were calculated by backward a study conducted by Mathias et al., one in seven women experience CPP. The economic selection of significant variables. Results: The mean age was 52.5 ± 4.4 years. With burden can be substantial, with previous estimates of 2.8 billion dollars per year. (1) regard to menopausal status, 16% were premenopausal, 16% were perimenopausal, and Dyspareunia is defined as recurrent or persistent pain associated with sexual intercourse 68% were postmenopausal. The mean age of menopause was 46.5 ± 5.8 years. Of the 749 and affects approximately 8-21% of women in the United States (19, 20). Dyspareunia women, 59 (7.8%) answered that they had urinary urgency without stress incontinence may lead to sexual dysfunction and may affect a woman’s reproductive health and overall and were classified as having OAB. In bivariate analysis, there were no differences in sense of well-being. Previous estimates indicate that 88% of sexually active CPP patients the main sociodemographic characteristics between women with and without OAB. report pain during or after intercourse (1).Treatment of chronic pelvic is challenging Approximately 37.2% of women with OAB reported vaginal dryness. This proportion due to a poor understanding of pain processing and physiology. A comprehensive was significantly higher than that of women without OAB (24%, p = 0.01). With regard approach is ideal and may include physical therapy, medications, or cognitive behavioral to self-assessment of health, we found that women with OAB reported excellent or good therapy. Pelvic floor physical therapy (PFPT) is an effective treatment for pelvic floor health (52.5%) less frequently than women without OAB (68%, p = 0.02). There were dysfunction. One modality used in PFPT is electrical stimulation (ES). ES is delivered in no differences in smoking, consumption of alcohol, presence of obesity, in parity, the multiple ways including peripheral nerve stimulation, a transcutaneous electrical nerve number of vaginal deliveries and caesarean sections and sexual activity between women stimulation (TENS) unit, or sacral neuromodulation using an implantable device. The with and without OAB. In the final statistical model, multiple analysis using Poisson mechanism of action for ES is unclear. One theory, termed the gate theory, suggests regression showed an association between OAB and vaginal dryness (PR 1.75; 95% that electrical stimulation of nerves via a specific dermatome results in a blocking or CI 1.13–2.69; p = 0.012) and bilateral oophorectomy (PR 2.21; 95% CI 1.11–4.40; p gating effect at the dorsal horn of the spinal cord. This inhibits the transmission of pain = 0.025). Conclusion: OAB affects approximately 8% of climacteric Brazilian women impulses to the upper nervous system. Also, low frequency stimulation of the dermatome aged 45–60 years. A personal history of bilateral oophorectomy and vaginal dryness are can increase the level of endorphins, providing pain relief. (2) Despite its efficacy and factors that are independently associated with the occurrence of OAB, highlighting the benefits, ES through PFPT is time intensive and dependent upon a health care provider’s importance of the effects of estrogen on female genital tract health. Health professionals schedule. It often causes the patient social embarrassment resulting in its inaccessibility. Although ES provides pain relief, even highly motivated patients report that anxiety prohibits them from participation in physiotherapy (6). InControl Medical created a

61 POSTER PRESENTATIONS line of products FDA approved for urinary incontinence and fecal incontinence (10). where appropriate and p-values < 0.05 were considered to be statistically significant. These devices are non-implanted, customizable, intra-vaginal probes made of medical Results: 30 patients were enrolled at 2 study centers. All patients were Caucasian with grade silicone and provide electrical stimulation to the pelvic floor. One of the devices, ages between 34-68 (58.6 +/- 8.8). The average age of onset of menopause was 48.9 ApexM™ provides electrical stimulation at frequencies alternating between 13 Hz and (+/- 7.6) years, and the average age of onset of vulvar and vaginal atrophy symptoms 50 Hz and allows the clinician to adjust the intensity as well as the duration. We propose was 51.2 (+/- 8.3) years. No patients withdrew from the study or were discontinued due a novel treatment using ApexM device in the comfort and privacy of the patient’s home. to an adverse event. 27/30 returned for the 3-month follow up visit. On a 10 cm VAS, Using this device, we will deliver low power electrical stimulation and adjust the power pain improved by 1.7 (+/- 3.2), burning by 1.4 (+/- 2.9), itching by 1.4 (+/- 1.9), dryness to a sensory threshold to prevent muscle contraction. The goal of the study is to evaluate by 6.1 (+/- 2.7), dyspareunia by 5.1 (+/-3.0), and dysuria by 1.0 (+/- 2.4). Before the first the use of a personal intravaginal electrical stimulation device set to a sensory threshold treatment, VHI scores ranged from 8-20 (14.4 +/- 2.9) and changed to 16-25 (21.4 +/-2.9) in the treatment of CPP. Design: We propose a randomized controlled trial comparing (p<.001) at the follow up visit. 25/30 (83%) of patients had an increase in comfortable the investigated device to a sham device. Subjects will perform 12 minute sessions, six dilator size from baseline to 3-months follow up. Baseline FSFI scores ranged from times each week for a total of 12 weeks. The primary outcome is pain control using the 2-25 (11.3 +/- 7.3) and changed to 2-33.9 (20.1 +/- 11.0) (p<.001) at 3-months follow visual analog scale and brief pain inventory (18). Secondary goals include the effect of up. Prior to second and third treatments, 86.6% (26/30) of patients said they were better ES on quality of life using SF-36, sexual function measured by FSFI, and overall use or much better than at the previous treatment and 13.3% (4/30) said they were the same of pain medications. Assessments will be conducted at baseline, 4 weeks, 8 weeks, and using the PGI scale. 26/27 (96%) of patients were satisfied or extremely satisfied with the 12 weeks. Results: Data collection in process. Conclusion: If a positive effect is seen, treatment. Ease of treatment was rated at 4.8 (+/- 0.4), 4.8 (+/- 0.4) and 5.0 (+/- 0.2) for a domiciliary vaginal TENS device can be offered to patients with CPP. Patients would the first, second, and third treatments respectively. Conclusion: A novel fractional CO2 be able to take pelvic floor rehabilitation from the office into their home. Furthermore, it laser seems to be an effective and safe treatment for women suffering from symptoms would justify a larger, multi-center, randomized controlled trial comparing the ApexM™ of Genitourinary Syndrome of Menopause (GSM). Vaginal dryness and dyspareunia device to standard in office physical therapy. associated with GSM are greatly and rapidly improved with this novel therapy, which may represent a promising new treatment option for women suffering from this common and distressing condition. A randomized controlled trial comparing this therapy to P-46. hormonal therapy will be initiated in the near future. What is the most prevalent metabolic syndrome component that cause sexual dysfunction in postmenopausal women? Gustavo M. Slva, MD, Sônia Maria Rolim Rosa Lima, Benedito Fabiano dos Reis. P-48. Departamento de Obstetrícia e Ginecologia, Faculdade de Ciências Médicas da Santa Evaluation of the Hyaluronic Acid in murine cervix after treatment with Casa de São Paulo, São Paulo, Brazil steroid hormones combined with the metoclopramide Objective: To realize overview of the most prevalent Metabolic Syndrome (MetS) Regina C. Teixeira Gomes, PhD2,1, Carina Verna, Dr3, Ariadne S. Leal, Ms3,1, José M. component item causing more sexual dysfunction (SD) in postmenopausal women. Soares Júnior, MD, Ph.D4, Ricardo S. Simões, Dr4, Manuel J. Simões, PhD1. 1Department Design: This is a case-control study. The group consisted of postmenopausal women of Morphology, Federal University of São Paulo, São Paulo, Brazil; 2Gynecology, Federal that usually seek treatment at the Santa Casa de São Paulo Medical School, in the University of São Paulo, São Paulo, Brazil; 3Ophthalmology, Federal University of São period between February 2011 and February 2013. The women considered as being Paulo, São Paulo, Brazil; 4Obstetrics and Gynecology, Faculty of Medicine University postmenopausal were those with amenorrhea ≥ 1 year and FSH ≥30mUI/mL. The MetS of São Paulo, São Paulo, Brazil diagnosis was determined by following the guidelines defined by the ATP III (Adult Objective: To evaluate the influence of the long-time treatment of sex steroids combined Treatment Panel): (1) Abdominal circumference ≥88cm; (2) HDL-cholesterol ≤50mg/ with the metoclopramide on hyaluronic acid in the mice cervix. Design: 100 female dL; (3) triglycerides ≥150mg/dL; (4) arterial blood pressure ≥130/85mmHg; and (5) mice (non or – ovariectomized, ovx) were divided into ten groups with 10 animals/each: fasting glucose ≥110mg/dL. The women considered as carrying MetS were those with Control groups of the experiments: CG (control, non-ovx group) and OG (ovx group): at least three of the components described. The assessment of their sexual function treated with saline solution; and metG (met group/non ovx) and metOG (met group/ was performed by using the FSFI. Postmenopausal women with an active sexual life ovx): treated with metoclopramide (met). Experiment with hormonal treatment: EG were included in the study and submitted to standardized anamnesis. Results: All of (Eovx group): 17β-estradiol; PG (Povx group): progesterone and, EPG (EPovx group: the MetS diagnosis components, including systemic arterial hypertension(SAH), 17β-estradiol associated to progesterone. Experiment with hormonal treatment combined when analyzed separately by the Chi-square test, were associated with higher levels with metoclopramide: metEG (met/E group/ovx): 17β-estradiol plus met; metPG (ovx/ of SD, with significant differences found in the Study and Control Groups (p <0.001). met/P group): progesterone plus met and, metEPG (ovx/met/EP group): 17β-estradiol Conclusion: When we analyze the diagnostic parameters for MetS we find significant conjugated to progesterone plus met. The treatments started after 30 days of the bilateral differences when we compare them with those from the control group in all these aspects. ovariectomy and, all animals were treated for 50 consecutive days subcutaneous with We observed that some factors have already been singly described in the literature as injections (saline solution or metoclopramide) and the hormone dissolved in sunflower risk factors. In our study, however, all of them had an important role, which led us to oil for gavages. After 50 days the animals were euthanized and the cervix were removed understand that MetS is the main predictor of SD when it is compared to any isolated to evaluate the hyaluronic Acid concentration by Elisa-Like fluorometric assay method. component of the syndrome. Data were statistically analyzed by ANOVA (p<0.05). Results: The concentration of HA: (OG=metG) and (PG=metO) > compared to CG and compared to groups treated with sex steroid hormones with or without metoclopramide (p <0.05), and finally P-47. (OG=metG) > compared to (PG=metO), (p <0.05). In comparing the other groups there Use of a novel fractional CO2 laser for the treatment of genitourinary was no significant difference. Conclusion: Our results allow us to some conclusions: syndrome of menopause 1. The ovariectomy increases the concentration of the HA and the treatment with Eric R. Sokol, MD1, Mickey Karram, MD2. 1OB/GYN, Stanford University, Stanford, metoclopramide reduces the concentration of the HA. 2. The combined action of the CA; 2OB/GYN, The Christ Hospital, Cincinnati, OH sex steroids showed that the progesterone modulates the action of the 17β-estradiol on Objective: The primary objective was to assess the safety and efficacy of a novel synthesis of the HA in the cervix of the ovariectomized animals. 3. The metoclopramide fractional CO2 laser for the treatment of Genitourinary Syndrome of Menopause (GSM). interferes on synthesis of the HA in the cervix of the animals with ovaries, and 4. The Secondary objectives were to: 1. Assess the effect of treatment on female urogenital metoclopramide no interferes in action of the exogenous steroid hormones on synthesis health using the “Vaginal Health Index” (VHI) score 2. Assess the effect of treatment of the HA in the cervix of the ovariectomized animals. on vaginal wall pliability by tracking the maximum dilator size tolerable for the patient 3. Assess the change in vaginal pH before and after each treatment session 4. Assess the effect of treatment on female sexual function using the “Female Sexual Function Index” P-49. (FSFI) specific questionnaire 5. Assess the effect of treatment on general quality of life Middle-aged female sexual dysfunction and multimorbidity: a population- using the “Short Form 12” (SF-12) questionnaire 6. Assess the degree of physician ease based study of treatment using a 5-point Likert scale 7. Assess the rate of patient satisfaction with Ana L. VALADARES, MD, PHD. 1OBGYN, UNICAMP, Belo Horizonte, Brazil; treatment using the Patient Global Impression of Improvement (PGI) Design: This study 2Women’s health, UNIFENAS, Belo Horizonte, Brazil was IRB approved. Women who suffered from GSM, met inclusion criteria and had not Objective: To evaluate association between multimorbidity and sexual dysfunction in used any hormone replacement therapy, vaginal estrogen or vaginal lubricants for the women aged 45 to 60 years in a cross-sectional population-based study in a specific past 3 months were enrolled. A baseline gynecological examination was performed and southern Brazilian city. It was also evaluated factors associated with sexual dysfunction the largest tolerable dilator was determined. Vaginal pH was measured before initiating in the group of women with multimorbidity. Design: Cross-sectional population-based treatment and at each subsequent visit. 10 cm Visual Analog Scales (VAS) measuring study conducted in a southern Brazilian city with 736 women (household survey) aged symptoms of vulvo-vaginal atrophy (pain, vaginal burning, vaginal itching, vaginal from 45 to 60 years old, representative of a population of 257,434 women, to obtain dryness, dyspareunia and dysuria) and VHI scores were completed prior to each treatment data on multimorbidity and sexual dysfunction, as part of a broader study on women’s and at 3-months follow up. Each patient also completed FSFI and SF-12 questionnaires, health. The Instrument used to collect data included four sections: sociodemographic and the PGI and vaginal exams were performed after each treatment and at the 3-month information, health habits, health problems, and self-reported health status. It was follow up visit. Patient satisfaction with treatment was measured on 5-point Likert scales created by taking three other preexisting questionnaires into consideration: Economic (1=very dissatisfied, 5=very satisfied). After each procedure, the physician rated the ease Classification Criteria of Brazil, Menopause rating symptoms (MRS) and SPEC- Short of treatment using a 5-point Likert scale (1=very difficult, 5=very easy). Treatments Personal Experiences Questionnaire (to evaluate sexual dysfunction) Associations were were performed in the outpatient clinics with no anesthesia, and each patient received determined between multimorbidity and sexual dysfunction and sexual dysfunction 3 laser treatments spaced 6 weeks apart. Laser energy was transmitted through a novel and demographic, behavioral and medical characteristics. The diseases included were 360° vaginal probe and the full depth of the vagina was treated. Adverse events were hypertension, diabetes mellitus, dyslipidemia,myocardial infarction, stroke, deep assessed at all visits. Student’s paired two-sample t-tests were used for comparisons venous thrombosis or pulmonary embolus.asthma or bronchitis, chronic rheumatic

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diseases, depression, anxiety and cancer. Results: From the 736 women, 53% reported P-51. multimorbidity and from these 49.6% reported having sexual dysfunction. The average Association of stress, anxiety and depression conditions with the presence age of the entire group was 52.5 (± 4.4) years. With respect to menopausal status, 16% of co-morbidities in patients in menopause and post-menopause transition were premenopausal, 16% perimenopausal, and 68% postmenopausal. The average age stage. of menopause was 46.5 (± 5.8) years. Multiple regression analysis showed no association Imelda Hernández, MARISELA ADRIANA NUÑEZ RODRIGUEZ, RESIDENTE. between sexual dysfunction and multimorbidity. Multiple regression analysis showed Biología de la Reproducción Humana, Hospital Juárez de México, México, Mexico no association between sexual dysfunction and multimorbidity. Sexual dysfunction in Objective: Objective: transition to menopause and post-menopause can be a source of whole sample (with and without multimorbidity) was associated with sexual sexual stress, anxiety, or depression derived from the presence of physical manifestations, such activity in the last month (PR=0.27, CI95% 0.22-0.33, p<0.001), having physical activity as sleep quality disruption, cognitive deterioration, vasomotor symptoms, and sexual ≥2 times a week (PR=0.70, CI95% 0.58-0.84, p<0.001), menopause rating symptoms problems. Women present stress, anxiety, and / or depression during their transition to (MRS)>8 (PR=1.25, CI95% 1.09-1.43, p=0.002), perimenopausal or postmenopausal menopause and post-menopause, with 20 – 50 % prevalence. These conditions have status (PR=1.57, CI95% 1.13-2.17, p=0.007), Alcohol use ≥ 1 drink per week (PR=0.81, been associated with an increase in coronary disease and stroke rates. We performed a CI95% 0.67-0.97, p=0.025) and anxiety (PR=1.15, CI95% 1.01-1.31, p=0.039). In pilot study in women who went to the climacteric clinic at the Juárez Hospital of Mexico the group with multimorbidity, the main factors associated with sexual dysfunction (2014), in transition stage to menopause and post-menopause. Thirty women were were sexual activity in the last month (PR=0.31, CI95% 0.25-0.39, p<0.001), anxiety included to whom the DASS 21 scale was applied to determine the presence and level of (PR=1.33, CI95% 1.15-1.53, p<0.001) and physical activity (PR=0.70, CI95% 0.56- stress, anxiety, and depression. It was found that there is greater frequency of depression 0.87, p=0.002). Conclusion: There was no association of multimorbidity and sexual and stress in the transition stage to menopause, a direct relationship with increase of dysfunction in this sample of women aged 45 to 60 years. The main factors associated co-morbidities in patients with moderate to severe stress and anxiety, such as chronic with sexual dysfunction in women with multimorbidity in this sample were lack of sexual systemic high blood pressure, type 2 diabetes mellitus, and metabolic syndrome, as well activity in the last month, physical inactivity, and anxiety. This highlights the importance as increase in total cholesterol, triglycerides, LDL, and insulin resistance. Therefore, the of sexual activity, psychological health and physical activity for a satisfactory sexual life objective of this research was to expand the pilot study to correlate the findings with those in the case of women with multimorbidity. previously obtained, and to determine if there is any association between the grade of Factors associated to sexual dysfunction – Multiple Poisson regression * stress, anxiety, and depression with an increase of co-morbidities in patients in transition stage to menopause and post-menopause. Design: Design: cross-sectional, prospective, observational study; the sample selection was through simple random sampling. The size was determined statistically with a level of confidence of 95 % and percentage of error of 5 % (n = 83 women). To assess the level of stress, anxiety, and depression, the DASS-21 scale was applied (comprised of 21 questions with high internal consistency, Cronbach alpha of 0.87-0.94 with adequate validity). The analysis of the variables to determine the association between stress, anxiety, and depression with insulin resistance, dyslipidemia, metabolic syndrome, high blood pressure was made using two variable linear regression models, and Spearman correlation coefficient (rho). A statistically significant value was considered with a p < 0.05. Results: Results: eighty-three women from 51 to 60 years of age were included (mean 54.5): 9 women in transition to menopause, 23 with * Analysis considering the cluster (census tracts) spontaneous early menopause, 15 with spontaneous late menopause, and 36 with induced menopause. Forty-four women (55%) presented stress; 42 women (52.5 %) anxiety; and 41 women (51.4 %) depression. A positive association of stress was observed with high SLEEP AND MOOD POSTER PRESENTATIONS serum triglyceride levels (rho: .294 p=0.008), total cholesterol (rho: .265 p=0.018), and metabolic syndrome (rho: .273 p=0.014). Anxiety showed a positive association with high triglyceride levels (rho: .301 p=0.007), and insulin resistance presence (rho: .262 P-50. p=0.019). As far as depression is concerned, a statistically significant positive association Examining Differences in Cortical Thickness in Perimenopausal Middle was observed with high total cholesterol levels in serum (rho: .326 p=0.003). High blood Aged Females with Major Depressive Disorder and Healthy Controls pressure had a positive association with the presence of anxiety (rho: 0.400 p=0.000) and Gésine L. Alders, MSc (PhD Candidate)1,3, Luciano Minuzzi, MD, PhD1,3, Geoffrey B. depression (rho: 0.641 p=0.000). Conclusion: Conclusions: this study shows that there Hall, PhD2, Lauren Cudney, MSc1, Meir Steiner, MD, MSc, PhD, FRCPC1,3, Claudio is a high prevalence of stress, anxiety, and depression in these life stages of women and Soares, MD, PhD, FRCPC, MBA1,3, Benicio Frey1,3. 1Women’s Health Concerns Clinic, shows that there is a statistically significant association between the presence of stress, St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 2Department of Psychology, anxiety, and depression with insulin resistance, high total cholesterol and triglyceride Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada; 3Mood serum levels, metabolic syndrome, and high blood pressure. We obtained similar results Disorders Program, St. Joseph’s Healthcare Hamilton, Hamilton, ON, Canada to those reported in the pilot study. Accordingly, it is essential to perform a comprehensive Objective: Females may be at increased risk of developing major depressive examination of women who present stress, anxiety, and / or depression to prevent and disorder (MDD) during perimenopause. Few studies have examined possible effects avoid the appearance of metabolic and cardiovascular complications. Gratitude: to my of perimenopause on brain structure in this population with MDD. This study aims professor Dr. Imelda Hernández Marín for her support and dedication in this project. to examine differences in cortical thickness in middle aged females with MDD and healthy control participants. Design: Twenty-four healthy control participants (mean age = 51.1±5.1 years), and 19 unmedicated participants with MDD (mean age = P-52. 51.1±4.5 years) were included in the analysis. Depression symptoms were assessed Stressful Life events and depressive symptoms in early postmenopausal with the Montgomery-Åsberg Depression Rating Scale (MADRS), with healthy control Chinese women – a population-based cohort study participants reporting mean MADRS scores of 3.2±2.5, and MDD participants reporting Suzanne C Ho, MSc, MPH, PhD, FACE, FACN1, Zhenzhen Liang1, Ruby HY Yu2. 1JC mean scores of 19.6±6.0. Whole brain T1-weighted anatomical images were collected School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong in a 3T MRI. Brains were examined for cortical thickness differences, using FreeSurfer Kong SAR, China; 2Department of Medicine and Therapeutics, The Chinese University for analysis of the high-resolution structural MRI images collected. Results: A Kruskal- of Hong Kong, Hong Kong SAR, Hong Kong Wallis rank sum test indicated a significant difference in right hemisphere cortical Objective: The prevalence of depression seems to increase during menopausal transition, thickness scores between MDD and CTRL groups, χ2 = 1145.862, p <0.001. A post while women also encounter many life stresses during midlife and menopausal period. hoc test demonstrated a significant difference in cortical thickness between groups in This study examined the occurrence of stressful life events (SLE) and its association with the right hemisphere frontal pole (p < 0.05), with the MDD participants having a greater the risk of developing clinically relevant depressive symptoms in early postmenopausal mean right frontal pole cortical thickness (2.88±0.3) than healthy control participants Chinese women. Design: From 2002 to 2004, 518 Chinese women aged 50-64 years, (2.69±0.3). Linear regression analysis indicated a positive relationship between age and and within 10 years since menopause (defined as 12 months since the cessation of cortical thickness in left hemisphere banks of superior temporal sulcus, R2 = .07, F= 4.62, the last menses) were recruited through random telephone dialing based on the most p < 0.05. Increases in age predicted a decrease in cortical thickness in left hemisphere recent residential telephone directory in Hong Kong. Information on sociodemographic, regions: parahippocampal cortex, R2 = .12, F = 6.54, p < 0.05, and superior parietal health (including social and psychological) and lifestyle variables were obtained cortex, R2 = .15, F= 8.24, p < 0.01. There was a positive relationship between age and based on structured questionnaire through face-to–face interviews. Study participants cortical thickness in right hemisphere rostral anterior cingulate cortex, R2 = .07, F= 4.24, were followed up and with repeated measurements at 3-year (T1) and at 5-year (T2) p < 0.05. Increases in age predicted a decrease in cortical thickness in right hemisphere: followup. Depressive symptoms were assessed using the Centre of Epidemiological inferior parietal cortex, R2 = .11, F= 6.29, p < 0.05, paracentral cortex, R2 = 0.09, F= 5.34, Study Depression scale (CES-D). A score of ≥16 was used to indicate clinically relevant p < 0.05, pars orbitalis cortex, R2 = 0.12, F= 6.61, p < 0.05, and supramarginal cortex, R2 depressive symptoms. Stressful Life Events (SLE) were assessed by a 21-item life-event = .09, F= 5.26, p < 0.05. Conclusion: In the present study unmedicated perimenopausal scale, adapted to the Hong Kong Chinese cultural context from the Holmes and Rahe females with MDD showed cortical thickening of the right frontal pole compared to Social Readjustment Rating Scale for Adults(2). Analysis on the association between healthy age-matched controls. This region has been implicated in functions including SLE over the past 2 years reported at T2, and the risk of having CES-D score ≥16 at T2 thinking about the future, and is important in surveillance of consequences predicted was conducted among women with CES-D score below 16 at T1. As such, 104 women to occur based on an ongoing series of actions. Patients with MDD have demonstrated with CES-D score ≥16 at T1 were excluded from the analysis. Potential demographic increased recruitment of frontal structures, compared to controls, when engaged in tasks confounders (age, marital status, birth place, work status, family income) were controlled requiring future thinking. Furthermore, our preliminary findings also indicate that age for in the multivariate logistic regression analysis on the relation between SLE and high appears to have a selective effect on changes in cortical thickness in middle aged females. depressive symptoms. Results: 11.9% of the 397 women (mean age 55.85, standard deviation=3.24) with CES-D score below 16 at T1 were found to have CES-D score

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≥16 at T2. The mean number of reported episodes of SLE over the past 2 years was P-54. 2.20 (range=0-9, SD=1.70). The five most common reported SLE were ‘death of a close SEVERE DETERIORATION OF THE QUALITY OF LIFE, friend or family member’ (39.8%), ‘personal injury or illness’ (26.4%), ‘become in-home PERCEIVED STRESS AND SLEEP DISORDERS ACCORDING TO caretaker’ (21.9%), ‘family member’s injury or illness’ (20.6%), and ‘unemployment CLINICAL HISTORY OF ABDOMINAL HYSTERECTOMY of adult children’ (17.9%). Women with at least one SLE over the past 2 years had Alvaro Monterrosa-Castro, Profesor1,2, Marlon Salguedo-Madrid, Estudiante1,2, katherin a significantly higher mean CES-D score of 10.61 compared with those without any Portela-Buelvas, Estudiante1,2, Joulen Mo-Carrascal, Estudiante1,2. 1Universidad de (mean=9.06) (p=0.047). Women with ‘relationship problems with spouse or children’, Cartagena, Cartagena, Colombia; 2Grupo de Investigación Salud de la Mujer, Cartagena, ‘death of spouse’, ‘relationship problems with friend or other family members’, Colombia ‘unemployment of spouse’, ‘housing or economic problems’, ‘sexual difficulties’, Objective: To compare the prevalence of severe deterioration of the quality of life, sleep and ‘personal and family members illness’ had higher mean CES-D scores (ranging disorders and presence of perceived stress according to clinical history of abdominal from 15.2 to 11.6 in descending order) compared with women reporting other SLE. hysterectomy Design: Methods: Cross-sectional study that is part of the CAVIMEC The prevalence of having CES-D score ≥16 increased among women with increasing (Calidad de Vida en la Menopausia y Etnias Colombianas) research project, which was number of SLE. Compared with those without any SLE, women who reported having carried out in women with mestizo ethnic group with ages between 40 and 59 years, who 1 to 4 SLE had a 2.56 fold (95% CI, 0.6-11.2) increased risk of having CES-D score were residents in the Colombian Caribbean. They were polled in their own communities ≥16 while those with 5-9 SLE had a 10.8 fold (95% C.I. 2.2-53.5) increased risk. A with the scales: Perceived Stress Scale (PSS-10), Menopause Rating Scale and the Jenkins dose-response relationship was observed. The results remained similar after controlling Sleep Scale. Results: 471 women participated, 237 were hysterectomyzed and 234 non- for the potential confounders. When treated as a continuous variable, each additional hysterectomyzed women who were polled in 2015. Those women with hysterectomy SLE experienced was associated with a 33% adjusted increased risk of having CES-D had significantly major age: 50[7.0] vs 45[7.5]. There were not observed differences in score ≥16 at T2 (OR=1.33, 95% CI: 1.12-1.58). Conclusion: Our study revealed that BMI, waist-hip ratio, diabetes, arterial hypertension, to smoke and hormonal therapy. The mid-life women encounter many SLE. Some specific SLE, particularly those related to average score of the perceived stress scale were similar in both groups, hysterectomyzed relationship problems, death of spouse, illness of self or family members and housing/ 19.5±3.3 and non-hysterectomyzed women 17.6 ± 4.7 (p>0.05). The average Jenkins economic problems were more likely to affect the depression level. Increasing number of Sleep Scale were hysterectomyzed 5.2 ± 3.9 and non-hysterectomyzed women 4.5 reported SLE was positively associated with an increasing risk of the onset of clinically ± 3.9 (p=0.97). A hysterectomy women reported presence mayor of “awakenings relevant depressive symptoms. Preventive measures targeting to the at risk women would during the night” and “morning wake up tired despite having slept as usual”. Neither, help alleviate the risk of developing depression in early postmenopausal women. differences in the prevalence of severe menopausal symptoms nor severe deterioration of the somatic, psychologic and of the quality of life were observed (p>0.05). 46% of P-53. the hysterectomyzed were urogenital severe deterioration compared with 36% of non Hippocampal volumetric analysis in unmedicated midlife women with hysterectomyzed (p=0.009). Conclusion: Differences were not observed in the severe major depressive disorder deterioration of the quality of life, stress and sleep disorders according to clinical history Herman Bami1,2, Sabrina Syan1,2, Geoffrey Hall, MSc, Ph.D3, Lauren Cudney1, Meir of hysterectomy Steiner, MD, MSc, PhD, FRCPC1,2, Claudio N. Soares, MD, PhD, FRCPC1,2, Benicio Frey, MD, MSc, Ph.D1,2, Luciano Minuzzi, MD, Ph.D1,2. 1St. Joseph’s Healthcare P-55. Hamilton, Hamilton, ON, Canada; 2McMaster University, Mississauga, ON, Canada; 3 Feeling of Unattractiveness in Peri- and Postmenopausal Women is Psychology, Neuroscience & Behaviour, McMaster University, Hamilton, ON, Canada Associated with Depressed Mood, Poor Memory, and Unsatisfactory Objective: The menopausal transition in women is a period of intense hormonal Sexual Relationship fluctuation and has been associated with an increased risk for the development of major 1 2 2 2 depressive disorder (MDD). The hippocampal complex (HC) is a brain region primarily Masakazu Terauchi, MD, PhD , Asuka Hirose , Mihoko Akiyoshi , Yoko Owa , Kiyoko Kato2, Toshiro Kubota2. 1Department of Women’s Health, Tokyo Medical and Dental associated with learning and memory but has been shown to be a critical region in the 2 pathophysiology of depression. Imaging studies have shown reduced hippocampal University, Tokyo, Japan; Department of Obstetrics and Gynecology, Tokyo Medical volumes in patients with depression. The present study examined the volumes of and Dental University, Tokyo, Japan HC in midlife women presenting with MDD compared to healthy controls. Design: Objective: This study was undertaken to investigate the prevalence and the determinants Unmedicated peri/postmenopausal women (N=19) and age-matched healthy controls of the feeling of unattractiveness in peri- and postmenopausal women. Design: The (N=19) underwent a high-resolution MRI scan. Volumes of interest corresponding to records of 351 women who enrolled in the Systematic Health and Nutrition Education the HC were manually drawn onto the MRI images, according to Pruessner et al (2000). Program at the Menopause Clinic of the Tokyo Medical and Dental University Hospital An automatic segmentation was also completed using Freesurfer imaging software. from November 2007 to December 2012 were subjected to a cross-sectional analysis. Depressive symptoms and cognitive functioning were assessed with the Montgomery– Their feeling of unattractiveness was estimated on the basis of their responses to the Åsberg Depression Rating Scale (MADRS) and the Cognitive Failures Questionnaire item #21 “Feeling unattractive” on the Menopausal Health-Related Quality of Life (CFQ), respectively. Normalized hippocampal volumes were compared between groups [MHR-QOL] Questionnaire. The effects of their background characteristics, including using age, MADRS and CFQ scores as covariates. A linear regression model was applied age, menopausal status, body composition, cardiovascular parameters, physical fitness, with group, age, MADRS and CFQ scores as predictors. Results: Significant differences vaginal dryness, and physical and psychological symptoms of menopause (MHR- in MADRS and CFQ scores were observed between the two groups (p<.001). Paired QOL and the Hospital Anxiety and Depression Scale [HADS]), on the feeling of t-tests showed significant differences between automatic and manual tracings for the right unattractiveness were assessed using multivariate logistic regression analysis. Results: ± ± and left hippocampal volumes (p<.001), with automatic tracings overestimating manually The average age of the participants was 52.4 6.7 years (mean standard deviation). traced volumes. The Pearson correlation between the two types of tracing was strong in The percentage of women who felt they were less attractive than before 3-4 times a week both the right (r=0.692, p<.001) and left (r=0.679, p<.001) HC. The data obtained from or more was 33.6%. Multiple logistic regression analysis revealed that the determinants the manual tracings revealed no significant differences in hippocampal volume between that were significantly associated with the presence of the feeling of unattractiveness after groups, upon adjusting for age and CFQ. A significant difference was however found adjustment were as follows (odds ratio [95% confidence interval]): (1) HADS depression in the automatic tracings of the left hippocampus between control and MDD patients score, 1.22 [1.11-1.35]; (2) MHR-QOL score for depression, 1.79 [1.37-2.37]; (3) MHR- (p=0.047), with a smaller hippocampal volume being displayed in patients with MDD. QOL score for poor memory, 1.79 [1.37-2.37]; (4) MHR-QOL score for dissatisfaction Stepwise linear regression analysis showed that group and MADRS score could predict with the sexual relationship, 1.65 [1.14-2.46]. Conclusion: Feeling of unattractiveness right hippocampal volume changes in the manual tracing (adjusted r squared=0.316, is highly prevalent in peri- and postmenopausal women. It is associated with depressed p=.003; group beta=-0.925, p=.003; MADRS beta=1.205, p<.001). MADRS scores were mood, poor memory, and unsatisfactory sexual relationship, rather than age or body also shown to have significant predictive ability for left hippocampal volumes in both composition. manual (adjusted r squared=0.114, p=.025; MADRS beta=0.373, p=.025) and automatic tracings (adjusted r squared=0.154, p=.010; MADRS beta=-0.422, p=.010). Conclusion: Automatic segmentation showed to overestimate HC volume in this population. This PHYSICAL ACTIVITY POSTER PRESENTATIONS preliminary study found no significant difference in peri/post menopausal women compared to age-matched control subjects in the manual hippocampal tracing. However, P-56. a significant decrease in left hippocampal volume was found in patients with MDD Menopausal Experience of Physical Activity compared to the control group in the automated tracings. Additionally, severity of Lily Stojanovska, PhD1, Vasso Apostolopoulos, PhD1, Erika Borkoles, PhD2. 1College depressive symptoms was found to be a predictor of changes in HC volumes in both of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia; 2Insitute manual and automatic tracings. of Sport, Exercise and Active Living, Victoria University, Melbourne, VIC, Australia Objective: Menopausal symptoms can be severe and disruptive to overall quality of life. HRT can ameliorate symptoms; however, associated side effects have resulted in alternative treatment options. Exercise is assessed as an alternative treatment option for alleviating menopausal symptoms. Maintaining active lifestyle can delay the onset of most conditions associated with ageing and with menopause. We identified the meanings of exercise to menopausal women, and the influence of menopausal symptom severity. Design: Interpretative phenomenological analysis was employed as the theoretical and methodological framework in this qualitative study. We conducted semi-structured interviews with eleven women with different levels of exercise participation and symptom severity. Women associate various meanings with the experience of exercise during menopause. Results: Regardless of exercise behavior and symptom severity,

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participants associated exercise with both physical and physiological benefits. The women with high-severity symptoms valued the role of exercise in fighting ageing, whereas women with low-severity symptoms associated exercise with feeling better able to cope with difficult situations. All of the participants recalled the presence of barriers to exercise. Conclusion: .Exercisers enjoyed exercise more than non-exercisers, and exercise participation was found to have more influence in the perception of symptom severity as a barrier to exercise than symptom severity itself.

P-57. Menopause and Avoidance of Physical Activity Lily Stojanovska, PhD1, Erika Borkoles, PhD2, Remco Polman, PhD2. 1College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia; 2Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, VIC, Australia Objective: Physical activity improves overall health in menopausal women. Lack of consistent findings of physical activity effects on symptom relief or menopausal management relates to not understanding why women avoid exercise whilst experiencing menopausal symptoms. We examined the association between menopausal symptom severity and self-reported physical activity behaviours and active living habits. Design: 506 women aged 52.5y accessed online survey. 77% of respondents were Caucasian, 60% perimenopausal and 40% postmenopausal. Greene Climacteric Scale; Perceived Stress Scale and Kaiser Physical Activity Scale were used to measure severity of symptoms; stress; household duties, active living activities and exercise behaviour respectively. Data was assessed for normality while descriptive statistics were analysed according to menopausal status. Stepwise linear regressions were used assessing differences in activity based on symptom severity controlling for menopausal status, age and stress. Results: Menopausal symptom severities for each category strongly correlated with each other and with perceived stress (rs > .35; ps < .001). Regression analyses showed association of menopausal symptoms with reduced participation in moderate intensity BONE AND MUSCLE POSTER PRESENTATIONS 2 2 exercise (R change= .04; Fchange = 2.98; p= .032) and reduced household activities (R change= .06; Fchange = 5.28; p=.002). Effects were observed after controlling reductions in activity associated with age, menopausal status and stress. 20% avoided activity due to symptoms P-59. including tiredness, heavy sweating, weight gain, irregular and heavy bleeding and Common Iliac Artery Vitamin D Receptor Expression Patterns During general lack of motivation. Conclusion: Severity of menopausal symptoms can have the Development of Atherosclerosis in Postmenopausal Nonhuman significant influence on self-reported activity women engage in and is associated with Primates avoidance of physical activities ranging from household duties to moderate and vigorous Xuezhi Jiang, MD1,3, Matthew S. Nudy, B.S.1,3, Susan E. Appt, DVM2, David M. exercise pursuits. O’Sullivan, PhD1, Jay R. Kaplan, PhD2, Peter F. Schnatz, D.O.1,3. 1ObGyn, The Reading Hospital, West Reading, PA; 2Pathology/Comparative Medicine, Wake Forest University, Winston-Salem, NC; 3ObGyn, Sidney Kimmel Medical College of Thomas P-58. Jefferson University, Philladelphia, PA Objectively measured physical activity (PA) and sedentary behavior (SB) Objective: The results of recent studies suggest that vitamin D receptor (VDR) expression are differentially associated with measures of body composition in pre- in the coronary arteries of female cynomolgus monkeys is negatively associated with versus postmenopausal women atherosclerosis extent and severity. The objective of this study is to assess the changes Lisa M. Troy, PhD, Marquis Hawkins, PhD, Sarah Witkowski, PhD. UMass Amherst, in VDR expression in the common iliac arteries of postmenopausal monkeys during the Amherst, MA development of atherosclerosis. Design: After 32 months of consuming an atherogenic Objective: Menopause is related to changes in body composition. PA is associated with diet, 37 premenopausal monkeys underwent ovariectomy. The same diet was then lower body fat % and higher lean mass in women. Less is known about differences consumed for an additional 32 months until necropsy. Atherosclerosis extent and VDR between pre- and postmenopausal women in terms of PA intensity and SB in relation expression were measured in the left iliac artery (LCI) at the time of ovariectomy, and to body composition. The objective was to examine associations between PA and in the right common iliac artery (RCI) at necropsy. Atherosclerosis severity (American SB and common measures of body composition (i.e., body mass index (BMI), waist Heart Association grading system) and VDR expression (VDR H-score) were quantified. circumference (WC), body fat (%BF), and lean mass (%LM)) in pre- and postmenopausal Results: Despite increasing atherosclerosis over the course of the study, the total mean women. Design: NHANES (2003-04 and 2005-06) data were used to examine PA and (SD) VDR H-score was significantly higher in the RCI in postmenopausal monkeys SB on body composition in 630 pre- (mean age 42.8y) and 274 postmenopausal (mean after consuming the athrogenic diet for a total of 64 months compared to the LCI of age 54.6y) women. Menopausal status was defined using self-reported data in women premenopausal monkeys who consumed the diet for 32 months (152.62[18.55] vs. aged 35-60y. Women were classified as premenopausal if menses in past 2 months; 126.15[22.13], p<.001). There was a significant positive correlation between the absolute postmenopausal if age>40y and no menses in past 12 months. Women reporting (and percentage) change in total H-score and absolute change of AHA severity from pre- hysterectomy or oophorectomy were excluded. ActiGraph accelerometers were used to to post-menopause (Absolute: r=0.43, p=.008; Percentage: r=0.44, p=.007). Conclusion: estimate time spent in light intensity PA (LPA), moderate/vigorous intensity PA (MVPA) Overall, contrary to our expectation, VDR expression was significantly increased in and SB using validated methods. SB was defined as a proportion of monitor wear time direct correlation with atherosclerosis increase in postmenopausal monkeys. A higher spent sedentary. %BF and %LM measured by DXA. Age-adjusted linear regression increase in VDR expression, from pre- to post-menopause, correlated with more severe models were used to examine associations between each measure of PA, SB and body atherosclerotic changes in the common iliac arteries. composition in pre- and postmenopausal women separately. Two-way interactions were used to determine differences in the main effect by menopausal status. Statistical significance was alpha=0.05. Results: Postmenopausal women had significantly higher P-60. mean BMI (29.7 vs 28.4 kg/m2 p<0.02), WC (97.7 vs 92.8 cm, p<0.01), and %BF (42 The Association between Common Iliac Artery Vitamin D Receptor vs 39%, p<0.01) and lower %LM (55 vs 58%, p<0.01); and less total movement (254 vs Expression and Atherosclerosis in Postmenopausal Nonhuman Primates 292 counts/minute, p<0.01), time in MVPA (17.3 vs 22.7 minutes, p<0.01), and more Matthew S. Nudy, B.S.1,2, Xuezhi Jiang, MD1,2, Susan E. Appt, DVM3, David M. sedentary time (61.6 vs 59.3 %, p=0.02) than premenopausal women. Time spent in O’Sullivan, PhD1, Jay R. Kaplan, PhD3, Peter F. Schnatz, D.O.1,2. 1ObGyn, The Reading LPA was similar between the groups (339.7 vs 350.8 minutes, p=0.15). Higher total Hospital, West Reading, PA; 2ObGyn, Sidney Kimmel Medical Colledge of Thomas movement, LPA, MVPA and lower SB were associated with lower BMI, WC, and %BF Jefferson University, Philadelphia, PA; 3Pathology/Comparative Medicine, Wake Forest and higher %LM in both groups, with the exception of LPA and BMI in premenopausal University, Winston-Salem, NC women (see Table). LPA was more strongly associated with each measure of body Objective: The vitamin D receptor (VDR) has been localized to many tissues in the composition in post- compared to premenopausal women (p for interaction <0.05). SB cardiovascular system including the coronary arteries of female nonhuman primates. The was more strongly associated with WC in post- compared to premenopausal women objective of the current study is to determine whether VDR expression in a peripheral (p for interaction=0.01). Conclusion: It appears LPA and SB may be more important artery (common iliac) is associated with atherosclerosis extent and severity in a cohort determinants of body composition in post- than premenopausal women. of postmenopausal cynomologus monkeys. Design: For 32 months, premenopausal cynomolgus monkeys (n=37) consumed an atherogenic diet containing a women’s equivalent of 1,200 mg/day of elemental calcium and 1,000 IU/day of vitamin D. After 32 months, the monkeys were ovariectomized and consumed the diet for an additional 32 months until artery specimens were collected at necropsy. Cross sections of the iliac artery were immunohistochemically stained for the VDR. Atherosclerosis extent was assessed by measuring iliac artery intimal (plaque) area (IA) and maximal intimal plaque thickness (MXIT). Plaque severity was determined using American Heart Association (AHA) atherosclerosis severity grades. Results: In the common iliac artery, a significant

65 POSTER PRESENTATIONS positive correlation was observed between the proportion of VDR negative cells and observed compared to controls after cancer treatment. Conclusion: Our results suggest plaque size (both cross-sectional area [r=0.578, p<0.001] and plaque thickness [r=0.523, that cancer treatment increase bone loss in postmenopausal women with cervical and p=0.001]). Also, a significant positive correlation was observed between the proportion endometrial cancer. of VDR negative cells and the AHA atherosclerotic lesion severity score (r=0.503, p=0.002). Conclusion: Lower VDR expression in the common iliac artery was associated with more severe atherosclerosis in female postmenopausal monkeys. Further research P-63. is needed to elucidate the extraskeletal benefits of vitamin D and the pattern of change in Osteoporotic Risk in Patients with Gynaecologic Cancer VDR expression over the natural course of atherosclerosis. Heungyeol Kim. Kosin University, Busan, Korea (the Republic of) Objective: Patients with cervical cancer have lower bone mass than women without cancer, whereas women with endometrial cancer have higher bone mineral density P-61. (BMD) than control subjects, possibly due to the prevalence of high body-fat mass. The Diagnostic Accuracy of FRAX in Predicting the 10-year risk of aim of this study was to compare BMD in patients with cervical cancer, endometrial Osteoporotic Fractures: A Systematic Review and Meta-analysis cancer, and controls. Design: We analysed and compared spinal and femoral BMD in Xuezhi Jiang, MD1,2, Morgan Gruner, BS1, Florence Trémollieres, MD, PhD3, Wojciech 130 patients with cervical cancer, 68 with endometrial cancer, and 140 age-matched Pluskiewicz, MD4, Elisabeth Sornay-rendu, MD5, Piotr Adamczyk, MD6, Peter F. menopausal female control subjects. We also compared serum calcium, phosphorus, Schnatz, DO1,2. 1ObGyn, The Reading Hospital, West Reading, PA; 2ObGyn, Sidney total alkaline phosphatase, osteocalcin, and urinary deoxypyridinoline levels. Results: Kimmel Medical college, Thomas Jefferson University, Philadelphia, PA; 3Centre de Compared with the control group, T-scores for some lumbar vertebrae (L4), the femoral Ménopause, Hôpital Paule de Viguier, Toulouse, France; 4Département and Clinic of neck, and Ward’s triangle were lower in patients with cervical cancer, whereas only L4 Internal Diseases, Medical University of Silesia, Katowice, Poland; 5INSERM Unit T-scores were significantly lower in patients with endometrial cancer. Deoxypyridinoline 831, Hospital E Herriot, Lyon, France; 6Department and Clinic of Pediatrics, Medical levels were significantly lower in women with endometrial cancer (P < 0.002) than in University of Silesia, Zabrze, Poland women with cervical cancer, but no other biochemical variable differed among groups. Objective: The aim of this study is to conduct a systematic review and meta-analysis Conclusion: Cervical cancer was associated with lower BMD and may be a risk factor on the performance of the WHO’s Fracture Risk Assessment (FRAX) instrument for for secondary osteoporosis. However, endometrial cancer generally seemed to have no predicting 10-year risk of Major Osteoporotic Fractures (MOF) and Hip Fractures (HF) damaging effect on bone. A larger follow-up study is required to clarify these findings. in populations other than their derivation cohorts. Design: PubMed, Google Scholar, Embase, Cochrane Library, and MEDLINE were searched for the English-language P-64. literature from 2008 to 2015. Limiting our search to articles that analyzed only MOF and / or HF as an outcome, 7 longitudinal cohorts from 5 countries (USA, Poland, France, The association between vitamin D and metabolic syndrome in Korean Canada, New Zeland) were identified and included in the meta-analysis. SAS NLMIXED postmenopausal women procedure (SAS v 9.3) was applied to fit the Hierarchical Summary Receiver Operating Hoon Kim, MD,PhD, Seung-Yup Ku, MD, PhD, Chang Suk Suh, MD, PhD, Seok Hyun Characteristics (HSROC) model for meta-analysis. Forest plot and HSROC plot was Kim, MD, PhD, Young Min Choi, MD, PhD, Jung Gu Kim, MD, PhD. Department generated by Review Manager (RevMan v 5.3). Results: Seven studies (n=57,027) were of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, analyzed to assess diagnostic accuracy of FRAX in predicting MOF. Using 20% as the Korea (the Republic of) 10-year fracture risk threshold, the mean sensitivity, specificity, and diagnostic odds ratio Objective: We aimed to study the factors affecting serum vitamin D level in Korean (DOR) along with their 95% confidence intervals (CI) are 10.25% (3.76% - 25.06%), postmenopausal women from the population-based study. Especially, the association 97.02% (91.17% - 99.03%) and 3.71 (2.73 – 5.05), respectively. For HF prediction, between metabolic syndrome (MS), which includes a cluster of major risk factors for using 3% as the 10-year fracture risk threshold, six studies (n=50,944) were analyzed. cardiovascular diseases and vitamin D was investigated. Design: This cross-sectional The mean sensitivity, specificity, and DOR along with their 95% confidence intervals study was based on nationwide representative survey data from the Korean National (CI) are 45.70% (24.88% - 68.13%), 84.70% (76.41% - 90.44%) and 4.66 (2.39 – 9.08), Health and Nutrition Examination Survey (KNHANES). A total of 703 postmenopausal respectively. Conclusion: Overall, FRAX performs better in identifying patients who women (mean age 64.8 years) were included from the KNHANES. The KNHANES will not have a MOF or HF within 10 years. However, a substantial number of patients has been conducted periodically since 1998 and is composed of data from the civilian, who developed fractures, especially MOF within 10 years of follow up, were missed non-institutionalized population of the Republic of Korea using a stratified, multi-stage by the baseline FRAX assessment using the 10 year intervention thresholds of 20% for sampling with a probability proportional to size. The sampling frame was based on the MOF and 3% for HF. 2005 population and housing census in Korea. MS was identified according to the new criteria from a joint scientific statement endorsed by major organizations including National Heart, Lung, and Blood Institute. Results: The association between MS and vitamin D was analyzed with adjustment for potential confounders including age, years since menopause, body mass index (BMI), smoking history, alcohol drinking, and physical activity or exercise. The serum level of vitamin D was significantly higher in postmenopausal women without MS compared to those with MS (22.2 vs 20.8 ng/ml, P=0.04). Also, BMI and physical activity or exercise were associated with the level of vitamin D (P=0.047 and 0.001, respectively). The participants with MS had significantly higher odds for vitamin D insufficiency (less than 20 ng/ml) (odds ratio: 1.48, 95% confidence interval: 1.07-2.06, P=0.02). However, the number of MS components was not associated with vitamin D concentration. After adjusting confounding factors, the glucose component of MS demonstrated an association with the value of vitamin D in postmenopausal women (P=0.01). Conclusion: In conclusion, vitamin D level is associated with MS in Korean postmenopausal women, and the participants with MS demonstrated significantly higher odds for vitamin D insufficiency.

P-65. Effect of vitamin D deficiency and daily calcium intake on BMD and P-62. osteoporosis in postmenopausal Korean woman Yaekyu Koh, M.D1,3, Jinae Lee2, Mi Kyung Song2, Min Kyoung Kim, M.D.1,3, Bo Hyon Changes in Bone Density after Cancer Treatment in Patients with 1,3 1,3 1,3 1 Cervicaland Endometrial Cancer Yun , Byungseok Lee , Seok Kyo Seo . Department of Obstetrics and Gynecology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic Heungyeol Kim1, Ari Kim2. 1Kosin University, Busan, Korea (the Republic of); of); 2Department of Biostatistics Collaboration, Yonsei University College of Medicine, 2Wonkwang University, Iksan, Korea (the Republic of) Seoul, Korea (the Republic of); 3Institute of Women’s Life Medical Science, Seoul, Objective: This study aimed to evaluate the impact of cancer treatment on bone mineral Korea (the Republic of) density (BMD) in the lumbar spine (LS) and femur in the postmenopausal women with Objective: This study aimed to determine the combined effect of vitamin D deficiency cervical or endometrial cancer without bone metastasis compared to normal control and daily calcium intake on BMD and osteoporosis in postmenopausal Korean women. postmenopausal women. Design: We retrospectively evaluated the BMD data in the Design: This study is a cross-sectional study of 3268 participants (more than 45 years and LS, femur neck (FN) and trochanter (FT) by dual-energy X-ray absorptiometry and younger than 70 years Korean postmenopausal women without any thyroid dysfunction) laboratory data of bone turnover markers at baseline and after one year in 130 patients using data from the 2008-2011 Korean National Health and Nutrition Examination with cervical cancer, 68 patients with endometrial cancer, and 225 healthy controls. Survey. Participants were divided into groups according to the 25(OH)D level (<20 and Results: There were no significant differences in the T-scores of basal BMD in LS and ^20 nmol/L) and the daily calcium intake(<400, 400-800, and ^800 mg/day). BMD femur between patients with endometrial cancer and controls, and only T-score of basal was measured using dual-energy X-ray absorptiometry at the femur and the lumbar spine BMD at the fourth lumbar vertebra (L4) was significantly lower in patients with cervical (L1-L4) and the serum vitamin D levels were measured by radioimmunoassay. Results: cancer compared to controls. One year later, T-scores of BMD at all LS sites and FN BMD in the femoral neck has a trend to be higher according to the daily calcium intake in patients with cervical cancer and T-scores of BMD at L3, L4, FN, and FT in those in lower 25(OH)D level group. Also, subjects who were taking sufficient calcium (^800 with endometrial cancer after cancer treatment were significantly lower compared to mg/day) showed similarly high BMD regardless of 25(OH)D level. Insufficient calcium controls. Lower proportions of normal BMD at all skeletal sites except L2 in patients (<400, 400-800 mg/day) group have a tendency of increasing BMD with higher 25(OH) with endometrial cancerand those at L1, L4, and FN in patients with cervical cancer were D level. However, BMD in the lumbar spine did not show any difference significantly

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related to the daily cacium intake and 25(OH)D level. ANCOVA analyses demonstrated P-68. subjects who are taking calcium less than 800mg per day and vitamin D deficiency had The reference value of skeletal muscle mass index for defining the increased risk of osteoporosis at femur neck. Conclusion: The low daily calcium intake sarcopenia of women in Korea and vitamin D deficiency were significantly associated with low BMD and increasing Hyoung Moo Park, Phd2, Tak Kim, MD, PhD1. 1Obstetrics and Gynecology, Korea Univ, prevalence of osteoporosis in postmenopausal Korean women older than 45 years. It Seoul, Korea (the Republic of); 2Obstetrics and Gynecology, Chung-ang Univ, Seoul, is important to taking sufficient calcium and vitamin D in order to decrease the risk of Korea (the Republic of) osteoporosis. Objective: Sarcopenia is considering important disease entity in elderly. Several study groups define the sum of the muscle masses of the four limbs as appendicular skeletal P-66. mass (ASM) to calculate appendicular skeletal mass index (SMI). The purpose of this A randomized study on the effect of vitamin D3 supplementation on study was to determine cut point of SMI for sarcopenia in Korean women. Design: This study was based on data obtained from the 2008-2011 Korean National Health skeletal muscle function in fallers postmenopausal women and Nutrition Examination Survey and (KNHANES). A whole body dual energy X-ray Luciana M. Cangussu, MSc, Jorge Nahas-Neto, PhD, MD, Claudio L. Orsatti, Flavia absorptiometry (DXA) scan were performed on individuals of ≥10 years old from July B. Dias, Eneida B. Schmitt, MD, Eliana A. Nahas, MD. Gynecology and Obstetrics, 2008 to May 2011. 11633 women were included in the analysis. ASM was calculated Botucatu Medical School-Sao Paulo State University, Botucatu, Brazil and SMI was obtained as ASM/heght2. Cutoff value was defined two standard deviations Objective: Objective: Hypovitaminosis D is common in postmenopausal women below mean values for young reference group. Results: Of 11,633 women aged 10- in worldwide. This condition may cause muscle weakness and fall, in addition to an 97years, mean and SD of year was 46.73 18.54years. The highest level of height was important loss of muscle mass.We aimed to evaluate the effect of supplementation of noted in 20’s and the highest total sum of skeletal mass was seen 14.87kg in 40’s. vitamin D alone (VITD) on muscle function in fallers postmenopausal women. Design: The highest value of SMI was noted in 60’s in Korean women. Cutoff value as mean Methods: In this double-blind, placebo-controlled trial, 160 Brazilian postmenopausal value of young women was decided with SMI of 30’s and 40’s that have peak ASM. women were randomized into two groups: VITD group, vitamin D3 supplementation Mean and standard deviation of SMI in those ages was 5.9 0.7kg/m2. A SMI of two 1,000IU/day orally (n=80) or placebo group (n=80). Women with amenorrhea ≥12months standard deviations below the mean SMI of reference groups was 4.4kg/m2 as cutoff and age 50-65 years, with a history of falls (previous 12 months) were included. Those value. Conclusion: This study shows that 4.4kg/m2 of SMI in Korean women was cutoff with neurological or musculoskeletal disorders, vestibulopathies, drug use that could value of sarcopenia. Further study is clearly required to decide cutoff value of SMI for affect balance and osteoporosis were excluded. The intervention time was nine months. sarcopenia, especially for Korean woman. Muscle mass was estimated by Total-body DXA (dual energy X-ray absorptiometry) and muscle strength by handgrip strength and chair-rising test. The plasma concentrations of 25-hydroxyvitaminD [25(OH)D] were measured by HPLC (high-performance liquid P-69. chromatography). The study was registered at and approved by the Brazilian Clinical CORRELATION BETWEEN OSTEOPOROTIC FRACTURE RISK IN Trials Registry under the registration number RBR-222wfk. Statistical analysis was 10 YEARS CALCULATED BY FRAX WITH AND WITHOUT BONE by intention-to-treat (ITT), using ANOVA, Student’s t-test, Tukey test and logistic DENSITOMETRY IN POSTMENOPAUSAL BRAZILIAN WOMEN regression. Results: Results: The mean age of the patients included was 58.8 ± 6.6 Lucia S. Costa-Paiva, MD, PhD, Yasmin Bastos, Luiza Borges, Luiz F. Baccaro, pHD, years in the VITD group and 59.3 ± 6.7 years in the placebo group, with time since Adriana O. Pedro, Aarao M. Pinto-Neto, MD, PhD. Obstetrics and Gynaecology, menopause of 12.0 ± 8.8 years and 12.3 ± 8.4 years, respectively (p>0.05). After nine Universidade Estadual de Campinas, Campinas, Brazil months average values of 25(OH)D increased from 15.0 ± 7.5 ng/ml to 27.5 ± 10.4 ng/ml Objective: The risk of osteoporotic fracture can be clinically evaluated based on clinical (+45.4%) in VITD group, and decreased 16.9 ± 6.7 ng/ml to 13.8 ± 6.0 ng/ml (-18.5%) risk factors and by bone mineral density (BMD), but these parameters are not good in placebo group (p <0.001). In VITD group, there was significant increased (+25.3%) predictors of fracture risk. Recently, Brazil was included in the fracture risk assessment in muscle strength of the lower limbs by chair-rising test (p=0.036). In women in the tool - FRAX-BRAZIL, but its use has been limited in clinical practice. Objective: placebo group, there was considerable loss (-6.8%) in the muscle mass (p = 0.030). The To compare Fracture Risk Assessment Tool (FRAX) calculations with and without rate of fall was higher in the placebo (+46.3%, p<.001), that presented an adjusted risk bone mineral density (BMD) in predicting the 10-year probability of major and hip of 1.9 (CI 95% 1.23-3.08) times higher of falls and 2.80 (CI 95% 1.43-5.50) times higher osteoporotic fractures in Brazilian postmenopausal women. Design: Methods: A cross- of recurrent falls than the VITD group. Conclusion: Conclusion: The supplementation sectional study was conducted with 402 women followed at the Menopause Ambulatory of vitamin D alone in fallers postmenopausal women provided significant protective at the Women’s Hospital Prof. Dr. José Aristodemo Pinotti in Campinas-SP. Inclusion factor against the occurrence of sarcopenia, with significant increases in muscle strength criteria was: postmenopausal women over 40 years of age and with amenorrhea of at and control of progressive loss of body muscle mass. * Financial support from FAPESP, least 12 months and who were never treated with any approved agents for osteoporosis. process number 2011/14447-1. Height, weight, FRAX questionnaire, femoral neck BMD (g/cm2) and T-score data were obtained. FRAX scores with BMD and without BMD were calculated in order to obtain P-67. the probability of major and hip fractures. Statistical analysis: To analyze the correlation Evaluation of risk factors for low bone mineral density in postmenopausal between the probability of fractures with and without bone densitometry, it was used the breast cancer survivors intraclass correlation coefficient (ICC). The Mann-Whitney test was used to compare Priscila F. Poloni, MD, Jorge Nahas-Neto, PhD, MD, Heloisa D. Vespoli, MD, Gilberto the average of FRAX scores with BMD and without BMD. Linear regression analysis Uemura, MD, Benedito Almeida-Filho, MD, Eliana A. Nahas, MD. Gynecology and was performed to evaluate the association between clinical risk factors, demographic Obstetrics, Botucatu Medical School-Sao Paulo State University, Botucatu, Brazil variables and the probability of fracture. Results: RESULTS: The 10-year probability Objective: Objective: We aimed to evaluate the risk factors for low bone mineral of major and hip fracture calculated using the FRAX-BRAZIL without BMD was density (BMD) in postmenopausal breast cancer survivors compared to postmenopausal 0.84% (±1.92) and 4.03 (±2.98%) and after the inclusion of BMD was 0.83% (±1.76) women without breast cancer (control). Design: Methods: In this case-control study, 112 and 4.05 (±2.98%), respectively. The intraclass correlation coefficient between the breast cancer survivors were compared with 224 postmenopausal women. Women with FRAX-BRAZIL with and without BMD was 0.76 (IC95% 0.716-0.799) for a major amenorrhea ≥12 months and age 45-75 years, histological diagnosis of breast cancer, fracture and 0.644 (IC95% 0.583-0.698) for hip fracture. The probability of fracture have completed surgical treatment, radiotherapy, hormone therapy, and chemotherapy that exceeded high risk thresholds using FRAX with BMD was 0.75% and 5.22% the (whenever recommended) and metastasis-free for at least five years were included. for major and hip fracture, respectively. The inclusion of the bone density showed a 10- The control group consisted of postmenopausal women without breast cancer, matched year probability of 1% and 11.44% for major and hip fractures, respectively. Then the by age and menopause status, in a proportion of 1 case to 2 controls. The risk factors treatment recommendation was consistent between the FRAX with and without BMD in for low BMD (osteopenia and osteoporosis) were assessed by interviews. Clinical and 99.75% of cases of major fracture and 93.78% for hip fracture. Factors associated with anthropometric data were collected. BMD was measured by DEXA (dual energy X-ray less variation of FRAX score with and without BMD were older age, lower BMD, lower absorptiometry) (HologicÒ, QDR-2000) at the lumbar spine (L1-L4) and femoral neck. T-score and no previous fracture both at major and hip sites. The body mass index was Logistic regression model (odds ratio, OR) was used to identify factors associated with associated with lower variation in the FRAX score only in major fracture. Conclusion: low BMD. Results: Results: The mean (SD) age of BCS was 61.3 (9.7) years, with a CONCLUSION: The probability of a major and hip fracture was low in the studied mean follow-up of 10.2 (3.9) years. BCS had a higher incidence of osteopenia (45.1%) population. The FRAX-BRAZIL presented a high correlation to estimate the probability and osteoporosis (22.3%) in the BMD at the femoral neck when compared to control of major fracture and moderate agreement for hip fracture. In the majority of women, (39.3% and 9.0%, respectively) (p=0.0005). The BMD at the lumbar spine did not FRAX alone provides the same prediction as FRAX associated with BMD. differ between groups (p=0.332). Univariate analyses, adjusted for age and time since menopause, revealed that chemotherapy (OR 6.90; 95%CI 5.57-9.77) was associated with higher risk for low BMD. Contrarily, regular physical exercise (OR 0.24; 95%CI 0.06-0.98) and body mass index ≥ 30kg/m2 (OR 0.09; 95%CI 0.02-0.37) reduced risk among BCS. Conclusion: Conclusion: Postmenopausal breast cancer survivors had a higher incidence of osteopenia and osteoporosis in femoral neck when compared to women without breast cancer. History of chemotherapy was indicator of risk for low BMD, whereas regular physical activity and high BMI reduced risk among breast cancer survivors.

67 POSTER PRESENTATIONS

P-70. height (muscle mass [kg]/height [m2]) and termed as skeletal muscle index (SMI), and Women’s Health Initiative Clinical Trials: The Effects of Calcium and free fat mass (FFM) was estimated using the Sun’s equation. An alternative cut-off value th Vitamin D Supplementation and Hormone Therapy on LDL-Cholesterol of LPO^0.320 μmol/L was defined on the basis of the 90 percentile of young healthy and Other Cardiovascular Disease Risk Factors subjects, and handgrip strength <20 kg according the Sarcopenia European Consensus. Results: We found that 33 (51%) of the women had low handgrip strength. A negative Peter F. Schnatz, D.O.1,2, Xuezhi Jiang, MD3,4, Matthew S. Nudy, B.S.3,4, David M. correlation between LPO and SMI was observed in women with low MS (r=-0.297, O’Sullivan, PhD3, Aaron K. Aragaki, M.S.5, Mark Williams, MD3, Erin LeBlanc6, Lisa p<0.05); other muscle mass markers were also related, but were not significant. In W. Martin, M.D.7, JoAnn E. Manson, MD, DrPh15, James M. Shikany, Dr.P.H.8, Karen women with normal/high MS we did not find correlation (Figure). All the muscle mass C. Johnson, MD9, Marcia L. Stefanick, Ph.D.10, Martha E. Payne, RD, PhD, MPH11, markers were low in women with high LPO and low MS, compared with women with Jane A. Cauley, DrPH12, Barbara V. Howard13, John Robbins, MD14. 1ObGyn & Internal low LPO and normal/high MS: SMI 7.2±0.7 vs. 7.9±0.7 kg/m2, p< 0.05; MM 16.6±1.8 Medicine, The Reading Hospital and Medical Center, Reading, PA; 2Departments of vs.19.3±1.7 kg, p<0.0001; FFM 40.3±3.2 vs. 45.5±3.7 kg, p<0.0001. Conclusion: Our ObGyn and Int Medicine, Thomas Jefferson University, Philadelphia, PA; 3ObGyn, findings suggest that the oxidative stress is related with loss muscle mass and low muscle Reading Hospital, Reading, PA; 4ObGyn, Thomas Jefferson University, Philadelphia, strength during perimenopausal period. This work was supported by grant DGAPA- PA; 5Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, UNAM IN224115. Seattle, WA; 6Center for Health Research NW, Kaiser Permanente, Portland, OR; 7Department of Int Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC; 8Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL; 9Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN; 10Prevention Research Center, Stanford University, Stanford, CA; 11Psychiatry, Duke University, Durham, NC; 12Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA; 13MedStar HEalth Research Institute, Hyattsville, MD; 14UC Davis Medical Center, Sacramento, CA; 15Preventive Medicine, Harvard Medical School, Boston, MA Objective: To analyze the treatment effect of calcium and vitamin D (CaD) supplementation, hormone therapy (HT), both CaD and HT, and neither on cardiovascular disease (CVD) risk factors. Design: A prospective, randomized, double-blind, placebo controlled trial among Women’s Health Initiative postmenopausal participants. In the HT trial a total of 27,347 women were randomized to HT (0.625 mg/d of conjugated equine estrogens [CEE] alone or 0.625 mg of CEE plus 2.5 mg of medroxyprogesterone acetate [MPA] daily) versus placebo. In the CaD trial, 36,282 women were randomized to 1,000 mg of elemental calcium carbonate plus 400 IU of vitamin D3 daily, compared with placebo. A total of 1,521 women participated in both trials and were in the 6% subsample of trial participants with repeated blood sample collections at baseline and years 1, 3, and 6. The predefined primary outcome of this analysis was low-density lipoprotein cholesterol (LDL-C) and other CVD risk factors (such as high-density lipoprotein cholesterol, triglycerides, glucose, blood pressure, weight, and waist circumference) as Figure. Correlation between lipoperoxides levels and SMI separated by muscle secondary outcomes reporting the average effect over both visits that occurred after CaD strength. randomization. Results: The average treatment effect with 95% confidence intervals during follow-up, in LDL-C, compared to placebo, was −1.6 (−5.5, 2.2) mg/dL for CaD- alone, −9.0 (−13.0, −5.1) mg/dL for HT-alone, and −13.8 (−17.8, −9.8) mg/dL for CaD CANCER POSTER PRESENTATIONS plus HT. The p-value for interaction was 0.26, indicating no evidence of a synergistic effect of CaD x HT on LDL-C. However, there was evidence that CaD x HT had a P-72. synergistic effect on decreasing LDL at low total intakes (dietary and supplements) of METABOLIC SYNDROME AS RISK FACTOR FOR BREAST vitamin D (p-int = 0.03) and calcium (p-int = 0.06). The effect of HT plus CaD, on all CANCER of the remaining CVD risk factors, tended to be larger in magnitude than the effects of Dayna P. Autun, Imelda Hernández. BRH, Hospital Juarez de Mexico, Mexico, Mexico either HT-alone or CaD-alone, but none of the HT x CaD interactions were statistically Objective: Metabolic syndrome is present in 46.6 % of menopausal women. Some significant. Conclusion: The average reductions in LDL-C during follow-up were greater studies (Colonna, ORDET, Me-Can) suggest that the existing association between among women randomized to both CaD and HT than for those randomized to either metabolic syndrome and breast cancer promotes carcinogenesis. Associated with this, intervention alone or to placebo. However, statistical tests for interaction between CaD obesity favors a chronic inflammatory condition, creating a favorable environment for and HT were non-significant. epithelial cell proliferation. In Mexico, the prevalence of obesity in women from 50 Average Group Means (95% CI) during follow-up of Treatment Group Effects to 59 years of age is of 47.6 %. Breast cancer is currently the first cancer death cause. Objectives: learn the association between metabolic syndrome and breast cancer; define the relative risk of breast cancer with each metabolic syndrome component. Design: An observational, comparative, cross-sectional and prospective trial was performed with women who went for the first time to the Breast Cancer and Climacteric Clinic. The metabolic syndrome was diagnosed based on the ATP III criteria. One hundred and two patients met the inclusion criteria and they were divided into 2 groups: 1) breast cancer and 2) no breast cancer, with 51 patients in each. Measures were made in each patient of weight, height, abdominal girth, blood pressure, HDL cholesterol, triglycerides, breast cancer histopatological diagnosis. They were examined using descriptive statistical methods. Additionally the groups were compared through odds ratios. Results: 45 % (n= 23) of patients with cancer and 47 % (n=24) without cancer had metabolic syndrome. The metabolic syndrome is not a breast cancer risk factor (OR 0.92); however, with the discrimination of the metabolic syndrome components based on the ATP III criteria, p-value: Overall comparison by row, not a two group comparison; p-interaction: hypoalphalipoprotein was determined to be the main risk factor, with OR 2.64 (86 %, HT*CaD interaction effect n=20); followed by hyperglycemia (OR 1.56), and hypertriglyceridemia (OR 1.09); ruling out abdominal girth (OR 0.77) and blood pressure (OR 0.34) as risk factors. Additionally, P-71. when the BMI was assessed, the findings show that obesity (BMI > 30) associated with Low muscle mass and decreased muscle strength in perimenopausal metabolic syndrome (56.2 % in group cases and 45.8 % in control group) represents a risk women and its relationship with oxidative stress factor for breast cancer development (OR 1.24) Conclusion: As the metabolic syndrome components and obesity represent public health problems and evidence was found of the Martha Sánchez-Rodríguez, PhD1, Mariano Zacarias-Flores, MD ObGyn2, Elsa Correa- existing association with breast cancer, it is essential to engage in timely interventions, Muñoz1, Víctor Manuel Mendoza-Núñez1. 1Facultad de Estudios Superiores Zaragoza, educating the women about changes in their diet and lifestyle to have a positive impact Unidad de Investigación en Gerontología, UNAM, México, DF, Mexico; 2Hospital on the prevention of chronic diseases. Gustavo Baz Prada, Instituto de Salud del Estado de México, Nezahualcóyotl, Mex, Mexico Objective: To determinate the lipoperoxide levels as oxidative stress (OS) biomarker in perimenopausal women and their relationship with loss of skeletal muscle mass and muscle strength. Design: We carry out a cross-sectional study with 65 perimenopausal women of Mexico City, 44-60 yr (51.2±3.6 yr). We measured lipoperoxides levels (LPO) by TBARS assay, muscle mass by bioimpedance analysis and muscle strength (MS) with a dynamometer. We also measured weight and height and we calculated the body mass index (BMI). Skeletal muscle mass (MM) was calculated using the bioelectrical impedance analysis equation of Janssen et al; absolute muscle mass was normalized for

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viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and apoptosis was assessed by flow cytometry. Results: KRG extracts inhibited cell proliferation and induced apoptosis in MCF-10A cells and MCF-7 cells in a concentration-dependent manner. KRG extracts inhibited protein expression of Bcl-2, Bcl-xL and Survivin, and induced expression of BAD, leading to activation of caspase 3 and cleavage of PARP, indicating caspase-dependent. Conclusion: KRG extracts inhibit cell proliferation and induce apoptosis in breast cells and breast cancer cells. KRG could be an alternative herbal supplementation having anti-proliferative effects on breast which might be used safely in postmenopausal women.

P-75. A preliminary study of the effectiveness as a screening of nipple aspiration fluid (NAF) for breast cancer risk assessment in Korean peri- and post-menopausal women by comparing with mammography and breast ultrasound Tak Kim, M.D.,Ph.D.1, Hang Yong Jang, M.D.1, Hoon Choi2. 1Department of Obstetrics and Gynecology, Korea University College of Medicine, Anam Hospital, Seoul, Korea (the Republic of); 2Department of Obstetrics and Gynecology, College of Medicine, Inje University, Sanggye Paik Hospital, Seoul, Korea (the Republic of) Objective: The HALO breast Pap test is an automated nipple aspiration fluid (NAF) P-73. system that was recently introduced into the market in Korea. Since NAF screening Histopathological analysis of ovarian tumors in pre- and post-menopausal has never been compared to either mammography or breast ultrasound, no evidence women in Korea of efficacy its use as a screening still remains investigational. We evaluated the Eun jeong Jeong. Department of Obstetrics and Gynecology, Busan Paik Hospital, Inje effectiveness as an aid of breast cancer screening with the NAF system by comparing University,, Busan,, Korea (the Republic of) with the mammography examination or the breast ultrasound results. Design: This is a Objective: The purpose of this study was to evaluate the histopathologic conditions of prospective study targeting Korean peri- and post-menopausal women who underwent ovarian tumors in pre- and post-menopausal women in Korea. Design: Women who mammography for routine screening or hormone therapy use, visiting three university had undergone surgery for ovarian tumors and histopathologically confirmed at Busan medical centers, during a 1-year study period from the date of institutional review board Paik Hospital in Korea from 1997 to 2013 were enrolled in this study. Histopathological (IRB) approval. Results: We sampled NAF from 237 Korean women with a median distribution of ovarian tumors according to menopausal status were analyzed.Ovarian age of 54.3±6 years. Of 237 separate assessments, 183 mammograms and 83 ultrasound tumors were classified as non-neoplastic and neoplastic and subdivided into several examinations were evaluated with NAF cytology. NAF with cells was obtainable from categories based on the World Health Organization’s classification system. Results: A 51.4% (122 of 237 participants) women sampled, and the sampling rate of breasts was total of 4013 cases with ovarian tumors were reviewed and 3090 (3090/4013, 77.0%) 60.2% (288 of 478 participants). There was no statistical correlation between NAF cases were premenopausal women and 923 (923/4013, 23%) cases were postmenopausal collection and age, BMI, menopausal status, breast feeding, breast cancer history, and women. The histopathological characteristics of 4013 cases with ovarian tumors by the breast imaging reporting of mammogram and ultrasound. However, participants menopausal status are summarized in Table 1. There were 1600 cases (39.9%) of non- with increased parity were more like to yield NAF (p=0.05). Conclusion: The rate neoplastic masses and 2413 cases (60.1%) of neoplastic masses. In the neoplatic masses, of sampling NAF in Korean women (51.4%) appears to be higher than in other Asian there were 1713 cases (71.0%) of benign tumors, 190 cases (7.9%) of borderline tumors women, but lower than in non-Asian women (American and European women). There and 510 cases (21.1%) of malignant tumors. Non-neoplastic masses such as simple was no statistical correlation between NAF collections of both NAF producers and cyst, follicular cyst, corpus luteal cyst, tubo-ovarian abscess and endometrioma were non-producers and the breast imaging reporting of mammogram and ultrasound. NAF significantly associated with premenopausal women (P < 0.0001). Of ovarian masses, producers were not more likelihoods of higher risk of developing breast cancer than endometrioma is the most common types of all tumors (888/4013, 22.1%) and commonly non-NAF producers by comparing with the breast imaging reporting. Although NAF occurred in premenopausal women (855/3090, 27.7%). Benign tumor were significantly with cytological evaluation can be used as a complement to other breast screenings, like higher in premenopausal women (P < 0.0001), especially in epithelial origins and germ routine mammograms and breast exams, but a nipple aspirate test should not take the cell origins. Boderline tumors were predominantly occured in premenopausal women place of the standard breast cancer screening technique. (P = 0.0001). Of malignancy tumors, epithelial origins were significantly associated in postmenopausal women (P = 0.0479), whereas germ cell origins were significantly associated in premenopausal women. Conclusion: We found that there were significant P-76. differences in the histopathological distribution of ovarian tumor between pre- and post- Clinical Characteristics of Breast Cancer Detected on Hormone Therapy menopausal women. Non-neoplastic masses, benign, borderline ovarian tumors were in Korean Women significantly associated with premenopausal women, whereas malignant tumors of Kyu-Sup Lee, MD PhD2, Sung-Tack Oh, MD PhD1, Jung-Bin Son, MD2, Jong-Kil Joo, epithelial origins were significantly associated with postmenopausal women. And we MD2. 1Department of Obstetrics & Gynecology, Chonnam University Medical School, observed the increased prevalence of endometrioma in Korea women during the last 16 Gwangju, Korea (the Republic of); 2Department of Obstetrics & Gynecology, Pusan years compared with previous report in 1980s. national university, Busan, Korea (the Republic of) Table 1. The histopathological characteristics of ovarian tumors by menopausal status Objective: This study was performed to assess the risk factors, histologic and clinical features of breast cancers occurred from postmenopausal women who receiving hormone therapy (HT). Design: We evaluated 40 breast cancer patients who receiving HT due to postmenopausal symptoms by reviewing their medical charts in university hospitals. Research variables including history of the patients, kinds and duration of received HT, term of the cancer outbreaking after starting HT, the radiological characteristics of breast, cancer stage, histologic type, tumor size, grade, lymph node metastasis, the estrogen receptor and the progesterone receptor status, and 5-year survival were investigated. Results: In risk factors of breast cancer patients, only one patient had familial history of breast cancer. No one had smoking history. Average body mass index (BMI) was 23.24 kg/m2. Twelve patients (30%) had estrogen only therapy, 13 patients (32.5%) had combined estrogen and progesterone therapy, 10 patients (25%) had tibolone therapy and the others consecutively received combination therapy of above regimens. Duration of treatment was 31 ± 27.9 (0.4 - 115) months. In distribution of the cancer outbreaking after starting HT, 4 cases (10%) was within 1 year, 5 cases (12.5%) within 1-2 years, 10 cases (25%) within 2-3 years, 4 cases (10%) within 3-4 years, 1 case (2.5%) within 4-5 years, and 16 cases (40%) within more than 5 years. Average diameter of tumor size was 1.7cm. Ductal type of histology consisted of 92.5% of tumor. Tumor stage 0 and I were appeared to 66% and grade I was showed 38% that was most frequent. Hormone P-74. receptor-positive breast cancers were 85% and 70% of patients had negative lymph node Effects of Korean red ginseng extract on breast cells and breast cancer metastases, and 5-year survival rate was 92%. Conclusion: Emerged breast cancers cells during HT in postmenopausal women had hormone receptor-positive tendency. The size Min Kyoung Kim, M.D.1, Yaekyu Koh, M.D1, Eun Bee Noh, M.D.1, Bo Hyon Yun1, and stage of these breast cancers were showed small and low, and represented low-grade Ji Young Lee2, Seok Kyo Seo1, Byungseok Lee1. 1Obstetrics and Gynecology, Yonsei differentiation. Recurrences of disease were uncommon and came out favorable 5-year University College of Medicine, Seoul, Korea (the Republic of); 2Obstetrics and survival rates (92%) and good prognosis. Gynecology, Konkuk University, Seoul, Korea (the Republic of) Objective: This study was to investigate the effects of Korean red ginseng (KRG) extracts on breast (MCF-10A) cells and breast cancer (MCF-7) cells. Design: MCF-10A cells and MCF-7 cells were cultured with different concentrations of KRG extracts. Cell

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P-77. P-79. The Effect of Hormone Therapy on Quality of Life and Breast Cancer The anti-proliferative effects of Maca on breast cancer cell lines Risk After Risk Reducing Salpingo-oophorectomy: A Systematic Review Lily Stojanovska, PhD1, Kristina Nelson, BSc1, Stephanie Day, PhD2, Vasso and Meta-analysis Apostolopoulos, PhD1. 1College of Health and Biomedicine, Victoria University, 2 Tasneem Siyam, BScPharm, MSc1, Sue Ross, PhD, MBA2,3, Sandra Campbell, MLS4, Melbourne, VIC, Australia; Burnett Institute, Melbourne, VIC, Australia Dean Eurich, BSc, MSc, PhD5, Nese Yuksel, BScPharm, PharmD1. 1Faculty of Pharmacy Objective: Cancer is a disorder of uncontrolled cell proliferation, caused by changes to and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; 2Department genes impairing normal mechanisms that regulate cell growth and division. The World of Obstetrics and Gynecology, Faculty of Medicine and Dentistry, University of Alberta, Cancer Research Fund has a body of convincing or at least probable evidence that dietary Edmonton, AB, Canada; 3Department of Obstetrics and Gynecology, Lois Hole Hospital/ intake and particular foods and nutrients can be both causative and preventative in cancer Robbins Pavilion Royal Alexandra Hospital, Edmonton, AB, Canada; 4Mackenzie Health and it is estimated that one third of cancers are linked to diet. Obesity, red/processed Science Center, University of Alberta, Edmonton, AB, Canada; 5School of Public Health, meat, alcohol and salt/salty food intake are considered increased risk factors, whereas University of Alberta, Edmonton, AB, Canada plant food intake of pulses and non-starchy vegetables, and foods containing folate, Objective: Women who are carriers of BRCA mutations are often challenged by Vitamin C, Selenium and β-Carotene are associated with decreased risk. Popular health the decision to uptake risk reducing salpingo-oophorectomy (RRSO) due to fear of food supplements are attributed with an array of health claims, many of which include symptoms associated with surgical menopause, and the subsequent need for hormone chemoprevention. Lepidium meyenii (Maca) is a popular supplement widely available in therapy (HT), that may further impact their risk of breast cancer. The objective of this retail outlets, yet its therapeutic mechanism is not well understood and rigorous studies systematic review was to identify, evaluate and synthesize evidence on the effect of HT in cancer are lacking. This study examined the anti-proliferative effects of Maca on a on the quality of life (QOL) and breast cancer risk, after RRSO in carriers of BRCA human breast cancer cell line, MCF-7 as to the chemoprotective potential of this plants. mutations. The effect of HT on other short and long term outcomes was also evaluated. Design: We previously demonstrated that Maca reduced symptoms of depression and Design: We searched electronic databases including MEDLINE, EMBASE, CINHAL, improved diastolic blood pressure in postmenopausal women. Given that breast cancer and others, from inception to March 21, 2014, to identify randomized controlled trials is a high risk factor in postmenopausal women, we determined the effects of Maca on (RCTs) and observational studies that addressed the effect of HT on the QOL and breast cancer cell lines in vitro. Maca a dried powders of raw product is largely insoluble breast cancer risk in women who have BRCA mutations or who have high risk of breast in water, and required soluble portion extraction prior to use in the cell-based assays. and ovarian cancer and who have undergone a RRSO. Two reviewers independently Breast cancer cell line MCF-7 was seeded in in triplicate in 96-well plates and incubated screened identified records for confirmation of eligibility, extracted data, and assessed with either crude or artificially digested extracts ranging from 0.01 mg/ml - 100 mg/ml methodological quality. Data synthesis included written evidence summaries and meta- for Maca. Media alone was used a background control. The difference in the amount of analyses. When sufficient qualitative homogeneity was demonstrated, outcome data were cells/well of the MCF-7 cell line, was attributed to the different growth rates of each pooled quantitatively. DerSimonian-Laird random effects method was used to calculate cell line in vitro. Results: The addition of Maca (0.1 mg/ml - 100 mg/ml) to MCF-7 weighted mean difference (WMD) and 95% CI of QOL. Generic inverse variance method cells over 8 days, showed some anti-proliferative effects at 100 mg/ml within the first was used to calculate pooled OR and 95% CI of breast cancer. Results: Of the 829 4 days compared to control. However, at lower concentrations there was no difference records identified, 8 met inclusion criteria. All studies were observational in nature. Four in cell proliferation, even though enhanced proliferation was noted at day 8 at 1.0 mg/ studies were considered of high methodological quality and 4 low quality. Across studies, ml and 10 mg/ml. Compared to control cells, Maca reduced MCF-7 breast cancer cell study populations were mostly comprised of BRCA 1 & 2 mutation carriers (88%) and proliferation. Conclusion: Very little is known about the effects of Maca in cancer, both pre and post-menopausal women at the time of RRSO (63%). The mean age of hence, we determined its anti-proliferative effects in vitro on human breast cancer cell women was 42 years (37-78). Of the 8 studies included, 4 assessed the effect on QOL. line, MCF-7. Maca may have anti-proliferative effects in cancer. Further research is All studies demonstrated improvement in QOL with HT. The pooled estimate of WMD required to determine in Mac has anti prolifertive effects in vivo. from random effect model was 3.26 (95% CI, 0.96-5.56, P = 0.005, I2 = 0%). HT users were less likely to have hot flashes (P = 0.0003), night sweats (P = 0.002) and vaginal dryness (P = 0.02) than non-users. The risk of breast cancer with HT was evaluated GLYCEMIC ABNORMALITIES in 3 studies. Mean duration of follow-up was 2.6 years (range 0.1-19.1). Two studies POSTER PRESENTATIONS reported a decreased risk with HT use, and one reported an increased risk, though none were statistically significant. The pooled OR from generic inverse variance meta-analysis showed a non-significant reduction in breast cancer risk (OR 0.63; 95%CI, 0.28-1.40, P = P-80. 0.26, I2 = 0%). Conclusion: Evidence from our review suggests that HT is a reasonable DXA assessment of adiposity is a better predictor of metabolic risk than approach for improving quality of life and menopausal symptoms, without negating the BMI breast cancer risk-reducing benefits of RRSO, at least in the short term. These findings Steven R. Goldstein, MD, Jacqueline Hirsch, M.D., Cheongeun Oh, Ph.D., Richard present a valuable source of information for patients contemplating RRSO, and their Nachtigall, Lila Nachtigall. NYU School of Medicine, New York, NY clinicians. Objective: There is a well know epidemic of obesity in the United States. It is a major factor in developing cardiometabolic abnormalities, although weight alone allows somewhat imprecise prediction. Body Mass Index (BMI) developed almost 175 P-78. years ago as a measure of relative weight based on an individual’s mass and height Effects of Müllerian Inhibiting Substance on myoma is expressed by WHO definitions, arbitrarily derived, as “normal weight, overweight, Jae-Yen Song2, Do Young Kim2, Youn-Jee Chung2, Mee-Ran Kim1, JangHeub Kim2. and obese.” BMI is neither age nor gender specific. Previously, we presented data 1OBGYN, Seoul St Mary’s hospital, Seoul, Korea (the Republic of); 2OBGYN, Catholic on a cohort of postmenopausal women where percent body fat was measured by university of Korea, Uijeongbu-si, Korea (the Republic of) dual x-ray absorptiometry (DXA) and converted into percentiles for age and gender. Objective: Müllerian inhibiting Substance (MIS), also known as anti-Müllerian hormone Approximately 20% of normal weight women were greater than the 75th percentile for (AMH), is known to not only act as a regulator of female reproductive function but total body fat (deemed “skinny fat”) while 20% of overweight women were between also inhibits the growth of Müllerian duct-derived tumors in vivo and in vitro. But the 25-75th percentile. All obese women were above the 75th percentile while 20% of normal role of MIS in myometrium and myoma is unclear. Therefore, this study is aimed to weight women were less than the 25th percentile (lean). This is not dissimilar to the confirm the expression of MISRII and effects of MIS on myometrium and myoma. work of Wildman et al that found that there are groups of individuals with metabolic Design: We gathered the tissues from the 26 patients who had hysterectomy for myoma dysfunction despite a lean prototype and healthy obese people who are protected from (24 myometrial tissues and 26 myoma tissues). We performed immunohistochemistry metabolic dysfunction. They assessed a cross sectional sample of 5440 participants in with rabbit polyclonal anti-human MISR II antibody. The cultured cells were exposed the National Health and Nutrition Examination Surveys (NHANES) 1999-2004, for to MIS and MTT assay. Induction of cell cycle and apoptosis was also observed in the cardiometabolic abnormalities including weight, blood pressure, C-reactive protein, cells treated with MIS as measured by using DNA PI staining and annexin V binding. fasting glucose, insulin resistance and serum lipids. They found that 23.5% of normal The cells were analyzed on a flowcytometer. We evaluated the expression of proteins weight adults were metabolically abnormal, while 51.3 % of overweight adults and which is related apoptosis and cell cycle arrest in myometrium and myoma. Results: 31.7% of obese adults were metabolically healthy. It has been established, however, that MISRII was strongly stained in myoma tissues, whereas myometrial tissues showed android or truncal adipose tissue distribution compared to gynoid (hips and buttocks) has weakly stained. The cultured myoma cells treated with MIS significantly exhibited a greater association with metabolic dysfunction. Thus, obesity related complications 26.4% growth inhibition in myoma but 7.7% in myometrium (P<0.05). Changes in cell are less associated with fat mass per se than the distribution of that fat. Dual X-ray cycle distribution after exposure to MIS demonstrated that S and G2M phases were Absorptiometry (DXA) uses small amounts of x-ray to produce a total body image. The decreased, G0G1 and subG0G1 phases were increased 8.9% and 24.3% in myoma and x-ray is composed of two energy levels that are absorbed differently by bone, lean and 3.2% and 8.3% in myometrium respectively. In the cultured myometrium and myoma fat tissues. These differences are used to determine the amount of lean and fat tissues cells treated with MIS increased 5.2% and 20.2% binding annexin V. Treatment with across the whole body. Realizing that location of body fat may be more relevant than MIS up-regulated p107 and p130, the cell cycle related protein and down-regulated Cdk2 total body fat, special software can measure visceral adipose tissue (VAT) expressed and caspase-3, the apoptosis related protein. Conclusion: We found that the expression either in pounds or volume. Traditional DXA yields percent body fat in the android of MISRII has difference between myometrial tissue and myoma. MIS induces G0G1 region and gynecoid region, yielding an A/G ratio. This study was undertaken 1) to cell cycle arrest and apoptosis of myoma. These finding suggest that MIS has a greater see the correlation between A/G ratio and VAT and 2) the correlation between BMI role on myoma than myometrium in cell cycle inhibition and apoptosis. Therefore, MIS and VAT. Design: 113 postmenopausal women who had a routine DXA scan for bone could be used as a biological modifier or therapeutic agent for the treatment of myoma. mass indication and who had had whole body scans for body composition were collected retrospectively and consecutively. GE Lunar Core Scan© software (GE, Milwaukee, WI.) was utilized. A/G ratio as well as VAT in pounds and volume were obtained. This was then compared to their BMI calculated by measuring their height and weight. Statistical analysis of the correlation was carried out using Spearman’s nonparametric

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correlation coefficient test because of the non-normality of data. Two sided p-values in women with metabolic syndrome than in those without metabolic syndrome among <0.05 were considered to be statistically significant. Statistical analysis was performed both premenopausal and postmenopausal women, showing a progressive increase (P for using R (www.R-project.org). Results: Correlation between VAT in pounds and volume trend G 0.001) in parallel with the progressive increment in the number of metabolic was rho=0.9999. The correlation between VAT and A/G ratio was rho=0.82 for both fat syndrome components in all women. When grouping by quartiles of cystatin-C, higher mass in pounds and fat volume. In addition, correlation between percent body fat in the cystatin-C levels group has increased odds ratio for metabolic syndrome (OR 5.626, 95% android region and VAT in either pounds or volume was also rho=0.82. However, the CI 1.574 - 20.106). With multiple regression analysis, the cystatin-C level was positively correlation between BMI and VAT (either pounds or volume) was rho=0.45. Conclusion: and independently associated with the metabolic syndrome in Korean healthy women This underscores the notion that BMI, while commonly employed in standard medical regardless menopausal status. Conclusion: Increased cystatin-C levels are significantly practice, does not correlate well with VAT, a well recognized risk factor for developing associated with metabolic syndrome. It may be used for screening for metabolic cardiometabolic abnormalities. Furthermore, the correlation between standard A/G ratio syndrome occurrence in healthy women. or even just percent fat in the android region on DXA, compared with VAT produced with newer proprietary software, is sufficiently strong to continue to use standard A/G ratio as a surrogate for visceral adiposity, although, further prospective study is necessary P-83. to see its actual correlation with cardiometabolic parameters. The Association between Serum Uric Acid Level and Incidence of Metabolic Syndrome according to Menopausal Status in Korean Women SunSuk Kim, Kyu Sup Lee, KaYoung Yoon, Si Eun Han, YoonHwa Kim. Department of P-81. Obstetrics and Gynecology, Pusan National University, Busan, Korea (the Republic of) Reproductive aging and associated hormonal changes are related Objective: To assess the relationship between serum cystatin-C level and metabolic to metabolic syndrome and cardiovascular disease risk factors in syndrome components in healthy Korean womenThe aim of this study is to investigate menopausal African women the association between serum uric acid level and metabolic syndrome according to Nicole G. Jaff, PhD Research Fellow1,2, Shane A. Norris, PhD1, Tracy L. Syman2, Marketa menopausal status in Korean women Design: A total of 2,241 women who visited to the Toman2, Frederick Raal3, Nigel J. Crowther, PhD2. 1MRC/Developmental Pathways health promotion center at Pusan National University Hospital from 2010 to 2014 were for Health Research Unit (DPHRU), University of the Witwatersrand, Johannesburg, included in this cross-sectional study. Self-report questionnaires and interviews with South Africa; 2Department of Chemical Pathology, University of the Witwatersrand, healthcare providers were used to assess disease history, medication history, menstrual Johannesburg, South Africa; 3Department of Internal Medicine, University of the history and body size measuring. Anthropometric measurements and laboratory results Witwatersrand, Johannesburg, South Africa were compared as presence of metabolic syndrome and menopausal status by student-t Objective: The prevalence of metabolic syndrome (MetS) and cardiovascular disease test. Logistic regression analysis was performed between presence of metabolic syndrome (CVD) risk factors increase in women as they transition into menopause. Whether and presumable predictive factors, such as age, menopause and serum uric acid. Results: this is due to reproductive or chronological aging, or both is not fully known. There is The prevalence rate of metabolic syndrome were 7.45% (63/846) in pre-menopausal little research on this topic in midlife sub-Saharan African women, although obesity, group and 23.87% (333/1395) in menopausal group. Serum uric acid level was higher in diabetes and hypertension are all prevalent in this group. Therefore, the aim of this menopausal women than premenopausal women (4.6 ± 1.1 vs. 4.3 ± 0.9. P = 0.000). And, study was to determine whether reproductive aging and associated hormonal changes its concentration was also higher in metabolic syndrome than normal women regarding were related to MetS risk and CVD risk factors in this population. Design: Participants of menopausal statue (premenopause 4.7 ± 1.1 vs. 4.2 ± 0.8, P = 0.001, menopause 4.9 ± in this cross-sectional study were 702 black urban African women. The STRAW+10 1.3 vs. 4.5 ± 1.0, P = 0.000). Multiple logistic regression analysis showed serum uric acid criteria were used to define menopause stage with participants being classified into the and age have relationship with metabolic syndrome (OR: 1.453, 95% confidence interval following 4 groups: late reproductive, early and late menopause transition, early post- [CI]: 1.074-1.111, P = 0.000; OR: 1.092, 95% CI: 1.305-1.619, P = 0.000). Conclusion: menopause, late post-menopause. Fasting blood samples were used to determine the We could find out some potential of uric acid as predictive factor for metabolic syndrome levels of follicle stimulating hormone (FSH), estradiol (E2), dehydroepiandrosterone in premenopausal and menopausal group. Further investigation is required to clarify the (DHEA), dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone binding relationship between serum uric acid, menopause and metabolic syndrome. globulin (SHBG), lipids, glucose, insulin, leptin and adiponectin using standardized laboratory techniques. Insulin resistance was quantified using the HOMA method. P-84. Total body fat, lean mass and bone mineral density were analyzed using dual-energy X-ray absorptiometry whilst abdominal visceral and subcutaneous fat thickness were Metabolic Syndrome: predictive factor for endometrial polyps in measured using ultrasound scans. The MetS was diagnosed using the harmonized postmenopausal women guidelines (Alberti et al., Circulation 2009;120:1640-5). Trends across the 4 menopausal Flavia B. Dias, Daniel Spadoto-Dias, MD, Priscila F. Poloni, MD, Lucia Delmanto, groups were analysed using ANCOVA whilst multivariate analyses were conducted MD, Jorge Nahas-Neto, PhD, MD, Eliana A. Nahas, MD. Gynecology and Obstetrics, using logistic and linear regression. Results: The prevalence of MetS was 49.6%, and Botucatu Medical School-Sao Paulo State University, Botucatu, Brazil of obesity was 67.8%. The MetS components that were present at the highest prevalence Objective: Objective: We aimed to evaluate the clinical predictive factors for levels were: elevated waist circumference (>80cm) at 89.7%, hypertension at 65.0% endometrial polyps in postmenopausal women compared to postmenopausal women and low HDL (<1.3mmol/L) at 59.7%. Levels of total cholesterol (p<0.0005), LDL without endometrial polyps. Design: Methods: In this case-control study, 132 patients (p<0.0005), triglyceride (p=0.01), systolic (p<0.0005) and diastolic (p<0.05) blood with histopathologic diagnosis of endometrial polyp were compared with 264 without pressure were all significantly higher in postmenopausal compared to premenopausal endometrial alterations (control), seeking healthcare at a Public University Hospital. groups, and there was a trend for glucose (p=0.05) and MetS (p=0.05) prevalence to In the study group were included women underwent hysteroscopic polypectomy, with be higher in the postmenopausal groups. Multiple regression analyses and ANCOVA amenorrhea ≥ 12 months and age ≥ 45 years. The control group consisted of women showed that the higher levels of cholesterol and LDL in postmenopausal women were with amenorrhea ≥ 12 months and age ≥ 45 years, no postmenopausal bleeding and related to higher FSH concentrations, the higher systolic blood pressure was linked to endometrial thickness < 5mm by transvaginal ultrasonography, in a proportion of one lower estradiol levels, whilst the higher glucose, diastolic blood pressure and MetS case to two controls (1: 2). Clinical, anthropometric [body mass index (BMI) and prevalence levels were related to age. Adiponectin was strongly (p<0.001 for all waist circumference (WC)], laboratory and ultrasonographic data were collected for analyses) and inversely (but positively with HDL) correlated with HOMA and LDL evaluating the predictive factors of endometrial polyps. For statistical analysis were used levels and with all components of the MetS, except blood pressure. Conclusion: These the Student-t, chi-square tests and logistic regression method (odds ratio-OR). Results: data demonstrate that in a population of urban African women with a high prevalence of Results: A higher percentage of women with polyps were obese (72%) compared to obesity, the levels of CVD risk factors were higher in post- than pre-menopausal women control (39%) (P<.0001). The WC was higher among patients with polyps (P=0.0001). due to the influence of the hormone changes that characterize the menopause transition We observed a higher incidence of diabetes, hypertension and dyslipidemia in patients and the influence of chronological aging. There was a tendency for MetS prevalence to with endometrial polyps (P<.0001). According to the diagnostic criteria of the US be greater in postmenopausal women, but this was due to age. Adiponectin was found to National Cholesterol Education Program: Adult Treatment Panel III (NCEP/ATP III), be a strong correlate of components of the MetS and related CVD risk factors. 48.5% of women with polyps and 33.3% in the control group were classified as having metabolic syndrome (P=0.004). Analysis of risk for endometrial polyp was higher in patients with: BMI ≥ 25kg/m2 (OR 4.66; CI95%2.16-10.05); glucose ≥ 100mg/dl (OR P-82. 2.83; CI95%1.36-5.90); dyslipidemia (OR 7.02; CI95%3.70-13.32); diabetes (OR2.58; The relationship between serum cystatin-C level and metabolic syndrome CI95%1.05-6.32); and metabolic syndrome (OR 2.76; CI95%1.18-6.46) compared to according to menopausal status in Korean healthy women control. Conclusion: Conclusion: In postmenopausal women, obesity, dyslipidemia, Jong Kil Joo, SunSuk Kim, Si Eun Han, KaYoung Yoon, Kyu Sup Lee. Department hyperglycemia and the presence of metabolic syndrome were predictive factors for of Obstetrics and Gynecology, Pusan National University, School of Medicine, Busan, endometrial polyps. Korea (the Republic of) Objective: To assess the relationship between serum cystatin-C level and metabolic syndrome components in healthy Korean women Design: We performed a cross- sectional analysis of the data of 3,670 Korean community-dwelling women who participated in the annual health checkup at Pusan National University hospital. Metabolic syndrome was defined by the updated National Cholesterol Education Program/Adult Treatment Panel III criteria. Multiple logistic regression analysis was performed to estimate the association between cystatin-C levels and metabolic syndrome. One-way analysis of variance, followed by posttest for linear trends, was performed to evaluate the relationships between cystatin-C levels and the number of metabolic syndrome components. Results: The mean level of cystatin-C was significantly higher

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P-85. Multiple regression analysis of the variables associated with the presence of metabolic Differences of prevalence and components of metabolic syndrome syndrome in the total sample -HIV positive and negative women [n = 537 (a)] according to menopausal status Sung-Tack Oh, MD PhD1, Kyu-Sup Lee, MD PhD2, Jong-Kil Joo, MD2, Jung-Bin Son2. 1Department of Obstetrics & Gynecology, Chonnam University Medical School, Gwangju, Korea (the Republic of); 21Department of Obstetrics and Gynecology,, Pusan national university, Busan, Korea (the Republic of) PR: prevalence ratio; 95%CI: 95% confidence interval. Missing information: (a) Objective: Metabolic and endocrinologic alterations is developed at menopausal 46 in the whole group. transition of women and these alterations can have an effect on prevalence of metabolic Variables considered: age in years; skin color: white or other; physical activity: syndrome. Therefore, we evaluated the prevalence of metabolic syndrome and differences up to 2 times per week or 3 or more times per week; education: 0–7 years or 8 of components as menopausal status of women who visited our health screening clinic. years or more; family income : up to US$750.00 or more than US$750.00; house Design: We surveyed body sizes, blood pressures and other several blood tests from residents: up to 2 or more than 2; smoking: yes or no; alcohol consumption: yes or January 2006 to December 2010 in University Hospitals by retrospectively reviewing no; menopausal status: pre and perimenopause or post menopause; weight gain: medical records. These results were compared as presence of metabolic syndrome yes or no; hormone therapy: yes or no; self-rated health: excellent or good or not and menopausal status. Differences of the components of metabolic syndrome as the so good or bad; use of HAART: yes or no; other chronic diseases : yes or no; BMI: menopausal status and occurrences of metabolic syndrome as the age and the menopausal up to 25 and more than 25; FSH: less than 40 and 40 or more; TSH: up to 4.5 and status are investigated. Results: In premenopausal and postmenopausal women, the more than 4.5; group: HIV or control. prevalence of metabolic syndrome were 8.69% and 21.85%, respectively. More body weight, high BMI and cholesterol were checked in women who have metabolic syndrome irrespective of menopausal status. Low high density lipoprotein was most prominent REPRODUCTION POSTER PRESENTATION component of metabolic syndrome irrespective of menopausal status. Hypertension and high blood sugar were showed meaningful proportions in postmenopausal women. The P-88. prevalence of metabolic syndrome was unrelated to the menopausal status by regressively analyze, but meaningfully increased related to aging. Conclusion: Menopausal Post-reproductive Aged Women: In Support of Health Screening alterations restrictively effect on occurrence of metabolic syndrome and aging is more Guidelines for Assisted Reproductive Technology (ART) Using Donor effect on it. But more detailed and additional studies are needed about determining the Oocytes relation of metabolic syndrome in women who surgically menopaused and receiving Taleen MacArthur, Gloria Bachmann, M.D., MMS, Charletta Ayers, M.D., MPH. hormone therapy. Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ Objective: As more post-reproductive aged women opt to pursue pregnancy with advanced ART technologies, the menopausal practitioner will become more involved in P-86. counseling, screening and referral of menopausal women for these services. This review Metabolic syndrome in Brazilian postmenopausal women will evaluate current ART screening practices in the United States and propose discussion Benedito F. Reis, MD2,1, Laryssa S. Ribeiro, academic2, Diego L. Aguiar, academic2, surrounding more universal guidelines for ART candidacy in post reproductive aged Sonia Maria R. Rolim-Lima, MD1, Lyliana Coutinho R. Barbosa, PhD2, Antonio Marcos women using donor eggs/embryos. The review will also assess the similarities and C. Francisco, PhD2. 1Obstetrics and Gynaecology, FCMSCSP, São Paulo, Brazil; guidelines in the adoption process of a post-birth child as compared to the process of 2Gynecology, UNIVAS, Pouso Alegre, Brazil ‘adoption’ of a donor egg/embryo with ART. Design: A review of articles on PubMed Objective: To compare the prevalence of Metabolic Syndrome (MS) according to and official websites pertaining to ART, advanced maternal age, and ART screening over the criteria of the National Cholesterol Education Programm ATP III (NCEP) and the the last twenty years was conducted. Results: Despite the increasing use of ART with American Diabetes Association (ADA) in Brazilian postmenopausal women. Design: All donor eggs/embryos in post-reproductive aged women, there are no universal guidelines 124 postmenopausal women attended from 2013 to 2014 in climacteric clinic in Vale do in use in the US for determining candidacy with regard to maternal health. As national Sapucai University (UNIVAS) were classified according to the SM criteria by the NCEP trends move towards women delaying childbearing, the cohort of post-reproductive age and ADA. Results: The prevalence of MS in the population of 124 women was 47.6% women looking towards ART using donor oocytes as a fertility option is expanding. (59 cases) by the NCEP and 55.6% (69 cases) by the ADA. There was an accretion of The American Society for Reproductive Medicine (ASRM) states that healthy women ten new diagnosed cases of metabolic syndrome by the ADA criteria, however without over fifty who are prepared for parenthood are good candidates for ART through oocyte significant difference. Conclusion: The prevalence of MS in the population was similiar donation, but advises that older women be counseled as to the increased obstetric risk using NCEP and ADA criteria.There was an accretion of ten new diagnosed cases of associated with advanced maternal age. This society recommends a thorough medical metabolic syndrome by the ADA criteria, however without significant difference. evaluation and age appropriate health screening, and that women should be discouraged from pursuing pregnancy if they have a health condition that may increase maternal P-87. or fetal risk. However, the issue raised is whether more comprehensive guidelines that would be utilized for all post reproductive women that address screening and acceptance Factors associated with metabolic syndrome in middle-aged women with for ART be developed with the assistance of practitioners caring for midlife and older and without HIV women. That each older woman be screened by the same set of guidelines by all 1,2 1 1 Ana L. VALADARES, MD, PHD , Livia Akl , Aarao M. Pinto-Neto, MD, PhD , Lucia centers rather than guidelines that are individualized at each health center offering ART 1 1 S. Costa-Paiva, MD, PhD . Obstetrics and Gynecology, UNICAMP, Campinas, Brazil; services. Further, a discussion that is initiated by the topic of oocyte donation is whether 2 womens health, UNIFENAS, Belo Horizonte, Brazil guidelines for potential patients who want to use donated oocytes more closely follow Objective: This study investigated if metabolic syndrome was associated with HIV present adoption guidelines. In adoption, a post-birth child is brought into a family’s infection. To evaluate the prevalence of metabolic syndrome (MetS) and associated home while in ART a pre-birth child is brought into a family’s or individual woman’s factors in middle-aged women with and without human immunodeficiency virus home. In both cases, a third party is enlisted to help facilitate parenthood. Despite the (HIV). Design: This cross-sectional study included 273 HIV-infected and 264 HIV- fundamental similarities between them, the screening processes for adoption appear negative female outpatients aged 40–60 years. MetS was diagnosed as having a waist to be more comprehensive than those for ART with a donor oocyte. Conclusion: A circumference ≥ 80 cm and two or more of the following: triglyceride ≥ 150 mg/dL, universal template of practice with input from practitioners caring for post reproductive high density lipoprotein cholesterol < 50 mg/dL, systolic blood pressure ≥ 130 mmHg or aged women should be considered. Universal guidelines would create more consistency diastolic blood pressure ≥ 85 mmHg, and blood glucose ≥ 100 mg/dL. Sociodemographic, in caring for this cohort of older women seeking ART services and utilizing oocyte clinical, and behavioral factors were evaluated. Results: The prevalence of MetS in the donation. HIV group was 46.9% compared with 42.2% in the seronegative group (P = 0.340). MetS was more prevalent in the HIV group in postmenopausal women (P = 0.032), in women taking hormone therapy (P = 0.040), in women with excellent/good self-related HEALTH SERVICES POSTER PRESENTATIONS health (P = 0.011), and in women with body mass index (BMI) > 25 kg/m2 (P = 0.005). In the 273 patients with HIV, 91% were taking HAART, and approximately 74% had a nadir CD4 above 200/mm3. The main risk factor for acquisition of the infection was P-89. heterosexual transmission, the mean duration of infection was 9.9 years, and the mean Evaluation of Shared Decision Making Between Patients and Providers duration of therapy was 9.4 years. Overall, multiple regression analysis showed MetS to Improve Menopause Health Outcomes was associated with BMI > 25 kg/m2 (prevalence ratio (PR): 2.34; 95% confidence Laura M. Borgelt, PharmD, FCCP, BCPS, NCMP2, Robin Liston, MPH1, Kelli interval (CI): 1.70-3.21; P < 0.001), aging (PR: 0.05, 95%CI: 1.02-1.07; P < 0.001), Giacomini, BS3, Miriam Dickinson, PhD3. 1National Research Network, AAFP, and the use of highly active retroviral therapy (HAART) (PR: 1.48; 95%CI: 1.13-1.94; Leawood, KS; 2Clinical Pharmacy and Family Medicine, UCD, Aurora, CO; 3Family P = 0.005). Conclusion: The HIV-positive group had good immunological status as Medicine, UCD, Aurora, CO demonstrated by viral suppression and high CD4 levels. However, HIV-positive women Objective: Shared decision making (SDM) between patients and providers honors who were postmenopausal or had a high BMI showed a significantly higher prevalence provider knowledge and emphasizes patients’ values and preferences. Using tablet of MetS. Overall, the main factors associated with MetS were use of HAART, being technology to engage patients and providers in innovative practice-based research that overweight, and aging. There is a need for a better approach, awareness, and education of incorporates SDM may lead to improved health outcomes and increased satisfaction both HIV-positive and HIV-negative women to prevent weight gain and MetS. For HIV- with the healthcare experience. Given that approximately half of women between the positive middle-aged women, choosing effective HAART with fewer adverse effects on ages of 45-60 years experience at least one menopausal symptom, it is important to metabolism is an important aspect to prevent MetS. This should be considered in clinical offer individualized treatment options. Hormone therapy (HT) has been proven to be the practice to reduce the risk of MetS in this population. most effective treatment for menopausal symptoms and is an acceptable option in many

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women up to 59 years; however, long-term use appears to impose greater risks than prescribed systemic HT for the indication of GSM. Conclusion: Family physicians benefits. It is equally important to ensure that women between 60-65 years stop using are the first-line providers of menopause management for Canadian women. This is HT unless deemed appropriate. Other treatments, including non-prescription therapies, the largest study to provide information about the perceptions and attitudes of Ontarian may be more appropriate for individual situations. Breast cancer risk increases with age family physicians towards menopausal medicine, as well as delineating the prescribing and medications are recommended for women at an increased risk; however, use is low. practices of this group. Despite the majority of this highly motivated group (by virtue of Therefore, women coming in and out of the menopause transition require individualized their attendance at a mature women’s health conference) rating themselves as comfortable evaluation and management. The primary objectives are to evaluate the impact of managing menopausal symptoms, this survey demonstrates the variety of evidence and SDM among health care providers and women age 45-65 years regarding menopause, non-evidence based practices occurring amongst these physicians. Results from this postmenopause, HT use, breast cancer risk, lifestyle changes and improved information study indicate that opportunities for continuing medical education with a specific focus collection related to these issues. Design: Using a stepped wedge randomized design, on the prescription of menopausal HT may be beneficial to enable family physicians to 9 primary care practices throughout the U.S., located in varied geographic areas (e.g., provide the best possible care to menopausal women. rural, suburban, urban) were enrolled, with 1 to 4 participating providers per site. Up to 650 peri- and post-menopausal women aged 45-65 years seen at a routine appointment between August 2014 and August 2015 were recruited to participate. Tablet technology P-91. incorporated surveys, health assessment tools with scoring algorithms, and educational The Clinical Utility of a Blood Test Incorporating Age, Sex, and Gene videos. The Menopause Rating Scale and Breast Cancer Risk Assessment Tool were Expression in the Evaluation of Women Presenting with Stable Symptoms combined into a Menopause Health Assessment report which was printed, saved to a Suggestive of Obstructive Coronary Artery Disease in a Large Primary secured server for uploading into an electronic health record (EHR) and available on the Care Registry (PRESET): Subgroup Analysis of the Primary Efficacy tablet at point-of-care. Videos provided women guidance on how to enhance discussions Endpoint about SDM with their provider. Patients completed surveys of selected domains (e.g., Gregory Pokrywka, MD, FACP, FNLA, NCMP1, Joseph A. Ladapo, MD, PhD2, Richard whole-person orientation) from the Ambulatory Care Experiences Survey (ACES). Wright, MD, FACC3, Paul McLaughlin, MD4, Bruce Maniet, DO5, David Sharp, DO6, Providers completed pre- and post-assessments for a webinar that included: menopause Linda Ross, MPH7, Lin Huang, PhD7, Mark Monane, MD, MS7, Matthew Budoff, terminology; physiologic changes that occur in perimenopause and through menopause; MD8. 1Johns Hopkins University School of Medicine, Baltimore, MD; 2NYU Langone assessment tools for menopausal symptoms and breast cancer risk; clinical trials and Medical Center, New York, NY; 3Pacific Heart Institute, Santa Monica, CA; 4Paul E position statements that have provided evidence to influence clinical practice; therapeutic McLaughlin MD, Mount Sterling, KY; 5Bells Medical Clinic, Bells, TX; 6Doctors for options to manage the symptoms of menopause; and communication strategies to Health, Omaha, NE; 7CardioDx, Inc., Redwood City, CA; 8UCLA Community Medical discuss symptoms and treatment options with patients. Providers also completed a Center, Los Angeles, CA modified version of the ACES survey. Baseline and end of study EHR data queries Objective: Better methods are needed for the evaluation of women presenting to the will be used at each participating practice to: evaluate changes in rates for diagnosis of primary care physician (PCP) office with symptoms of obstructive coronary artery menopause and/or postmenopausal status; use of therapies for menopause symptoms for disease (CAD), as current methods are characterized by test overutilization, high costs, women age 45-59 years; and women age 60-65 years with a menopause diagnosis or patient exposure to appreciable risks from radiation and contrast-dye reactions, and postmenopausal disorder prescribed HT. Evaluation of the data will describe gaps that diagnostic uncertainty. A previously validated blood-based test combining age, sex, may exist between diagnosis and appropriate treatment. Results: Outcomes from the and gene expression levels into an algorithmic score has been shown to have a 96% EHR data include: documented diagnosis of menopause or postmenopausal state; rate of negative predictive value in a combined population of men and women in determining a prescription use to manage menopausal symptoms in women age 45-59 years; and rate patient’s current likelihood of obstructive CAD, thereby helping primary care clinicians of HT discontinuation in women age 60-65 years. Frequency of discussions between rule out obstructive CAD diagnosis in low-to-intermediate risk symptomatic patients. patients and providers regarding menopausal symptoms, breast cancer risk prevention We hypothesized that information from the age/sex/gene expression score (ASGES) and lifestyle changes (e.g., diet, exercise, alcohol) will also be presented. Patient and would change medical decision making during the evaluation of participants presenting provider satisfaction with communication, interpersonal treatment, patient trust, whole with stable chest pain or anginal equivalent symptoms. The primary outcome of this person orientation, health promotion, and satisfaction with SDM will be included. An analysis was the association between ASGES and referrals for further cardiac evaluation assessment of provider knowledge will also be included Conclusion: Conclusions will in women. Design: The prospective PRESET Registry (NCT01677156) enrolled stable, be determined with completion of data analysis. non-acute adults evaluated for obstructive CAD from 21 US primary care, community- based practices over a one-year period. Primary care physicians, nurse practitioners, and P-90. physician assistants at primary care practices were educated and trained on the use and Perceptions and attitudes towards menopausal hormone therapy (HT) interpretation of the ASGES through a standardized in-service program. The laboratory reported the patient’s ASGES to the primary care provider within a median of three amongst family physicians attending a mature women’s health conference days from the blood draw, who were then able to incorporate the ASGES test results, in in Ontario, Canada conjunction with other clinical information, into their medical decision-making process Kelsey E. Mills, MD, FRCSC, NCMP, Michelle Jacobson, MD, FRCSC, NCMP, Wendy for further diagnostic evaluation. Data collected included the patient demographics, L. Wolfman, MD, FRCSC. Obstetrics and Gynecology, University of Toronto, Toronto, comorbidities, and clinical presentation, and the clinician’s treatment plan before vs. ON, Canada after receiving the ASGES results. We evaluated the relationship between the ASGES Objective: The goal of this study was to evaluate the perceptions and attitudes towards results (predefined as low [ASGES ≤15] or elevated [ASGES >15]) and decision-making, menopausal HT, as well as the prescribing practices, of family physicians attending a including cardiology referrals and downstream cardiac diagnostic tests. Results: In the mature women’s health conference in Ontario, Canada. Design: A paper survey was registry cohort of 718 evaluable patients, 369 (51%) were female participants with a included in the orientation package of all registered participants attending a mature median age of 59 years, median BMI of 29, and median ASGES of 9 (range, 1-40). women’s health conference in April 2015 in Toronto, Ontario, Canada. Patients were The ASGES test showed that 272 of 369 patients (74%) had low scores. With regard invited to complete the survey, which was anonymous and did not collect identifying to further diagnostic evaluation, which included either referral to cardiology and/or demographic information. Completion of the survey was voluntary. Survey questions advanced cardiac testing (MPI, ECHO, CCTA, ICA), 21 of 272 (8%) of women with evaluated the perceptions of primary care providers towards duration of use of HT, low ASGES and 31 of 97 (32%) of women with elevated ASGES were referred to prescription preferences for types of systemic estrogens and progestogens, and cardiology or advanced diagnostic testing (OR 0.18, p<0.0001). The overall MACE event preferences for the management of genitourinary syndrome of menopause (GSM). We rate for the female cohort was 0.5% (2/369, both events were judged to be unrelated to assessed these providers’ comfort levels with managing menopausal symptoms and with the investigational agent or procedure) at 30-days post-ASGES. Conclusion: A blood prescribing hormonal and non-hormonal treatments for menopausal issues. We also test incorporating age, sex, and gene expression was adopted into clinical practice and evaluated their current prescribing practices with regards to compounded bioidentical showed clinical utility in helping clinicians rule-out obstructive CAD as the cause hormone therapies. Results: The response rate for this survey 59.4% (n=164) and of women’s symptoms in this large community-based primary care patient registry the average length of time in practice for responders was 19.8 years (range 0.5-43). presenting with typical and atypical symptoms suggestive of obstructive CAD. There 75.0% of these family physicians perceived that they were “comfortable” or “very was a statistically significant and clinical relevant reduction in referral to cardiology comfortable” with managing menopausal symptoms. Of the six physicians (3.6%) who and advanced cardiac testing among low ASGES women who have a low current felt “uncomfortable” or “very uncomfortable” managing menopause, four had been in likelihood for obstructive CAD, thus preventing unnecessary—and potentially harmful practice for more than 30 years. Non-hormone therapy for menopause management and invasive—downstream cardiac testing. The ASGES blood test may help address an was used by 58.5% of clinicians who reported that they were comfortable managing important diagnostic challenge in cardiovascular medicine in the care of mid-life women. menopause. The majority of respondents, 61.5%, prescribed systemic HT. 80.4% of physicians preferred transdermal administration of estrogen. The most widely used progestogen for endometrial protection was oral micronized progesterone (81.0%), and/ or progestin-containing intrauterine devices (50.1%). 22.5% of respondents who reported being comfortable with prescribing HT, prescribed compounded progesterone for topical (transdermal or vaginal) application. 74.7% of physicians who were comfortable prescribing HT thought that in the absence of contraindications, a newly menopausal woman should stay on HT for five years or less. Compounded bioidentical hormone therapy was prescribed by 13.8% of practitioners who were comfortable managing menopause, and by 12.8% of all respondents. For the treatment of GSM, the most commonly used treatment was non-estrogen containing vaginal moisturizers (78.0%). Local estrogen was used in cream (77.4%), suppository (71.3%) and ring (42.6%) formulations, but only 55 physicians (33.5%) used all three. 17.1% of respondents

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P-92. period and analyzed using descriptive statistics. Change in healthcare resource utilization An Approach to Improving the Care of Women Aged 45 to 64 through including referrals, lab orders, diagnostic procedures, and follow-up visits were analyzed the Implementation of a Women’s Health Assessment Tool and Clinical using retrospective analysis of the EHR data from the past 12 months prior to the patient’s Decision Support Toolkit (WHAT/CDS) visit. Results: 110 women (mean age: 54.3, SD=5.9) completed the WHAT questionnaire (30% response rate). The majority of women had entered menopause (77.3%) and rated Terry Silvestrin1, Karin Coyne, MPH, PhD2, Anna Steenrod, MPH2, David Gross, their overall health as “good”, “very good”, or “excellent” (88.0%) WHAT questionnaire Pharm D3, Canan Esinduy, MD3, Angela Kodsi, Pharm D3, Gayle Slifka, Pharm D, results showed that most women had experienced depressive mood (63.6%), hot flashes CPEHR3, Lucy Abraham3, Anna Araiza, MPH3, Andrew Bushmakin3, Xuemei Luo, (61.9%) or anxiety (60.9%) in the last three months. About half of the women indicated PhD3. 1MultiCare Tacoma Women’s Specialists, Tacoma, WA; 2Evidera, Bethesda, MD; that they had experienced sexual problems (51.2%), dryness or discomfort of the vagina 3Pfizer, Inc, New York, NY (52.7%), or bladder problems (55.5%). A third of the women (44.5%) had at least Objective: To describe the Women’s Health Assessment Tool (WHAT) and Clinical one diagnosis of UI, VVA, depression, or VMS during the well-woman visit. There Decision Support (CDS) toolkit implementation process within an integrated delivery was a 72.2% increase in the number of diagnoses for all four conditions made during system (IDS) and to assess patients’ and providers’ perceptions about the WHAT/ the patient’s annual visit (n=31 new diagnoses) vs. previous 12-month period (n=18 CDS toolkit. Design: The WHAT/CDS toolkit is comprised of two components: 1) diagnoses). Most new diagnoses were for VMS (n=15) or VVA (n=11). Fifty-nine The WHAT, a 35-item, web-based patient-reported questionnaire to assess four health laboratory tests were ordered during the well-woman visit compared to 37 during the conditions (depression, UI, VMS, and VVA); and 2) The CDS, a toolkit built into the previous 12-months for patients diagnosed with UI, depression, VVA or VMS. Similarly, electronic health record (EHR) to support the delivery of evidence-based care. The 32 procedures or diagnostic test were ordered during the well-woman visit compared to WHAT/CDS toolkit was piloted over a 4-month period through an IDS in the South 20 during the previous 12-months for patients diagnosed with UI, depression, VVA or Puget Sound area of Washington State. Women, aged 45-64, scheduled for an annual VMS. Conclusion: There was a 72.2% increase in the number of diagnoses for all four well-woman visit, were asked to complete the WHAT questionnaire online through their conditions made during the patient’s annual visit when using the WHAT which indicates MyChart patient portal prior to their appointment. A provider received a summary of the that the WHAT questionnaire can help identify conditions relevant to mid-life women. patient’s responses, which were uploaded into the EHR and triggered the CDS toolkit There was also an increase in the number of diagnoses and laboratory tests ordered after to support clinical decision-making during the patient’s visit (Figure 1). Patients’ and the implementation of the WHAT/CDS toolkit. providers’ perceptions of the WHAT/CDS toolkit were collected through surveys and qualitative interviews. Results: Over the 4-month pilot period, 110 women (mean age: 54.3, SD=5.9) completed the WHAT questionnaire (30% response rate) and 12 providers used the WHAT/CDS toolkit. A third of the women (n=37, 33.6%) had at least one new diagnosis of UI, VVA, depression, or VMS during the well-woman visit. Two-thirds of patients (n=76) and providers (n=8) completed the feedback surveys and five providers participated in a qualitative interview to discuss the implementation process. The majority of the patients (69.8%) agreed that they felt more prepared for their annual visit and that the WHAT questionnaire helped their discussions with their provider. Most women (59.2%) felt the WHAT/CDS toolkit improved their quality of care and 70% agreed they would use the WHAT questionnaire again. Most provider survey responses were neutral although 50% agreed that the WHAT/CDS toolkit captured pertinent information. Qualitative interviews provided additional insight and support for the WHAT/CDS toolkit with providers reporting that the WHAT/CDS toolkit streamlined patient visits, improved communication between the provider and patient, and allowed patients to feel more ownership over their healthcare. Most interviewed providers indicated that they would use the WHAT/CDS toolkit again (60%). Conclusion: Patients and providers’ perceptions of the WHAT/CDS toolkit provide evidence to support the use of the toolkit to improve the care of mid-life women during their annual well-woman visits.

Figure 1. Women’s Health Assessment Process

P-93. Outcomes Assessment of Implementing the Women’s Health Assessment Tool and Clinical Decision Support Toolkit (WHAT/CDS) within an Integrated Delivery System Terry Silvestrin1, Anna Steenrod, MPH2, Karin Coyne, MPH, PhD2, David Gross, Pharm D3, Canan Esinduy, MD3, Angela Kodsi, Pharm D3, Gayle Slifka, Pharm D, CPEHR3, Lucy Abraham3, Anna Araiza, MPH3, Andrew Bushmakin, MS3, Xuemei Luo, PhD3. 1MultiCare Tacoma Women’s Specialists, Tacoma, WA; 2Evidera, Bethesda, MD; 3Pfizer, Inc, New York, NY Objective: To evaluate outcomes after implementing a newly developed Women’s Health Assessment Tool and Clinical Decision Support Toolkit (WHAT/CDS) toolkit during annual well-women visits and to compare patients’ health resource utilization pre and post implementation. Design: This observational project recruited women aged 45 to 64 attending one of three medical sites in an Integrated Delivery System (IDS) in the South Puget Sound area of Washington state for an annual health visit. Prior to their visit, women were asked to complete the Women’s Health Assessment Tool [WHAT]), a 35-item web-based patient-reported health questionnaire to assess four highly prevalent health conditions in mid-life women: depression, urinary incontinence [UI], vasomotor symptoms [VMS] and vulvovaginal atrophy [VVA]. A physician received a summary of the patient’s responses to the questionnaire which were uploaded into the patient’s electronic health record (EHR) and triggered a clinical support decision (CDS) toolkit to support the physician’s clinical decision making during the patient’s annual visit. Data from the WHAT questionnaire and patients’ annual visits were collected over a 4-month

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