THURSDAY CONCURRENT SESSION #1 at baseline, week 12 and months 6, 9 and 12. Changes from baseline to month 12 in lipid and coagulation parameters, blood glucose, and cardiovascular events are summarized descriptively. Results: 1835 women were randomized and took ≥1 capsule of daily S-1. E2/P4 (mg/mg) of 1/100 (n=415), 0.5/100 (n=424), 0.5/50 (n=421), 0.25/50 (n=424) or Effects of Hormone Therapy on Heart Fat and Atherosclerosis placebo (n=151). Total cholesterol and LDL-cholesterol levels numerically decreased Progression in Recently Postmenopausal Women from KEEPS Trial from baseline to month 12, HDL-cholesterol levels remained similar to baseline and Samar R. El Khoudary, PhD, MPH1, Qian Zhao1, JoAnn E. Manson2, Maria M. Brooks1, triglycerides levels increased (Table). Few women had triglycerides and cholesterol Nanette Santoro3, Dennis M. Black4, Mitchell Harman7, Marcelle I. Cedars4, Paul N. increases (≥50 mg/dL or above normal levels) at 12 months with TX-001HR (6-11% and Hopkins8, Ann E. Kearns6, Virginia Miller6, Hugh S. Taylor9, Matthew J. Budoff5. 1-4%, respectively) vs placebo (7% and 3%). Fasting glucose levels remained similar 1University of Pittsburgh, Pittsburgh, PA; 2Harvard Medical School and Brigham and to baseline at 12 months. Antithrombin activity and factor XIV and protein S levels Women’s Hospital, Boston, MA; 3University of Colorado, Aurora, CO; 4University tended to decrease from baseline compared with placebo, and time for activated partial of California San Francisco, San Francisco, CA; 5Los Angeles Biomedical Research thromboplastin, prothrombin time, fibrinogen levels and prothrombin international Institute, Torrance, CA; 6Mayo Clinic, Rochester, MN; 7Phoenix Veterans Affairs normalized ratio remained similar to baseline at 12 months. Two women experienced Health Care System, Phoenix, AZ; 8University of Utah Health, Salt Lake City, UT; “coronary heart disease” adverse events considered not related to treatment: unstable 9Yale University, New Haven, CT angina in one subject (E2/P4 0.5/50), and angina and coronary artery disease in Objective: Heart fat depots, within [epicardial adipose tissue (EAT)] and outside another (E2/P4 1/100). The woman who experienced unstable angina also experienced [paracardial adipose tissue (PAT)] the pericardium, have been linked to increased subarachnoid hemorrhage and cerebellar infarction, neither considered treatment related. cardiovascular disease risk. Postmenopausal women have greater volumes of heart fat One case of deep vein thrombosis (DVT) with E2/P4 0.5/50 was reported in a woman than premenopausal women. Recent evidence suggests a role of endogenous estrogen with a family history of DVT. Conclusion: Twelve months of TX-001HR treatment in in heart fat accumulation, possibly limited to PAT. The impact of hormone therapy menopausal women with VMS and an intact uterus had minimal clinically meaningful (HT) on heart fat buildup is unknown. We evaluated the differential effects of HT effects on lipid, glucose, or coagulation parameters. Observed changes in triglyceride on the accumulation of heart fat depots and their associations with coronary artery levels, antithrombin activity, factor XIV, and protein S were consistent with oral estrogen calcification (CAC) progression in recently postmenopausal women. Design: KEEPS therapy. Although this trial lacked statistical power to assess these outcomes, VTE rates, was a multi-center, randomized, clinical trial of the effects of oral conjugated equine cardiovascular disease, and cerebrovascular events were as expected for a postmenopausal estrogens (o-CEE) and transdermal 17β-estradiol (t-E2), both with progesterone, population. If approved, TX-001HR may provide the first oral combination of E2/P4 for compared to placebo, on 48-month subclinical atherosclerosis progression in recently the treatment of VMS in menopausal women with a uterus. postmenopausal women. Heart fat volumes and CAC were measured on CT scans at Sources of Funding: TherapeuticsMD baseline and 48 months later. Significant CAC progression was defined as present if (1) baseline CAC score = 0 and 48 month CAC Agatston score >0 ; (2) baseline CAC score >0 to <100 and annualized change in CAC score ≥10 ; or (3) baseline CAC score ≥100 and annualized percent change in CAC score ≥10%. Changes in heart fat depots were tested using Wilcoxon signed test and compared by treatment group using Kruskal– Wallis test. Associations between change in heart fat volumes and CAC progression as well as effect modification by HT type were tested using logistic regression adjusting for age, race, study site, education, physical activity, smoking, alcohol intake, lipids, systolic blood pressure, waist circumference, anti-hypertensive medications and baseline heart fat volume. Results: Of 727 randomly assigned women, 474 [mean age (SD): 52.7(2.6); 78.1% White] had heart fat volumes and CAC scores at baseline and 48 months. EAT volume increased significantly over time in the placebo group [median (Q1, Q3): 2.12(-4.58, 6.36) cm3, P=0.003] but not in the o-CEE [-0.05(-5.93, 6.12) cm3, P>0.99] or the t-E2 group [1.68(-4.07, 4.91) cm3, P=0.07]. PAT volume did not change significantly in any group. Changes in EAT and PAT did not vary by treatment group. KEEPS only included women whose screening CAC score was < 50, resulting in 88.4% of participants having CAC=0 at baseline. At 48 month CAC progressed in 14% of the study participants. Changes in EAT and PAT were not significantly associated with CAC progression overall. However, assigned treatment significantly modified the association between changes in PAT and CAC progression in adjusted model, P=0.02, such that changes in PAT were associated with greater CAC progression risk only in t-E2 group [OR (95% CI) per 1 SD of PAT change: 2.8(1.3, 5.9)]. Conclusion: There was no significant difference among treatment groups in 48 month changes of heart fat depots. However, there was a suggestion that O-CEE slowed progress on heart fat accumulation, although not in the t-E2 group. Greater PAT changes were associated with greater CAC progression risk only in the t-E2 group. The current findings support the notion that EAT and PAT are distinct fat depots and suggest a complex role of HT in the accumulation of heart fat depots and their associations with CAC progression in recently postmenopausal women. Sources of Funding: KEEPS: Aurora Foundation to the Kronos Longevity Research Institute, NIH P50 AG 44170 to VMM, 1 UL1 RR024150, Mayo CTSA 1 UL1 RR024150, the Mayo Foundation, CTSA UL1 RR024139, UL1 RR024131 from the NCRR. Study medications: supplied in part by Bayer Health Care and by Abbott aPTT: activated partial thromboplastin time; INR: international normalized Pharmaceuticals. The ClinicalTrials.gov number is NCT00154180. KEEPS Heart Fat ratio. Ancillary study: NHLBI R21HL140011. S-3. S-2. Evaluation of Systemic Effects of a Vaginal Estradiol Softgel Capsule Effects of Single-Capsule 17β-Estradiol/Progesterone (TX-001HR) on (TX-004HR) in Menopausal Women with Moderate-to-Severe Dyspareunia Metabolic Parameters and Cardiovascular Outcomes in Menopausal Lisa C. Larkin MD, MD5, Andrew M. Kaunitz, MD1, James Liu, MD2, Shelli Graham, Women of the REPLENISH Trial PhD3, Brian Bernick, MD3, Sebastian Mirkin, MD3, Ginger Constantine4. 1University Rogerio Lobo, MD1, James Liu, MD2, Andrew M. Kaunitz, MD3, Brian Bernick, MD4, of Florida College of Medicine-Jacksonville, Jacksonville, FL; 2University Hospitals Shelli Graham, PhD4, Ginger Constantine5, Sebastian Mirkin, MD4. 1Columbia University Cleveland Medical Center, Cleveland, OH; 3TherapeuticsMD, Boca Raton, FL; Medical Center, New York, NY; 2University Hospital Cleveland Medical Center, 4EndoRheum Consultants, LLC, Malvern, PA; 5Lisa Larkin MD and Associates, Cleveland, OH; 3University of Florida College of Medicine-Jacksonville, Jacksonville, Mariemont, OH FL; 4TherapeuticsMD, Boca Raton, FL; 5EndoRheum Consultants, LLC, Malvern, PA Objective: TX-004HR (an investigational, vaginal softgel capsule of low-dose, Objective: TX-001HR (TherapeuticsMD, Boca Raton, FL), an investigational product solubilized 17β-estradiol, designed to be mucoadhesive and rapidly dissolving) that combines 17β-estradiol and progesterone (E2/P4) in a single, oral softgel capsule, significantly improved vaginal physiology and dyspareunia (primary endpoints) as well as significantly reduced the frequency and severity of moderate-to-severe vasomotor dryness (secondary enpoint) in menopausal women with moderate-to-severe dyspareunia symptoms (VMS) in menopausal women of the REPLENISH trial (Lobo et al, Obstet as their most bothersome symptom in the phase 3 REJOICE trial (NCT02253173).1 Gynecol 2018, in press). The objective of this report is to summarize safety endpoints Improvements were achieved with negligible to very low systemic absorption of related to metabolic parameters and cardiovascular outcomes from REPLENISH. estradiol with doses of 4 µg, 10 µg and 25 µg (the 4 µg and 10 µg doses have been Design: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, submitted for FDA approval).2 Systemic levels of estradiol with 10 µg and 25 µg doses placebo-controlled, multicenter trial that evaluated 4 TX-001HR doses vs placebo in were shown to be lower than with the same doses of a commercially available vaginal menopausal women (40-65 years) with a uterus. Women were randomized to E2/P4 estradiol tablet (Vagifem®) in head-to-head studies.3 This report summarizes the effects doses or placebo in a proportion of ~11:1. Clinical laboratory measurements were taken of TX-004HR on clinical outcomes that previously have been reported to be influenced by systemic estradiol absorption.4 Design: REJOICE was a randomized, double-blind, S-5. placebo-controlled, multicenter study that evaluated 4 µg, 10 µg, and 25 µg TX-004HR Comparing written and verbal delivery of a treatment regimen to women versus placebo in menopausal women (40-75 years) with vulvar and vaginal atrophy with overactive bladder: single-blinded, randomized controlled trial (VVA) and moderate-to-severe dyspareunia. Safety endpoints (cardiovascular [CV] and Lindsay Shirreff, MD, FRCSC, MSc(HQ)1, Michelle Anderson2, Colleen McDermott, breast effects and venous thromboembolism [VTE]) in the total population that could be MSc, MD, FRCSC1. 1Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, ON, affected by systemic estradiol absorption were assessed. Twelve-lead electrocardiograms Canada; 2University of Toronto, Toronto, ON, Canada (ECGs) and breast exams were performed at baseline and week 12. Treatment-emergent Objective: Overactive bladder (OAB) is a common condition among older women adverse events (TEAEs) of special interest were summarized descriptively. Serum sex requiring a multifaceted treatment approach, usually communicated by physician to hormone binding globulin (SHBG) was measured at baseline and weeks 2 and 12 in a patient in the clinic setting. The objective of this two-centre, single-blinded, randomized subset of women (n=72). Results: From the safety population, 764 women (mean age controlled trial was to determine if a written list of six management strategies for OAB 59 years) were randomized to 4 µg (n=191), 10 µg (n=191) or 25 µg TX-004HR (n=190), improves both immediate and delayed recall of these recommendations compared to a or placebo (n=192). Seven CV TEAEs were reported (Table 1): complete heart block, traditional, verbal discussion. Design: Between May 2016 and February 2018, women palpitations, and sinus node dysfunction as well as sinus bradycardia and first degree newly diagnosed with OAB were randomized to either the intervention group where atrioventricular block identified in one woman at the end of study that were considered they received a transcribed list of six treatment recommendations or to the control mild. Only the 2 cases of palpitations were considered possibly related to treatment. group where the same six recommendations were communicated only verbally by their No CHD, VTE or other thrombotic episodes were reported. There were no treatment- physician. Patients in both groups were asked to recall treatment recommendations related, clinically significant adverse ECG changes. Two women in the 4 μg TX-004HR immediately following their appointment and two weeks later. A score out of six group had reports of mild hypertension as a TEAE. Three women (n=1 each; 4 μg, was assigned at each time point based on the number of recommendations patients 10 μg, placebo) had mild blood pressure increases reported as TEAEs; one was considered could remember. Scores at each point of recall were compared between groups. not treatment related (10 μg), while the others were considered possibly related. Ten Results: For those recruited to the study (n=60) and randomized, there were no breast-related TEAEs were reported (Table 1), of which 6 occurred with placebo; all significant differences between group demographics for age, education, income, or but two (breast mass and fibrocystic breast with placebo) were considered as possibly or language. Immediate total recall scores on treatment recommendations were significantly probably related to treatment. Other than these TEAEs, no clinically significant breast better for those who received the handwritten list compared to those who received only events were reported. Changes from baseline for SHBG with TX-004HR ranged from verbal communication (P=0.004). There was no difference in two-week total recall scores 1.9±16.6 to 3.0±11.7 nmol/L at week 2 and -0.6±16.0 to 4.4±27.0 nmol/L at week 12, between groups. Recall scores compared for each of the six recommendations were not and were comparable to changes with placebo at the same time points (-2.1±11.7 and significantly different between the written and verbal recommendations at immediate 10.2±41.7 nmol/L, respectively), with no dose-related pattern. Conclusion: Evidence or two-week follow up. Conclusion: A written list of recommendations can improve of systemic effects of TX-004HR was not observed in the 12-week REJOICE trial. No OAB patients’ immediate recall of a suggested treatment regimen but does not impact clinically meaningful differences in cardiovascular or thrombotic-related adverse events, recall two weeks later. Distributing written lists in the ambulatory setting may have the or blood pressure were found between TX-004HR and placebo. Lastly, there was no potential to improve quality and delivery of care for OAB patients. evidence of estrogen-related clinical outcomes or liver metabolism such as an increase in Sources of Funding: A departmental grant from Mount Sinai Hospital (Department of 1 serum SHBG suggesting systemic absorption. Constantine G, et al. Menopause 2017;24: Obstetrics and Gynaecology) was awarded to support this project. 409-416 2Archer DF, et al. Menopause 2017;24:510-516 3Pickar JH, et al. Climacteric 2016;19:181-187 4Pickar JH, et al. Expert Opin Drug Saf 2017;16:941-954 Sources of Funding: TherapeuticsMD THURSDAY CONCURRENT SESSION #2 Treatment-emergent Adverse Events S-6. Caucasian women have greater gains in subcutaneous abdominal adiposity in the years leading up to menopause compared to African- American women Kara Marlatt, PhD, MPH1, Robbie Beyl, PhD1, Jennifer Lovejoy, PhD3, Steven Smith, MD2, Leanne Redman, PhD1. 1Pennington Biomedical Research Center, Baton Rouge, LA; 2Translational Research Institute for Metabolism and Diabetes, Orlando, FL; 3Arivale, Inc., Seattle, WA Objective: Menopause is characterized by estrogen deficiency and results in commensurate metabolic changes (e.g., weight gain, increased abdominal adiposity, insulin resistance). The differential impact of the menopause transition in different races, particularly among African-Americans (AA), is not well understood. Many health S-4. statistics for AA women are significantly worse compared to Caucasians; therefore, Effect of age, time since menopause and previous hormone therapy on the understanding the deleterious impact of menopause on metabolic health among women of different races is of great public health significance. The Healthy Transitions study response to intravaginal 6.5 mg prasterone (R01: ‘Menopause Effect on Obesity, Energy Balance, and Insulin’) was a pioneering, David Archer, MD1, Fernand Labrie2, Celine Martel2, Érick Moyneur3. 1CONRAD 2 3 prospective cohort study conducted between 1997-2006 at the Pennington Biomedical Clinical Research Center, Norfolk, VA; Endoceutics Inc., Quebec, QC, Canada; Statlog Research Center with the overall objective to examine the impact of menopause on Econometrics Inc., Montreal, QC, Canada ® changes in body composition, fat distribution, and cardiometabolic risk factors in AA Objective: To analyse the effect of intravaginal 6.5 mg prasterone (Intrarosa ) in and Caucasian women. Design: Ninety-four healthy women (25 AA, 69 Caucasian) subgroups who participated in the clinical trials performed with women suffering were phenotyped annually for up to 7 y for changes in body composition, abdominal from moderate to severe (MS) pain at sexual activity (dyspareunia) identified as their fat distribution, and hormone levels. At enrollment, women were aged 43 y or older most bothersome symptom (MBS) of vulvovaginal atrophy (VVA). This analysis and pre-menopausal (i.e., had at least five menstrual periods in the prior 6 months intends to assess the potential influence of age, time since menopause, and previous and follicle-stimulating hormone (FSH)<30 mIU/mL). Women taking hormones were hormone therapy (HRT) on the response to treatment. Design: Data obtained from two excluded. All women in the present analysis transitioned through menopause (indicated independent prospective, randomized, double-blind and placebo-controlled clinical trials as Year 0) during follow-up, which was defined by absence of menstruation for 1-y and were combined to evaluate the effect of daily intravaginal 6.5 mg (0.50%) prasterone FSH>30 mIU/mL. Annual assessments included: (1) body composition (fat mass, fat-free administered for 12 weeks on MS/MBS dyspareunia in different subgroups of women mass) by Hologic QDR2000 DXA; (2) abdominal fat distribution including subcutaneous depending on their age (≤ 55 yrs and ≥ 56 yrs), time since menopause (1-2 yrs, 3-5 yrs adipose tissue (SAT), deep (dSAT) and superficial (sSAT), visceral adipose tissue (VAT), and ≥ 6 yrs) and had or not received previous HRT. Results: In 406 women treated with and total adipose tissue (TAT) by computed tomography; (3) fasting blood collection 6.5 mg prasterone and 234 women who received placebo, the difference from placebo for quantitative insulin-sensitivity check index (QUICKI); and (4) hormone levels. in the improvement of the severity score of MS/MBS dyspareunia was of 0.44 unit and Results: At menopause onset, women overall had a mean age 53±2 y and BMI 27.0± 0.36 unit in women aged ≤ 55 yrs [n=123; 57] and ≥ 56 yrs [n=283; 177], respectively. 5.8 kg/m2. As expected, estradiol decreased and FSH increased throughout the menopause On the other hand, the improvement of MS/MBS dyspareunia was of 1.59, 0.59 and transition. Compared to the pre-menopausal state (2-6 years before menopause), women 0.27 unit for prasterone in comparison to placebo in women who were menopausal since weighed significantly more at menopause onset, characterized by greater total fat 1-2 yrs [n=22; 11], 3-5 yrs [n=59; 27], and ≥ 6 yrs [n=325; 196], respectively. Finally, mass and increased abdominal SAT, VAT, and TAT (all p<0.05 from Year 0). In the women who previously received HRT [n=184; 115] before taking intravaginal prasterone 2-6 years before menopause, Caucasian women had significant increases in weight, fat had an improvement of their MS/MBS dyspareunia of 0.45 unit over placebo in mass, SAT, dSAT, sSAT, VAT, and TAT (all p<0.05 from Year 0) compared to AA women comparison to a difference from placebo of 0.32 unit in women who did not receive HRT (Fig. 1, all p<0.05). No significant between-race differences in fat-free mass, VAT, previously [n=222; 119]. Conclusion: No major influence of age and previous hormone ® estradiol, FSH, or QUICKI were observed. At menopause, AA women weighed therapy was observed on the response to intravaginal 6.5 mg prasterone (Intrarosa ). The significantly more than Caucasians, but no other between-race differences in body smaller effect on dyspareunia observed with a longer time since menopause deserves composition, QUICKI, or hormones were observed. Conclusion: The menopause further investigation in order to optimize treatment. transition may impact Caucasian women more than AA women in terms of subcutaneous Sources of Funding: This study was funded by Endoceutics Inc. adipose tissue deposition. No race differences in body composition were observed at menopause onset which suggests that AA women had a worse pre-menopause body S-8. adiposity profile yet maintained adiposity levels throughout the menopause transition Modifying Effect of ApoE4 Genotype on the Association Between while Caucasian women caught up in body adiposity. Metabolic Phenotype and Subclinical Atherosclerosis in Postmenopausal Sources of Funding: NIH Grant #s: NIDDK-R01-DK50736A (PI: Lovejoy); NIDDK- Women T32-DK064584 (to Marlatt); U54-GM104940 (LA CaTS). Registered trial on Intira Sriprasert, MD1,3, Wendy Mack, PhD1,2, Howard Hodis1,2, Roksana Karim, PhD1,2. ClinicalTrials.gov (Healthy Transitions; NCT00412269). 1Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; 2Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA; 3Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: Both metabolic risk factors and presence of ApoE4 genotype are known to have effects on coronary heart disease. We examined the interaction between these two factors for their associations with subclinical atherosclerosis among early and late postmenopausal women using baseline data from the Early versus Late Intervention Trial with Estradiol (ELITE). Design: Postmenopausal women from the ELITE trial with available ApoE4 genotype were included in the analysis. Women were categorized into healthy, high blood pressure, and poor metabolic clusters based on the levels of baseline glucose, the HOMA insulin sensitivity score, ketones, triglycerides, high density lipoprotein cholesterol, low density lipoprotein cholesterol, hemoglobin A1c, and systolic and diastolic blood pressure using k-means clustering analysis. ApoE4 genotype was S-7. classified as either ApoE4+ (homo- or heterozygous for E4 allele) or ApoE4-. General Increased Anxiety and Depressive Symptoms Are Associated with linear models were used to test whether the cross-sectional association between metabolic Abnormal Resting Cardiac Autonomic Function in Peri- and clusters and baseline common carotid intima media thickness (CIMT) differed by ApoE4 genotype after adjusting for age. A longitudinal analysis was also performed Postmenopausal Women with Hot Flashes 1 1,2 3 using mixed effects analysis to evaluate the modifying role of ApoE4 genotype on the Polly Fu, MD , Carolyn Gibson, PhD, MPH , Wendy Mendes, PhD , Michael Schembri, association between metabolic clusters and CIMT progression over a median follow BS4, Alison Huang, MD, MAS, MPhil1. 1Department of Medicine, University of 2 up of 4.8 years. Results: A total of 497 women with information on CIMT, ApoE4 California San Francisco, San Francisco, CA; San Francisco Veterans Affairs Health genotype (343 women with ApoE4+ and 154 women with ApoE4-) and metabolic Care System, San Francisco, CA; 3Department of Psychiatry, University of California San 4 cluster (208 healthy, 190 high blood pressure and 99 poor metabolic) were included Francisco, San Francisco, CA; Department of Obstetrics, Gynecology, and Reproductive in the analysis. In cross-sectional analysis among all women, ApoE4+ women in the Sciences, University of California San Francisco, San Francisco, CA poor metabolic cluster had the highest CIMT(SE) of 832.41(17.45) μm, compared to Objective: The menopause transition is marked by an increased prevalence of mood other groups of women. In the ApoE4- group, CIMT significantly differed between symptoms in midlife women, including anxiety and depression. Prior research in healthy and high blood pressure clusters (p=0.004) and in the ApoE4+ group, CIMT non-menopausal populations have suggested that both anxiety and depression may be was significantly higher in the poor metabolic cluster compared to healthy (p=0.0003) associated with alterations in cardiac autonomic function that are in turn associated and high blood pressure (p=0.001) clusters. ApoE4 genotype significantly modified the with cardiovascular disease or adverse cardiovascular outcomes. We aimed to examine effect of metabolic cluster on CIMT (interaction p=0.001). In stratified analysis by early whether anxiety and depressive symptoms are associated with an adverse cardiac (<6 years) and late (≥10 years) postmenopause, the highest CIMT was consistently seen in autonomic profile among midlife women with hot flashes. Design: The Menopausal ApoE4+ women in the poor metabolic cluster in both early and late postmenopause strata. Treatment Using Relaxation Exercise (MaTURE) trial was a parallel-group, single- Among late postmenopausal women, metabolic cluster was significantly associated with blinded, randomized trial of slow-paced respiration for treatment of hot flashes in CIMT (p=0.04) and there was a significant synergistic effect of both factors on CIMT peri- and postmenopausal women, age 40 to 59 years old, with at least four hot flashes (interaction p=0.02), whereas the interaction was marginally significant among the early reported per day. Anxiety and depressive symptoms were assessed as continuous scores menopausal women (interaction p=0.05). These results were not observed on longitudinal on multiple validated self-administered questionnaires. State anxiety (i.e., fluctuating, analysis of CIMT with a median follow up of 4.8 years. Conclusion: ApoE4+ women transitory emotional state in reaction to perceived threats) and trait anxiety (i.e., stable with poor metabolic phenotype have higher levels of subclinical atherosclerosis, individual tendency towards perceived threats) were measured using the Spielberger particularly when they are further from menopause. These results have significant clinical State Trait Anxiety Inventory (STAI). Cognitive anxiety (i.e., mental component of and public health implications as preventive intervention strategies targeted to these high anxiety associated with fear of future adverse events) was assessed using the anxiety risk women can substantially reduce the burden of coronary heart disease, which is the subscale of the Hospital Anxiety and Depression Scale (HADS). Depressive symptoms leading cause of death in women globally. were assessed using Beck Depression Inventory-II (BDI-II) and the depression subscale Sources of Funding: None of HADS. Main outcomes of cardiac autonomic function included pre-ejection period Table: CIMT by metabolic clusters and ApoE4 genotype among early and late (PEP) and respiratory sinus arrhythmia (RSA), both measured during a resting period postmenopause stratum at baseline and 12 weeks using impedance cardiography and electocardiography. PEP, the time from the start of cardiac ventricular depolarization to the opening of aortic valve, is a marker of sympathetic activity. RSA, the variability of the heart rate during the typical respiratory cycle, is a marker of parasympathetic activity (i.e., cardiac vagal tone). Multivariable repeated measures linear regression models examined associations between anxiety, depressive symptoms, and cardiac autonomic markers, adjusted for age and body mass index. Results: Among the 121 participants[HA1] (mean age 53 years old), no significant differences in mean anxiety or depression scores were detected between the paced respiration and the music control groups at baseline or 12 weeks. Resting cardiac autonomic parameters were similar at baseline and at 12 weeks with no significant between-group differences. Greater trait anxiety and cognitive anxiety were associated with lower RSA, reflecting decreased parasympathetic activity (β=-0.03, p<0.01 for STAI Trait Anxiety; β=-0.06, p=0.01 for HADS Anxiety Subscale). Greater depressive symptoms were also associated with lower RSA (β=-0.03, p=0.02 for BDI-II; β=-0.06, p=0.02 for HADS Depression Subscale). Greater state anxiety was associated with shorter PEP, reflecting higher sympathetic activity (β=-0.24, p<0.01), but no other significant associations between anxiety or depression and PEP were detected. Conclusion: Among peri- and postmenopausal women with hot flashes, greater self-reported anxiety and depression were associated with lower levels of cardiac vagal tone, while greater state anxiety was associated with higher resting sympathetic nervous CIMT reported as μm; Model adjusted for age; Tukey-Kramer method as used to system activation. Findings suggest that midlife women with increased anxiety and test for pairwise comparisons depressive symptoms may have an unfavorable cardiac autonomic profile with potential implications for their overall cardiovascular risk. Sources of Funding: This study was funded by grant #5R01AT005491 from the National Center for Complementary and Integrative Health. Dr. Huang was supported by a Paul B. Beeson Career Development Award in Aging Research from National Institute on Aging (1K23AG03833) and the American Federation on Aging Research. Dr. Gibson was supported by an Advanced Fellowship in Women’s Health from the Veteran’s Affairs Office of Academic Affiliations. S-9. was assessed based on sensitivity and specificity and the optimal probability threshold Menstrual Cycle Length over the Menopause Transition is Associated was chosen to maximize the product of the two parameters. Individual-level health with Subclinical Atherosclerosis after Menopause: The Study of Women’s care claims of women aged 45 years and above with at least one year of observation Health Across the Nation Daily Hormone Study from Truven Health MarketScan® Commercial and Medicare Supplemental Databases covering the period from 01/2010 to 09/2016 were used. Women with ≥ 2 VVA or Samar R. El Khoudary, PhD, MPH1, Xirun Chen1, Karen A. Matthews, PhD1, dyspareunia diagnoses (ICD9: 627.3, 625.0; ICD-10: N94.1, N95.2) on separate visits Amanda Allshouse2, Sybil Crawford3, Carol A. Derby5, Rebecca C. Thurston1, were identified as the “true” VVA cases. The random forest classifier was built using Rasa Kazlauskaite4, Nanette Santoro2. 1University of Pittsburgh, Pittsburgh, PA; a sample of 20% of all eligible women (training: 15%; test: 5%) and the prevalence 2University of Colorado, Aurora, CO; 3University of Massachusetts, Worcester, MA; of probable cases of VVA was estimated on the remaining women with no diagnosis 4Rush University School, Chicago, IL; 5Albert Einstein College of Medicine, Bronx, NY of VVA. Candidate predictive variables were assessed throughout the women’s Objective: Irregular menstrual cycles have been associated with cardiovascular disease observation period and included relevant diagnoses, medications, type of health care (CVD) risk. Using data from the SWAN Daily Hormone Study (DHS), we characterized providers seen, and intensity of health care resource use measured in amounts paid by trajectories of menstrual cycle length over the menopause transition (MT) and tested the insurance plan. The importance of each candidate variable was determined based on whether these trajectories are associated with postmenopausal carotid atherosclerosis. their ability to discriminate between diagnosed VVA and non-VVA cases, calculated Design: SWAN DHS includes 875 participants who collected daily, first-morning voided with the Gini measure of impurity. Results: A total of 2,883,527 women meeting the urine for an entire menstrual cycle or up to 50 days, annually until post-menopause or eligibility criteria were selected, of whom 263,251 (9.1%) were diagnosed with VVA. for up to 10 years. This analysis includes DHS participants who became postmenopausal A probability threshold of 30% yielded the highest sensitivity (97.4%) and specificity and had: a. an available final menstrual period (FMP) date; b. at least 2 annual DHS (71.6%). The classifier identified 801,036 (30.6%) probable cases of VVA in the collections with cycle length recorded; and c. a postmenopausal measurement of sample of non-diagnosed VVA women. The top 10 most important predicting factors carotid intima-media thickness (cIMT). Cycle length was defined as the number of days included: number of obstetrics and gynecology visits/examinations, outpatient resource from the start of one cycle to the start of the next. Group-based trajectory modeling use, length of observation, pharmacy (outpatient) resource use, number of diagnoses of was used to characterize cycle length trajectories in relation to the FMP which then vaginal infections (vaginitis), symptomatic menopausal or female climacteric states, and were linked to postmenopausal cIMT using linear regression. The final model included radiologist visits, increasing age, and number of diagnoses of urinary track infections and race/ethnicity, covariates collected concurrent with cIMT, and pre/early peri-menopausal stress incontinence. Conclusion: The VVA classifier developed performed well. Among CVD risk factors. Results: We evaluated 218 women with 862 cycles over the MT women not diagnosed with VVA, 30.6% were identified as probable cases, bringing the (mean age±SD at time of cIMT: 58.86±2.34 years). Three distinct cycle length overall prevalence of VVA in this population of commercially insured women at 36.9%. trajectories were identified (Figure-A): 1) Stable: 54.3% of study participants followed Considering the clinical, psychological, and emotional burden resulting from VVA and a stable cycle length trajectory up to their FMP, 2) Late-increase: 26.6% followed its associated symptoms and signs, proper identification and treatment of this condition a late increase in cycle length trajectory as early as 2 years before the FMP, 3) has the potential for significant improvements in the quality of life of a large fraction of Early-increase: 19.1% followed an early increase in cycle length trajectory as early women of menopause age and significant reductions in health care resource utilization as 5 years before the FMP. In final model, women with the late-increase pattern had and costs. Further research is warranted to improve the accuracy of the VVA classifier. significantly lower postmenopausal cIMT (mean(SE): 0.72(0.03)mm) than women with Sources of Funding: This study was funded by Endoceutics Inc. the stable (0.77(0.02)mm, P=0.04) pattern. Women with an early-increase pattern did not differ from those with stable cycle length pattern (Figure-B). Conclusion: Women who experienced a pattern of late increases in cycle length close to the FMP had less evidence of carotid atherosclerosis than those with minimal changes in cycle length. Patterns of TOP-SCORING ABSTRACT PRESENTATIONS cycle length over the MT appear to be a marker of future vascular health that may help identify groups at greater risk of atherosclerosis after menopause. S-11. Sources of Funding: SWAN has grant support from the NIH, DHHS, through the Does mindfulness moderate perceived stress and menopause-related NIA, NINR and ORWH (Grants U01NR004061; U01AG012505, U01AG012535, symptoms in midlife women? U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, Richa Sood, MD MS FACP NCMP, Carol Kuhle, DO, Ekta Kapoor, MD, U01AG012495). Jacqueline Thielen, MD, Karla Frohmader, PhD, Kristin Mara, Stephanie S. Faubion, MD, FACP, NCMP, IF. Mayo Clinic, Rochester, MN Objective: Midlife women frequently experience stress. Stress can amplify menopause- related symptoms and adversely impact women’s quality of life. Mindfulness, a technique of paying attention on purpose, in the present moment, and non-judgmentally is thought to mitigate stress by decreasing emotional reactivity and maladaptive, negative ruminative thinking. In this study, we sought to assess the associations of mindfulness, menopause-related symptoms and perceived stress among midlife women. Design: In this cross-sectional study, 1744 women ages 40-65 years, who presented to the Women’s Health Clinic at Mayo Clinic, Rochester, MN between January 2015 and December 2016 were included. Participants completed the Menopause Rating Scale (MRS), Perceived Stress Scale-4 (PSS-4), and Mindfulness Attention Awareness Scale (MAAS) at the time of their clinical visit. The pair-wise associations between mindfulness, stress, and menopausal symptom burden measures were assessed using correlation coefficients and linear regression. All statistical tests were two-sided, and the threshold statistical significance was set at p<0.05. Results: The mean age of participants was 53.4 years (±6.1). The total mean MRS score was 13.9 (±7.5), mean PSS-4 score was 5.1 (±3.5); the mean MAAS score was 4.4 (±0.9). Higher mindfulness scores correlated with lower MRS scores (correlation -0.492; one point increase in MAAS score correlated with 3.97 point decrease in MRS score; CI 3.64-4.30, p<0.001) and with lower PSS-4 scores (correlation -0.529; a one point increase in MAAS mean score correlated with a 1.98 point decrease in PSS-4 score (95% CI -2.13, -1.83), p<0.001). Higher MRS scores correlated with higher PSS-4 scores (correlation 0.552; a one point increase in MRS score correlated S-10. with a 0.26 point increase in PSS-4 score (95% CI 0.24 to 0.27, p<0.001) (Figure 1). Estimation of the Underdiagnosis Rate of Vulvovaginal Atrophy among Correlation of higher mindfulness and PSS-4 was more robust in women with higher Women in Health Insurance Claims MRS scores (MRS > 17 = -1.76; 95% CI -2.06 to -1.47 vs. MRS < 17 = -1.45; 95% Érick Moyneur1, Katherine Dea1, Francis Vekeman1, Fernand Labrie2. 1StatLog CI -1.62 to -1.27). PSS-4 scores had the highest correlation with psychological domain Econometrics, Montreal, QC, Canada; 2Endoceutics Inc., Quebec, QC, Canada symptoms on MRS (correlation 0.665; Slope: 0.62; (95% CI 0.58 to 0.65, p<0.001) as Objective: Vulvovaginal atrophy (VVA) is known to be underreported due to the compared to the somato-vegetative and urogenital symptoms (correlation 0.332 and reluctance of women to discuss VVA symptoms with their health care provider and the 0.227, respectively; p<0.001). Conclusion: Among midlife women ages 40-65, higher lack of knowledge about the relative role of sex steroids and aging on the occurrence of mindfulness correlated with lower menopausal symptom scores as well as lower stress VVA symptoms. The objective of this study was to develop a classifier using machine scores. Higher menopausal symptom scores correlated with higher perceived stress. learning techniques to estimate the proportion of women without a diagnosis of VVA In women with higher symptom burden (MRS >17), the correlation of mindfulness with who are probable cases and determine the most important predictors of VVA status. lower stress was even more robust. Further, mindfulness correlated with lower stress Design: Prediction of the VVA status was achieved using a random forest classifier, a more strongly for the psychological domain of MRS compared to the somato-vegetative tree-based ensemble method that compiles and aggregates the predictions of thousands and urogenital domains. Although additional studies are needed in more diverse settings of component decision trees using artificial intelligence. This technique was favored over to replicate our findings, this study provides a strong signal for the potential role of more traditional approaches such as the logistic regression since it does not require an mindfulness in improving psychological symptoms, emotional response to menopausal a priori selection of predictors nor does it impose a specific functional form for the link symptoms and stress in women during midlife. between VVA status and the predictors. VVA status was determined based on whether Sources of Funding: None. the proportion of all decision trees predicting a positive VVA status (i.e., probability of VVA) was above a certain threshold. The performance of the classifier developed S-12. (CTX ptrend-value 0.22, PINP ptrend-value 0.53)(Table). Conclusion: Our results do not Hypertensive Disorders of Pregnancy and Gestational Diabetes as Risk support the utility of serum CTX level or PINP level to independently predict hip fracture Factors for Hot Flashes in Midlife Women risk in women in this age group. These results will inform future guidelines regarding the Rhoda J. Conant, MD1, Yamnia Cortés, PhD, MPH, FNP2, Janet Catov, PhD2,3, potential utility of these markers in fracture prediction. Karen A. Matthews, PhD2,4, Sybil Crawford5, Monique Hedderson, PhD6, Rebecca C. Sources of Funding: The WHI program is funded by the National Heart, Lung, Thurston2,4. 1OB/GYN, University of Oklahoma Health Science Center, Edmond, OK; and Blood Institute, National Institutes of Health, U.S. Department of Health and 2Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Human Services through contracts HHSN268201600018C, HHSN268201600001C, PA; 3OB/GYN, University of Pittsburgh, Pittsburgh, PA; 4Psychiatry, University of HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. Additional Pittsburgh, Pittsburgh, PA; 5Medicine, University of Massachusetts, Worcester, MA; support for these analyses was provided by US Public Health Service Research grants: 6Division of Research, Kaiser Permanente, Oakland, CA AR053105 and AR048919. Objective: Most (60-80%) women experience hot flashes (HF) during the menopausal transition. HF have been associated with vascular endothelial dysfunction beyond standard cardiovascular disease risk factors and estradiol. Hypertensive disorders in pregnancy (HPD) and gestational diabetes mellitus (GDM) are associated with vascular and endothelial dysfunction. Given a similar pathophysiology, we hypothesize that women with a history of HDP and GDM may experience a greater burden of HF. We further hypothesize that nulliparous women may have fewer HF. Design: A longitudinal analysis was performed that included data from 2,249 women who completed a pregnancy history questionnaire at the 13th visit of the Study of Women’s Health Across the Nation (SWAN). Women were asked if they had “any of the following pregnancy complications: preeclampsia/toxemia (high blood pressure and proteinuria), gestational hypertension or pregnancy induced hypertension, gestational diabetes (no diabetes pre-pregnancy).” Accordingly, women were classified as nulliparous, no HDP/GDM, or a history of HPD/GDM. HF were assessed at baseline and at each of the 13 follow-up visits over 15 years. Women with hysterctomy/oophorectomy and study observations with hormone therapy use were excluded. HF were recorded as any vs none; 0 days, 1-5 days, 6+ days in past two weeks. Participant characteristics were compared across our exposure groups (nulliparous, no HDP/GDM, history of HDP/GDM) using ANOVA or Kruskal-Wallis tests for continuous data and Chi-Square or Fisher’s Exact for categorical variables. Pregnancy history was examined in relation to HF using generalized estimating equations adjusting for race/ethnicity, financial strain, education, study site and menopausal stage. Results: At time of the pregnancy questionaire, women were on average 61 years of age. Out of the 2249 individuals included in the analysis, 395 (17.6%) women were included in the nulliparous group, 1646 (73.2%) in parous women without HPD/GDM and 208 (9.2%) in parous women with HPD/GDM. Of the women in the HPD/GDM group, 176 (85%) women had a HPD only, 27 (13%) had GDM and 5 (2%) reported both. Women in the HPD/GDM group had a more adverse cardiovascular disease risk factor profile including higher BMI; antihypertensive, lipid-lowering medications and anti-diabetic medication use; and lower HDL levels (p<.01). In age-adjusted models, compared to women with no HDP/GDM, nulliparous women had a lower odds of reporting any HF (OR: 0.81, 95% CI: 0.71, 0.92), and women with HPD/GDM had a greater odds of any HF (OR: 1.20; 95% CI: 1.01, 1.42). In addition, while nulliparous women had a lower odds of frequent HF (6+ days), the HPD/GDM group had a greater odds of frequent HF (OR: 1.19, 95% CI: 1.00-1.41). In age-adjusted models, these associations were attenuated after controlling for site, race/ethnicity, financial strain, and particularly education. Conclusion: HDP/GDM may be modestly associated with a greater number of HF. Meanwhile, nulliparty may be associated with fewer HF. Associations between S-14. pregnancy history and HF were attenuated after adjusting for education, suggesting the Efficacy of Internet-based Cognitive Behavioral Therapy for Treatment- important role of social factors in pregnancy outcomes and HF. Sources of Funding: SWAN has grant support from the National Institutes of Health induced Menopausal Symptoms in Breast Cancer Survivors: Results of a (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute Randomized Controlled Trial 1 1 2 of Nursing Research (NINR) and the NIH Office of Research on Women’s Health Vera Atema, MSc , Marieke van Leeuwen, PhD , Hester S.A. Oldenburg, MD, PhD , 3 1 4 (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, Marc van Beurden, MD, PhD , Jacobien M. Kieffer, PhD , Myra S. Hunter, PhD , 1 1 U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). Neil K. Aaronson, PhD . Division of Psychosocial Research and Epidemiology, 2 This work was also supported by the NIH, National Heart Lung and Blood Institute The Netherlands Cancer Institute, Amsterdam, Netherlands; Department of Surgical 3 (K24123565 to Thurston). The content of this abstract is soley the responsibility of the Oncology, The Netherlands Cancer Institute, Amsterdam, Netherlands; Department of 4 authors and does not necessarily represent the official views of the NIA, NINR, ORHW Gynecology, The Netherlands Cancer Institute, Amsterdam, Netherlands; Department or NIH. of Psychology, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, United Kingdom Objective: Treatment-induced menopause causes significant symptom burden for S-13. women who have undergone adjuvant treatment for breast cancer (BC). Hot flushes and Bone turnover and Risk of Hip Fracture: A Case-Control Study in the night sweats (HF/NS) are the most common and disruptive symptom of the menopause. Women’s Health Initiative Previous studies have demonstrated that cognitive behavioral therapy (CBT), delivered Carolyn J. Crandall, MD, MS1, Sowmya Vasan2, Andrea LaCroix3, Meryl LeBoff4, in group format, is effective in alleviating menopausal symptoms and particularly Jane Cauley5, John A. Robbins6, Rebecca Jackson7, Douglas Bauer8. 1University of HF/NS, in healthy women and BC survivors. In-person CBT can, however, be California, Los Angeles, Los Angeles, CA; 2Fred Hutchinson Cancer Research Center, inconvenient for some women and negatively affect program compliance. A promising Seattle, WA; 3University of California, San Diego, La Jolla, CA; 4Brigham and Women’s approach is to use the Internet to make this form of CBT more accessible and feasible. Hospital, Boston, MA; 5University of Pittsburgh, Pittsburgh, PA; 6UC Davis Medical We evaluated the efficacy of Internet-based CBT, with or without therapist guidance, Center, Sacramento, CA; 7The Ohio State University, Columbus, OH; 8University of on frequency and impact of HF/NS, overall levels of menopausal symptoms, sleep California San Francisco, San Francisco, CA quality, sexual functioning, psychological distress and health-related quality of life in Objective: To determine the associations of serum C-terminal telopeptide of type I BC survivors with treatment-induced menopausal symptoms. Design: We randomly collagen (CTX) and serum procollagen type 1 aminoterminal propeptide (PINP)with assigned 254 BC survivors to a therapist guided or a self-managed Internet-based CBT hip fracture risk among postmenopausal women aged 50-79 years at baseline. group or to a control group. Inclusion criteria included, amongst others, the presence Design: We performed a case-control study (400 cases, 400 controls) nested within of at least 10 or more problematic HF/NS per week, for a period of at least 2 months. the prospective Women’s Health Initiative Observational Study, which enrolled Women randomized to the intervention groups had access to a 6 week CBT program participants at 40 U.S. clinical centers. Cases were women with incident hip fracture including online psychoeducation, behavioral monitoring and cognitive restructuring, not taking osteoporosis medication; hip fractures were confirmed using medical records. supplemented by relaxation exercises and homework assignments. Women allocated to Untreated controls were matched by age, race/ethnicity, and date of blood sampling. the guided CBT group also received a telephone intake and weekly online feedback Serum CTX and serum PINP were analyzed on 12-hour fasting blood samples. Main from a trained therapist. Self-report questionnaires were administered at baseline (T0), outcome measures were incident hip fracture risk (mean follow-up 7.13 years). at 10 weeks (T1) and 24 weeks (T2) post-randomization. We used mixed-effects-models Results: After adjustment for body mass index, smoking, frequency of falls, history of to compare groups over time. Results: The mean age of the study sample was 47.4 fracture, calcium and vitamin D intake, and other relevant covariates, neither serum CTX (SD = 5.5) years. At baseline, women reported, on average, 50.8 (SD = 40.9) hot flushes level nor serum PINP level was statistically significantly associated with hip fracture risk and 18.4 (SD = 13.4) night sweats per week. The mean impact of the HF/NS was rated a 4.9 (SD = 1.9) on a 10 point scale (higher scores indicate more impact). Nearly 86% S-16. of women in the guided CBT group and 62% of women in the self-managed CBT Estetrol, the Next Generation of Hormone Therapy: Results of a Phase 2b group completed the CBT program. Compared with the control group, the guided and Dose-finding Study in Postmenopausal Women (E4 Relief) self-managed CBT groups reported a significant decrease in the impact of HF/NS (effect Wulf H. Utian, MD PhD DSC FRCOG FACOG FICS. RMR, Beachwood, OH size [ES] = .63 and .56; P < .001) and improvement in sleep quality (ES = .57 and .41; Objective: Objective: Estetrol (E4) is a promising natural estrogen in development P < .001). The guided CBT group also reported a significant decrease in overall levels by Mithra Pharmaceuticals. E4 is produced by the fetal liver, crosses the placenta, and of menopausal symptoms (ES = .33; P = .010), hot flush frequency (ES = .34; P = .019) is detected from the 9th week of gestation in maternal urine. Its half-life is approx. and night sweats frequency (ES = .64; P = .006). These effects remained significant at 28 hours. E4 works in a unique way; on the one hand it acts as an estrogen agonist in longer term follow-up, with smaller effect sizes. Additional long-term effects for the bone, vagina, endometrium, brain, and the cardiovascular system, and on the other hand self-managed CBT group included reduced overall levels of menopausal symptoms it acts with mixed agonist and antagonist estrogenic activity in liver and breast. This and HF/NS frequency. No significant effects were observed for sexual functioning, results in an absence of effect of E4 on the biomarkers of hemostasis, an absence of psychological distress or health-related quality of life. Conclusion: Internet-based CBT, impact on triglycerides, and lower levels of breast cell stimulation. In contrast to other with or without therapist guidance, has salutary effects on the frequency and impact estrogens, E4 blocks the cell surface associated ERα, and inhibits the membrane ERα of HF/NS, overall levels of menopausal symptoms and sleep quality. Further analyses effects of estradiol. Therefore, E4 It is the first Native Estrogen with Selective action should inform us about the cost-effectiveness of both formats of the Internet-based CBT in Tissues (NEST). In preliminary studies using E4 in postmenopausal women, 2 to program. If demonstrated to be cost-effective, this program would be a welcome addition 40 mg E4 once-daily improved vaginal cytology, vasomotor symptoms (VSM), and to clinical care for BC survivors with treatment-induced menopausal symptoms. bone turnover markers. Our objective here is to present data of a recently completed Sources of Funding: This trial was funded by the Dutch Cancer Society and the phase 2b study. Design: Design and methods: E4 Relief was a multicenter, randomized, Netherlands Cancer Institute. placebo-controlled, double-blinded, dose-finding study. Postmenopausal women, aged 40-65 years were studied in various European countries. Entry criteria included ≥7 moderate to severe hot flushes (HF) per day, or ≥50 moderate to severe HF in the week FRIDAY CONCURRENT SESSION #1 preceding randomization. Non-hysterectomized women were included if TVUS showed a bi-layer endometrial thickness ≤5 mm. Women were randomized to 2.5; 5; 10; or 15 mg S-15. E4, or placebo, once-daily, for a period of 12 weeks. The primary endpoint was the 17β-Estradiol/Progesterone in a Single, Oral, Softgel Capsule change in frequency and severity of HF. Other efficacy parameters included the effects on genitourinary symptoms, lipid and glucose metabolism, hemostatic and bone (TX-001HR) Significantly Increased the Number of Symptom-free Days markers. Health-related quality of life was assessed with the Menopause Rating Scale in the REPLENISH Trial (MRS). Endometrial thickness and bleeding control were the key safety parameters 1 2 3 Andrew M. Kaunitz, MD , Ginger Constantine , Brian Bernick, MD , Sebastian Mirkin, for non-hysterectomized women. Results: Results: In total, 257 women were treated; 3 1 MD . University of Florida College of Medicine-Jacksonville, Jacksonville, FL; 200 completed the 12 week study period. Mean age was 54.2 years, mean duration of 2 3 EndoRheum Consultants, LLC, Malvern, PA; TherapeuticsMD, Boca Raton, FL amenorrhea 4.8 years, and 12.5% of the women were hysterectomized. The weekly Objective: An investigational combination of 17β-estradiol (E2) and progesterone frequency of HF decreased in all groups. At week 12, the difference in frequency between (P4) in a single, oral, softgel capsule (TX-001HR; TherapeuticsMD, Boca Raton, FL) 15 mg E4 (-84%) and placebo (-63%) was significant (p<0.05), as well as the difference in significantly reduced the frequency and severity of moderate-to-severe vasomotor severity: -44% for 15 mg E4, and -27% for placebo (p<0.05). In the 15 mg E4 group, 90% symptoms (VMS) without increasing the incidence of endometrial hyperplasia in had ≥50% reduction in HF, and almost 80% a ≥75% reduction (p<0.01). Genitourinary 1 postmenopausal participants of the REPLENISH trial. The objective of this analysis symptoms also decreased, with significant effects for vaginal pain associated with sexual was to examine the responder rates and number of symptom-free days with TX-001HR activity (p<0.01), and vaginal dryness (p<0.05) vs placebo. The maturation index showed vs placebo. Design: REPLENISH (NCT01942668) was a phase 3, randomized, double- a dose-related increase in the number of superficial cells. A dose-related decrease was blind, placebo-controlled, multicenter trial that evaluated TX-001HR in postmenopausal observed for the bone markers CTX-1 and osteocalcin. The mean MRS total score was women (40−65 years) who had an intact uterus and VMS. A VMS substudy examined reduced by 50.6% for 15 mg E4 vs 37.4% for placebo; all domains contributed to this 4 co-primary efficacy endpoints of change in frequency and severity of moderate- improvement. No endometrial hyperplasia was observed. Endometrial thickness returned to-severe hot flushes at weeks 4 and 12 with TX-001HR doses vs placebo. Women to baseline after progestin therapy at treatment completion. The 15 mg E4 dose had no with moderate-to-severe hot flushes (≥7/day or ≥50/week) were randomized 1:1:1:1:1 effect on hemostasis parameters and triglycerides, and increased HDL cholesterol and to daily E2/P4 of 1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, 0.25 mg/50 mg, or glucose tolerance. No unexpected adverse events were noted. Conclusion: Conclusion: placebo. Responders groups were women who had at least 50% or 75% reductions in A daily oral dose of 15 mg E4 appears to be the most effective dose for the treatment their moderate-to-severe VMS. The weekly number of symptom-free days (days without of menopausal VMS. All doses improved genitourinary symptoms and induced a lower moderate-to-severe hot flushes) with TX-001HR vs placebo was determined using a bone turn-over, indicating a favorable estrogenic effect. There were no apparent safety mixed effects model for repeated measures. Results: There were 726 women eligible concerns, and E4 was well tolerated. Estetrol could be the pathway to a next generation of for the VMS efficacy analysis (E2/P4 of 1 mg/100 mg [n=141], 0.5 mg/100 mg [n=149], hormone therapy for the full spectrum of postmenopausal symptoms, since it is a unique 0.5 mg/50 mg [n=147], 0.25 mg/50 mg [n=154], or placebo [n=135]). Significantly natural compound whose activity and safety profile differs from that of other estrogens. more (P<0.05) women who took TX-001HR vs placebo were ≥50% responders and Accordingly, E4 can be considered as the first oral equivalent to transdermal estrogens ≥75% responders at week 12 (Figure). The proportion of women without severe hot with potentially more breast safety. If confirmed in larger trials, E4 (as first NEST) could flushes (i.e., sensation of heat with sweating that causes cessation of activity) at week represent a significant improvement to women’s healthcare and daily practice. 12 was 55.6%, 47.3%, 42.7%, and 43.0% for E2/P4 doses of 1 mg/100 mg, 0.5 mg/100 Sources of Funding: Mithra Pharmaceuticals mg, 0.5 mg/50 mg, and 0.25 mg/50 mg, respectively, compared with 26.1% for placebo (P≤0.01). Conclusion: In the REPLENISH trial, the combined formulation of E2/P4 in a single, oral, softgel capsule significantly increased the number of symptom-free days S-17. vs placebo, and more women taking TX-001HR had 50% and 75% reductions in their Interferential current: a new option to treat sexual complains in moderate-to-severe VMS. By demonstrating reductions in the frequency and severity of Premature ovarian insufficiency women in use of hormone therapy. A moderate-to-severe VMS with TX-001HR relative to placebo, this analysis extends the Randomized clinical trial trial’s primary efficacy results. In addition, no cases of endometrial hyperplasia noted Helena P. Giraldo, Doctorate, Cristina L. Benetti-Pinto, Ticiana Mira, Daniela A. Yela, 1 among participants. If approved, TX-001HR may provide a new treatment option for phd, Paulo c. Giraldo. Obstetrics and Gynecology, University of Campinas, Campinas, those women with moderate-to-severe VMS who need endometrial protection, including Brazil 1 those who prefer taking bioidentical hormone therapy. Lobo RA et al, Menopause Objective: To evaluate the treatment with Interferential Current, compared with 2017;24:1430-1431 the use of estriol cream, in sexual function of women with POI, in use of HT. Sources of Funding: TherapeuticsMD Design: A randomized clinical trial was carried out with 40 women diagnosed with POI, between the ages of 18 and 50, sexually active and in use of oral hormone therapy (HT). These women filled out a validated questionnaire on sexual function (FSFI) and an informed consent form, as well as data on age, time of diagnosis, length of HT use, and frequency of sexual intercourse. They were randomly assigned to treatment either in a group of electrical stimulation of the pelvic floor with Interferential Current (IC group) (Endophasys NMS-0501 Device - KLD Biosystems Electronic Equipment Ltd.) in a total of 8 individual sessions of 20 minutes each throughout 4 weeks (electrodes were placed over the vulvar lips on both sides). The control group was treated with vaginal estriol creme applied daily for 4 weeks, 0,5 mg/day (E group). The FSFI total score and domains (desire, excitement, lubrication, orgasm, satisfaction, pain) were evaluated in the beginning and after each treatment. The results were compared within and between both treatments. Results: Mean age, time of diagnosis and length of HT for E and IC groups was respectively 35.5±8.2 and 38.7±5.86 years old; 9.15±8.88 and 9.30±8.26 years; 8.1±9.9 and 8.3±8.5 years, without differences between them. The Women with ≥50% or ≥75% Reductions in Moderate-to-Severe Hot Flushes at total initial and final FSFI was not different between groups, revealing improvement in Week 12 both. For each group, when comparing the FSFI before and after the interventions, the results are as follows: difference for the E group was 2.78±5.04(p=0.001) and for the IC group was 4.37±5.96(p=0.004). However, the differences between final and initial S-19. FSFI score was -2.78 ± 5.04 and 4.37 ± 5.96, p=0.291, with a greater improvement in the Sleep and Light Therapy for Peri-menopausal Depression IC group. The differences between the domains showed an improvement of lubrication Barbara L. Parry, MD1, Charles Meliska, PhD1, Diane Sorenson, MPH1, Sharron E. and pain in both groups, but the improvement in orgasm and satisfaction domains Dawes, PhD1, Fernando Martinez, BA1, Ana Lopez, BS1, Richard Hauger, MD1,2, ocurred only in the IC group. The lubrication difference was 1.16±1.22(p=0.001) for Daniel Kripke, MD1. 1Psychiatry, UNIV OF CALIFORNIA, SAN DIEGO, La Jolla, the E group and 0.75±1.31(p=0.014) in IC group. The difference in pain domain in CA; 2San Diego VA Healthcare System, LA JOLLA, CA group E: 0.68±1.30(p=0.006), and in group IC 1.00±1.47(p=0.005). And for IC group Objective: We previously observed that plasma melatonin circadian rhythms were phase- exclusively, where there was improvement, the difference of the orgasm score was delayed (shifted-later) in perimenopausal-PM (by FSH) depressed patients (by DSM-IV 0.90±1.42(p=0.010); and satisfaction score difference was 0.70±1.28(p=0.021). Sexual criteria). We also had observed the therapeutic value of total and partial wake therapy frequency was 2.45±0.94 initially, 2.30±1.38 final and difference -0.15±1.23 for E (formerly known as critically-time sleep restriction) and light treatment independently in group(p=0.344). And 2.30±1.49 initially, 2.80±1.74 final and 0.50±1.85 difference for other depressive disorders linked to women’s reproductive cycle (premenstrual dysphoric the IC group(p=0.176). When comparing the difference between sexual frequency before disorder, peripartum depression). The aim of this study was to test the hypothesis that and after and between both groups, it can be seen that there was a decrease in the E group peri-menopausal (PM) depressed patients (DP, by DSM-IV criteria), who have melatonin and increase in the IC group leading to a statistical difference with improvement in the IC circadian rhythms which are phase-delayed (shifted later) compared with PM normal group(p=0.041). Conclusion: In women with POI using HT, both treatments have proven controls (NCs), will improve their mood and sleep more after an intervention of sleep and to be effective in improving global FSFI scores as well as lubrication and pain domains light therapy designed to phase-advance (shift earlier) their melatonin circadian rhythms especifically. However, the treatment with interferential current appears to be superior than after a control condition designed to phase-delay them. Design: In a randomized to the use of estriol vaginal cream, due to also improving the orgasm and satisfaction parallel design in 17 peri-menopausal women, we administered at home either 1) a domains as well as enabling an increase in sexual activity. Revealing a new alternative Phase Advance Probe (PAP): 1-night of late-night wake therapy (LWT: sleep 9 pm-1 for the treatment of such sexual complaints am) followed by 8 weeks of morning (AM) bright (> 1350 lux) white light (BWL) for Sources of Funding: grant#2015/8334-0, São Paulo Research Foundation(FAPESP) 60 min starting within 30 min of habitual wake time or 2) a Phase Delay Probe (PDP): Comparisson of total FSFI score and domains for estriol vaginal cream or interferential 1-night of early-night wake therapy (EWT: sleep 3-7am) followed by 8 weeks of evening current treatments in women with POI in use of HT. (PM) BWL for 60 min ending 30 min before habitual sleep onset time, and assessed the effects on overnight urinary melatonin (6-sulphatoxy-melatonin; 6-SMT), objective sleep/activity (actigraphy), mood (Hamilton and Beck depression ratings) and subjective sleep (Pittsburgh Sleep Quality Index-PSQI) measures. Cosinor analyses were applied to multiple overnight urine samples to estimate 6-SMT Onset and Offset Time, and Acrophase (time of occurrence of the maximum 6-SMT secretion). Results: Multi- and univariate analyses of covariance (MANCOVA, ANCOVA) showed DPs who received the PAP had a significant phase-advance in 6-SMT offset (Mean ± SD = 2 h 15 min ± 12 min, p=.042) and a marginal advance in 6-SMT onset (mean = 1 h 57 min ± 3 h 21 min, p=.081, while DP receiving the control condition (PDP) showed non-significant phase- delays in offset (mean = 51 ± 38 min, p>.05) and onset (mean = 1 hr 27 min ± 1 h 46 min p>.05). After the PAP, NCs reported sleep worsening somewhat on the PSQI global component with a mean score decrease (-0.833 ± 3.07, p>.05), while DP women reported a non-significant sleep improvement (mean increase in global score of +1.0 ± 2.6, p>.05). After the PAP, greater phase-advance in 6-SMT Acrophase was associated with greater improvement in Hamilton mood score (r = +.985, p = .002). In DP receiving the PAP, S-18. Hamilton mood score improved significantly (+70%, p=.007) after both 2 weeks and A critical appraisal of vasomotor symptom assessment tools used in 8 weeks; in contrast, we found no significant mood improvement after the control PDP (p>.05). Conclusion: A non-pharmacological and non-hormonal treatment of sleep and clinical trials evaluating estrogen therapy compared to placebo light therapy, designed to correct the abnormal timing of melatonin circadian rhythms Marie K. Christakis, MD, MPH2,1, Wen Shen, MD, MPH3, Donna Strobino, PhD2. in perimenopausal depressed women improves mood and sleep within 2 weeks when 1Obstetrics & Gynecology, University of Toronto, Toronto, ON, Canada; 2Bloomberg administered at critical times targeted to the underlying chronobiological disturbance. School of Public Healh, Johns Hopkins University, Baltimore, MD; 3Obstetrics & Larger N’s are needed to verify these results, and in the future design treatments to Gynecology, Johns Hopkins University, Baltimore, MD individual circadian pathologies, the aim of personalized, precision medicine. Objective: Vasomotor symptoms (VMS) have consistently been reported to be the Sources of Funding: 1R01MH118225 leading predictor of Health-Related Quality of Life (HRQOL) among perimenopausal women, and the strongest indication for treatment. The presence of VMS also affects work performance during an otherwise productive time in a woman’s career. The North FRIDAY CONCURRENT SESSION #2 American Menopause Society endorses the use of oral estrogen for the treatment of VMS based on evidence from a recent Cochrane meta-analysis of 24 randomized clinical trials. While the Cochrane review acknowledges limitations in the data as a result of S-20. heterogeneity of outcome measures, it concludes that there is sufficient evidence that oral Increased Risk for Cardiovascular Disease Among Postmenopausal estrogen reduces the frequency and severity of VMS. While frequency and severity of Women with Diabetes and Comorbid Posttraumatic Stress Disorder VMS provide objective measures of symptomology, they are only an indirect assessment Carolyn Gibson1,2, Yixia Li3, Sabra Inslicht1,2, Karen Seal1,2, Amy Byers1,2. 1San Francisco of HRQOL and do not account for medication side effects. Accordingly, the objective VA Health Care System, San Francisco, CA; 2University of California, San Francisco, of this review is to critically appraise the outcome measures used in these clinical trials San Francisco, CA; 3NCIRE-The Veterans Health Research Institute, San Francisco, CA to evaluate whether there is adequate evidence to suggest that oral estrogen improves Objective: Posttraumatic stress disorder (PTSD) is a common but under-recognized HRQOL. Design: The 2004 Cochrane review evaluating oral hormone replacement for condition affecting the health and well-being of an estimated one in ten women. A the management of VMS was assessed. Each trial included in the meta-analysis was growing body of evidence suggests that PTSD may contribute to risk for diabetes and evaluated with respect to the study design, outcome measures, and methods of analysis. cardiovascular disease (CVD), primary health concerns among postmenopausal women. Results: A total of 24 randomized, double-blind, placebo-controlled clinical trials were However, these relationships have largely been evaluated among male Veterans and appraised. Six trials were excluded from the Cochrane meta-analysis due to inadequate relatively healthy civilian women. Further, it is not known if PTSD may augment CVD reporting of outcome measures. Of the remaining 18 trials, 15 trials did not directly assess risk among women with diabetes, a relationship that has been demonstrated in women HRQOL and used surrogate measures of HRQOL including symptom frequency and with comorbid depression and diabetes and has implications for comprehensive clinical severity. Many used physician-graded symptom scales which may introduce bias. One management. In this study, we examined independent and additive associations between trial used the generic QOL subscale of the General Health Questionnaire (GHQ) to assess PTSD and diabetes with time to incident CVD in a large sample of postmenopausal the impact of hormone therapy. This subscale does not ask menopause-specific questions women Veterans, a population at high risk for these concerns. Design: We examined and has not been validated among perimenopausal women. Two trials used the Greene national Department of Veterans Affairs medical record data from women Veterans Climacteric Scale (GCS), a validated outcome measure in perimenopausal women, aged 55 and older. We used ICD-9 codes to categorize women with posttraumatic stress to directly assess the impact of estrogen on HRQOL. While both studies showed an disorder (PTSD), diabetes, and cardiovascular disease (CVD; myocardial infarction, improvement in HRQOL in the hormone-treated group compared to placebo, the sample congestive heart failure, and/or cerebrovascular disease). Fine-Gray proportional hazards size was small (n=118) and the effect was modest. Conclusion: While oral hormone models were used to examine associations between PTSD, diabetes, and comorbid PTSD therapy may improve VMS symptom scales, there is a paucity of evidence on whether and diabetes at baseline (2008-2011) with incident CVD over a four-year follow-up it improves HRQOL in perimenopausal women. Future studies using validated, patient- period (2012-2015), accounting for the competing risk of death. Data from women reported outcome measures that directly assess HRQOL among perimenopausal women with CVD at baseline were excluded. All models were adjusted for age, education, and are needed to answer this question. income, as documented in the medical record; and hypertension, hyperlipidemia, and Sources of Funding: None obesity, as indicated by ICD-9 codes. Results: In this sample of 150,791 postmenopausal women Veterans (mean age 62.64 ± 8.03 years), 9% had PTSD, 17% had diabetes, and 2% had comorbid PTSD and diabetes at baseline. The four-year cumulative incidence rate of CVD outcomes was 12%. Adjusting for demographic and clinical risk factors, risk of incident CVD was approximately 50% higher for women with PTSD or diabetes alone at baseline (PTSD HR 1.47, 95% CI 1.38-1.57, p<.001; diabetes HR 1.49, 1.44- menopausal transition. The purpose of this analysis is to evaluate the impact of self- 1.55, p<.001), and 2-fold higher for women with comorbid PTSD and diabetes at reported history of preterm and term SGA birth on maternal BP and incident hypertension baseline (HR 1.96, 95% CI 1.80-2.12, p<.001). Conclusion: Among postmenopausal during the menopausal transition. Design: A longitudinal analysis was conducted with women Veterans, both PTSD and diabetes independently increased CVD risk over a 1772 women (45% white, 29% black, 6% Hispanic, 20% Chinese) from SWAN. four-year period, and significantly compounded risk when they co-occurred beyond Women were included in this analysis if they completed a detailed reproductive history the effects of either condition alone. The pronounced effect of these exposures over a questionnaire at the 13th SWAN visit and had BP data at baseline and at least one other relatively brief period raises questions about mechanisms of risk, and opportunities for visit. BP and anti-hypertensive use were assessed annually, over a 7-year follow-up. intervention, in this vulnerable and understudied population. These findings add to the Linear mixed effect models were used to estimate progression of BP in two ways; limited literature examining the health-related impact of PTSD among postmenopausal across 1) chronological years (baseline to 7 years) and 2) years since the final menstrual women, and highlight the importance of this under-recognized condition in the health of period (range -16 to +8 years). Generalized estimating equations were used to examine women across the lifespan. the association between history of preterm and term SGA birth with BP categories Sources of Funding: This work was supported by the U.S. Department of Defense (normal, elevated, stage 1 and stage 2 hypertension). In a subsample of women without grant W81XWH-11-2-0189 (ALB), which was administered by the Northern California reported hypertension or anti-hypertensive use at baseline, Cox proportional-hazards Institute for Research and Education and with resources of the San Francisco Veterans regression estimated incident hypertension. Models were adjusted for age at baseline, Affairs Medical Center, and the Department of Veterans Affairs grant CX001119 (ALB). site, race/ethnicity, financial strain, body mass index, smoking status, physical activty, Work was also supported in part by the Advanced Fellowship in Women’s Health medications (lipid-lowering, anti-diabetic), parity, and age at first birth. Linear mixed program in the San Francisco VA Health Care System (CJG). models also adjusted for anti-hypertensive use. Sensitivity analyses were performed excluding women with self-reported hypertension or diabetes during pregnancy. Results: At the baseline SWAN visit, women were on average 47 years old. One hundred S-21. ninety-seven women (11%) reported ever having a preterm birth and 164 (9%) reported MeToo and Women’s Health: Sexual Harassment, Sexual Assault, and a prior term SGA birth. Compared to women with all terms births, the odds of elevated Midlife Women’s Health blood pressure/hypertension were 1.47 (95% CI: 1.07, 2.01) and 1.48 (95% CI: 1.02, 2.15) Rebecca C. Thurston1, Yuefang Chang, PhD1, Roland von Känel, MD2, Karen A. times higher for women with a preterm and term-SGA birth, respectively. Systolic BP Matthews, PhD1. 1University of Pittsburgh, Pittsburgh, PA; 2University Hospital Zurich, was significantly higher at the final menstrual period in women with term SGA births Zurich, Switzerland (p<0.05), and decreased after the final menstrual period (β=-0.62, p=0.04). History Objective: Sexual harassment and assault are prevalent experiences in women. These of preterm birth was associated with incident hypertension (HR: 1.46, 95% CI: 1.27, experiences are understood to be important to women’s lives and functioning, yet 1.67) over a 7-year follow-up even after excluding women with reported hypertension their implications for women’s health remain less well understood. We first examined or diabetes during pregnancy (HR: 1.49, 95% CI: 1.26, 1.76). Term SGA birth was not the prevalence of sexual harassment and assault in a sample of nonsmoking midlife significantly associated with incident hypertension. Conclusion: This study suggests that women. We next tested whether women with a history of harassment and/or assault preterm birth may increase the risk of incident and prevalent hypertension that occurs had poorer mental and physical health at midlife. Design: 304 (72% White, 28% non- with chronological aging. While prior term SGA birth is associated with greater risk of White) nonsmoking women ages 40-60 were recruited. All women were free of clinical prevalent hypertension in midlife, it is also related to decreasing systolic BP after the cardiovascular disease (CVD), had their uterus and at least one ovary, and were not final menstrual period. Additional analyses are necessary to examine if rate of change using select medications (hormone therapy, insulin, beta blockers, calcium channel differs across stages of reproductive aging. These findings are important as elevations in blockers, selective serotonin reuptake inhibitors, serotonin-norepinepherine reuptake blood pressure in these groups of women may be linked to future cardiovascular disease. inhibitors). All women underwent an interview, physical and anthropometric measures Sources of Funding: The Study of Women's Health Across the Nation (SWAN) [height, weight, systolic (SBP) and diastolic blood pressure (DBP)], a fasting blood draw has grant support from the National Institutes of Health (NIH), DHHS, through the [glucose, insulin, lipids, high sensitivity C-reactive protein (hsCRP)], three days of sleep National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) actigraphy monitoring, 24-hours of electrocardiogram (for heart rate variability) and and the NIH Office of Research on Women's Health (ORWH) (Grants U01NR004061; completed validated questionnaires (Center for Epidemiologic Studies for Depression U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, Scale, Spielberger State Trait Anxiety Inventory, Pittsburgh Sleep Quality Index, Brief U01AG012553, U01AG012554, U01AG012495). The content of this manuscript is Trauma Questionnaire including questions about lifetime history of sexual harassment solely the responsibility of the authors and does not necessarily represent the official and assault). Associations between sexual harassment and assault and health indices were views of the NIA, NINR, ORWH or the NIH. Yamnia I. Cortés was supported by the separately tested in linear regression models adjusting for covariates associated with the Cardiovascular Epidemiology Training Program (T32 HL083825, PI: Orchard). outcome at p<.10 [e.g., age, race/ethnicity, education, body mass index (BMI), snoring, shift work, co-morbidities, and medications: anti-hypertensive, lipid-lowering, anti- inflammatory, anti-coagulant, psychotropic, sleep medications]. Interactions with race/ S-23. ethnicity were tested in all models. Results: 19% of women reported workplace sexual Dietary soy intake and mortality outcome in Chinese breast cancer harassment, 22% of women reported a history of sexual assault, and 10% of women survivors experienced both exposures. Women with a history of sexual harassment were more likely Suzanne Ho, PhD1, Winnie Yeo2, Ashley CK Cheng3, Carol CH Kwok3, Roselle Lee1, Iris to be college educated (71% vs 55%, p=.03), and yet have greater financial strain (46% CK Lee2, Carley KL Cheung2, Aprille Sham1, Aggie Ip1, Yuan-Yuan Lei2, Yi-Qian He2. vs. 28%; p=.0006) than their non-harassed counterparts. Neither harassment nor assault 1JC School of Public Health and Primary Care, The Chinese University of Hong Kong, varied by race/ethnicity. Controlling for covariates (e.g., age, race/ethnicity, education, Shatin, Hong Kong; 2Department of Clinical Oncology, The Chinese University of Hong BMI, snoring, shift work, medication use), sexual harassment was associated with Kong, Hong Kong, Hong Kong; 3Department of Oncology, Princess Margaret Hospital, higher blood pressure [SBP: b(SE)=3.96(1.94), p=.04; DBP: b(SE)=2.40(1.29, p=.06], Hong Kong, Hong Kong greater triglycerides [b(SE)=.15(.06), p=.01], poorer sleep quality [b(SE)=.15(.07), Objective: The incidence of Breast cancer (BC) has been increasing in Asian women. p=.03], and for non-White women (interactions harassment*race p<.05), poorer With earlier detection and advances in cancer treatment, BC survival has improved objective sleep continuity [more wake after sleep onset: b(SE)=.32(.16), p=.05] and a substantially. Soy foods have generated considerable interest among BC survivors for more pro-inflammatory state [greater hsCRP, b(SE)=.58 (.27), p=.04]. Sexual assault promoting health; but have also raised much concern because of conflicting reports of was associated with greater depressive symptoms [b(SE)=4.01 (1.13), p=.0004], higher soy effects on BC prognosis. This study aimed to investigate the association of pre- anxiety [b(SE)=3.78(1.34), p=0.005], poorer sleep quality [b(SE)=.24(.06), p<.0001], diagnosis dietary soy intake and all-cause mortality among BC survivors in Hong and for White women (interaction assault*race, p<.05), lower heart rate variability Kong Chinese women. Design: A cohort study comprising 1,497 BC survivors were during sleep [respiratory sinus arrhythmia, b(SE)=-.17(.08), p=.04] adjusting for recruited since 2010 from two regional hospitals offering breast cancer treatment. covariates. Conclusion: Sexual harassment and assault were prevalent in this sample of The two hospitals offered breast cancer treatment to one-third of BC cases in Hong nonsmoking, CVD-free midlife women and may have negative implications for women’s Kong. All participants were diagnosed with primary BC within 12 months of study mental and physical health. entry, and had no prior history of breast or other cancers. Face-to-face interviews based Sources of Funding: This work was supported by the National Institutes of Health, on structured questionnaire were conducted at entry to collect information on socio- National Heart Lung and Blood Institute (R01HL105647, K24123565 to Thurston); and demographic, medical, reproductive, and lifestyle factors. Clinical information was the University of Pittsburgh Clinical and Translational Science Institute (NIH Grant obtained from medical records. Anthropometric measurements were also obtained based UL1TR000005). on standardized protocol. Soy food intake during the year prior to diagnosis was collected based on previously validated soy food frequency questionnaire1, and soy isoflavone intake estimated based on local soy food content2. Data collection was repeated at S-22. 18-, 36-and 60-month follow-ups. Information on all-cause mortality up till November 2017 Impact of prior preterm or term small-for-gestational age birth on was obtained from active follow-up and computerized clinical management system, with maternal blood pressure throughout the menopausal transition in the 100% completion rate. Results: The mean age of the cohort at entry was 51.8±9.07 years Study of Women’s Health Across the Nation (SWAN). and 47.8% were postmenopausal. 83.3% of the BC were of the invasive ductal carcinoma Yamnia Cortés, PhD, MPH, FNP, Emma Barinas-Mitchell, Maria M. Brooks, Karen A. type, and about 80% of cancer stage 0-1. 96 deaths (5.9% among premenopausal and 7% Matthews, PhD, Janet Catov, PhD. University of Pittsburgh, Pittsburgh, PA postmenopausal) occurred during the followup period (mean 50.89±16.86 months). The Objective: Women who deliver a preterm or term small-for-gestational age (SGA) mean pre-diagnosis soy isoflavone intake was 9.73 (±11.35) mg/day. After adjustment infant may be at increased risk for cardiovascular disease, perhaps related to higher for the potential confounders (age, education, body mass index, types of therapies, blood pressure. While there is evidence that women with a preterm and SGA birth have ER/PR status, cancer stage, menopausal status, and dietary energy intake), all-cause modestly higher blood pressure (BP) prior to pregnancy and through early adulthood mortality was observed to be lower among women belonging to the middle tertile of (age 18-40), there is limited evidence on whether these differences persist during the energy adjusted soy isoflavone intake (Hazard ratio 0.64, 95% C.I. 0.37-1.09), while those of the third quartile had 5% lower mortality risk but statistically not significant. FEATURED POSTER PRESENTATIONS Stratified analysis showed the adjusted mortality hazard ratio to be 0.45 (95% C.I. 0.2-1.0) for premenopausal, and 0.94 (95% C.I. 0.43-2.05) for postmenopausal survivors belonging to the middle intake tertile. This study is still ongoing and further analyses P-1. would reveal the effect of post-diagnosis soy isoflavone intake on BC survival. NT-814, a novel dual NK1,3 receptor antagonist results in immediate Conclusion: Our prospective data showed that moderate level of pre-diagnosis soy intake improvements in bothersome post-menopausal symptoms. was associated with a lower risk of all-cause mortality, particularly in premenopausal Stephen Pawsey1,2, Elizabeth Ballantyne1,2, Mike Trower, PhD1,2, Mary Kerr1,2. 1KaNDy BC survivors. 1Chan SG, Ho SC, Kreiger N, et al. Dietary sources and determinants of Therapeutics Ltd, Stevenage, United Kingdom; 2NeRRe Therapeutics, Stevenage, United soy isoflavone intake among midlife Chinese women in Hong Kong. J Nutr 2007;137: Kingdom 2451-2455. 2Chan SG, Murphy PA, Ho SC, et al. Isoflavonoid content of Hong Kong soy Objective: To assess the preliminary efficacy and speed of onset of effect of NT-814,

foods. J Agr Food Chem 2009;57:5386-5390. a novel, non-hormonal, neurokinin (NK)1,3 antagonist, in women with bothersome post- Sources of Funding: This Study has been supported by the World Cancer Research Fund menopausal symptoms Design: This was a randomised, double-blind, placebo-controlled International Grant: No.2010/249 and 2014/1197. study. Generally healthy female subjects aged 40-65 years experiencing 7 to 20 hot flashes per day received NT-814 or placebo once daily in sequential, escalating dose cohorts. Subjects were resident in a clinical pharmacology unit for the first 7 of the S-24. 14-day treatment period. Efficacy was assessed by recording the frequency and The Johns Hopkins Menopause Curriculum App, a pilot study severity of hot flash (HF) and night-time awakenings (NTA) in a diary twice daily 1 2 3 4 Isa I. Ryan, MD , Belinda Chen, MD , Teresa Johnson, PhD , Nicole Sokol , Wen Shen, for 1 week before and throughout the 2-weeks of treatment. Safety, tolerability and 1 1 2 MD, MPH . GYN/OB, Johns Hopkins, Baltimore, MD; Internal Medicine, Johns pharmacokinetics were also evaluated. Results: 76 subjects received placebo (N=18), 3 Hopkins, Baltimore, MD; Health Sciences Informatics, Johns Hopkins, Baltimore, MD; 50 mg, 100 mg 150 mg (N=15 per dose) or 300 mg NT-814 (N=13). Demographics and 4 POC-IT, Johns Hopkins, Baltimore, MD baseline characteristics were generally well matched at baseline. In the second week of Objective: The postmenopausal population will increase dramatically over the next treatment the higher doses of NT-814 resulted in profound reductions from baseline in the decades. Women are expected to live past their eighties and spend approximately one frequency of both moderate/severe daytime HF (up to 84%) and NTA (up to 81%) that third of their lives in menopause. Physicians who are knowledgeable in menopause were highly significant compared to placebo (37% and 32%). Additional analyses were medicine are greatly needed. Our educational objective is to provide a real time step-by- undertaken to evaluate the speed of onset. For the 150 mg dose the improvements were step guide for the evaluation, diagnosis, management and treatment of menopausal significantly better than placebo on the first day of treatment for both endpoints (HF 2.65 women. This menopause curriculum will be easily accessed on a smartphone via an app fewer flushes, p<0.05; NTA 1.27 fewer awakenings, p<0.05) and remained significant and consulted for information as the patient is being interviewed. Furthermore, within throughout the 14-day treatment period. The maximum separation from placebo was healthcare education a need exists for a menopause curriculum. However, practical achieved by day 7. (HF 5.87 fewer flushes, p=0.0001; NTA 2.7 fewer awakenings, application of knowledge to the clinical arena has been more challenging. GYN/OB p<0.05). For the 300 mg dose, the improvements for HF were also significant from resident clinics are filled with young women of reproductive age. Internal Medicine day 3 onwards and for NTA were significant on a number of days from Day 3 onwards. resident clinics have patients with multiple comorbidities and high acuity. Trainees often Although there appeared to be numerical differences between the 150 and 300 mg don’t see enough menopausal patients to achieve and maintain comfort and competence. doses, exposure response modelling showed no difference between them. NT-814 In this setting, a smartphone app can be an invaluable educational modality. We was well tolerated with no safety concerns. Conclusion: NT-814 resulted in profound hypothesize; this innovative system will significantly improve patient satisfaction, in improvements in HF frequency that, somewhat remarkably, were apparent after the first addition to improving providers’ effectiveness. Our primary objective, in this pilot study, dose and persisted for 14 days. There were also rapid and marked improvements in the was to test this app with OB/GYN residents at a large academic institution to assess the number of night time awakenings. Improvements in HF and sleep have been reported as efficacy of the app as an effective teaching tool as well as the perceived user-friendly early as Day 3 for other NK antagonists; this is the first report of improvements in HF quality of the app. Design: A mobile device app was created with 24 modules focusing frequency and night-time awakening on the first day of treatment and raises the prospect on core competencies regarding care of menopausal women both for management of of NT-814 rapidly treating a range of bothersome post-menopausal symptoms. NT-814 acute symptoms and preventative health. The first pilot session was performed on 15 will be progressed into a Phase 2b dose finding study shortly. OB/GYN residents during their protected educational time in May 2018. The residents Sources of Funding: NeRRe Therapeutics Ltd sponsored the study were given a 24 question, multiple-choice test targeting core competencies of menopause clinical knowledge and instructed to use the Menopause App to answer the questions. Afterwards, the answers were reviewed and discussed in detail. The residents were then P-2. asked to perform a survey with psychometrics of the app to evaluate the user-friendly Vaginal microbiota, local immunity and symptoms in postmenopausal quality of the app. Results: Of the residents present, 50% were interns, 25% were second women years and 25% were fourth years. The average test score was 78.3% correct. In terms Yelena Yeprikyan1, Svetlana Yureneva1, Angelina Glazunova1, Andrey Donnikov2, of the psychometric assessment of the app via post-test survey, 60% indicated that the Larisa Ezhova2. 1Gynecological Endocrinology, National Medical Research Center for app was “moderately effective at providing clear content” and “moderately effective at Obstetrics, Gynecology and Perinatology n. a. V. Kulakov of Ministry of Healthcare, providing engaging content”. Conversely, 90% indicated that the app was “very effective Moscow, Russian Federation; 2National Medical Research Center for Obstetrics, or extremely at providing relevant content” and 80% indicated that they were “very to Gynecology and Perinatology n. a. V. Kulakov of Ministry of Healthcare, Moscow, extremely likely to use the app again in the future” and “very to extremely likely to Russian Federation recommend use of the app to a colleague”. On the free text aspect of the survey, the most Objective: To investigate the vaginal microbiota in postmenopausal women and to common constructive criticism was improving the search function and simplifying the explore the association between the severity of vaginal symptoms, microbiota, local organization of the content. Overall, the residents reported that the strongest aspect of immunity and vulvovaginal atrophy. Design: The study included 136 women with the app was its content, reporting “it’s a needed tool and it’s packed full of information”. a postmenopausal period from 1 year to 20 years. Diagnosis of VA was based on Conclusion: Our goal is to improve health care for menopausal women by expediting cytological method of investigation (the calculation of the index of maturation of the the healthcare provider’s learning process and thereby improving patients’ experiences. vaginal epithelium (IMVE - the norm is ≥ 65%)). The PCR-RV method was used to A mobile app can effectively provide healthcare professionals instantaneous access to quantify the vaginal micribiota, taking into account the total bacterial mass (TBM), the fundamentals and recommendations in real time, “at the bedside”. Menopausal women number and fraction of lactobacilli. There are no normal criterions to describe the normal are cared for by a host of different providers both in terms of profession and specialty. vaginal microbiocinosis in postmenopausal women, so we proposed the classification We will continue to improve this app by piloting it with other departments, including of “conditioned normocenosis” with a lactobacillus share of more than 80%. Also, Internal Medicine residents. Additionally, this is an interactive educational tool that we studied the state of local immunity of vaginal mucosa: mRNA of cytokine genes: allows real-time assessment of knowledge gaps for learners when used in a didactic IL1B, IL6, IL8, IL10, IL12A, IL 18, TNF, TGF B, CD45, CD68, TLR4, GATA3, setting. We plan on eventually reformatting the testing methodology by using common CD69 and B2M reference gene by the PCR-RV method according to the instructions clinical patient scenarios that target core competencies for the test rather than simple of “DNA-Technology”, Russia. Results: In women, as the duration of postmenopause multiple choice questions devoid of clinical context. Also, we will reformat the method progresses there is a 6-8-fold decrease in the total bacterial mass for every 5 years. in which the test is administered by providing an allotted time period for participants to In women with VA, the vaginal microflora is redistributed: against the background of a complete said clinical scenarios and evaluate how many can be assessed in the given time significant decrease of lactobacilli (Lactobacillus spp. (p <0.0001)), obligate anaerobic period in order to more accurately reflect using the app during clinic. microorganisms become the main representatives of the microbiocenosis. So, it can Sources of Funding: Pfizer Grant be concluded that in patients with VA, the bacterial mass is mainly represented by the anaerobic flora of the vagina, and in women without VA– by lactobacilli. The severity of vaginal symptoms was mostly related to vaginal microbiota composition than the presence or absence of VA in postmenopausal women. Patients in the observation groups had no significant leukocyte reaction. There were no statistically significant differences found between patients with VA and without VA during comparing the number of leukocytes in microscopy of vaginal smears as a function of the state of the vaginal microbiocenosis. In our study expression of mRNA of immune response genes were evaluated in all patients. Since the level of expression of the studied genes differed in postmenopausal women depending on VA presence/absence as well as on the state of microflora (normocenosis and dysbiosis), a comparison group was selected for the evaluation of mRNA expression of genes, which included women without VA and normocenosis. In the other groups expression levels of mRNA were normalized by the median of the expression level of At the trabecular bone region, the percentage of total glycosaminoglycans (GAGs) that gene in the group of comparison. In patients with VA the mRNA expression genes was higher in GV and the percentage of only sulfated GAGs was higher in (GVI), was significantly lower of IL12 and TNF by 2 times, IL18 by 7.7 times, TGFB by 3.75 while the higher content of chondroitin sulfate in shafts of femurs was seen in (GV). times, CD68 by 3.5 times, GATA 3 by 9 times, and ILIB 2 by times in relation to the Conclusion: Our data indicate that soybean isoflavones improve bone quality in femurs group of comparison. The increase in the share of opportunistic microflora from TBM of type 1 diabetics rats by increasing histomorphometric parameters, the content of GAGs in combination with VA is accompanied by a more pronounced change in the cytokine and mature type I collagen fibers. cascade: the mRNA expression of IL 12 is down by 19 times, IL 18 by 100 times, TNF by Sources of Funding: This study was funded by Fundacão de Amparo à Pesquisa do 4.5 times, TGFB by 9 times, CD 68 by 12 times, GATA 3 by 12.5 times (p <0.05) times Estado de São Paulo (FAPESP) Number: 2014/17077-9 in relation to the group of comparison. Conclusion: The severity of vaginal symptoms is mostly related to vaginal microbiota composition than the presence or absence of VVA in postmenopausal women. In postmenopausal women with VVA the level of mRNA P-5. of cytokine genes expression (IL 1B, IL 12, IL 18, TNF, TGFB, CD 68, GATA3) is Efficacy and safety of bazedoxifene (Viviant) in postmenopausal women significantly decreased. It may be the result of a decrease in the functional activity of with osteoporosis and osteopenia vaginal epithelium and decline of lactobacilli level. Hee Dong Chae, Do-Young Kim, Hyun-Jin Kim, Sung-Hoon Kim, Byung-Moon Kang. Sources of Funding: none Obstetrics and Gynecology, University of Ulwan College of Medicin, Asan Medical Center, Seoul, Korea (the Republic of) Objective: To evaluate the efficacy and safety of bazedoxifene in women with P-3. postmenopausal osteoporosis and osteopenia Design: A prospective pilot study was Estrogen deficiency and diabetes may impair bone formation and performed in Asan Medical Center from May 2014 to January 2018 and the eligible collagen turnover in periodontal tissue of female rats. patients were followed up for up to 15 months. Patients were screened and women with Gisela R. Sasso, postdoctoral fellow1, Rinaldo Florencio-Silva, Post Doctoral2, Caio C. osteoporosis or osteopenia were included. Subjects received bazedoxifene 20 mg per Fonseca, Doctorate2, Luana C. Cezar, Doctorate3, Paulo C. Franco2, Cristiane d. Teixeira2, day, followed by visits at months 1, 3, 9, and 15. Bone mineral density (BMD) of lumbar Manuel d. Simões2, Manoel J. Girão1. 1Ginecology, Federal University of São Paulo, São spine and hip was measured using DXA (Dual X-ray absorptiometry) at months -24 Paulo, Brazil; 2Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, and -12, at the start of the study, and at month 12. Safety and tolerability evaluations Brazil; 3ICB, Universidade de São Paulo, São Paulo, Brazil included adverse event reports, physical examinations and clinical laboratory tests, Objective: Increasing evidence indicates that both diabetes and estrogen deficiency at including chemical and lipid assessments. Other safety monitoring included breast menopause increase the susceptibility to periodontitis. This opens the question whether examination, mammography, and gynecologic ultrasound. Results: Ninety-nine patients post-menopausal women with diabetes are more likely to develop periodontal diseases. were enrolled, and 97 patients completed the study in 15 months. Eleven patients On the other hand, evidence concerning the effects of estrogen deficiency on periodontal (11.3%) showed significant improvement in lumbar spine BMD at month 12 (p < 0.05), tissue in diabetic patients are still scarce. Thus, we aimed to evaluate the combined however total hip BMD showed no statistically significant improvement. Fifty-nine of effects of estrogen deficiency and diabetes in the periodontal tissue of female rats. the 97 patients (60.8%) maintained the lumbar spine BMD, and 71 patients (73.2%) Design: Thirty adult female Wistar rats were ovariectomized (OVX) or SHAM-operated had no significant change in femur BMD. Twenty-four (24.7%) showing a decrease (SHAM). Three weeks after surgery, diabetes was induced by an intraperitoneal injection in lumbar spine BMD and 9 patients (9.3%) showing a decrease in femur BMD prior of streptozotocin (65 mg/kg i.v) in some SHAM and OVX rats, and confirmed by serum to administration of bazedoxifene obtained sustained BMD after medication. Sixteen glucose levels analysis. The animals were then assigned into the following groups: (I) of the 97 patients (16.4%) complained of dyspepsia, fourteen patients (14.4%) showed Sham; (II) OVX; (III) OVX+E (treated with 10µg/Kg/day of 17β-estradiol); (IV) diabetic an increase in liver enzymes, and 8 patients (8.2%) had shoulder pain, but these events Sham; (V) diabetic OVX; (VI) diabetic OVX+E. The animals were subcutaneously did not lead to discontinuation of medication. There were no serious adverse events treated with estradiol or vehicle for 60 consecutive days and body weight was monitored including venous thromboembolism, coronary heart disease, cerebrovascular accidents, once a day. After treatments, the animals were euthanized and fragments of maxillae breast cancer, or endometrial carcinoma. Conclusion: Bazedoxifene prevented bone loss containing periodontal tissue of the first molars were removed and fixed in 4% and reduced bone turnover and was generally safe and well tolerated in postmenopausal paraformaldehyde. After decalcification the samples were embedded in paraffin. Sagittal women with osteoporosis and osteopenia. sections were subjected to the Picrosirius red method for collagen evaluation in polarized Sources of Funding: None light microscopy, or to immunohistochemistry for the detection of Runx-2 (a marker of osteoblast formation). Results: Body weight was significantly lower in diabetic rats compared to non-diabetic ones. A lower birefringence intensity of collagen fibers, as P-6. well as a lower immunoreactivity of Runx-2 were observed in the periodontal ligament Evidence of autophagy participation in osteoclast activity following of all diabetic and OVX rats, compared to non-diabetic SHAM animals. These effects estrogen withdrawal in alveolar bone of ovariectomized rats were more evident in rats with both condition (OVX + diabetes). Nonetheless, estradiol Rinaldo Florencio-Silva, Post Doctoral1, Gisela R. Sasso, Post Doctoral2, Manuel d. treatment alleviated these effects. The observed decrease in birefringence of collagen Simões1, Estela Sasso-Cerri3, Paulo S. Cerri3. 1Morfologia e Genética, Universidade fibers indicates a lower content of these structures in the periodontal ligament of OVX Federal de São Pailo, SP, Brazil; 2Ginecologia, Universidade Federal de São Paulo, SP, and diabetic rats. In addition, the reduced Runx-2 immunostaining suggest an impairment Brazil; 3Histologia, UNESP, Araraquara, Brazil of alveolar bone formation in OVX and diabetic rats. Conclusion: Our results suggest Objective: It has been reported that estrogen influences bone health by regulating that estrogen deficiency and diabetes promote deleterious effects in periodontal tissue osteocyte autophagy, a cell survival pathway. As autophagy has been shown to play of female rats, by at least in part, impairing collagen turnover and osteoblast formation. important roles in osteoclast activity, we hypothesized that estrogen status influence These were more evident when both conditions were present and estrogen replacement osteoclast autophagy. Here, we evaluated the effects of estrogen status in the seems to counteract these effects. immunoexpression of autophagy markers in alveolar bone osteoclasts of ovariectomized Sources of Funding: NONE rats. Design: Thirty adult female Wistar rats were ovariectomized (OVX) or SHAM- operated (SHAM). After three weeks, six OVX and six SHAM rats were sacrificed whereas the remaining rats received daily subcutaneous injections of estrogen (30 BONE HEALTH POSTER PRESENTATIONS mg/kg bw, OVXE group), or vehicle solution (SHAM and OVX groups) for 15 days (n=6 rats/group). Serum estradiol levels were measured by electrochemiluminescence immunoassay and the fragments of maxilla containing the alveolar bone of the first P-4. molars were removed and fixed in 4% formaldehyde buffered at pH 7.2 with 0.1 M Effects of soybean isoflavones and 17β estradiol on bone tissue of type 1 sodium phosphate. After decalcification in 7% EDTA, the fragments were embedded diabetic rats in paraffin. Sections were subjected to the TRAP method (osteoclast marker) or to the Adriana F. Carbonel, Post Doctoral1,2, Ricardo S. Simões, Post doctoral fellow2,1, immunohistochemical detections of beclin-1 and MAP-LC3α (autophagy markers). The Edmund C. Baracat, Professor2,1, Jose M. Soares Junior, Professor2,1, Manuel d. Simões1,2. number of TRAP-positive osteoclasts and the number of immunolabelled multinucleated 1Morphology and Genetics, Federal University of São Paulo, São Paulo, Brazil; giant cells (MNCs) was computed along the alveolar bone surface of the first molar, 2Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil at x100 magnification. Statistical analysis was performed by ANOVA/Tukey post-hoc Objective: The aim of this study was to evaluate the effects of soybean isoflavones or test. Results: The serum estradiol levels decreased significantly (p<0.01) in the OVX- 17β estradiol on bone tissue of ovariectomized rats with type 1 diabetics Design: Sixty group compared with SHAM and OVXE groups. Three weeks after surgical procedures, adult, virgin, female rats underwent ovariectomy were randomization into six groups a significant increase (p<0.05) in the number of TRAP-positive osteoclasts as well as in of ten animals each: GI = Sham control ovariectomized animals; GII = Sham control the number of beclin-1- and MAP-LC3α-immunolabelled MNCs was observed in the diabetic ovariectomized animals; GIII = control ovariectomized that received propylene bone surface of rats from OVX group in comparison with SHAM group. In addition, glycol vehicle; GIV = control diabetic ovariectomized animals receiving propylene glycol estrogen treatment reduced significantly (p<0.05) the number of TRAP-positive vehicle; GV = diabetic ovariectomized animals treated with soy isoflavones (150mg/kg osteoclasts and the number of immunolabelled MNCs for autophagy markers. As MNCs by gavage); GVI = diabetic ovariectomized rats treated with estrogen (17ß-estradiol, located along the alveolar bone surface are presumably osteoclasts, these results support 10mg/kg, subcutaneously). After treatment, the rats were euthanized and their distal a possible association between autophagy and increased osteoclast activity following femurs were removed for histological routine, histochemistry and biochemical study. estrogen depletion. Conclusion: The estrogen depletion increases the immunoexpression Histological sections were stained with hematoxylin-eosin or subjected to picrosirius of autophagy markers in alveolar bone osteoclasts, whereas estrogen replacement red methods. Results: In distal femurs, the trabecular bone volume was higher in the counteracts these effects. Future studies are needed to determine whether the modulation groups treated with estradiol (GVI), when compared to isoflavone, while the cortical of autophagy in osteoclasts is efficient against post-menopausal bone loss. bone width and the presence of mature type I collagen fibers were higher in (GV). Sources of Funding: CAPES P-7. P-9. Association between Bone Mineral Density and Dietary Calcium Intake No association between serum vitamin D level and bone mineral density in Postmenopausal Women: a Korean Population–based Study or BMD change over 4.6 years in postmenopausal Korean women Hoon Kim, MD,PhD, NCMP, Seung-Yup Ku, Chang Suk Suh, MD, PhD, Seok Sunmie Kim, M.D. PhD.1, Jin Ju Kim, M.D. PhD1, Min-Jeong Kim, M.D.1, Hyun Kim, Young Min Choi, Jung Gu Kim. Dept. of OB/GYN, Seoul Nat’l Univ. Seokhyun Kim, M.D., PhD2. 1Seoul National University Hospital Gangnam Center, College of Medicine, Seoul, Korea (the Republic of) Seoul, Korea (the Republic of); 2Obstetrics and Gynecology, Seoul National University Objective: Calcium is an essential nutrient for bone health and calcium intake has been College of Medicine, Seoul, Korea (the Republic of) encouraged for elderly population to prevent osteoporosis. However, mean dietary Objective: We aimed to evaluate the correlation between serum vitamin D level calcium intake in Asian population was reported to be low due to lower intake of dairy and bone mineral density and BMD change over time in postmenopausal women. food compared to that of Western countries and few studies reported the effect of dietary Design: Retrospective cohort study involving 1051 postmenopausal Korean women over calcium intake on bone in Asian population. The aim of the present study is to investigate age 50 (age range of 50~81), who visited Seoul National University Gangnam Center the association between bone mineral density (BMD) and dietary calcium intake from the during 2010-2011(baseline measurement) and during 2015-2016 (follow-up data) for Korean population, in which low calcium intake is highly prevalent. Design: This study routine health check-up and who had undergone both dual energy X-ray absorptiometry was performed using the data from the Korea National Health and Nutrition Examination (DEXA) and serum 25-hydroxyvitamin D (25OH-D) level measurement. We intended to Survey (KNHANES), conducted by the Korean Ministry of Health and Welfare. This evaluate the association between serum 25OH-D and bone mineral density and changes cross-sectional nationwide representative survey has been conducted to evaluate health in bone mineral density (BMD) over 5 years in this population. Results: The mean age of and nutritional status of Korean population, using a probability proportional to size the participants were 57.9 (50 – 81) and the mean follow up interval was 4.6 years. The sampling with stratification and multi-stage samples. In KNHANES, BMD was assessed mean T-scores of BMD at L1-4, femoral neck and total femur were -0.26 (-3.5 – 3.9), during 2008-2011 and categorized into 3 groups according to the criteria of World Health -0.48 (-2.7 – 6.2) and -0.26 (-3.0 – 4.3) respectively. For BMD categories, 595 (56.6%) Organization and the food frequency questionnaire (FFQ) was used to evaluate dietary participants had normal BMD (lowest T-score > -1.0), 430 (40.9 %) had osteopenia intakes. Postmenopausal women without a history of hormone therapy or osteoporosis (-2.5 < lowest T-score ≤ -1.0) and 26 (2.5 %) had osteoporosis (lowest T-score ≤ -2.5). medication were included and women with uncertain menopausal status were excluded The changes in T-score over study period were -0.29 (-2.3 - 1.8) at L1-4, -0.24 (-3.3 - 0.9) from analysis. Finally, a total of 3,287 postmenopausal women were included to at femoral neck and -0.17 (-2.4 - 2.6) at total femur. Mean serum 25OH-D level was 23.2 ± determine the association between BMD and dietary calcium intake. Results: The mean 8.9 ng/ml; 243 (23.1%) of all participants had sufficient range of serum 25OH-D (≥ 30ng/ dietary intake of calcium was 402 mg/ day in study population. In addition, lower dietary ml); 363 (34.5%) were in insufficiency range (20 ≤, < 30 ng/ml) and 445 (42.4%) were calcium intake was more frequently observed in older postmenopausal women and a in insufficiency range (< 20ng/ml). There were no significant correlations between serum daily calcium intake less than 400 mg/day was found in 42.9% (women aged ≤ 49 years), 25OH-D level and BMDs of all three sites at baseline. The incidences of osteopenia and 51.8% (50-59 years), 62.7% (60-69 years), 70.0% (70-79 years) and 80.4% (≥ 80 years) osteoporosis were not different among three groups according to serum 25OH-D level (P<0.001). Complex sample analysis showed that participants with low calcium intake (sufficient vs. insufficient vs. deficient groups). In addition, there was no correlation demonstrated greater probability of having higher systolic blood pressure, higher level between baseline serum 25OH-D level and BMD change over time. Conclusion: Serum of triglyceride and parathyroid hormone, and lower level of high-density lipoprotein and 25OH-D levels were not related to BMD level or BMD change over time in this population. 25-hydroxyvitamin D (All P< 0.05). After adjustment for confounders including age, Sources of Funding: none years since menopause, body mass index and physical activity, BMD at lumbar spine and proximal femur showed a positive interaction with dietary calcium intake (P< 0.05). In post-hoc analysis, this significant association was found only in osteoporotic women. P-10. Conclusion: In conclusion, lower calcium intake was observed in older postmenopausal Vitamin D status and its relationship with bone mineral density and population and dietary calcium intake was significantly associated with BMD in Korean incidence of metabolic syndrome in postmenopausal women of Pusan and postmenopausal women, especially in osteoporotic women. Gyeongnam province of Korea Sources of Funding: The present study was supported by grant no 04-2016-0350 from Juseok Yang, Hwi Gon Kim, Yong Jung Song, Yong-Jin Na. Pusan National University the SNUH Research Fund. Yangsan Hospital, Yangsan, Korea (the Republic of) Objective: The aim of this study is to determine the prevalence of vitamin D deficiency in postmenopausal women of Pusan and Gyeongnam province in Korea and to evaluate P-8. its relationship with bone mineral density levels and metabolic syndrome. Design: Study Bone Mineral Density and Metabolic Syndrome in Postmenopausal subjects were 332 postmenopausal Korean women with a mean age of 54.5 years who Women: a Korean Population–based Study visited Pusan National University Yangsan Hospital from January 2013 and December Hoon Kim, MD,PhD, NCMP, Seung-Yup Ku, Chang Suk Suh, MD, PhD, Seok 2017. All data is derived from the initial laboratory result and measurement at first Hyun Kim, Young Min Choi, Jung Gu Kim. Dept. of OB/GYN, Seoul Nat’l Univ. visit. Serum 25-hydroxyvitamin D (25(OH)D) by chemiluminescence immunoassay College of Medicine, Seoul, Korea (the Republic of) was used to evaluate the vitamin D status. Bone mineral density (BMD) was measured Objective: It has been suggested that bone mineral density (BMD) and cardiovascular with dual-energy X-ray absorptiometry in lumbar vertebrae and femur. Vitamin D disease have overlapping risk factors and share pathophysiological mechanisms. The deficiency was defined according to the National Osteoporosis Society guideline 2013. present study was conducted to investigate the association between BMD and metabolic The new International Diabetes Federation definition was used as a diagnostic criteria syndrome (MetS), a cluster of major risk factors for cardiovascular diseases from the for metabolic syndrome (MS). Results: Clinical characteristics of our study population Korean population-based study. Design: This study was based on the data from the Korea are shown in table 1. The prevalence of suboptimal vitamin D level of this study which National Health and Nutrition Examination Survey (KNHANES), conducted by the includes deficient (<12 ng/ml) and inadequate (<20ng/ml) 25(OH)D status was 60.2% Korean Ministry of Health and Welfare. This cross-sectional nationwide representative (n=200). The BMD of total lumbar (g/cm3) and femur neck (g/cm3) did not show survey has been conducted to evaluate health and nutritional status of Korean population, correlation with the level of serum 25(OH)D (coefficient -0.0012, p-value 0.118) Overall using a stratified, multi-stage sampling with a probability proportional to size. BMD was MS prevalence in our study population was shown to be 16.6% (n=55) and serum 25(OH) measured during 2008-2011 in KNHANES and categorized into 3 groups according to D level of non-MS population was higher than MS population with statistical significance the World Health Organization’s criteria. MetS was diagnosed according to the criteria (p=0.017). There was a tendency of study population with sufficient serum 25(OH)D from a joint scientific statement endorsed by major organizations including National level to have less MS than inadequate and deficient groups (p=0.073). There was a Heart, Lung, and Blood Institute. Postmenopausal women without a history of hormone seasonal variation of serum 25(OH)D level in this study population. The serum 25(OH) therapy or osteoporosis medication were included and women with uncertain menopausal D level was higher in summer season (from May to October, 20.6±9.0) than in winter status were excluded from analysis. Finally, a total of 3,394 postmenopausal women were season (from November to April, 17.7±12.0) with statistical significance (p<0.001). included to determine the association between BMD and MetS. Results: Overall 1,573 Conclusion: About 60% of postmenopausal women of Pusan and Gyeongnam province postmenopausal women (46.3%) had MetS and mean age of women with MetS were of Korea had suboptimal serum 25(OH)D level. This study did not show significant significant higher compared to non-MetS women (65.4 years vs 62.7 years, P<0.001). correlation between BMD and vitamin D status. Postmenopausal women without MS Complex sample analysis showed revealed that MetS was not associated BMD at the had higher serum 25(OH)D level than that of women with MS. In this study there was lumbar spine and proximal femur with adjustment for potential confounders (age, years seasonal variation of serum 25(OH)D level which should be discussed in the later study. since menopause, body mass index and physical activity). Also the presence of MetS did Further study will be necessary to establish preventative strategy for postmenopausal not have an effect on the probability of having low BMD. Analysis between BMD and women in Korean population for optimization of serum 25(OH)D level. five components of MetS demonstrated significantly higher BMD at femur neck (FN) Sources of Funding: None in women with waist circumference ≥ 80cm, which is cut-off value for Asian women Clinical Characteristics (0.622 g/cm2 vs 0.612 g/cm2) Conclusion: In conclusion, MetS is not associated with BMD in Korean postmenopausal women, but high waist circumference has a positive relationship with FN BMD. Sources of Funding: The present study was supported by grant no 04-2015-0920 from the SNUH Research Fund.

† Values are in mean ± standard deviation *Represents statistical significance (p-value < 0.05) P-11. thickness of the periodontal ligament as well as the intensity of birefringence of collagen Associated Factors to Bone Mineral Density Among Midlife Women: fibers were higher in PE (p ≤ 0.05) when compared to Sham and MELA Groups, whereas A Population-Based Study similar results were found among the MET and MELA + MET Groups. Osteocalcin Taise Dobner2, Karen Oppermann1,2. 1Medical School of Passo Fundo University, Passo immunostaining showed higher positivity in both the osteoblasts of alveolar process and Fundo, Brazil; 2São Vicente de Paulo Hospital, Passo Fundo, Brazil cells of the periodontal ligament of EP, MET and MELA+MET Groups, as compared Objective: Introduction: Osteoporosis has become a health problem especially for to the Sham and MELA Groups, whereas Hyaluronic Ac immunostaining appeared midlife women, due to the estrogen decline and greater longevity. Several factors similar among the groups. Conclusion: Isolated Melatonin effect appeared to be more contribute to reduction in bone mineral density (BMD). Objective: Evaluate the BMD efficient in the maintenance of bone area and periodontal ligament thickness of rats in in a midlife women sample Design: This study is part of a longitudinal population-based the permanent estrous phase. study of menopausal status, conducted in Passo Fundo, in Southern Brazil. A first cross- Sources of Funding: CAPES sectional study was performed in1995 and a second wave was assessed in 2001. A third follow-up was initiated in 2010. A total of 301 women were enrolled. Seventeen women P-13. were excluded due to previous hysterectomy and could not be classified according to Poor Nutrition and Weight Loss in Young Adulthood has Persistent menopausal status, resulting in a sample of 284 women (pre-, peri- and postmenopause). Through standard questionnaire demographic characteristics, current use of hormone Effects on Postmenopausal Bone Health Beverly Tchang, MD, Michelle Warren, MD. Endocrinology, NewYork Presbyterian therapy (HT) for menopausal complaints, smoking status (no, past or current use) and Columbia University Medical Center, New York, NY alcohol intake (g/day) were collected. Anthropometric measurements were performed Objective: The finding of a severely low bone mineral density (BMD) score in in duplicate and included body weight, height. Assessment of habitual physical activity the perimenopausal period raises suspicion for inadequate bone accretion in the (PA) was performed with a digital pedometer (BP 148, TechLine, São Paulo, Brazil), premenopausal years. We present two patients with history of amenorrhea and eating during 7 days. Subjects were encouraged not to alter their PA habits during the study. The disorders with severe osteoporosis and fractures in early menopause. Design: Case sum of the steps/day was averaged over the total time period. Participants were classified report. Results: Case 1: A 55-year-old Caucasian woman with anorexia nervosa (AN) as physically inactive (<6000 steps/day) or active (≥6000 steps/day). Serum 25(OH) presented to clinic for osteoporosis. She reported AN and over-exercising since age 10. D (sensitivity=1.6ng/mL) was measured with radioimmunoassay (DiaSorin, Stillwater, She ascribed to a vegan/vegetarian diet since late teens, with occasional bone broth. USA). BMD was assessed in the lumbar spine (LS), femoral neck (FN) and total femur She had long periods of amenorrhea until menopause at age 44. Patient had her first (TF) by dual-energy X-ray absorptiometry and expressed in g/cm2. Analysis of variance fracture at age 48 when she fell down two flights of stairs, resulting in multiple thoracic and the Χ2 test were used to analyze the characteristics of the sample associated with compression fractures. A bone density scan showed a BMD T-score of -5.8 at the spine. the menopausal status. A multiple linear regression model was set up with BMD as She continued to sustain multiple fractures from age 49-51: metatarsal fractures without a dependent variable to test the independent association of each clinical relevant preceding trauma, rib fractures from a fall while walking, and a pelvic fracture from a fall variable on the bone mass. Results: The mean age was 57.4±5.4 years. The majority of on black ice. Patient saw an osteoporosis specialist a few months after her pelvic fracture participants were Caucasian (82.7%) and postmenopausal women (83.4%), with median and had reported calcium intake of three servings a day but avoiding dairy. Her exam time of menopause of 70 months. HT was used by 15.8% of peri- and postmenopausal at that time was notable for a weight of 43.5 kg and a BMI of 15.9 kg/m2. Laboratory women. Current smoking was found in 19.3%. Regarding PA, the median of steps was work-up revealed a 25-hydroxyvitamin D level of 6 ng/ml, and she was started on 4619 (2787 – 6868), 31.6 % of women were active, and there was no difference in PA vitamin D 3000IU daily for possible osteomalacia, followed by anabolic therapy with among the menopausal status. The average of 25(OH)D and BMI were 21.7±6.5ng/dL, teriparatide, which she self-discontinued after only 2 weeks due to back pain. A repeat and 27.4±8.4Kg/cm2, respectively, and there was no difference on these values among bone density scan 12 months later showed unchanged spine T-score of -5.7. She was the menopausal status groups. The mean of BMD was: TF 0.96±0.14g/cm2; FN lost to follow up until she presented again two years later with a spine T-score of -6.1. 0.92±0.13g/cm2 and LS 1.09±0.17g/cm2, and postmenopausal women had lower BMD Because she was averse to anabolic therapy, hormone replacement therapy was offered in the 3 sites compared to pre-menopausal women (TF: p=0.009; FN and LS: p<0.001). in addition to dietary counseling. Case 2: A 58-year-old Caucasian woman presented to Table 1 describes a multiple linear regression analysis in which the age effect surpasses clinic for osteoporosis. She had had menarche at age 11, followed by a year of irregular menopausal status on BMD. Conclusion: In this sample of midlife women, age and menses, then developed amenorrhea after significant weight loss. Irregular menses smoking had a negative association with BMD; BMI and 25(OH)D showed a positive resumed when she regained weight to a peak of 68.9 kg around age 17. She has had effect on BMD. There was a tendency to a positive effect of HT on lumbar spine. 2 children without incident. Menopause occurred around age 47. Four years later, she Sources of Funding: None started to lose weight again, to a low of 40.8 kg and BMI 15.5 kg/m2. Her first fracture Table 1. Multiple linear regression analysis with BMD (g/cm2) as dependent variable occurred at age 53 when she fell on the street and fractured the head of the humerus. The following year, she fractured her left shoulder, right wrist, and pelvis in the setting of three separate bike accidents. Patient denied excessive exercise and reported a vegetarian/ vegan diet. On exam, she weighed 45.0 kg with a BMI of 17.0 kg/m2. Labs were notable for hyponatremia, anemia, low FSH of 0.3 mIU/ml [ref: 25.8-134.8 mIU/ml], elevated beta-carotene at 173 mcg/d [ref: 3-91 mcg/dl], and mildly elevated 24-hour free cortisol of 61 mcg/d [ref: <50 mcg/d]. A bone density scan showed a spine T-score of -4.6, She was placed on hormone replacement (estradiol 0.5mg/northindrone acetate 0.1mg). The patient was also seen by a metabolic bone specialist who started her on teriparatide. BMD improved by 20% at the spine and 8% at the hip after only 9 months. * Model adjusted for PA and Alcohol intake, R2: Lumbar Spine BMD: 0.286; R2 Anabolic therapy was followed by denosumab. Her most recent bone density, after femoral neck: 0.374; R2 Total femur: 0.361 10 months of denosumab and 1.8 kg of weight gain, showed improvement to -3.7 at the spine. Conclusion: Early epidemiologic studies observed the severity of low bone P-12. mineral density in young women with anorexia nervosa, and furthermore, found that the BMD does not fully normalize even years after treatment of the eating disorder. Melatonin and metformin effects in bone tissue of rats in the permanent The pathophysiology behind AN’s detrimental effects is multifactorial, often involving estrous phase concurrent hypogonadism, hypercortisolism, growth hormone resistance, and adipocyte 1 2 Gisela R. Sasso, postdoctoral fellow , Rinaldo Florencio-Silva, Post Doctoral , dysfunction in addition to malnutrition. Weight regain and resumption of menses are 2 2 1 Cristiane d. Teixeira , Adriana F. Carbonel, Post Doctoral , Luiz F. Fuchs, Post Doctoral , independent predictors of BMD improvement. Presentation of severe osteoporosis in 3 2 1 Ricardo d. Simões , Manuel d. Simões . Ginecology, Federal University of São Paulo, the postmenopausal woman with a history of abnormal menses should prompt further 2 São Paulo, Brazil; Morfologia e Genética, Universidade Federal de São Paulo, SP, investigation into diet and weight history. 3 Brazil; Ginecology, Universidade de São Paulo, SP, Brazil Sources of Funding: None Objective: To evaluate and compare the effects of melatonin and metformin in the alveolar process and periodontal ligament of rats in the permanent estrous. Design: 35 adults, albinos and virgins female rats, at the age of 3 months of were kept P-14. in cages with water and food ad libitum. Seven of these animals were maintained on Effects of long-term postoperative use of dienogest on bone mineral 12 hours light/dark cycle and was considered the Sham Group (Sham). The others 28 density in patients with endometriosis animals were kept in continuous light for four weeks, to induce a state of permanent Sang Ho Yoon, M.D., Ph.d.1, Kyu Ri Hwang, M.d., Ph.D.2. 1Obstetrics and Gynecology, estrous, which was confirmed after daily collection of vaginal swabs for 21 consecutive Dongguk University Ilsan Hospital, Goyang, Korea (the Republic of); 2Obstetrics days. The animals were then equally divided into the following groups: Control Group and Gynecology, Seoul National University Boramae Medical Center, Seoul, Korea (PE); Group treated with Melatonin (0.4 mg / ml) diluted in drinking water (MELA); (the Republic of) Group treated with Metformin (50 mg / kg) by gavage (MET) and Group treated with Objective: The current treatment strategy for endometriosis includes the long-term Melatonin and Metformin associated (MELA+MET). After 60 days of treatment, the post-operative use of medications after surgery to prevent the recurrence of symptoms animals were anesthetized and euthanized by transcardiac perfusion and fragments and lesions. Several studies have demonstrated the efficacy, safety and tolerability containing the maxillary alveolar process and periodontal ligament of the first molar of dienogest (DNG) for the treatment of endometriosis. As DNG inhibits ovulation, were removed, fixed, decalcified in EDTA and processed for paraffin embedding. Some there could be concern about its negative effect on bone health, especially with long- sections were stained with hematoxylin and eosin for histomorphometric analysis and term use. This study was performed to evaluate the effects of long-term postoperative others for picrosirius Red method and immunohistochemistry method for detection of use of DNG on bone mineral density (BMD) in patients with endometriosis. osteocalcin and Hyaluronic Acid. Results: The bone area of the alveolar process, the Design: The clinical data of 53 reproductive-aged women who had been treated with DNG (2mg/day) for 12 months or more after surgery for endometrioma were analyzed. CARDIOVASCULAR/OBESITY/METABOLIC HEALTH The primary study outcome was change in lumbar spine and femur neck BMD by dual POSTER PRESENTATIONS energy X-ray absorptiometry (DXA) measured before and after DNG treatment. Results: Mean age was 36.9 years, and mean body mass index (BMI) was 22.2 kg/m2. The mean duration of DNG treatment was 12.8 months (range: 11~24months). Baseline BMD P-16. at the lumbar spine and femur neck was 0.990 ± 0.116 g/cm2 (Z-score; 0.01 ± 0.92) Effects of Single-Capsule 17β-Estradiol/Progesterone (TX-001HR) on and 0.763 ± 0.097 g/cm2 (Z-score; 0.03 ± 0.87), respectively, which were all within the Weight and Blood Pressure in Menopausal Women of the REPLENISH expected range. After 12 months of DNG treatment, BMD was significantly decreased Trial at the lumbar spine and femur neck, compared to baseline (lumbar spine, - 3.56%; femur David Archer, MD1, James Pickar, MD2, Shelli Graham, PhD3, Ginger Constantine4, neck, -2.13%), respectively. Significant correlations of clinical characteristics with Sebastian Mirkin, MD3. 1Clinical Research Center, Eastern Virginia Medical School, BMD decrease after treatment were not observed. In addition, no patient experienced Norfolk, VA; 2Columbia University Medical Center, New York, NY; 3TherapeuticsMD, endometrioma recurrence during DNG treatment. Conclusion: This study suggests Boca Raton, FL; 4EndoRheum Consultants, LLC, Malvern, PA that there could be a possible bone loss after long-term DNG treatment after surgery of Objective: Body weight and adipose distribution are known to change during the endometrioma, therefore, it needs to be checked BMD in reproductive-aged women who menopausal transition. In the REPLENISH trial, an investigational combination of take DNG over the long term. 17β-estradiol and progesterone (E2/P4) in a single, oral softgel capsule was shown Sources of Funding: None to significantly reduce the frequency and severity of vasomotor symptoms (VMS) in menopausal women with a uterus (Lobo RA et al, Obstet Gynecol, in press). The objective of this report of data from the REPLENISH trial is to examine the effects of BREAST HEALTH POSTER PRESENTATION E2/P4 on weight and blood pressure (BP). Design: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated P-15. TX-001HR for relief of moderate-to-severe VMS in menopausal women. Women (aged 2 Model Calculated Breast Cancer Risk Assessment of Women Attending 40−65 years, body mass index [BMI] ≤34 kg/m , BP ≤140/90 mm Hg) with moderate- Community Breast Cancer Education Events to-severe hot flushes (≥7/day or ≥50/week) and a uterus were randomized approximately 11:1 to daily E2/P4 of 1 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, 0.25 mg/50 mg, or Lisa C. Larkin MD, MD1, Alexandra Magnante, BS2. 1Lisa Larkin MD and Associates, placebo for the overall safety population (all patients who were randomized and took ≥1 Cincinnati, OH; 2Human Genetics, Cincinnati Children’s Hospital, Cincinnati, OH capsule of E2/P4). Safety endpoints assessed throughout the study included body weight Objective: Most women are aware that one in eight women will develop breast cancer and sitting BP. Measurements and changes from baseline to month 12 were summarized in her lifetime, and of guidelines recommending annual mammography; however, most with descriptive statistics. Potentially clinically important changes were defined as women are unaware of their individual risk of breast cancer, the estimate that 30% of increases or decreases from baseline as follows: weight (≥15% and ≥25 lb [11.3 kg]), breast cancer is related to lifestyle, or prevention strategies. The objective of our study systolic BP (≥20 mm Hg, with absolute value ≥160 or ≤90 mm Hg), and diastolic BP was to inform women in Cincinnati, OH about their individual breast cancer risk using (≥15 mm Hg, with absolute value ≥90 or ≤60 mm Hg). Results: The safety population validated risk assessment tools, educate them about lifestyle strategies for risk reduction, included 1835 women who took E2/P4 of 1 mg/100 mg (n=415), 0.5 mg/100 mg (n=424), and identify women who might benefit from genetic counseling, enhanced screening, 0.5 mg/50 mg (n=421), 0.25 mg/50 mg (n=424), or placebo (n=151). Patients had a mean or chemoprevention. Providing women with a model-calculated risk assessment and age of 55 years, mean BMI of 27 kg/m2, and mean weight of 72 kg; 65% were white education may empower women to pursue strategies for breast cancer risk reduction, and 32% were black. There were no clinically meaningful differences or trends in the and individualized breast cancer care. Design: Five breast cancer risk assessment events, mean changes from baseline to month 12 in body weight or in systolic or diastolic BP advertised through web and social media, were held in Cincinnati, OH between August (Table). Weight gain was reported as a treatment-related, treatment-emergent adverse 2017 and January 2018. Attendees completed a questionnaire to calculate lifetime breast event in a small number of women (E2/P4 of 1 mg/100 mg [n=7, 1.7%], 0.5 mg/100 mg cancer risk using the Tyrer-Cusick (V8) and Gail models. Women with a history of breast [n=6, 1.4%], 0.5 mg/50 mg [n=7, 1.7%], 0.25 mg/50 mg [n=11, 2.6%], and placebo cancer were excluded; those under age 35 were excluded from Gail Model calculation, [n=2, 1.3%]). Twenty-six women had weight changes deemed potentially clinically and women without breast density information were excluded from Tyrer-Cusick (V8) important, 13 had weight increases and 13 had weight decreases (Table). Incidence calculation. Risk assessment results and personalized recommendations were provided of hypertension considered related to treatment was low (E2/P4: 0.2-1.2%; placebo: to each woman at each event in advance of a 50-minute educational lecture about 0%). Discontinuation rates due to weight gain (E2/P4: 0.2-0.9%; placebo: 0.7%) or breast cancer risk factors, risk assessment models, prevention strategies, and screening. hypertension (E2/P4: 0-0.5%; placebo: 0.7%) were also low. Conclusion: The phase 3 Genetic counseling referral was suggested based on NCCN guidelines; consideration of REPLENISH trial showed a significant effect of TX-001HR on moderate-to-severe VMS chemoprevention was recommended to women with a Gail Model 5-year risk greater in menopausal women with a uterus with no clinically significant differences in adverse than 3%; lifestyle modification was recommended to women at a lifetime risk >15% and events compared with placebo (Lobo RA et al, Obstet Gynecol, in press). Additionally, enhanced screening was recommended to women at a lifetime risk greater than 20%, vital sign data from this trial presented here demonstrated that up to 12 months of calculated by Tyrer-Cusick (V8). Results: A total of 91 women registered for the events TX-001HR use had minimal changes and no clinically important effects on body weight and completed the questionnaire. Attendees’ ages ranged from 23 to 80, with a mean age or BP in menopausal women. These encouraging data suggest that TX-001HR may of 51. One woman was excluded because of a personal history of breast cancer. Eighty- become a new oral E2/P4 option for treating moderate-to-severe VMS in menopausal one women had Gail Model risk calculated; nine women under age 35 were excluded. women with a uterus. Fifity-six women (62.2%) provided breast density information and had Tyrer-Cusick Sources of Funding: TherapeuticsMD (V8) risk calculated. Of the 90 participants, 24 (26.7%) met NCCN guidelines for genetic Table. Changes from Baseline to Month 12 in Body Weight and Blood Pressure consultation. Of the 81 participants who had Gail Model risk assessment performed, with TX-001HR five (6.2%) met criteria for chemoprevention. Of the 56 women who had Tyrer-Cusick (V8) model risk assessment performed; 24 (42.9%) of women were identified to have a risk >15% and met criteria for recommendation for lifestyle intervention to lower risk; 15 (26.8%) were identified to have a lifetime risk >20% and recommended to consider enhanced screening. Thirty two (57.1%) women had calculated risk higher than, nine (16.1%) had calculated risk equal to, and 15 (26.8%) had calculated risk lower than the age-matched population risk. Perceived risk was compared to population risk estimates; nine women did not provide a perceived lifetime risk estimate. Of the remaining 47 women, 20 (42.6%) underestimated, 17 (37.8%) accurately estimated and 10 (22.2%) overestimated their risk compared to average age matched population lifetime risk. Conclusion: Women are uninformed about their individual risk of breast cancer and breast cancer prevention strategies. Individual breast cancer risk assessment is infrequently performed in clinical care settings and when done as part of community breast cancer education events is a novel approach to inform women. Of the women who participated in the events, 43% were identified to be at elevated lifetime risk >15% and lifestyle intervention was recommended. Additionally, 27% met criteria for genetic consultation, 6% met criteria for chemoprevention, and 27% met criteria for consideration of enhanced screening. Community based breast cancer education and risk assessment PCI: potentially clinically important (changes at month 12) provides an opportunity to identify women at elevated risk and educate them. Individual risk assessment, identification of women at high risk, and education, performed as part of community-based breast cancer education events may facilitate lifestyle changes and other interventions that may result in breast cancer prevention and earlier detection. Sources of Funding: None P-17. as VEGF. The levels of reactive oxygen species, total antioxidant capacity and lipid Effects of bazedoxifene on physical activity and body composition in peroxidation were analyzed as biomarker of oxidative stress. Results: Treatment with ovariectomized female mice estrogen showed a largest increase in the layers of vagina epitelium than with isoflavones. Christine Cabelka, MPT WCS CLT, Angus Lindsay, Cory W. Baumann, Dawn A. Lowe. These hypertrofic effects agree with expression elevation of Ki67 and VEGF, which University of Minnesota, Minneapolis, MN did not occur with the caspase 3, indicating that isoflavones have great proliferative Objective: Menopause is associated with decreased levels of physical activity. Estrogen effect in the vagina. Similar results were also observed on superoxide quantification, treatment after ovariectomy in mice has been shown to reverse and prevent this decline. PCR and Western blotting, which show that isoflavone has a protective effect against Selective estrogen receptor modulators (SERMs) are a class of drugs which work through oxidative stress in diabetic rats. Conclusion: Our results indicate positively the trophic the estrogen receptors with a tissue-selective effect. Bazedoxifene is the newest generation therapeutic potential of isoflavones, which mean a protective effect and can contribute to SERM to be FDA approved in conjunction with conjugated estrogen for prevention of the development of effective therapies to decrease the symptoms of menopause. postmenopausal osteoporosis and treatment of moderate to severe hot flashes. The tissue Sources of Funding: This study was funded by Fundacão de Amparo à Pesquisa do specific effects of bazedoxifene have yet to be fully elucidated. The purpose of this study Estado de São Paulo (FAPESP) Number: 2014/17077-9 is to determine the effects of bazedoxifene on levels of physical cage activities and body composition after ovariectomy in mice. Design: Forty C57BL6J mice were randomized P-20. into 4 groups: sham+placebo, OVX+placebo, OVX+E2, OVX+BZA. Echo MRI for body Association of Adiponectin and Vitamin D Level in the Obese Pre- and composition was performed prior to and 7 wk after ovariectomy (OVX) surgery. 24-h cage activity measures were collected 8 wk after surgery. Results: Mice treated with Postmenopausal Women Supon Yawichai, M.D.1, Unnop Jaisamrarn, M.D., M.Sc.1, Ammarin Suwan, M.D.2,1, OVX+placebo and OVX+BZA gained more weight than sham+placebo and OVX+E2 Sukanya Chaikittisilpa, M.D., M.Sc.1. 1Department of Obstetrics and Gynecology, treated mice over the 8-wk trial. In addition, fat mass increased by 8% in OVX+placebo Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 2Department of and OVX+BZA treated mice as compared to OVX+E2 treated mice (p<0.001). Total time Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand spent being active was no different among groups (p=0.075). Conclusion: Despite no Objective: To study the association between level of serum adiponectin and level differences in levels of cage activities, bazedoxifene did not protect against ovx-induced of serum vitamin D in the obese premenopausal and postmenopausal women fat mass or body weight gain. Design: Cross-sectional annalytic study Results: This cross-sectional study was Sources of Funding: NIH Grant R01 AG031743 conducted at the King Chulalongkorn Memorial Hospital (KCMH) in cooperate with Chula Clinical Research Centre (Chula-CRC) from December 2016 to July 2017. P-18. It had been approved by Chulalongkorn Institutional Review Board (IRB). One hundred Effects of soybean isoflavones in rats model with metabolic syndrome and nineteen obese Thai women, aged 45 to 55 years old, were recruited in this cross- Adriana F. Carbonel, Post Doctoral1,2, Ricardo S. Simões, Post doctoral fellow2,1, sectional study. There were 60 premenopausal women and 59 postmenopausal women Gisela R. Sasso, postdoctoral fellow1,2, Edmund C. Baracat, Professor2,1, Jose M. Soares with body mass index (BMI) > 25 kg/m2. We measured weight, height, hip and waist Junior, Professor2,1, Manuel d. Simões1,2. 1Morphology and Genetics, Universidade circumference. The percentage of body fat and visceral fat were measured by bioelectrical Federal de São Paulo, São Paulo, Brazil; 2Obstetrics and Gynecology, University of São impedance analysis (BIA) technology with Tanita SC-330. (Table 1) Serum adiponectin Paulo, São Paulo, Brazil and serum 25-hydroxy vitamin D (25OHD) were analyzed by ELISA method and Objective: We have two dependent hypotheses. The first is related to the metabolic chemiluminescent method, respectively. Descriptive and correlation statistics by Pearson syndrome could address the pathophysiology of the postmenopause. To understand if and Spearman’s rho were performed. Serum adiponectin in postmenopausal group in metabolic syndrome the activation of PPAR is affected leading to the deregulation of (7.7 ± 3.7 μg/ml) was significantly higher than premenopausal group (5.6 ± 3.8 μg/ml) lipid metabolism and if isoflavone can restore lipid homeostasis through the re-activation (p = 0.003). Serum vitamin D in postmenopausal group (15.2 ± 6.4 ng/ml) was of PPARγ in the liver. Design: We used 30 female rats that after birth from 1 to 5 days significantly lower than premenopausal group (20.2 ± 4.7 ng/ml) (p <.0001). There was were administered subcutaneously 0.1mg / kg of testosterone propionate. After induction no correlation between serum adiponectin and vitamin D in both groups (r = -0.049, the rats were divided into three groups and endometrium removes (ovariectomized): GI: p = 0.71 and -0.167, p = 0.21 in pre- and post-menopause, respectively). Figure 1 sham group, GII: rats treated with propylene glycol vehicle and GIII: rats treated with Conclusion: Serum adiponectin showed no correlation with serum vitamin D in the soy isoflavones 150 mg / kg; rats were monitored daily for two consecutive months. At obese premenopausal and postmenopausal women the end of the experiment, the rats were anesthetized and euthanized using a deepening Sources of Funding: Ratchadaphiseksomphot Endowment Fund, Faculty of Medicine, of the anesthetic plane. The endometrium and liver were collected and processed for Chulalongkorn University analysis of morphology and molecular biology. The ANOVA test was used, followed by Table 1. Participants baseline characteristics the Bonferroni test. Results: Showed that control rats increased body weight (p <0.01) compared to isoflavones (P <0.01). Interestingly, no differences were found in relation to food intake in any of the groups, which demonstrated that the reduction in body weight of the GIII group is due to the effects of FSI and not due to food consumption. Along with an increased body weight of the control rats there was a significantly decrease insulin sensitivity (p <0.001) compared to ISF-treated, which were able to increase insulin sensitivity significantly (P <0.01) A morphological analysis of the endometrium showed ISF did not proliferate endometrial epithelium (p <0.01). The analysis of lipids in the liver through the fat droplet quantification technique, showed that in the control that testosterone propionate induced lipid accumulation in the liver; (P <0.01) and FSI can improve it (p <0.01). Conclusion: Preliminary results indicate that isoflavones interact in the metabolic syndrome induced by testosterone propionate and these observations are important because it leads us to understand (biochemical analysis) and whether in the liver PPARy is inactivated in the metabolic rats and if ISFs can reactivate PPARYs. Sources of Funding: This study was funded by Fundacão de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Number: 2014/17077-9

P-19. Soybean isoflavones decreases oxidative stress in the vagina of type 1 diabetic rats Adriana F. Carbonel, Post Doctoral1,2, Ricardo S. Simões, Post doctoral fellow2,1, Jose M. Figure 1 Correlation of Adiponectin and Vitamin D in Pre- and Postmenopause Soares Junior, Professor2,1, Edmund C. Baracat, Professor2,1, Manuel d. Simões2,1. Group 1Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil; 2 Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil P-21. Objective: To assess the effects of isoflavones and 17ß-estradiol related to oxidative stress and apoptosis on the vaginal epithelium of a diabetic rat model. Design: Sixty Association of carotid artery intima-media thickness increase in patients adult, virgin, female rats underwent ovariectomy were randomization into six groups with osteoporosis diagnosis of ten animals each: GI = Sham control ovariectomized animals; GII = Sham control EUNICE ZAVALA CHAPARRO, DOCTOR, ANA CAROLINA SALAZAR ROMO, diabetic ovariectomized animals; GIII = control ovariectomized that received propylene RESIDENTE, Imelda Hernández Marín, Head of the Human Reproduction Biology glycol vehicle; GIV = control diabetic ovariectomized animals receiving propylene glycol service. HUMAN REPRODUCTION BIOLOGY, HOSPITAL JUAREZ DE MEXICO, vehicle; GV = diabetic ovariectomized animals treated with soy isoflavones (150mg/kg by Mexico City, Mexico gavage); GVI = diabetic ovariectomized rats treated with estrogen (17ß-estradiol, 10mg/kg, Objective: To identify the association of carotid artery intima-media thickness increase subcutaneously). Treatment took place over 30 consecutive days. After euthanasia, a in patients with osteoporosis. Secondary objective: to gain knowledge of the frequency portion of the vagina was immersed in liquid nitrogen for RT-qPCR and western blotting of atheroma plate and its calcification in patients with osteoporosis. Design: Cross- (Bax and BCL-2), and another portion was processed for paraffin embedding. Sections sectional, observational, and descriptive study. Patients diagnosed with osteoporosis were stained with hematoxylin and eosin for histomorphometry and evaluated for were evaluated through carotid artery ecography to measure the intima-media thickness. apoptosis by immunohistochemistry (cleaved caspase-3 and BCL-2), and Ki67 as well The examination was made to patients diagnosed with osteoporosis (n=40) in the Climacteric and Osteoporosis clinics of the Human Reproduction Biology service of the International Conference on Harmonisation Harmonised Tripartite Guideline and the Hospital Juárez de México from May 2017 to May 2018. The selected patients were with the Guidelines for Good Clinical Practice and applicable regulatory requirements. compared with a control group of the same age without an osteoporosis diagnosis (n=40). The protocol was approved by the Research Ethics Committee of the FCMSCSP and Results: After measuring the bone mineral density (T-score) and performing a carotid of the HMLMB (CAAE Permit 40594814.4.0000.5479) and under the Clinical trials ultrasound, both variables were correlated with a Spearman and Mann-Whitney test. The ID NCT02430987. Results: Almost all scores in FSFI, desire, arousal, lubrication, findings indicate that there is a negative correlation (reverse) between the LS (lumbar orgasm, satisfaction, excluding pain score, were statistically lower in women with segment) T-score and the average carotid intima-media thickness that is statistically altered triglycerides (p <0.05). The presence of FSD was statistically higher in women significant (Spearman test -0.31, p<0.005). Chart 1. Also a negative correlation (reverse) with increased triglycerides (p <0.05) compared to women with normal triglycerides, was found between the LH (left hip) T- score and the average carotid intima- thickness regardless of the diagnostic criteria used. There was no significant association in the that is statistically significant (Spearman test -0.31, p <0.005). Chart 2. The patients with scores of the desire, excitation, lubrication, orgasm, satisfaction and pain domains, nor in osteoporosis had a significantly greater thickness of the intima-media (mean 0.71 vs. the FSFI total scores in relation to CA and HDL parameters (p> 0.05). The orgasm score 0.67 Mann-Whitney p<0.05). The patients with osteoporosis had atheromatous plaque was statistically lower in women with altered glycemia (p = 0.037) than in those with more frequently than the control patients (15 vs. 7.9%). In the calcification analysis, normal glycemia. The scores desire, excitation, lubrication and total FSFI scores were the patients with osteoporosis had frequency of 12%, while none of the control patients statistically lower in women with SAH (p <0.05). The presence of FSD was statistically presented it. Conclusion: The patients with osteoporosis presented greater thickness higher in women with SAH (p = 0.018, p = 0.035 respectively) in both FSFI cut-offsmin of the carotid intima-media when compared with patients without osteoporosis. They relation to women without this diagnosis. All scores of the FSFI domains of desire, also presented atheroma plaque and its calcification more frequently, when compared excitement, lubrication, orgasm, satisfaction, total score, diagnosis of FSD by both cut- with patients without osteoporosis. This finding may imply the direct association of offs were statistically lower in postmenopausal women with MetS (N = 153) (p < 0.05) osteoporosis in cardiovascular disease. when compared to women without this diagnosis (N = 138), except for the pain score Sources of Funding: NONE (p = 0.913). The presence of FSD was statistically higher in women with MetS, regardless of the diagnostic criteria used (p <0.05). Conclusion: We conclude that the diagnostic component of MetS that causes more sexual dysfunction is triglycerides. SAH is also an important factor. Regardless of the isolated comparison of the diagnostic components of MetS, the isolated presence of MetS was notable causing injury in the female sexual response in postmenopausal women. Sources of Funding: None

P-23. Metabolomic changes with randomized hormone therapy and associations with coronary heart disease in the Women’s Health Initiative Kathryn Rexrode, MD, MPH1, Olga Demler, PhD1, Nina Paynter, PhD1, Simin Liu, MC, ScD2, JoAnn E. Manson1, clary clish, PhD3, Raji Balasubramanian, ScD4. 1Medicine, Brigham and Women’s Hospital, Boston, MA; 2Epidemiology, Brown University, Providence, RI; 3Broad Institute, Cambridge, MA; 4Epidemiology, University of Massachusetts, Amherst, Amherst, MA Objective: In the WHI hormone therapy (HT) trials, treatment with oral conjugated equine estrogen and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), while conjugated equine estrogen alone (CEE) did not. In addition, HT has been hypothesized to have different effects on those with underlying cardiovascular disease or high-risk individuals, than those with healthier vasculature. To better understand these findings, we sought to compare the effects of HT on metabolomic profiles in the two randomized HT treatment arms in the WHI, and to further compare differences by CHD case control status. Design: Plasma metabolites were available on 2306 women as part of prior nested case/control study of CHD with a mean of 3.7 years from randomization to CHD incidence. A total of 934 women in the HT trials had metabolomic measures at both baseline and 1 year, had no cardiovascular disease prior to measurement, and were adherent to their randomized treatment in the 24 hours prior to the year 1 blood sample. A total of 675 metabolites were measured by liquid chromatography/ mass spectroscopy. Differences in metabolite abundance between treatment groups were evaluated in linear regression models, with metabolite levels at year 1 as outcome, while adjusting for baseline metabolite levels and CHD case control status. Statistical significance was based on likelihood ratio tests and the Benjamini Hochberg method was used to control the false discovery rate (FDR) at 0.05. The change P-22. in each metabolite due to treatment was quantified as the ratio of the median change in Evaluation of the main diagnostic component of metabolic syndrome that metabolite levels (i.e. baseline to Year 1) observed in the treatment arm compared to its causes more damage to the female sexual response: final findings placebo arm. An interaction term between HT and case/control status was used to evaluate SONIA MARIA ROLIM ROSA LIMA, PhD1, Gustavo M. Dutra da Silva, PhD differences in metabolites by baseline risk. Results: Of the 934 women with meeting our student1,2, BENEDITO F. DOS REIS, PhD1, SOSTENES POSTIGO, MD1, Carolina F. inclusion criteria, the distribution by WHI arm included 263 in CEE active, 240 CEE Macruz1. 1Obstetrics and Gynaecology, Santa Casa of Sao Paulo Medical School, São placebo, 196 CEE+MPA active, and 235 in CEE+MPA placebo; approximately half in Paulo, Brazil; 2São Francisco University, Bragança Paulista, Brazil each group became subsequent CHD cases The mean age was 66.7 years. HT resulted Objective: To evaluate the diagnostic component of Metabolic Syndrome with greater in substantial changes in metabolomics profiles at year 1, compared to placebo. After 1 impact in sexual response in postmenopausal women. Design: A cross-sectional, year, 413 metabolites significantly differed with CEE+MPA, and 486 differed for CEE, prospective, case-controlled study was carried out by interviewing 1,100 postmenopausal in comparison to placebo, while 89 demonstrated significantly differences in metabolite women at the Climacteric of the FCMSCSP and of the HMLMB. Women are regularly change CEE active and CEE+MPA active. Changes in metabolites from baseline to seen in these institutions to perform routine climacteric exams. After performing year 1 significantly differed for 27 metabolites (interaction term FDR P<0.05). When care and evaluation of inclusion and exclusion criteria, 291 women were invited to examined by case/control status, 20 of these metabolites had more than a 10% difference participate in the study. All participants signed the Free and Informed Consent Form. in the effect of CEE+MPA comparing cases to controls, including 17 lipid metabolites. The women considered as being postmenopausal were those with amenorrhea ≥ 1 year One of these, C36:4 hydroxy phosphatidyl choline (PC), was shown in prior work to and FSH ≥30mUI/mL. Sexual function was assessed by completion of the Female Sexual be significantly associated with CHD among women who were not taking HT. While Function Index (FSFI). A score of 5 or less on the combination of items comprising the both active treatment arms showed increases in C36:4 hydroxyPC levels compared with desire domain of the FSFI questionnaire was used to define the diagnosis of HSDD in placebo, CEE+MPA resulted in a 91% increase while CEE alone demonstrated a 24% postmenopausal women. We consider that a score of 6 or more the woman does not increase. Moreover, increases were significantly larger in women who became cases present with HSDD. The types of diagnosis based on the DSM -IV- TR. The diagnosis of than controls. Conclusion: Randomized HT resulted in broad changes in metabolomics sexual dysfunctions was established by a sexology specialist experienced and trained in profiles in the WHI, with differences by treatment arm and by underlying cardiovascular diagnosing FSD using structured clinical interviews. The Beck Depression Inventory was risk status. used to exclude depression in patients with a history of the disease. The MetS diagnosis Sources of Funding: NHLBI contract: HHSN268201300008C, as well as was determined by following the guidelines defined by the Adult Treatment Panel (ATP contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, III) (8): (1) Abdominal circumference (AC) ≥88cm; (2) HDL-cholesterol ≤50mg/dL; HHSN268201600003C, and HHSN268201600004C (NIH, NHLBI, US Department of (3) triglycerides ≥150mg/dL; (4) arterial blood pressure (SAH) ≥130/85mmHg; and (5) Health and Human Services). fasting glucose ≥110mg/dL. The women considered as carrying MetS were those with at least three of the components described. The study was carried out in compliance with the protocol and principles established in the Declaration of Helsinki (1996 version), P-24. P-26. Breast vascular calcifications and their relationship with cardiovascular Relation of menopausal symptoms with autonomic cardiac modulation risk in post-menopausal women of the Human Reproduction Biology Patricia M. Martinelli1,2, Rodrigo D. Raimundo, PhD1,3, Alex R. Norberto1,3, Valdelias X. service of the Hospital Juárez de México Pereira, PhD1,3, Isabel C. Sorpreso, PhD2,3, Luiz C. de Abreu, PhD1,2. 1Faculdade 2 Imelda Hernández Marín, Head of the Human Reproduction Biology service, ANA de Medicina do ABC FMABC, Santo Andre, Brazil; União Educacional do Norte 3 CAROLINA SALAZAR ROMO, RESIDENT HUMAN REPRODUCTION BIOLOGY, UNINORTE, Rio Branco, Brazil; Faculdade de Medicina FMUSP, Universidade de EUNICE ZAVALA CHAPARRO, RESIDENT HUMAN REPRODUCTION Sao Paulo, Sao Paulo, Brazil BIOLOGY. Hospital Juárez de México, Mexico City, Mexico Objective: To evaluate the behavior of cardiac autonomic modulation according to the Objective: Establish the relationship between breast vascular calcifications and intensity of menopausal symptoms in climacteric women. Design: A cross-sectional cardiovascular disease risk (CVD), based on the American Heart Association (AHA) study was conducted at the Rio Branco Municipal Health Department, Acre, from scale, in post-menopausal women of the Human Reproduction Biology service of the October 2016 to July 2017. All study participants signed the informed consent form. Hospital Juárez de México. Design: A sample of 206 patients was used to calculate The research was approved by the Ethics and Research Committee (1,748,393/2016). the frequency of breast vascular calcifications, showing 16% with a confidence level The study population is comprised of women aged 40-65 years, with menopausal of 95%. Two hundred and six menopausal patients who went to the menopause clinic symptoms following the criteria of diagnosis of Crematorium. Exclusion criteria were: from September 1, 2017 to April 30, 2018 were chosen (post-menopausal stage +2 use of antidepressants, angiotensin-converting enzyme inhibitors, beta-blockers; feverish in accordance with STRAW +10). A bilateral mastography and the lipid profile state; cardiomyopathies, decompensated heart failure; use of hormone therapy; abnormal were requested for all the patients. We calculated the CVD using the AHA tool. The genital bleeding of unknown cause, hysterectomized patients and volunteers with any mammographic images were examined to identify the presence or absence of vascular type of alteration in the ECG tracing. The following parameters of the pilot study calcifications. The Mann Whitney U test and X2 were used for the statistical analysis. were considered: the RMSSD index of heart rate variability, mean of the first group of Results: A statistically significant relationship was identified between cardiovascular 42.93±39.33, mean of the second group of 25.56±14.6, confidence level of 95%; sampling risk and the presence of breast vascular calcifications (P<0.05, RR 5.97, OR 19.53, error of five percentage points, test power of 80%, for unilateral testing, resulting in a CI 95% 9.31-40.9, sensitivity 74%, specificity 87%, positive predictive value 73%, required sample of 37 people for each group. All subjects answered a questionnaire negative predictive value 87%). The variables of the AHA calculator that show a containing a sociodemographic, clinical questionnaire and an instrument to measure the statistically significant relationship with presence of vascular calcifications are: diabetes intensity of the menopause symptoms, Kupperman Index (KI), containing 11 questions, mellitus (P <0.05, RR 1.95, OR .339, CI 95% 0.175, 0.659), high blood pressure where the total score classified the symptoms as slight (up to 19) moderate between (P <0.05, RR 2.20, OR 1.42, CI 95% 0.793-2.73), and age (P<0.05). The variables of 20 and 35) and intense (above 35). In cardiac modulation, basal blood pressure (BP), the AHA calculator that did not show a statistically significant relationship with the basal heart rate (HR), and RR intervals of electrocardiogram, measured for 20 minutes presence of vascular calcifications were: total cholesterol (P >0.05, RR .5781, OR .447, in dorsal decubitus and spontaneous breathing, were measured with the Polar RSCX800 CI 95% 0.242-0.827), and high density cholesterol (P >0.05, RR 1.305, OR 1.47, CI 95% heart rate monitor. The capture was subjected to digital filtering in Polar Precision 0.793-2.73). Conclusion: The finding of breast vascular calcifications in the Performance SW software (version 4.01.029) and Kubios software. The 110 volunteers mammographic study is associated with higher cardiovascular risk. The cardiovascular were divided into two groups according to the intensity of menopausal symptoms: complications represent the first cause of death in the population. It is essential to group 1 (mild symptomatology) and group 2 (moderate / severe symptomatology). continue with the research and finding of tools that guide us towards the timely For the analysis of the data a descriptive statistic of average and standard deviation, identification of patients at high risk of suffering an acute coronary syndrome. The breast besides the simple and absolute frequency, was performed. Results: When we verified mastography is a routine test in women over 40 years of age as cancer screening. When the socioeconomic, demographic and clinical characteristics according to the intensity breast vascular calcifications are found simultaneously, it helps to identify the patients of the menopause symptoms it was observed that there was homogeneity among the with high cardiovascular risk. groups, regardless of the symptomatology presented in relation to age, menarche age, Sources of Funding: None menopause age, body mass index, circumference abdominal and systolic blood pressure. The variables were statistically different and increased in the group of moderate / intense intensity in diastolic blood pressure (group 1: 118.9 ± 13.01 and group 2: 128.81 ± P-25. 15.10, p=0.013) and in the vasomotor symptoms (group 1: 1.69 ± 2.31 and group 2: Relationship between age and cardiac autonomic modulation in 4.37 ± 4.30, p=0.0001). Volunteers with a KI ≥ 20 had income lower than 2 minimum climacteric women in Western Amazonia wages (100%, p: 0.06), not having paid work (62.9%, p=0.060) and comorbidities Patricia M. Martinelli1,2, Rodrigo D. Raimundo, PhD1, Alex R. Norberto1,3, Valdelias X. (19.4%, p=0.047). The linear indexes in the frequency and time domain according to Pereira, PhD1,3, Isabel C. Sorpreso, PhD2,3, Luiz C. de Abreu, PhD2,1. 1Faculdade the intensity of the symptoms measured by the KI were evaluated through the heart de Medicina do ABC FMABC, Santo Andre, Brazil; 2União Educacional do Norte rate variability, in which the light symptomatology group presented an increase in the UNINORTE, Rio Branco, Brazil; 3Faculdade de Medicina FMUSP, Universidade de mean RR intervals (MeanRR - group 1: 901.74±123.25ms, group 2: 843.35±122.65ms, Sao Paulo, Sao Paulo, Brazil p=0.0444); (RMSSD - group 1: 31.40±19.40ms, group 2: 22.70±12.72ms, p=0.008); Objective: To evaluate the behavior of cardiac autonomic modulation according to the percentage of adjacent RR intervals with duration difference greater than 50 ms the age of women in climacteric. Design: A cross - sectional study was carried out (pNN50 - group 1: 14.32±15.64%, group 2 - 5.80±8.41%, p=0.005); and high frequency at the Rosangela Pimentel Figueira Health Center, Rio Branco, Acre, from October variable (HF - group 1: 49.52±16.46nu, group 2: 42.92±17.72nu, p=0.047), and 2016 to July 2017. Participants signed the Informed Consent Form. Approval of the the group with moderate and intense symptomatology had a higher value in the low Ethics and Research Committee - 1,748,393 / 2016. Women between 40 and 65 years frequency variable (LF - group 1: 51.02±16.11nu, group 2: 69.44±103.76 nu, p=0.061). old were included. Exclusion criteria were: use of antidepressants, antihypertensives, Conclusion: Women with moderate to severe menopausal symptoms had low income, electrocardiographic tract alteration of less than 95% of beats of sinus origin. unpaid work, comorbidities and high values of diastolic blood pressure. There was a A sociodemographic and clinical questionnaire was applied. In the cardiac modulation predominance of parasympathetic autonomic cardiac behavior in the group of women collection, baseline arterial pressure (BP), heart rate (HR) and capture of the RR intervals with mild menopausal symptomatology and high sympathetic activity in the group of of the electrocardiogram waves measured 20 minutes in dorsal decubitus were measured women with moderate to severe symptoms. using the Polar RSCX800 cardiofrequency meter. Digital filtering was done on Polar Sources of Funding: None Precision Performance SW and Kubios software. The 110 volunteers were divided into two groups: group 1 (40 to 50 years) and group 2 (51 to 65 years). Descriptive P-27. statistics and comparison between groups of continuous variables were performed with Student’s t test for independent samples, non-parametric Mann-Whitney test; bivariate Effect of Estradiol Dose and Serum Estradiol Level on Coagulation and correlation analysis the Pearson test; the level of significance of 5% (p <0.05), through Anti-coagulation Factors in Early and Late Postmenopausal Women in SPSS software. Results: The groups were homogeneous regarding menarche age, body the REPLENISH trial. mass index, waist circumference, diastolic blood pressure, systolic blood pressure and Intira Sriprasert, MD1,4, Howard Hodis1,2, Brian Bernick, MD3, Sebastian Mirkin, MD3, vasomotor symptoms. Menopausal age was different between groups 1: 42.60±7.60 years Wendy Mack, PhD1,2. 1Preventive Medicine, Keck School of Medicine, University of and group 2 48.12±5.11 years; p=0.042. Group 1 presented stable marriage (74.0%, Southern California, Los Angeles, CA; 2Atherosclerosis Research Unit, Keck School of p= 0.027) and group 2 schooling ≤ 8 years (82.6%, p=0.008) and comorbidities (23.9%, Medicine, University of Southern California, Los Angeles, CA; 3TherapeuticsMD, Boca p=0.009). heart rate variability in group 1 presented SDNN 29.42±17.64ms, group 2: Raton, FL; 4Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, 22.38±14.12ms, p=0.031; the percentage of RR intervals pNN50 group 1: 11.71±14.08%, Chiang Mai, Thailand Group 2 6.55±10.30%, p=0.009; frequency group (HF group 1: 405.88±498.88ms2, group Objective: This post-hoc analysis evaluated the association of randomized estradiol (E2) 2 234.43±266.93ms2, p=0.017) and group 2 presented lower sympathetic activity in the dose and achieved serum E2 level on coagulation and anti-coagulation factors in early low frequency variable (LF group 1 377.44±313.41ms2, group 2 226.73±278.38ms2 (<6 years) compared with late (≥10 years) postmenopausal women in the REPLENISH p=0.0001). Conclusion: Cardiac autonomic modulation had a parasympathetic trial. Design: REPLENISH was a randomized, double-blinded, placebo-controlled, multi- predominance and less sympathetic activity in the group of women under 50 years of center trial testing endometrial safety and efficacy on moderate-to-severe vasomotor age in climacteric women. symptoms of TX-001HR, an investigational, oral combined E2 and progesterone (P4) Sources of Funding: None (1.0 mg/100 mg, 0.5 mg/100 mg, 0.5 mg/50 mg, 0.25 mg/50 mg) agent in postmenopausal women. Mixed-effects linear models tested the association of E2 dose and serum E2 level with coagulation and anti-coagulation factors; prothrombin time (PT), activated partial thromboplastin time (APTT), antithrombin (AT), fibrinogen (FIB), protein C (PROTC), and protein S (PROTS) over 12 months adjusted for serum P4. The change in each factor was estimated per 0.25 mg E2 dose and per 1 pg/mL E2 level. The effect urogenital (-0.28 [95% CI -0.45, -0.11], p=0.001) MRS-II subscores. With CR treatment, of serum P4 level was also evaluated. Results: A total of 1327 early and 318 late the vegetative and the urogenital MRS-II subscores significantly improved (-0.81 [95% postmenopausal women were included. Mean age (SD) was 53.1(3.7) years vs. 58.4(4.1) CI -1.57, -0.04], p=0.039 and -0.64 [95% CI -1.26, -0.01], p=0.045). Total MRS-II years; mean time-since-menopause was 2.4(1.8) years vs. 14.2(3.9) years in early and had the same trend (-1.43 [95% CI -3.16, 0.30], p=0.11). Intergroup comparisons did late postmenopause. Late-postmenopausal women had higher systolic blood pressure not reveal significant differences for any endpoint or when adjusting for confounders. and lower serum E2 levels at baseline (p<0.05). Demographic characteristics across E2 Conclusion: In contrast tountreated menopausal women, body weight and metabolic dose groups were similar. Higher E2 dose was significantly associated with reduced parameters did not change in menopausal women treated with either MHT or CR. Both, PT (p=0.003) and PROTC (p=0.0006) in late postmenopause, and with lower AT and MHT and CR significantly improved menopausal symptoms. PROTS in both early and late postmenopause. With longer time-since-menopause, the Sources of Funding: Zeller Medical AG, Romanshorn, Switzerland inverse E2 dose effect on all coagulation and anticoagulation factors became stronger (p interaction<0.001). Higher serum E2 level was significantly associated with lower AT (p<0.001) and PROTS (p=0.002) in early postmenopause, lower PT (p=0.02) among late P-29. postmenopause and lower PROTC in both early and late postmenopause. With longer Relationship between blood oxidative stress markers and cardiovascular time-since-menopause, the inverse serum E2 level effect on PT, PROTC, PROTS and disease risk in Mexican women in process of aging FIB became stronger (p interaction <0.05). No significant main effect of serum P4 level Martha A. Sanchez-Rodriguez, PhD1, Mariano Zacarias-Flores, ObGyn MD2, Victor was found. Conclusion: E2 dose and serum E2 level were significantly associated with Manuel Mendoza-Nuñez, PhD1. 1Unidad de Investigación en Gerontología, Facultad de decreased coagulation and anti-coagulation factors among early and late postmenopausal Estudios Superiores Zaragoza, UNAM, Mexico City, Mexico; 2División de Ginecología women, and the effect was stronger with longer time-since-menopause. Serum P4 level y Obstetricia, Hospital General Dr. Gustavo Baz Prada, Nezahualcoyotl, Mexico did not alter the association between E2 dose and serum E2 level with any coagulation or Objective: To determine the relationship among different oxidative stress biomarkers and anti-coagulation factor. TX-001HR had no affect on PT in early postmenopausal women, the 10-year cardiovascular risk score in middle age and older women. Design: We carry whereas in late postmenopausal women PT was significantly decreased with increasing out a cross-sectional study with 558 community-dwelling women (40-69 yr) from Mexico E2 dose and serum E2 level. These results suggest that timing of estradiol therapy and City (healthy, diabetic or hypertensive) divided in three groups: a) 200 premenopausal serum E2 level related to time-since-menopause could modify venous thromboembolism women (47.1±3.4 yr); b) 251 early postmenopausal women (51.7±3.3 yr), and c) 107 (VTE) risk1. 1Hodis HN, Mack WJ, Henderson VW, Shoupe D, Budoff MJ, Hwang- late postmenopausal women (62.5±3.4 yr). We measured plasma malondialdehyde level Levine J, et al. Vascular Effects of Early versus Late Postmenopausal Treatment with (MDA) by the TBARS assay, erythrocyte superoxide dismutase (SOD) and glutathione Estradiol. New England Journal of Medicine. 2016;374(13):1221-31. peroxidase (GPx), uric acid levels and total plasma antioxidant status (TAS) with Randox Sources of Funding: TherapeuticsMD grant kits as oxidative stress biomarkers. Glucose, total and HDL cholesterol levels were also Regression estimate of coagulation and anti-coagulation factors change per 0.25 mg measured; and blood pressure was obtained using a mercury sphygmomanometer. The increase of E2 dose and 1 pg/mL serum increase of E2 level by time-since-menopause sociodemographic data, included smoke history, were collected. Using age, systolic blood pressure (treated or not treated), total and HDL cholesterol levels, smoking and diabetes status, we computed each woman’s 10-years Framingham general cardiovascular disease (CVD) risk score. For the evaluation, we classified 4 categories of percentage of CVD risk using quartiles as: no risk (<3.3%), mild (3.31-5.80%), moderate (5.81-11.70%) and high (≥11.70%) to compare the oxidative stress biomarkers. Results: One hundred nine women (20%) had high CVD risk, which 54 (51%) were late postmenopausal women. SOD and GPx activities, and TAS level were statistically lower in women with high CVD risk (Table). A negative correlation between SOD activity and CVD risk score was observed (r=-0.125, p<0.01); GPx activity and total antioxidant status also shown low negative correlation. MDA levels were not significant. A multi-variate model including MDA levels and antioxidant biomarkers showed SOD activity to be the main contributor to explain the increase in CVD risk score, since for every 0.1U/g Hb decrease in SOD activity, CVD risk score increases by 4.2%. Conclusion: Our findings suggest that blood enzymatic and non-enzymatic antioxidants decrease when 10-years Framingham CVD risk score increase, showing a low response to oxidative events when the women aging. Sources of Funding: This work was supported by grant DGAPA-UNAM IN306517. Table. Results of antioxidants stratify by 10-years cardiovascular disease risk.

Estimates are from mixed effect model adjusted for baseline measure and P4 level *tests interaction between E2dose, E2 level with time-since-menopause (years)

One-way ANOVA with Dunnett test as posthoc, *p<0.05, †p<0.0001, ‡p<0.01. P-28. SOD: superoxide dismutase, GPx: glutathione peroxidase, TAS: total antioxidant Effect of CIMicifuga racemosa on metaBOLIC parameters in women status. with menopausal symptoms – a retrospective cohort study (CIMBOLIC) Petra Stute, M.D.1, Lena Ost, M. D.2, Lukas Buetikofer, Ph. D.3, Sabine Nebel, Ph. D.4, Catherine Zahner4. 1Obstetrics and Gynecology, Inselspital Bern, Bern, Switzerland; GENITOURINARY/VAGINAL HEALTH 2Obstetrics and Gynecology, Hospital Interlaken, Interlaken, Switzerland; 3CTU Bern and POSTER PRESENTATIONS Institute of Social and Preventive Medicine (ISPM), University Bern, Bern, Switzerland; 4Zeller Medical AG, Romanshorn, Switzerland Objective: Body weight increases during the menopausal transition often accompanied P-30. by adverse changes in metabolic parameters on which menopausal hormone therapy Efficacy and Safety of Ospemifene in Menopausal Women with Moderate (MHT) has a positive impact. Rodent studies with Cimicifuga racemosa (CR) (Ze450, to Severe Vaginal Dryness: A phase 3, Randomized Double-Blind CR extract) also indicate a beneficial effect. The aim of this retrospective study was Placebo-Controlled Multicenter Clinical Trial to compare the impact of Ze450 to MHT on body weight and metabolic parameters David Archer, MD1, Steven Goldstein2, James Simon, MD3, Arthur Waldbaum4, in symptomatic menopausal women. Design: Monocenter retrospective cohort study. Steven Sussman5, Corrado Altomare6, Julie Zhu6, Yuki Yoshida7, Samuel Schaffer8, Women above age 40 with first consultation between 2009-2016 were screened. Women Graziella Soulban8. 1Eastern Virginia Medical School, Norfolk, VA; 2New York Center treated with either MHT or CR treatment and having at least one follow-up consultation for Women’s Health Research, New York, NY; 3Women’s Health Research Consultants, were included into the final analysis. Endpoints were body weight, metabolic serum Washington, DC; 4Downtown Women’s Healthcare, Denver, CO; 5Lawrence OB/ parameters (lipids, glucose, insulin, HOMA-IR) and menopausal symptoms (Menopause GYN Associates, Lawrenceville, NJ; 6Shionogi, Inc, Florham Park, NJ; 7Shionogi, Inc, Rating Scale (MRS)-II). Cantonal ethic committee No 2016-01179. Statistical analysis Florham Park, NJ; 8Duchesnay, Blainville, QC, Canada was performed using uni-/multivariate linear mixed-effects regression assuming a Objective: Genitourinary syndrome of menopause (GMS), comprising vulvovaginal linear effect of time. Results: 769 women were screened, 174 women were eligible atrophy (VVA), impacts the health and quality of life of postmenopausal women. Genital for analysis (CR: n=32, MHT: n=142). Baseline characteristics (age, BMI, fasting lipid symptoms of VVA include vaginal dryness as a most bothersome symptom (MBS) which profile, fasting glucose, insulin, HOMA-IR, blood pressure, serum hormones) did not over time leads to sexual dysfunction and emotional distress and remains a condition differ between groups. However, reproductive stage differed significantly with more of unmet need. The objective of the study was to evaluate the safety and efficacy of CR (83%) than MHT (55%) treated women being postmenopausal (p=0.038) while total ospemifene, an oral, selective estrogen receptor modulator and nonhormonal option, for MRS-II score did not differ between groups. Median follow-up time was 12 months. the treatment of vaginal dryness as the MBS of postmenopausal women with VVA. In both groups, mean change per year was not significant for body weight and serum Design: This Phase 3, multicenter, randomized, double-blind, placebo-controlled study lipids, glucose, insulin and HOMA-IR. With MHT, total MRS-II significantly improved assessed the efficacy and safety of ospemifene in menopausal women with vaginal dryness (-0.99 [95% CI -1.42, -0.55] per year, p<0.0001) as well as the vegetative (-0.24 [95% as MBS of VVA. Eligible subjects were postmenopausal, age 40-80 with moderate to CI -0.45, -0.03], p=0.022), psychological (-0.48 [95% CI -0.71, -0.25], p<0.0001) and severe vaginal dryness as a self-reported MBS of VVA. Subjects were randomized (1:1) to ospemifene 60 mg once daily or placebo for 12 weeks. Co-primary efficacy endpoints were the change from baseline to Week 12 in: the percentage of parabasal and superficial cells, vaginal pH, and the severity of the MBS of vaginal dryness. For each of percentage of parabasal and superficial cells, and vaginal pH, a mixed-effects model for repeated measures approach was used; a generalized estimating equations model was used for the MBS of vaginal dryness. In these models, repeated measurements of the change from baseline at Week 4, 8, and 12 were the response variable. Other endpoints evaluated included vaginal pain associated with sexual activity, percentage of responders (a composite of increase from baseline of ≥ 10 in maturation value, decrease of ≥ 0.5 in vaginal pH, and decrease of ≥ 1 in categorical score for severity of MBS of vaginal dryness) and female sexual function index (FSFI). Results: 631 subjects were enrolled into the study and included in the intention-to-treat (ITT) population (ospemifene=316; placebo=315). The differences between treatment groups in change from baseline to Week 12 for each of the co-primary efficacy endpoints were statistically significant (p < 0.0001). These differences between treatment groups for co-primary endpoints were observed as early as Week 4 and continued through Weeks 8 and 12. The severity of vaginal pain associated with sexual activity, among the other VVA symptoms assessed, Figure 1: Responders with TX-004HR at Weeks 2 and 12 also showed a significantly greater reduction from baseline in the ospemifene group compared to placebo by week 12. The percentage of responders significantly increased P-32. in the ospemifene group compared to placebo at weeks 4 and continued through weeks Introitus as a Surrogate Site for Vaginal pH and Biomoleculars: 8 and 12 with a statistically significant increase in the FSFI score in the ospemifene Pre-menopausal vs Post-Menopausal Women Comparison group at week 12. In the safety population, overall treatment-emergent AEs (TEAE) were Miranda Farage, Ph.D., Gina fadayel, B.S, MT-ASCP, Hong Jian Dai, Yuli Song, Ph.D., reported within Week 12 for 35.3% of subjects in the ospemifene group and 33.3% of Yu Wang, M.Sc. Corporate R&D, Procter and Gamble, Mason, OH subjects in the placebo group. There were no TEAEs of deep vein thrombosis or breast Objective: Post-menopause is usually associated with major physiological, biophysical, cancer, and no deaths. Consistent with previous trials, subjects with intact uteri showed a anatomical and microbiological changes as compared to the reproductive years. These slight mean endometrial thickening with ospemifene treatment; a mean increase of 0.63 changes can lead to unique symptoms that might affect women’s quality of life. mm in the ospemifene group compared to a mean decrease of 0.23 mm in the placebo In general, objective measures for vaginal atrophy (VA) rely mainly on obtaining group. No cases of endometrial hyperplasia or carcinoma were observed. Conclusion: specimen/data from the vaginal area. For many women with VA, the vaginal opening The results of this double-blind, randomized, placebo-controlled Phase 3 trial support (e.g. introitus) may constrict and lose elasticity thereby making it difficult and unpleasant that ospemifene 60 mg daily may be efficacious and safe in the treatment of moderate to have a practitioner obtain samples from the vaginal area. However, objective measures or severe vaginal dryness as the MBS of VVA. Ospemifene demonstrated statistically of VA are largely restricted to vaginal pH and vaginal maturation index which typically significant superiority over placebo for all co-primary efficacy endpoints by Week 12. require insertion of a speculum to create adequate access to the internal area. These The effectiveness of ospemifene was evident at week 4 and maintained through the vaginal procedures are invasive and can be painful especially among women who suffer study at Weeks 8 and 12. Endometrial findings at 12 weeks showed slight increase in from VA. The goal is to reduce the painful vaginal procedures many women with VA endometrial thickness and no cases of hyperplasia or carcinoma. experience during sample collections and clinical evaluation. A research program was Sources of Funding: None initiated to investigate whether the introitus can be used as a surrogate site for the vagina. The objective is to investigate whether the introitus reflects the vaginal site, we conducted P-31. a clinical study to evaluate certain bio-molecular measures, protein levels, and pH in both A 17β-estradiol, Softgel, Vaginal Capsule (TX-004HR) had an Early pre-menopausal and post-menopausal women. Design: A total of 20 female subjects (age Onset of Action for Treating Vulvar and Vaginal Atrophy (VVA) and 21-70), who met all entrance criteria and signed the informed consent, were enrolled Moderate-to-Severe Dyspareunia in the study and assigned to one of two groups; 10 pre-menopausal females (Pre-M), 10 post-menopausal females receiving no form of hormone replacement therapy (Post-M Ginger Constantine, MD1, Leah S. Millheiser, MD2, Andrew M. Kaunitz, MD4, Non-HRT) and showing signs of urogenital atrophy. The pH was measured using pH Shelli Graham, PhD3, Brian Bernick, MD3, Sebastian Mirkin, MD3. 1EndoRheum litmus paper. Quantification of biomolecules was obtained from two genital sites of Consultants, LLC, Malvern, PA; 2Stanford University School of Medicine, Stanford, interest: vagina and introitus from both Pre-M and Post-M groups using the Medscand CA; 3TherapeuticsMD, Boca Raton, FL; 4University of Florida College of Medicine- Cytobrush Plus Kit (used for standard Pap Smear Test). Results: As expected, the vaginal Jacksonville, Jacksonville, FL pH was significantly higher for the Post-M Non-HRT group as compared to the Pre-M Objective: An investigational, vaginal softgel capsule with low-dose solubilized group since we specifically recruited post-menopausal women with vaginal atrophy. 17β-estradiol (TX-004HR; TherapeuticsMD, Boca Raton, FL), designed to be rapidly When the pH was compared in the introitus vs. vaginal of pre-M, values were very dissolving and mucoadhesive, significantly improved superficial and parabasal cell similar: 4.2 ± 0.42 vs. 4.1 ± 0.32, respectively. For the post-menopausal group, the pH percentages, vaginal pH, and dyspareunia vs placebo in menopausal women with VVA was 7.5 ± 1.08 at the introitus vs. 7.6 ± 0.84 in the vaginal area. The concentrations and moderate-to-severe dyspareunia in the phase 3 REJOICE trial (NCT02253173; of glycogen, lactic acid, total Natural Moisturizing Factor (NMF), and proline were Constantine et al, Menopause 2017;24:409-16). The objectives were to determine significantly higher in pre-menopausal vs postmenopausal groups at both genital sites. responder rates at wk 2 and how wk-2 findings may predict wk-12 responders. However, very similar levels were obtained between introitus and vaginal of each group. Design: In the REJOICE trial, menopausal women with VVA and dyspareunia received The total NMF and proline suggest a greater hydration level in pre-menopausal vs. post- TX-004HR 4 µg, 10 µg, or 25 µg, or placebo for 12 wks. Responders had ≥2 of the menopausal women. Protein levels were significantly higher in the pre-menopausal vs. following: vaginal superficial cell percentage >5%, vaginal pH <5.0, or improvement post-menopausal at both sites. The Introitus protein levels were higher than the vaginal from baseline in dyspareunia ≥1 category. In the efficacy evaluable (EE) population, the site in both groups. Conclusion: Limited biomolecular and biophysical data exist proportion of responders was calculated by dividing the number of positive responders by comparing different genital sites of pre-M vs. post-M women. There were significant women with available responder data. Odds ratios for a positive response at wk 12 given differences in biomolecular concentrations in the genital area between pre and post- a positive response at wk 2 were calculated. Results: Of 764 enrolled, 695 constituted menopausal women on non-HRT. The initial differences in biomarkers suggest reduced the EE population. The proportion of responders was 74%-82% with TX-004HR doses glucose metabolism and hydration in post-menopausal vs. pre-menopausal women. vs 24% with placebo at wk 2, and 72%-80% vs 33% at wk 12 (Figure 1). The odds of Similarities in pH and biomolecular concentrations in introitus vs. vaginal support that being a responder with TX-004HR were 9- to 14-fold higher than that with placebo the introitus is a suitable surrogate skin site for obtaining certain vaginal measurements. at wk 2, and 5- to 8-fold higher at wk 12. When all women (independent of treatment Additional clinical studies support these findings. The more we can find similarity [including placebo] in the EE population were analyzed in aggregate, similar percentages between introitus & vaginal sites the more we can alleviate the pain of women specially of responders were observed at wk 2 (65%) and wk 12 (66%). When women taking with vaginal atrophy symptoms, to improve their Quality of life. active treatment only were analyzed in aggregate, 80% respond at wk 2 and 78% at Sources of Funding: None wk 12. In addition, of women who responded at wk 12, 85% had responded at wk 2. Being a responder at wk 2 highly predicted being a responder at week 12 in the total EE population (OR 13.1; 95% CI, 8.8-19.7) and in the active treatment groups only (OR 7.9; 95% CI, 4.7-13.2). Conclusion: A consistent effect of TX-004HR in menopausal women with moderate-to-severe dyspareunia was observed as early as 2 weeks of therapy as shown by the high percentage of responders. A positive response to TX-004HR at wk 2 predicted a positive response at wk 12. Sources of Funding: TherapeuticsMD P-33. their initial presentation and after hormone treatment were examined. Photographs Randomized, Double-blind, Placebo-controlled Multicenter Study to from August 1, 2007 through December 1, 2017 displaying the vulva, vestibule, Evaluate Vulvar Health from Photograph Images Taken at Investigative urethral meatus and vagina were reviewed. Results: A total of 110 menopausal women Sites of Consenting Subjects Participating in the Efficacy and Safety (mean age 62 ± 13 years) with sexual health complaints met inclusion and exclusion criteria. A total of 2125 vulvoscopic photographic images were reviewed. The mean of Ospemifene in Patients with Moderate to Severe Vaginal Dryness, a follow-up from initial office visit was 2.6 ± 1.3 years. In all 110 cases, pre-treatment Symptom of Vulvo-vaginal Atrophy (VVA) due to Menopause vulvoscopic photographic images showed varying degrees of resorption of labia minora, 1 2 3 4 Irwin Goldstein, MD , James Simon, MD , Andrew M. Kaunitz, MD , Corrado Altomare , telescoping of the urethral meatus, atrophy of the glans clitoral, vestibular erythema and 4 4 5 5 1 Yuki Yoshida , Julie Zhu , Samuel Schaffer , Graziella Soulban . Sexual Medicine, pallor, minimally robust peri-urethral tissue, and minimal vaginal rugae with thin, pale 2 Alvarado Hospital, San Diego, CA; Women’s Health Research Consultants, and dry vaginal mucosa. Longitudinal vulvoscopic photographic image changes in 61% 3 4 Washington, DC; University of Florida, Jacksonville, FL; Shionogi Inc., Florham Park, of cases revealed varying degrees of improved genitourinary tissue health as assessed 5 NJ; Duchesnay Inc., Blainville, QC, Canada by the presence of pink, moist, vestibular tissue with re-growth of the labia minora, loss Objective: The goal of this trial was to validate the use of vulvar photography for of urethral meatal telescoping, growth of the clitoral glans, and growth of the anterior assessment of vulvar health in women with moderate to severe vaginal dryness due vaginal wall peri-urethral tissue. Non-compliance with medications, medication side to menopause in a large study. This multicenter, randomized, double-blind, placebo- effects, excessive medication costs, and other health care provider discontinuation of controlled study assessed the efficacy and safety of ospemifene 60 mg QD in medications were the chief reasons for failure. Conclusion: Longitudinal vulvoscopic postmenopausal women (age 40-80) with moderate to severe vaginal dryness as the most photographic images of women in menopause with sexual dysfunction and GSM can bothersome symptom (MBS) of VVA due to menopause. Three experts independently be utilized to effectively “monitor” genitourinary tissue health changes associated with assessed vulvar photographs using the multi-item Vulvar Imaging Assessment Scale hormone therapy. (VIAS) to measure vulvar anatomical effects of ospemifene versus placebo. A secondary Sources of Funding: None aim was to compare imaging data from the VIAS to other objective measures in the study including Vaginal and Vulvar Health Indices, assessed by investigators at each site. The Vaginal Health Index (VHI) evaluated fluid secretion, overall elasticity, P-35. pH, condition of epithelial mucosa, moisture. The Vulvar Health Index (VuHI) is a Safety and Efficacy of Hybrid Fractional Laser for Symptoms of GSM: visual examination rating labia majora, labia minora, clitoris, introitus appearance Prospective Multi-Center Study: 3 and 6 Month Interim Analysis and elasticity, color, discomfort and pain, presence of other findings, as normal/mild/ Nathan L. Guerette, MD, FACOG, FPMRS1,2. 1Intimate Wellness Institute, Richmond, moderate/severe. Design: Images were captured at research sites with a Canon SL1 VA; 2Female Pelvic Medcine Institute, Richmond, VA camera system, sent to a dedicated secure central digital monitoring system and uploaded Objective: Genitourinary syndrome of menopause (GSM) is a new terminology to a dedicated clinical services website accessed by each reviewer. The reviewers to describe symptoms occurring secondary to vulvovaginal atrophy. Energy based underwent technical/logistical training, then independently assessed vulvar images devices including laser and radio-frequency devices have demonstrated positive results based on pre-established criteria using a color calibrated 27” high resolution standardized in treatment of GSM. This is the first multi-center prospective study to evaluate the color monitor. They were blinded to subject identifiers, investigator information and safety and efficacy of hybrid fractional laser utilizing simultaneous delivery of 2940nm treatment arm. Study photographs were graded (none (0), mild (1), moderate (2), severe Erbium and 1470nm Diode wavelengths to treat symptoms of GSM. Design: Prospective, (3), cannot evaluate) for each of 9 criteria: labia major loss, labia minora loss, clitoris multi-center study at 5 centers in U.S., 51 peri- and post-menopausal females (mean age size, urethral glans prominence, introital stenosis, introital pallor, introital erythema, 59±6.5) with at least 2 self-reported symptoms of GSM enrolled. 33 subjects completed introital moisture, mucosal inflammation, and other findings as outlined by the VIAS. 3 month follow-up visit and 24 subjects completed 6 month follow-up. This is findings Results: 631 subjects were enrolled, randomized, and included in the intention-to-treat of those subjects. Baseline demographics and exam recorded. Vaginal Health Index Scale population (ospemifene=316; placebo=315). The VIAS score, range 0-27, was graded at (VHIS), Vaginal Maturation Index (VMI), Female Sexual Function Index questionnaire baseline and Wk 12, with lower values indicating better vulvovaginal health. The mean (FSFI), and Day-to-day Impact of Vaginal Aging questionnaire (DIVA) scores VIAS score at baseline was similar in both treatment groups (ospemifene, 13.8; placebo, collected at baseline and follow-up visits. Histological samples collected at baseline, 14.1). The difference between treatment groups in least square (LS) mean change from 3, 6 and 12 month follow-up visits. Subjects received 3 treatments at 4 week interval baseline in mean VIAS total score was -1.0 (p = 0.0118) at wk 12, representing a greater (settings: 1470nm – 200-600 um [density 6-15%], 2940nm – 200-300 um [density decrease in the ospemifene group relative to the placebo group. The VHI, range 5-25, 7-14%]). Follow-up visits conducted at 1, 3, 6 and 12 months after third treatment. was graded at baseline and Wk 12, with higher values indicating better vaginal health. Results: FSFI demonstrated significant improvement in all domains at 3 and 6 months The mean VHI total score at baseline was 13.0 in both groups. The difference between (p<0.05) percent improvement of 44-164% (table 1). DIVA scores had significant groups in LS mean change from baseline in VHI total score was 2.5 at Wk 4, 2.9 at Wk improvement in all domains at 3 and 6 months (p<0.05), percent change of 39-75%. 8, and 2.8 at Wk 12 (all p < 0.0001), representing greater increases in the ospemifene Maturation index improved at 3 and 6 months with decrease in % of parabasal cells group. The VuHI, range 0-21, was graded at baseline and Wk 12, with lower values and increase % of superficial cells. Overall VMI improved 12% at 3 months and 18.5% indicating better vulvar health. The mean VuHI total score at baseline was similar in at 6 months. VHIS statistically improved in all domains (elasticity, epithelial integrity, both groups (ospemifene, 7.6; placebo, 7.7). The difference between groups in LS mean lubrication) with a percent improvement of 58-153% (table 2). Significant histological change from baseline in VuHI total score was -0.8 (p = 0.0002) at Wk 4 and -1.1 to -1.2 changes occured with 100% increase in epithelial thickness at 6 months and 54% change at Wks 8 and 12 (both p < 0.0001), a statistically significant decrease in the ospemifene at 3 months (Figure 1). No adverse events reported. Conclusion: The 3 and 6 month group compared to placebo. Conclusion: Use of vulvar photography and the VIAS data demonstrates that the hybrid fractional laser, with simultaneous delivery of 2940nm correlated with Vaginal and Vulvar Health Indices. These results were consistent with Erbium and 1470nm Diode wavelengths, is safe and efficacious treatment for GSM with the improvement of vaginal dryness as the MBS of postmenopausal women with VVA. statistical improvements in vaginal health, sexual function, and quality of life. This approach to assess MBS of menopausal women should be considered for future Sources of Funding: Sciton (Palo Alto, CA, USA) clinical trials. Table-1: FSFI p-values and percent improvement Sources of Funding: None

P-34. A Retrospective Single Center Study of Longitudinal Vulvoscopic Findings of Photographic Images of the Vulva, Vestibule, Urethral Table 2: VHIS p-value and % Improvement Meatus and Vagina in Menopausal Women with Female Sexual Dysfunction Pre- and Post-Hormonal Treatment Stephanie da Silva, MD2, Sue W. Goldstein, BA, CSE, CCRC2, Irwin Goldstein, MD1,2. 1Sexual Medicine, Alvarado Hospital, San Diego, CA; 2San Diego Sexual Medicine, San Diego, CA Objective: Genitourinary syndrome of menopause (GSM) is associated with signs and symptoms of genitourinary atrophy secondary to estradiol and androgen deficiency. It is hypothesized that longitudinal vulvoscopic assessment utilizing photographic images of the vulva, vestibule, urethral meatus and vagina would allow the health care provider to objectively “monitor” effectiveness of hormone therapy in menopausal women with symptoms of GSM. Design: This single site retrospective study examined longitudinal vulvoscopic findings documented by photographic images of the vulva, vestibule, urethral meatus and vagina to examine the clinical benefit of hormonal replacement strategies for the management of menopausal women with sexual dysfunction and GSM. Bioidentical hormonal therapy is designed to keep serum estradiol, progesterone and calculated free testosterone values levels at ideal values considered 25 - 50 pg/ml, 1.0 ng/ml and 0.8 ng/dl, respectively. Management also includes daily topical vestibular and vaginal application of compounded estradiol and testosterone cream and more recently intravaginal DHEA inserts. Both naturally and surgically menopausal women were included who were either peri-menopausal or post-menopausal at their initial visit, with at least one follow-up vulvoscopy. Women who had undergone cosmetic vulvar or vestibular surgery were excluded. Vulvoscopic photographic images of women at P-36. P-37. Improvement of vaginal vascularization in postmenopausal women with Nella™ NuSpec™ is a Novel Tool for Increased Comfort for Peri and genitourinary syndrome with isoflavones derived from Glycine max (L.) Post Menopausal Patients during Intravaginal Exams Merr vaginal gel. Maria Lalli1, Michael Krychman, MD2. 1CEEK Womens Health, Portland, OR; 2Southern Juliana V. Honorato, Masters, SONIA MARIA ROLIM ROSA LIMA, PhD, Maria California Center for Sexual Health, Newport beach, CA Antonieta L. Galvão da Silva, Professor Doctor. Gynecological endocrinology and Objective: Genitourinary syndrome of menopause includes vaginal atrophy that affects Menopause, Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil women in their peri and postmenopausal stages of life. Symptoms include a drop in Objective: To analyze the effect of the isoflavones derived from Glycine max (L.) estrogen, leading thinning of vaginal tissues, and causing dyspareunia and discomfort Merr vaginally in the improvement of the vascularization of the vaginal epithelium. during intravaginal exams. As a result, many women avoid pelvic exams due to anxiety Design: A pilot project, double-blind, randomized, placebo-controlled was carried out, over the potential for this discomfort. Current specula are not designed to optimize including 9 patients, randomly assigned to Group 1 (Isoflavones) and Group 2 (Placebo). comfort for these patients and often require a level of discomfort for the patient in order Group 1 received 1g of isoflavone vaginal gel derived from Glycine max (L.) Merr 4%, for the clinician to obtain optimal visibility and accessibility. The Nella NuSpec is a with a plastic applicator, for daily use during 12 weeks. Group 2 received 1g of placebo Class II, FDA-exempt speculum developed to improve the experience of an intravaginal gel, with similar package, color and consistency, used in the same way. Vaginal micro- exam. The design focuses on narrow bills for increased patient comfort and enhanced biopsies were collected before and after the 12 weeks of treatment. Histological and visibility enabled by integrated retractors for vaginal tissue sidewall retention. The immunohistochemical analysis was performed to count blood vessels per field in the speculum also has a novel handle and locking mechanism design that is ergonomic vaginal epithelium, before and after the intervention. The data were evaluated using for both patient and clinician, and is made of an autoclavable polymer that is warm Mann-Whitney and Wilcoxon tests. Results: There was no significant difference to the touch and does not require the addition of lubricant for comfortable insertion. between groups in terms of age, time after menopause, weight, BMI and basal number of Design: An IRB-approved (ClinicalTrials.gov, # NCT03123367) interventional, blood vessels per field in vaginal epithelium (Table 1). After intervention, the increase randomized, controlled, parallel-assignment study was conducted to evaluate the product of vessels in Group 1 (isoflavones) was statistically significant (p: 0.043), which was not across 2 clinical sites. Women aged 18 and over who met screening criteria were invited observed in Group 2 (p: 1.0) (Table 2), and the difference of both groups was significant to participate. 41 women were enrolled (n=20 device, n= 21 control) between the ages (p: 0.014) (Figure 1). Conclusion: Preliminary results showed that Glycine max (L.) of 24 and 68 (mean age 48.3). Informed consent was documented and HIPPA-compliant Merr treatment significantly increased vaginal wall vascularization in postmenopausal and protected data was collected on paper forms through patient and clinician post-exam women compared to placebo. questionnaires. Participants were compensated with a gift card (50USD). Reported here Sources of Funding: FAPESP - Fundação de Amparo à Pesquisa do Estado de São Paulo is one arm of a larger 4 arm study. Of the 41 women, 32 were of typical perimenopausal Table 1: Patient baseline characteristics (mean, median, SD*, minimum, maximum and or postmenopausal age and included in this analysis. A smaller subset of women (n=13; pValue**) 31.7%) were postmenopausal and are an additional analysis. Results: Patient Results: For the subset of patients 40 and over, when asked to compare to their previous exam, 80% of patients (12 of 15) in the device arm rated the exam as better or significantly better vs. only 23.5% (4 of 17) in the control arm. When comparing to their last exam, 100% of postmenopausal NuSpec patients (5 of 5) reported that this exam felt better or significantly better. For all patients 40 and over in the device group, 93.3% (14 of 15) agreed or strongly agreed that the speculum felt comfortable overall and upon insertion vs 82.3% (14 of 17) of those in the control group. Of the 5 postmenopausal patients who experienced the device, 100% agreed or strongly agreed the NuSpec felt comfortable upon insertion vs. 62.5% of postmenopausal patients that experienced the control device (5 of 8 patients). Clinician Results: During 86.7% (13 of 15) of device exams with women over age 40, clinicians agreed or strongly agreed that visibility was good, while within the *SD - standard deviation control group that percentage was 76.5% (13 of 17). In terms of providing easy access, **p < 0,01 (Mann-Whitney Test) in 86.7% of device exams (13 of 15), clinicians agreed or strongly agreed, while in the Table 2: Comparison of blood vessels per field values at baseline and 12 weeks in Group control group the percentage was 64.7% (11 of 17) agreeing or strongly agreeing and 1 (Isoflavones) and Group 2 (Placebo), medians and pValue* 17.6% (3) disagreeing or strongly disagreeing and 17.6% (3) unsure. Analyzing only the postmenopausal exams, clinicians stated they agreed or strongly agree on good visibility for 100% of device exams (5 of 5), while in the control group the value was 75% (6 of 8). Similarly, with 100% (5 of 5) of NuSpec exams on postmenopausal patients, clinicians agreed or strongly agreed that the device provided easy access to the cervix vs. during control exams, clinicians agreed on good accessibility during only 62.5% of exams (5 of 8). No adverse events were reported. Conclusion: While demonstrating increases in patient comfort, the NuSpec also showed improvements in visibility and accessibility for clinicians with peri and postmenopausal patients. NuSpec™ is a novel speculum option that provides clinicians an opportunity to improve comfort for peri and postmenopausal patients by considering the symptoms of genitourinary syndrome of menopause, leading to potentially increased patient satisfaction (an important emerging quality metric in health care delivery) and increased visit compliance. *p Value<0,01 (Wilcoxon Sources of Funding: Funding: Ceek Women’s Health

P-38. The Placebo Effect for a Medical Device Treating Vaginal Laxity Michael Krychman, MD1, Stacie Bell, PhD2, Deborah Wilkerson2. 1Southern California Center for Sexual Health, Newport beach, CA; 2Medical affairs, Viveve Medical, Englewood, CO Objective: There is substantial placebo effects when examining therapeutic interventions for female sexual health. Some studies estimate that the placebo effect can be as high as 40-50%. With increasing intervention, it is known that the placebo effect becomes may become more pronounced and one would anticipate a significant placebo effect from a medical device such as radiofrequency and or laser intervention. Randomized controlled trials that are blinded and have a placebo study design are of paramount importance as is the need for longitudinally following up participants for accurate documentation of adverse effects. Many prospective case series, while support provocative results for implementing innovative technology in the field of sexual gynecology, robust RCT is sparse. This radiofrequency trial was conducted to determine the placebo effect for a medical device treating women who are complaining of vaginal laxity/looseness Design: A prospective, longitudinal, randomized, blinded, placebo-controlled, multi- center clinical study was carried out for the treatment of vaginal laxity. This international study is the first and only of its kind ever done for the medical treatment for the condition of vaginal laxity. Subjects were randomized in a 2:1 ratio to either the active (90 J/cm2) Test) or sham (≤1 J/cm2) treatment groups. Nine sites were chosen in multiple countries (Italy, Figure 1: Comparison of number of blood vessels per field before (blue), and after Spain, Canada and Japan). Subjects were followed up at 72 hrs, 10 days, and 1, 2, 3, 12 weeks of treatment (green), in Group 1 (Isoflavones) and Group 2 (Placebo) and 6 months post-treatment. Patient reported outcomes included a 7-point likert scale assessment for vaginal laxity. Results: A total of 155 subjects that did not have any major protocol deviations are included in this analysis. Results show a statistically significant, clinically meaningful difference at 6 months between active and sham, with the active for presenting vulvovaginal symptoms, while the use of hormonal therapy was a group 3 times more likely to report “no laxity” (p≤0.006). However, the sham treatment protective factor, 0R: 0.20 [IC95% 0.04-0.90] (p <0.005). Conclusion: The presence of group showed a substantial treatment effect itself, with a 31%, 33%, and 19% increase in vulvovaginal symptoms was estimated in two out of five women. The consumption of “no laxity” at months 1, 3, and 6, respectively. Conclusion: In order to adequately power alcohol, psychotropic drugs, high blood pressure and sedentary lifestyle were identified and design future research initiatives, investigators must take into account the possibility as a risk factor for vulvovaginal symptoms. of a substantial “sham effect” for laxity and vaginal function studies; underscoring the Sources of Funding: None importance of placebo/sham-controlled trials to ensure that the effect being seen is VULVOVAGINAL SYMPTOMS QUESTIONNAIRE [VSQ-21] PREVALENCIA actually due to the investigational technological intervention or product. Further RCT PORCENTUAL with a sham controlled arm should become the goals standard when assessing efficacy and safety for a novel medical device in gynecological care. Sources of Funding: This research was funded by Viveve Medical

P-39. Lubrication Improvement in the Sub Analysis Report From the Viveve l Trial: Effect of Single-Session, Cryogen-Cooled Monopolar Radiofrequency Therapy on Sexual Function. Michael Krychman, MD1, Hank hauser2, Stacie Bell, PhD2, Deborah Wilkerson2. 1Southern California Center for Sexual Health, Newport beach, CA; 2Medical affairs, Viveve Medical, Englewood, CO Objective: Vaginal laxity is a patient reported impactful medical condition often self- defined as the complaint of ‘excessive vaginal looseness’. Vaginal laxity is considered to result primarily from stretching of the introitus during vaginal delivery and to be associated with reduced vaginal sensation during intercourse, reduced sexual satisfaction, with subsequent negative impact on self-esteem and sexual relationships. Recent data is emerging that demonstrates improved sexual function and satisfaction in women with vaginal laxity who have undergoing ‘vaginal rejuvenation’ procedures including surgery, laser and radiofrequency treatments. Design: The Geneveve Procedure/ Viveve’s Cooling Monopolar Radio Frequency technology to provide a non-ablative, minimally- invasive approach to creating heat deep within the layers of vaginal soft tissue, while keeping the surface cool. It is a single, 30-minute, office-based, treatment of the vaginal P-41. introitus to improve sexual function. We report a new detailed sub-analysis from the Cost-Effectiveness Analysis of APEX M™ Pelvic Floor Therapy for the VIVEVE I Trial that focuses specifically on sexual function. Results: This trial was Treatment and Management of Female Urinary Incontinence a RCT program where subjects randomized to active treatment (n = 73) had greater Anna Camille Moreno, DO1, Sabrina Sikka1, Holly Thacker1, Belinda Udeh2. 1Women’s improvement than sham subjects (n = 35) on all Female Sexual Function Index (FSFI) Health Institute, Cleveland Clinic Foundation, Cleveland, OH; 2Neurology and domains of sexual function at 6 months post intervention. The analysis of covariance Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, OH change from baseline analyses showed statistically significant improvements, in Objective: The aim of this study was to assess the efficacy and cost-effectiveness of favor of active treatment, for sexual arousal (p = 0.004), lubrication (p = 0.04), and APEX M™ pelvic floor therapy for women with urinary incontinence (UI) as compared orgasm (p = 0.007). In addition, active treatment was associated with clinically to women who followed a standard treatment plan (prescription medications/pelvic floor important and statistically significant improvements in sexual desire [Odds ratio = 3.01 physical therapy/surgery). Design: This is a retrospective, descriptive, cohort chart (1.11–8.17)], arousal [OR = 2.73 (1.06–7.04)], and orgasm [OR = 2.58 (1.08–6.18)]. review study of women presenting with UI to the Cleveland Clinic Womens Health Clinic Conclusion: This sub analysis showed CMRF therapy is associated with statistically between April 1, 2014-January 31, 2018. Forty-seven women who purchased the APEX significant and clinically important improvements in sexual function in women with M™ device and participated in a treatment protocol, including home practice sessions vaginal laxity. The improvement in the lubrication domain is of importance for the 6x/week for 3 months were compared to 236 women who were eligible and determined post-menopausal female. Further randomized clinical programs are underway to further to benefit from the use of APEX M™ but chose not to purchase it. Patient subjective examine and study the use of RF in the post-menopausal patient population. responses about their current incontinence status, specifically the number of incontinence Sources of Funding: This research was funded by Viveve Medical episodes as well as the number of female incontinence pads were documented at their initial and follow-up visits scheduled within the study period. All health care utilization, P-40. including prescription medications relating to UI documented within the electronic Vulvovaginal Evaluation in Afro-Descendants Postmenopausal Women medical record after purchase/refusal of the device was abstracted from each patients Alvaro Monterrosa-Castro2,1, María Carolina Galofre-Martínez2,1, Leidy Carolina Durán- chart. A cost was assigned to each utilization category based on average costs and Méndez2,1, Angélica Monterrosa-Blanco2,3. 1Universidad de Cartagena. Colombia, reimbursements for provider visits, pelvic floor physical therapy, and common surgical Cartagena, Colombia; 2Grupo de investigación Salud de la Mujer, Cartagena, Colombia; procedures according to the Cleveland Clinic Women’s Health Institute cost analysis. 3Universidad de la Sabana, Chia, Colombia Prescription medication costs were assigned as wholesale acquisition costs according Objective: The vulvovaginal manifestations are part of the symptoms that should to RxPriceVerify. Patient demographics, including zip code data, was collected along be evaluated in gynecological care. It seems that there are no studies that define the with any reported barriers to the purchase of APEX M™. Main Outcome Measures. prevalence of these manifestations in post-menopausal women of afro-descendants The following main outcomes were calculated: 1) number of incontinence episodes in Colombia. The objective to establish the prevalence and factors associated with documented at the initial and follow-up visits of patients who purchased APEX M™; 2) vulvovaginal manifestations in postmenopausal Afro-descendant women. Design: A number of female incontinence pads used at the initial and follow-up visits of patients cross-sectional study that is part of the CAVIMEC research project (Quality of life in who purchased APEX M™; 3) cost comparison between APEX M™ and other direct the menopause and ethnic groups of Colombia) carried out in 147 Afro-descendants costs including prescription medications, pelvic floor physical therapy sessions, surgical postmenopausal woman, healthy women living in populations of the Colombian interventions, and female incontinence pads in patients who used APEX M™ compared Caribbean. Anonymous, voluntary study, with prior informed consent, carried out in the to those who didn’t use the device; 4) identification of any sociodemographic factors communities of residence. A questionnaire with sociodemographic characteristics was that were barriers to the purchase of APEX M™ Results: There was significant benefit applied, which included the Vulvovaginal Symptoms Questionnaire [VSQ-21] composed to the group who purchased the APEX M™ device on improvement of incontinence of 21 questions that are grouped into four domains: symptoms (items 1 to 7), emotions episodes, number of incontinence pads and liners based on follow-up comparison data. (items 8 to 11), impact on the life (items 12 to 15), impact on sexual desire (16), presence Moreover, the data provide support that APEX M™ is a cost-effective approach in of sexual activity (17) and impact of symptoms on sexual activity (18 to 21). The answer the treatment and management of urinary incontinence compared to usual care or no options yes / no in the last week, which are rated as 1/0, respectively. Unadjusted logistic intervention including provider visits, prescription medications, pelvic floor physical regression was performed. Analysis with EPI-INFO-7. Results: The average age was therapy sessions, surgical interventions, and female incontinence pads. There were 53.2 ± 4.1 years, 57.2% were living together, the menopausal age was 49.1 ± 2.5 and 142.6 less incontinence episodes after using APEX M™ based on treatment protocol. the average years of amenorrhea was 4.0 ± 3.0. Half had undergone hysterectomy and The average cost of female incontinence pads used in the initial visits prior to use of a quarter had intervened while they were still menstruating. 24 (16.3%) had at least APEX M™ was $43.34 compared to the average cost of female incontinence pads one of the symptoms. The most prevalent condition was “your vulvar symptoms used in the follow-up visits after the use of APEX M™ was $8.93. Sociodemographic causing dryness during sexual activity” 42.6%. The prevalence of manifestations are factors that potentially serve as barriers to purchasing the device are also studied. observed in the table. 122 (82.9%) reported having sexual activity. The table presents the Conclusion: This study assessed that the one-time cost of APEX M™ pelvic floor therapy prevalences of vulvovaginal manifestations and impact. Weak correlation was observed is more cost-effective than no treatment. Routine care including buying bladder control with the number of glasses of alcohol per week rho: 0.24 [0.08 to 0.39], p = 0.002; pads, protected underwear, fitted briefs, tampon-like bladder support in the management weak negative correlation with age of the last menstruation rho -0.16 [-0.32 to -0.005], of urinary incontinence is costly long-term. It is apparent that more cost-effective studies p = 0.004. Alcohol consumption OR: 5.52 [IC95% 1.66-18.30], arterial hypertension need to be performed comparing economic evaluations of pharmacological and non- OR: 4.01 [IC95% 1.50-10.68], psychopharmaceutical consumption OR: 15.91 [IC95% pharmacological treatments of urinary incontinence. 2.87-87.95], and sedentary lifestyle OR: 17.39 [IC95% 1.72-174.99] were risk factors Sources of Funding: None P-42. P-43. Systemic Estradiol Levels with Low-Dose Vaginal Estrogens May Differ Effectiveness of InTone™ and InToneMV™ Pelvic Floor Stimulation by Dose and by Product Therapy for Women Suffering from Urinary Incontinence and/or Fecal Richard Santen, MD1, Sebastian Mirkin, MD2, Brian Bernick, MD2, Ginger Constantine, Incontinence MD3. 1Division of Endocrinology and Metabolism, University of Virginia Health System, Sabrina K. Sikka, MD, Anna Camille Moreno, DO, Holly Thacker. Women’s Health Charlottesville, VA; 2TherapeuticsMD, Boca Raton, FL; 3EndoRheum Consultants, LLC, Institute, Center for Specialized Women’s Health, Westlake, OH Malvern, PA Objective: Both urinary and fecal incontinence are chronic, debilitating diseases that Objective: Low-dose vaginal estrogens are approved for the treatment of the signs and can together, or independently, affect overall quality of life. General therapies for both moderate-to-severe symptoms (eg, dyspareunia) of vulvar and vaginal atrophy (VVA). often include medical management, pelvic floor strengthening, or surgical intervention. Despite these treatment options, many menopausal women are hesitant to use vaginal For women with urinary incontinence, pelvic floor physical therapy is often first line estrogens because of the potential of systemic absorption and safety consequences. therapy prior to medical management. The ability to strengthen the pelvic floor can often Systemic absorption of estradiol (E2) with low-dose vaginal estrogens is low, but varies times improve symptoms of urinary leakage but must be performed properly. It has been from product to product. In addition, positioning of the product, high in the vagina said that atleast 30% of women are unable to properly contract their pelvic floor muscles with an applicator or lower without an applicator, may influence E2 absorption.1 The (1). InTone™ and InToneMV™ are two voice-activated pelvic stimulating devices that objective of this study was to summarize systemic E2 levels with various low-dose provide visual biofeedback for the treatment of urinary and fecal incontinence. The vaginal estrogens measured by various methods. Design: PubMed was searched from Intone™ is a larger, inflatable device that is inserted into the vagina and used in the its inception to April 2018 for pharmacokinetic studies that examined systemic estradiol treatment of stress, urge, or mixed urinary incontinence. Alternatively, the InToneMV™ levels with vaginal estrogens. Because the lowest possible dose of vaginal estrogens is has a smaller inflatable probe that can be used with older women with a smaller pelvis recommended, studies using products with 25 µg or less of E2 or 0.3 mg conjugated to treat UI, or can be used rectally to treat FI. The InToneMV™ is unique in that it equine estrogens (CEE) were included. Systemic E2 levels at baseline (basal) and during can manage and treat both UI and FI, which no other device on the market can do. treatment, area under the curve (AUC), and maximum estradiol concentrations (Cmax) To date, there has been one prospective pilot study that has shown subjective and were summarized. Since more specific assays (gas chromatography/mass spectroscopy objective improvement in urinary symptoms in women with UI with the use of the [GC/MS/MS], bioassay) have less cross-reactivity with other steroids and typically Intone™ device. There are not any long-term retrospective studies that have measured yield lower values than less specific assays (radioimmunoassay [RIA], enzyme-linked the quality of life, the use of liners, or daytime/nighttime urination in women using immunosorbent assay [ELISA]), E2 levels should not be compared when measured the Intone™ and InToneMV™. The purpose of this study is to measure efficacy the with different assay methods, thus, E2 levels were also stratified by type of detection Intone™ or InToneMV™ devices at 12 weeks for both UI and FI. Design: This was assay (studies for which assays were not reported were not included). Units of E2 were a retrospective chart review of women who purchased the InTone™ or InToneMV™ converted to pg/mL when needed. Results: Basal levels of estradiol were 3.1-4.9 using within the Cleveland Clinic Foundation with diagnosis of stress, urge, overactive GC/MS/MS,2-6 3.2 pg/mL using a bioassay,7 undectable-14 pg/mL using RIA8-16 and bladder, and mixed urinary incontinence, fecal incontinence or fecal smearing. A total 17 7.6 pg/mL using ELISA. Mean E2 levels with treatment, AUC, and Cmax by detection of 64 women purchased the device and were trained on its use in an in office session assay and dose are shown in Table 1. In general, E2 systemic absorption decreased with lasting 12 minutes under clinician supervision. The twelve-minute session is divided the dose of vaginal E2. In the only head-to-head study comparing low-dose vaginal into two parts – 7 minutes of biofeedback, and 5 minutes of electrical stimulation. The estrogens, significantly lower E2 systemic absorption was observed with 10 µg and provider sets an initial stimulation level for the device in the office and the patient is 25 µg softgel capsules versus tablets of the same doses.3 In two studies that measured then instructed to go home and perform the same session 6 days a week for a total of E2 levels at different times of treatment, average and peak levels declined with use 12 weeks prior to returning to the office. At follow up visits, an attempt to increase the over time likely due to the estrogenization and thickening of the vaginal epithelium.3,4 stimulation level is made based off of the patient’s progress both clinically and based Conclusion: Systemic absorption of E2 with low-dose vaginal estrogens is low and on the quantitative data from the biofeedback. At follow up visits, subjective responses product dependent. Differences in the physical characteristics of their formulations, as about their current incontinence status at their follow-up visits scheduled within the well as positioning in the vagina, may affect absorption of these products. 1. Cicinelli, study period, April 2014-October 2017. Patient subjective impressions of the outcome et al. Am J Obstet Gynecol 2003;189:55-58 2. Archer, et al. Menopause. 2017;24:510- of their treatment were assessed based on provider documentation in the electronic 516 3. TherapeuticsMD. Data on file. 4. Eugster-Hausmann, et al. Climacteric. medical record. Results: For patients with urinary incontinence, there was a notable 2010;13:219-227 5. Labrie, et al. Menopause. 2009;16:30-36 6. Dorr, et al. Fertil Steril. decrease in the amount of daytime frequency and incontinence pad usage among those 2010;94:2365-2368 7. Santen, et al. Menopause. 2002;9:179-187 8. Weisberg, et al. who used the device for a total of three months. On average, women reported a 37% Climacteric. 2005;8:83-92 9. Notelovitz, et al. Obstet Gynecol. 2002;99:556-562 10. decrease in episodes of daily micturition and a 75% decrease in the number of pads Nilsson, et al. Maturitas. 1992;15:121-127 11. Nilsson, et al. Maturitas. 1995;21:33-38 used at 3 month follow up. When assessing sub-groups, of the 56% of women who 12. Mettler, et al. Maturitas. 1991;14:23-31 13. Ulrich, et al. Climacteric. 2010;13:228- were on concomitant hormone therapy during use of the device, 61% reported subjective 237 14. Naessen, et al. Am J Obstet Gynecol. 2002;186:944-947 15. Naessen, et al. Am improvement in atleast 2 or the 3 primary outcome measures. For those who had a prior J Obstet Gynecol. 1997;177:115-119 16. Smith, et al. Maturitas. 1993;16:145-154 17. hysterectomy or a history of pelvic floor surgery, only 27% of women reported subjective Manonai, et al. J Obstet Gynaecol Res. 2001;27:255-260 improvement in symptoms. For women with fecal incontinence, data was limited as Sources of Funding: TherapeuticsMD the patient population was small and only 62% of women followed up at 3 months. Table 1: Systemic Estradiol Levels: Basal, with Treatment, Maximum, AUC Women that did follow up, however, did report subjective improvement in fecal leakage and smearing. Conclusion: This study measured the efficacy of two well known pelvic stimulating devices, InTone™ and InToneMV™ for urinary and/or fecal incontinence. Results show a significant improvement in episodes of daytime urination and decreased pad use over three months in those suffering urinary incontinence. Further studies are needed, however, to assess the long-term effects of this device and its role specifically in fecal incontinence. Sources of Funding: None

P-44. Comparison of the vaginal microbiome of pre-and post-menopausal women Yuli Song, Ph.D., Yu Wang, M.Sc, Miranda Farage, Ph.D.. Corporate R&D, Procter and Gamble, Mason, OH Objective: Investigate and compare the vaginal microbiome of pre- and post-menopausal women on Non-Hormonal therapy. Design: Study design: 20 female subjects represent two groups (Non-estrogenized pre- and post-menopausal women) were enrolled in the study. Subjects were prescreened with criteria of vaginal pH and vaginal atrophy score (pH ≤5 and atrophy score ≤2 for pre-menopausal subjects and pH ≥5.5 and atrophy score ≥5 for postmenopausal subjects). Urogenital exam and atrophy assessment were aDelivered to the upper part of the vagina with an applicator. bManually inserted performed by trained medical staff, and vaginal and introitus pH were measured using to lower part of the vagina. pH strip. vaginal microbial swabs were collect from middle of the vaginal wall. The NR=not reported; UD=undectectable. vaginal microbiome was characterized by 16S rDNA sequencing. Results: The vaginal microbiome of pre- and postmenopausal women could be readily distinguished based on the kinds and relative abundance of dominant bacterial species. For premenopausal women, what we saw in this study is similar as what was observed in previous studies, the vaginal microbiome was dominated by lactobacilli, namely L crispatus, L. gasseri etc. However, a distinct bacterial community with a low relative abundance of Lactobacillus & an increased bacterial diversity is associated with post-menopausal women who have atrophy and low vaginal pH. Our findings were like those of previous reports that showed the relatively low proportions of lactobacilli in the vaginal microbial communities of postmenopausal women. Conclusion: A distinct bacterial community with a low relative abundance of Lactobacillus and increased bacterial diversity is associated with post- Results: Non-inferiority of the vaginal non-hormonal moisturizer was confirmed menopausal women with atrophy. This provides us with a critical opportunity to develop regarding the difference of the mean “total severity score” at the end of the trial compared consumer products that can help the aging process, improve women’s health, increase to baseline (PP; n=80, treatment with moisturizing cream; n=71, treatment with estriol comfort and genital skin health. We believe changes in the vaginal ecology driven in part cream; p=0.0002). Subjective symptoms (vaginal dryness, itching, burning, dyspareunia) by hormonal shifts, present an opportunity to impact women Quality of Life. and daily life impairment improved by both treatments without significant intergroup Sources of Funding: None difference. VHI also improved by both treatments. However, the difference between the treatments was significant in favor for vaginal estriol (p<0.0001). No serious adverse events. More adverse events related to vaginal estriol than to moisturizing cream. Positive P-45. global judgement of efficacy and tolerability was high (> 85%) for both treatments. Candida Glabrata Genital Mycotic Infections in Postmenopausal Diabetic Conclusion: A vaginal non-hormonal moisturizing cream significantly improves Women with Glycosuria postmenopausal vaginal atrophy symptoms and may be used as first-line treatment Monica Sridhar, MS33, Josephine Urbina, MD1, Mark G. Martens, MD, FACOG1,2, for vaginal atrophy in accordance with the recommendations of the North American Debra Gussman, MD, MBA1. 1ob-gyn, Hackensack Meridian Health, Ocean, NJ; Menopause Society. 2Academic Affairs, Reading Hospital Tower Health, Reading, PA; 3Undergraduate Sources of Funding: Dr. August Wolff GmbH & Co. KG Arzneimittel, Bielefeld, Medical Education, Rutgers, Robert Wood Johnson School of Medicine, Piscataway, NJ Germany Objective: 1) Recognize that postmenopausal women with poorly controlled diabetes or those using Sodium-glucose Cotransporter-2 (SGLT2) inhibitors are prone to glycosuria which increases the incidence of mycotic genital infections. 2) Examine the P-47. role of Candida glabrata infection and review the treatment options for azole-resistant 3D Optical Coherence Tomography: a non-invasive technique to evaluate vulvovaginitis. Design: We present two postmenopausal diabetic women with Candida changes in vaginal epithelial thickness related to menopause glabrata genital mycotic infections. Results: Patient #1 is a 57 year old woman with a Neha T. Sudol2, Yusi Miao, MS1, Yona Tadir, MD1, Zhongping Chen, MS, PhD1, diagnosis of Type 2 diabetes. She was noncompliant with recommendations for diet, Felicia Lane, MS, MD2. 1Beckman Laser Institute, UC Irvine, Irvine, CA; 2Obstetrics exercise, and medications. Her HbA1c was 9%. She was menopausal and had minimal and Gynecology, UC Irvine, Orange, CA stress urinary incontinence. She developed a chronic vulvovaginal yeast infection Objective: Histopathologic changes of Genitourinary Syndrome of Menopause (GSM) which did not resolve with oral fluconazole or miconazole vaginal cream. A genital are thought to be caused by diminishing estrogen which leads to abnormal extracellular yeast culture was obtained showing Candida glabrata. She responded to boric acid matrix turnover. However, limited vaginal histology is available in this population and vaginal suppositories. Patient #2 is a 65 year old woman with a 15 year history of published studies have varying results regarding long-term changes. Therefore, a need Type 2 diabetes. She had a history of recurrent vaginal yeast infections. This patient exists for non-invasive techniques to further understand the dynamic vaginal changes had overactive bladder syndrome and wore a urinary pad daily. She was started on and it’s response to treatment. Optical coherence tomography (OCT) is a non-invasive, canagliflozin when her glucose control deteriorated. She developed a vulvovaginal point-of-care technology that visualizes tissue microstructure with high spatial resolution. yeast infection that did not respond to oral fluconazole or miconazole vaginal cream. We sought to validate the use of endoscopic OCT in the human vagina, in vivo, and A genital culture showed Candida glabrata. She did not respond to either boric acid or demonstrate its capability in clinical practice. We hypothesized that changes measured amphotericin vaginal suppositories. She continued to have vulvar burning symptoms. by OCT correlate with conventional methods of tissue evaluation. Design: This was a She discontinued the use of canagliflozin and her symptoms resolved. Conclusion: prospective pilot study to evaluate the vagina with OCT in pre and post-menopausal Women with diabetes are prone to developing genital mycotic infections, specifically women. Subjects were recruited from the Department of Urogynecology. A brief history vulvovaginal candidiasis. Glycosuria promotes the attachment and growth of yeast to the was obtained to confirm subjects’ menopausal status. Approval from the Institutional vaginal mucosa increasing the incidence of symptomatic yeast infections in this patient Review Board (IRB) was obtained prior to enrollment. Three-dimensional (3D) optical population. Most episodes of vulvovaginal candidiasis involve Candida albicans. Women coherence tomography (OCT) was used to measure vaginal epithelial thickness (VET) with Type 2 diabetes mellitus have an increased incidence of non-albicans infections such and other sub-epithelial structures. A handheld OCT imaging probe was designed in the as Candida glabrata. It has been proposed that the increase in Candida glabrata prevalence shape of a round tethered tube (10 mm in diameter, 15 cm in length) and optimized for is due to the widespread usage of antifungal medications in the diabetic population, which patient comfort and high quality imaging. The probe was capable of capturing tissue promotes resistant yeast strains. It is recognized that SGLT2 inhibitors, which promote morphology and blood vessels up to 1.5 mm below the surface with 6 μm resolution. A urinary excretion of glucose, have been shown to be associated with a higher rate of both 360° cross-sectional view of the vaginal tissue was obtained in real-time by rotating the albicans and non-albicans genital mycotic infections. Candida glabrata incidence also endoscopic probe at 25 frames/second. Additionally, volumetric OCT scanning of the appears to increase with menopause. Clinical presentation can be different with non- entire vagina was obtained by withdrawing the probe at 2 mm/s. A complete scan was albicans vulvovaginal infection. Patients often report burning rather than itching. Vulvar completed in under 40 seconds. Using the 3D image, 30 randomly selection locations and vaginal inflammation may not appear as pronounced to examiners. On potassium were selected to calculate a mean epithelial thickness. The 3D reconstruction of the entire hydroxide wet preparations, yeast is seen only in the budding form not as hyphae or vagina was generated and the VET was assessed from the cross-sectional view. Statistical pseudo hyphae. A higher vaginal pH at the upper limit of normal is seen and an associated analysis was performed using ANOVA (significance p<0.05) to compare the VET among bacterial vaginosis is common. It is important to obtain yeast cultures for women with the subjects. Results: Four subjects were enrolled: 3 were pre-menopausal and 1 was symptoms that do not respond to the usual first line azole treatments. Our case study post-menopausal. All four subjects denied any discomfort with the probe and no adverse presents two patients with Type 2 diabetes who developed Candida glabrata genital events were reported. OCT images showed a clear distinction between epithelium and mycotic infections, which did not respond to azole therapy. Boric acid suppositories were lamina propria (figure 1). Compared to the pre-menopausal group, the VET for the successful in one patient. Neither boric acid nor amphotericin vaginal suppositories were postmenopausal subject was significantly thinner (P<0.01) (287±65 μm pre, 145±29 μm effective in eradicating the second patient’s symptoms perhaps because of the increased post). Conclusion: This pilot study represents the first attempt to evaluate the vagina, in presence of glucose substrate and the increased mycotic growth in the affected area as a vivo, using endoscopic OCT systems. Our finding of significant epithelial thinning after result of incontinence and urinary pad use. Type 2 diabetes is a common co-morbidity menopause is consistent with published histopathologic changes associated with GSM. in the United States. We should be aware of the increasing prevalence of non-albicans We demonstrate that OCT is a safe, non-invasive technique that provideshigh resolution genital mycotic infections and the appropriate treatment options which may include the microstructure images of the vagina, in vivo, that approaches the histologic level. Future discontinuation of agents which increase fungal growth. studies that evaluate quantitative changes in vaginal collagen, elastin, glycogen enriched Sources of Funding: None epithelial cells, and vascular density may provide valuable information about how the vagina changes with various medical conditions and treatments. Sources of Funding: NIH grant R01HL-127271, R01HL-125084, and P41EB015890 P-46. Multinational multicenter open-label randomized controlled parallel trial comparing vaginal non-hormonal moisturizing cream to vaginal estriol P-48. cream in postmenopausal women with vaginal dryness Trends of Vulvar Carcinoma in the US: Opportunity for Early Diagnosis 1 4 3 Petra Stute, M.D.1, Iris Schmidts-Winkler, M.D.2, Mareike Panz, Ph. D.2, Clarissa Masur, Sarah Thappa , Marianne Smith, MD , Mitchell Maiman, MD , Mario Castellanos, 2 1 2 Ph. D.2, Christoph Abels, M. D.2. 1Obstetrics and Gynecology, Inselspital Bern, Bern, MD . Touro College of Osteopathic Medicine, Harlem, NY; Ambulatory Medicine Switzerland; 2Dr. August Wolff GmbH & Co. KG Arzneimittel, Bielefeld, Germany, and Division of Research, Department of Medicine, Staten Island University Hospital - 3 Bielefeld, Germany Northwell Health, Staten Island, NY; Obstetrics/Gynecology, Staten Island University 4 Objective: Multinational multicenter open-label randomized controlled parallel trial Hospital - Northwell Health, Staten Island, NY; Department of Medicine, Staten Island to test for non-inferiority of a non-hormonal vaginal moisturizing cream compared to University Hospital - Northwell Health, Staten Island, NY vaginal estriol cream in postmenopausal women with vaginal dryness. Design: 172 Objective: As women enter their 70s, 80s and 90s, examination of the genital area is postmenopausal women with vaginal dryness were randomized to either a 6-week done less frequently. Over the past years, major professional societies have moved away treatment with a vaginal non-hormonal moisturizing cream or vaginal estriol cream. from recommending routine pelvic exams in older, asymptomatic women. Consequently, Application regimen followed the package leaflet. Primary endpoint was to prove non- vulvar examination is a mostly neglected component of the physical exam in this age inferiority of the non-hormonal moisturizer based on a “total severity score” defined group. In recognition of these recommendations, we chose to analyze U.S. trends in as a sum score of the single symptoms vaginal dryness, itching, burning and pain vulvar cancer incidence, age and stage at diagnosis, survival, and HPV-association. unrelated to sexual intercourse. Secondary endpoints were symptom intensity of single Design: From 1992-2014, cases of vulvar and cervical cancer were extracted from symptoms, daily life impairment, vaginal health index (VHI), and global judgement of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) efficacy and safety. Subjective and objective signs of vaginal atrophy were assessed and Centers for Disease Control. Data on age at diagnosis, stage of disease, and HPV- at every visit (n=3); in addition, symptoms were documented in a diary once weekly. association were analyzed. Incidence and mortality rates were extracted and calculated. Incidence rates stratified by age at diagnosis were calculated for anogenital cancers and compared to HPV-associated subtypes. Results: At age 50-54, cervical cancer had the HEALTH SERVICES AND SURVEYS highest rate per 100,000 at 12.4, while vulvar Ca had 3.4, vaginal 0.9, and anal 4.5. POSTER PRESENTATIONS At age 75 and above, vulvar Ca has the highest rate at 12.1 and an upward trend like vaginal Ca (3.5), while cervical (10.5) and anal Ca (7.2) decrease with age. From 1992- 2014 there was 14.3% increase in vulvar Ca rates. The median age at diagnosis for HPV P-50. (+) and (-) vulvar Ca are 66 & 68 years, respectively. Only 59% are identified early with Menopause Management Knowledge in Post-graduate Family Medicine, localized disease. The 5-year survival for localized vulvar Ca is 86.4%, while regional Internal Medicine and Obstetrics & Gynecology Residents: A Cross- disease is 56.9% and distant is only 17.4%. From 1992-2014, cervical Ca mortality Sectional Survey rates declined by 34.2%, in contrast vulvar Ca rates were unchanged. Conclusion: The Juliana Kling1, Kathy MacLaughlin, MD2, Peter F. Schnatz3, Carolyn J. Crandall, MD, incidence of vulvar cancer increases with age, with the median age of diagnosis 67 years. MS4, Lisa Skinner4, Cynthia A. Stuenkel, MD5, Andrew M. Kaunitz, MD6, Diana Bitner, Patients identified early with localized disease do well while advanced tumors have lower MD7, Kristin Mara8, Karla S. Fohmader Hilsaca8, Stephanie S. Faubion, MD, FACP, survival rates. Meanwhile, medical societies do not routinely recommend inspection of NCMP, IF8. 1Internal Medicine, Mayo Clinic, Scottsdale, AZ; 2Family Medicine, Mayo the external genital region. Not including an external genital exam in women > 65 years Clinic, Rochester, MN; 3Obstetrics, Gynecology and Reproductive Sciences, Reading is a missed opportunity to provide optimal care. PA and Thomas Jefferson University, Reading, PA; 4Internal Medicine, UCLA, Sources of Funding: None. Los Angeles, CA; 5Medicine, UCSD, San Diego, CA; 6Obstetrics, Gynecology and Reproductive Sciences, University of Florida, Jacksonville, FL; 7Obstetrics, Gynecology and Reproductive Sciences, Spectrum Health, Michigan State University, Grand Rapids, MI; 8Mayo Clinic, Rochester, MN Objective: We aimed to evaluate training in menopause management in post-graduate residents across different training programs. Design: A cross-sectional, anonymous survey was emailed to trainees at all post- graduate levels in family medicine (FM), internal medicine (IM), and obstetrics and gynecology (OB/GYN) at residency programs across the U.S. The survey evaluated attitudes potentially influencing menopausal hormone therapy (HT) prescribing, knowledge about HT, availability and type of training in menopause medicine, and demographic information. Results: 20 U.S. programs participated, providing 183 at least partially completed surveys (703 residents contacted; 26% response rate). Most trainees were between 26 – 30 years of age (77%), female (66%), and believed it was important or very important to be trained to manage menopause (94%). Statistically significant differences were seen between disciplines regarding menopause competency questions. OB/GYN and FM were more likely than IM residents to answer various knowledge questions correctly. For example, 53 % of OB/GYN, and 56% of FM would appropriately prescribe HT until age 50 to a prematurely menopausal woman, while only 23% of IM answered this question correctly (p<0.001). These trends matched self-selected comfort level with menopause management (somewhat/adequately prepared: FM = 75%, OB/GYN=69%, IM=50% p <0.001). Females were more likely than males to correctly diagnose menopause (89.5% vs. 71.2%, p=0.002); to restart HT for recurrent symptoms after discontinuation of HT (71.0% often/sometimes vs. 54.3%, p =0.01); and to indicate that training in menopause was very important or important (95.5% vs. 89.8%, p =0.006). Conclusion: FM, IM and OB/GYN residents recognize the importance of training in menopause management, but important knowledge gaps exist. Menopause management is becoming increasingly important as the number of symptomatic menopausal women rises. Identifying and P-49. addressing barriers to menopause training are needed. 302/Avogen a Novel Non-estrogenic Natural Avocado Molecule Induces Sources of Funding: Stephanie Faubion is a consultant for Mithra Pharmaceuticals Histomorphologic Change to Vaginal Mucosa and Associated Clinical and Procter and Gamble. Andrew M. Kaunitz consults for: AMAG, Bayer HealthCare Symptom Improvement in Vaginal Atrophy Pharmaceuticals, Mithra, Sebela, and Shionogi. He receives research grants (funds paid to Allan Wu, MD1,2. 1OBYGN and Reproductive Sciences, UCSD, Rancho Mirage, CA; University of Florida) from: Allergan, Bayer HealthCare Pharmaceuticals, Endoceutics, 2Stem Cell Research Center, UC, Riverside, Riverside, CA Mithra, and TherapeuticsMD. Objective: 302/Avogen is a natural product molecule isolated from the avocado and is a non-steroidal molecule within the lipid furane family. It has been used as a compound P-51. for dermal regeneration and treatment for basal cell and actinic lesions as a topical and Effective Delivery of a Menopause Curriculum oral herbal supplement. The molecule has also exhibited cancer stem cell inhibition Renee R. Eger, MD, Julia Shinnick, MD. Ob-Gyn, Women & Infants Hospital, in multiple myeloma in-vitro studies. Patients taking the oral herbal supplement had Providence, RI self reported previously to the manufacturer intra-vaginal use for menopausal related Objective: To investigate the modality of PowerPoint that most effectively improved vagina atrophy/dryness. The following preliminary IRB approved study (Protocol AV- objective assessments of knowledge related to menopause medicine. Secondary VS-301, IRB Approval IRCM-2017-172) is the first formal evaluation of 302/Avogen objectives included assessing changes in self-reported confidence in managing use in a gynecologic setting to determine safety and survey clinical impact if any. menopause issues and satisfaction with the presentations. Design: Prospective cross-over Design: 24 patients with menopausal vaginal atrophy or vaginal dryness were interviewed study of OBGYN and FM residents training at Women & Infants Hospital (WIH) over for adequacy for enrollment. 20 patients qualified for the study. Patients received a the 2017-2018 academic year. Residents took a 26 question multiple-choice test assessing 6 week supply of 302/Avogen and were required to use intravaginal every night prior objective baseline knowledge and learning style with dichotomous questions, and self to bed time. Patients received: a menopause rating scale (MRS) questionnaire, a 2mm confidence approaching menopause issues, as rated on a Likert scale, immediately before punch biopsy, vaginal pap smear, transvaginal ultrasound (for endometrial thickness) and randomization to a series of 3 PowerPoints, each < 30 slides, completed during regularly a serum hormone profile prior to and after 302/Avogen therapy. Results: All patients scheduled didactic time. Presentations varied by subject and formats. Formats included achieved clinical improvements on the MRS and specifically within the urogynecologic a classically styled presentation (typical), slides with only pictures accompanied by a sub scale related to vaginal dryness and sexual function. Histologic specimens revealed verbal narration (pictures), and slides that required participants to click certain areas improved rete peg penetration and stromal collagen deposition. Cytologic specimens to reveal information (interactive). PowerPoint topics included Menopause Basics revealed fewer sloughed cells and an increase in N:C ratio. No statistical difference (MB), Hormone Replacement Therapy and Treatment of Vasomotor Symptoms (HRT) in endometrial thickness or hormonal profile (estradiol, progesterone, DHEAS) was and the Genitourinary Syndrome of Menopause (GSM) (Table 1) Immediately after appreciated comparing before and after values. Conclusion: 302/Avogen appears to be completing all of the presentations, residents took the same post-test assessing objective well tolerated intravaginally with no major side effects. After 6 weeks of therapy positive knowledge and confidence, with additional questions assessing satisfaction on a Likert results in terms of moisturization, vascularization and overall improvement in dryness/ scale. ANOVA, T-tests, paired T-tests, Wilcoxon rank-sum, signed rank test, and mixed atrophy symptoms were photo documented and subjectively noted in all participating effects linear regression model were used for crossover analysis with two-tailed p-values patients. As the molecule does not seem to have any systemic estrogenic-like effects, the and p<0.05 considered significant. Results: Objective knowledge scores increased possibility of 302/Avogen remodeling the vaginal lining through non-Estrogen pathways significantly from pre-test to post-test for all three topics (p <0.05). GSM had the smallest presents a novel alternative for atrophic patients contra-indicated to conventional mean increase in post-test objective score, while HRT had the largest. Typical formats Estrogen therapy. had the greatest mean change in objective scores, while pictures had the least (0.68 points Sources of Funding: Supported by grant funding from Avosciences Medical. change; p=0.057). Conclusion: Residents had low baseline knowledge and confidence, though both increased significantly, regardless of topic or delivery format. Typical presentations were associated with the greatest increase in objective assessment scores, while pictures demonstrated the least, despite 44% of residents self-identifying as visual learners. Over 60% of residents indicated they were satisfied or completely satisfied with the traditional and interactive formats of PowerPoint. Sources of Funding: None with the other groups: estradiol vaginal insert, conjugated estrogen and estradiol creams. Table 1 Subjects and Formats by Group The data also showed that the ospemifene group had the lowest mean outpatient costs of any cohort. Additional research is ongoing to examine the predictors of adherence in patients utilizing the different formulations of the aforementioned medications. Sources of Funding: None

Table 2 Results P-53. The Impact of Shared Decision Making on Women Experiencing Menopausal Symptoms: Focus on Knowledge and Decision Making Regarding Treatment Options. Rebecca Jackson, MD1, Sandra Dayaratna, MD1, Rhea Powell, MD2, Randa Sifri, MD3, Katherine Sherif, MD2, Anett Petrich4, Sarah Hegarty4, Ronald Myers, PhD4. 1OBGYN, Thomas Jefferson.University Hospital, Philadelphia, PA; 2Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA; 3Family and Community Medicine, Thomas Jefferson University Hospital, Philadelphia, PA; 4Thomas Jefferson University Hospital, Philadelphia, PA Objective: To determine the effects of shared decision making on women’s knowledge and decisional conflict about treatment of menopausal symptoms Design: This pre-post study recruited study participants through physician referral and electronic medical record (EMR) review from the departments of obstetrics and gynecology, family medicine and internal medicine at a large urban academic medical center. The women were between 35 and 60 years of age, presenting with hot flashes, night sweats, vaginal dryness, or dyspareunia. After referral, the women were contacted by phone by the research coordinator who explained the study, obtained consent, administered a baseline survey that assessed treatment knowledge and decisional conflict related to menopausal symptoms, scheduled a shared decision making (SDM) call with a nurse educator, and then mailed each participant an informational brochure. During the SDM call, the nurse educator reviewed the brochure with the participant, verified her primary menopausal symptom(s), and completed a symptom-specific treatment SDM session to clarify patient treatment preference. The research assistant administered an endpoint telephone survey 60 days later. Change in treatment knowledge was measured by a 9 item true/ false quiz given at the baseline and endpoint surveys; change in Decisional Conflict Scale was assessed using 12 items with 4 subscales (clarity, informed, certainty, support). Results: A total of 118 women were referred to the study. The research assistant enrolled 48 women (41%) into the study. Of the 42 women that the nurse educator was able to reach, 5 indicated they had “Decided Against” all available options, 37 completed an P-52. SDM session, and 31 completed the endpoint survey. Among the 31 completing the Adherence, Persistence, and Healthcare Costs Associated with Ospemifene endpoint survey, knowledge increased significantly from 6.6 (SD 1.7) to 7.3 (SD 1.2) Compared with Local Estrogen Therapy Among Commercially Insured (95% CI: [0.2, 1.2]; p = 0.007 (Table 1). Decisional conflict decreased overall and within Women in the United States each of the subscales. Overall decisional conflict was 38.5 (SD 22.2) at baseline and Brooke Faught1, Jason Yeaw2, Katharine Coyle2, Samuel Schaffer3, Christiane Maroun3, 19.6 (SD 17.2) at endpoint survey, corresponding to a reduction in decisional conflict Graziella Soulban3. 1Women’s Institute for Sexual Health, Nashville, TN; 2IQVIA, of 21.1 points (95% CI: [-26.6, -11.2]; p <0.001) (Table 2) Conclusion: Women who Fairfax, VA; 3Duchesnay Inc., Blainville, QC, Canada underwent decision counseling displayed increased knowledge and reduced decisional Objective: To measure adherence and persistence associated with ospemifene, an oral, conflict related to treatment for menopausal symptoms. Results of this study suggest that selective estrogen receptor modulator and nonhormonal option indicated for the treatment SDM may increase patient treatment knowledge and reduce decisional conflict. Further of moderate to severe dyspareunia due to menopause, compared with local estrogen research is needed to validate these findings and assess the effects of SDM on treatment therapy (LET) (e.g., conjugated estrogens cream, estradiol [vaginal insert, cream]) in decision making. commercially-insured patients. Direct healthcare costs and resource utilization among Sources of Funding: Pfizer educational grant the treatment groups were also studied. Design: IQVIA’s Real-World Data Adjudicated Table 1. Change in knowledge (n=31) Claims - US Database provided data for this study. For inclusion in the study, patients had to have ≥ 180 days immediately preceding and ≥ 360 days immediately following their initial prescription (index date). Patients were required to have no prescriptions for an index medication in the pre-index period. Adherence was computed using the *from paired t tests proportion of days covered (PDC) and capped at 100%. Persistence was calculated Table 2. Change in decisional conflict (n=31) based on the time (in consecutive days) from index therapy initiation until the first observed gap in medication possession during the follow-up period (discontinuation, allowing 1.5 times the days supplied value of the prior prescription for refill), therapy switch, or the end of patient follow-up (12-months). All-cause healthcare costs were measured and reported over the 12-month post-index period for the medication cohorts. Results: The analysis included 86,946 total patients; 3,609 patients with ospemifene, 28,329 with conjugated estrogen cream, 14,845 with estradiol, 36,536 with estradiol cream and 3,627 with estradiol vaginal ring. The mean age for the ospemifene cohort *from paired t tests was 56.42 years, similar to the other product cohorts. The majority of ospemifene patients were enrolled in a preferred provider organization (PPO) plan (89.53%) compared with conjugated estrogens cream (75.44%), estradiol vaginal insert (80.75%), estradiol P-54. cream (82.86%), and estradiol vaginal ring (79.90%) (p<0.0001 across the category). Exploring Attitudes of the Health Care Community Towards Use of ART Total mean pre-index costs were lowest for ospemifene ($4,794.12) compared with the in Peri and Menopausal Populations other cohorts ($5,636.10; $5,743.59; $5,637.52; $5,575.46 for conjugated estrogens Kavisha Khanuja, MD, Taleen MacArthur, Gloria Bachmann, MD, MMS. OBGYN, cream, estradiol vaginal insert, estradiol cream and estradiol vaginal ring, respectively Rutgers Robert Wood Johnson Medical School, Carlstadt, NJ (p=0.0071)). During the pre-index period, almost one-third of patients had evidence Objective: With the advent of assisted reproductive technologies (ART), more of an anti-depressant or anti-hypertensive medication. Over the 12-month post-index reproductive options are widely available for menopausal women choosing to achieve period, ospemifene patients exhibited the highest adherence among non-ring medications pregnancy later in life. Recent fertility trends in the United States and other developed with a mean PDC of 0.392 compared with the other cohorts (conjugated estrogen cream nations have shown an increase in first-birth age and a decrease in fertility due to social, 0.201, estradiol vaginal insert 0.321, estradiol cream 0.217, estradiol vaginal ring 0.527; financial, and career goals. Consequently, demand and usage of ART to facilitate p<0.0001). Similarly, persistence for ospemifene patients was greater than that for the pregnancy has risen to a point where ART may be considered an option for menopausal other cohorts, except for the estradiol vaginal ring (22.83% vs. 4.99%, 16.40%, 6.27%, women who are seeking pregnancy as well as perimenopausal women who have failed 43.56% respectively; p<.0001). Total mean pharmacy costs were highest for the estradiol to achieve pregnancy with their own oocytes. This shift to a later-aged pregnancy vaginal ring ($4,593.53) compared with the other cohorts (ospemifene $4,587.17, introduces a potential need to include pregnancy counseling in perimenopausal and in estradiol vaginal insert $4,466.57, conjugated estrogen cream $4,251.30, estradiol cream early menopausal woman’s annual wellness visits. To study the acceptance of this type $4,005.19; p=0.0003). Ospemifene had the lowest total mean outpatient costs ($5,537.07) of counseling in older women, we surveyed the attitudes of the healthcare community and estradiol vaginal inserts the highest ($6,299.08; p=0.0011). Conclusion: The data towards age and biological motherhood. Design: An online survey was sent to the demonstrated that the ospemifene group had greater adherence and persistence compared Rutgers Robert Wood Johnson Medical School general email listserv, which included faculty, staff, and medical students. IRB approval was obtained prior to administration do not feel that VA facilities are able to meet their medical needs regarding menopause. and participation was entirely voluntary and consented. The survey was anonymous, Compared to minority women, a significantly higher proportion of white women HIPPAA compliant and administered using the platform Qualetrics. This software received menopause care outside VA; compared to whites and Hispanics, a significantly prevented participants from taking the survey more than once on the same device, so each higher proportion of black women reported not feeling comfortable receiving care for response was assumed to be from a unique individual. The listserv is entirely anonymous, menopause in the VA environment. Conclusion: Although most women would have and the study team did not have access to the individual emails of the participants. preferred to obtain menopause information from their VA providers, the most common Results: Surveys were sent to approximately 1,000 individuals and 118 unique responses sources of menopause information were the internet and family or friends. This is of were recorded, giving an 11.8% response rate. Of the 118 participants, ~77% identified concern, given the inaccuracy of many web resources. Despite the known detrimental as female, 21% as male, 1% as transgender women, and 1% as other. If faced with a effects of menopausal symptoms on health and quality of life and the fact that multiple life-threatening high-risk fertility or perinatal condition, 95% of respondents reported hormonal and nonhormonal treatments are available, many symptomatic women veterans they would still pursue fertility perseveration options. Further, 71.4% would be willing are not receiving treatment or, minorities in particular, not discussing their symptoms to pursue ART to achieve a pregnancy despite a high risk of a complicated pregnancy with their VA providers. Disparities in perception of menopausal care can be addressed for the mother and the potential of adverse consequences that may occur to the fetus. by providers initiating these discussions and tailoring the education of women according With regard to age of pregnancy, male and female participants answered similarly to the to their preferences and beliefs. question “what is the oldest age you feel a woman should be pregnant at?” with females Sources of Funding: Pfizer, Inc. answering a mean of 39.19 years, and males answering 38.16 years. For the oldest age at which a male should be a biological father, males answered 48.26 years while females answered 49.56 years. The survey also distinguished between biological parenthood and P-56. “co-parenting,” defined as taking on the full-time responsibilities of childcare until the Health Care Costs Associated with Depression, Anxiety, and Urinary child reaches adulthood, as in the case of adoption or caring for a child from a partner’s Track Infection in Women Diagnosed with Vulvovaginal Atrophy prior relationship. For co-parenting, participants stated that the oldest age for females Érick Moyneur1, Katherine Dea1, Francis Vekeman1, Fernand Labrie2. 1StatLog should be a mean of 53.9 years while for males it is 50.6 years. Conclusion: These Econometrics, Montreal, QC, Canada; 2Endoceutics Inc., Quebec, QC, Canada data verify that a negative connotation still exists pertaining to perimenopausal and Objective: Many women of menopausal age must deal with symptoms and signs of menopausal women’s biological fitness to undertake pregnancy at this time in their life vulvovaginal atrophy (VVA) daily, with only a fraction with a known diagnosis, and cycle. Interestingly, these data show that a difference between the concepts of biological few with a proper treatment. In addition to the direct symptoms, women with VVA are motherhood/fatherhood and co-parenting exists. Although age for co-parenting between at increased risk of developing depression, anxiety, and urinary track infection (UTI). the two sexes were similar, acceptable biological parenthood age for women was 10 years VVA and associated conditions may lead to increased health care costs, for both patients younger to the acceptable biological parenthood age for men despite research showing and payers. The study aimed to quantify the incremental health care costs associated with fetal consequences for both advanced maternal and paternal age. However, participants of depression, anxiety, and UTI in women diagnosed with VVA. Design: A retrospective the study were personally accepting of potential life-threatening risks and consequences cohort analysis of claims data from Truven Health MarketScan® Commercial and to mother and fetus in order to achieve a pregnancy regardless of maternal age. Given Medicare Supplemental Databases was conducted (01/2010-09/2016). Women had to the indication from these data that attitudes surrounding motherhood during menopause have ≥2 VVA/dyspareunia diagnoses (ICD9: 627.3, 625.0; ICD10: N94.1, N95.2) on are primarily adversely perceived, universal counseling for peri and menopausal women separate visits, be ≥45-year old and have ≥365 days of continuous insurance coverage interested in achieving pregnancy and motherhood does not appear to be a timely received before and after the first VVA/dyspareunia diagnosis. Anxiety was defined as having ≥2 concept in the health care community. To further the concept of routine pregnancy and separate visits with an anxiety diagnosis. Depression, which included major depression ART counseling in the peri and menopausal population and need to expand infertility disorder, was defined as having ≥2 separate visits with a depression diagnosis or one guidelines to include this group of women, additional research examining perspectives visit with a depression diagnosis and ≥1 dispensing of an antidepressant. Depression and of the general population will be done. anxiety were analyzed together. UTI was defined as having ≥1 visit with a diagnosis of Sources of Funding: None UTI. All three conditions were assessed in the year before or after the VVA diagnosis. The incremental health care costs per member per year (PMPY) associated with depression/ anxiety and UTI were calculated from VVA women with versus without the respective P-55. conditions. Total as well as outpatient, inpatient, and pharmacy costs were calculated, Advancing Menopause Care: What Women Want and results were stratified for women <65 and ≥65 years old. Results: A total of 125,889 Ana Palacio1,2, Leonardo Tamariz1,2, Stuti Dang1,2, Silvina Levis1,2. 1GRECC, Miami women with VVA were identified. VVA women with versus without depression/anxiety Veterans Affairs Healthcare System, Miami, FL; 2Medicine, University of Miami, were younger (mean [SD], 59.8 [9.2] vs. 61.1 [9.3], std. diff. = 0.14) and the opposite Miami, FL was observed for those with UTI (mean [SD], 61.9 [10.4] vs. 60.1 [8.6], std. diff. = 0.18). Objective: Women age 45-64 comprise almost half of the US female veteran population. The prevalence of depression/anxiety and UTI were 30.9% and 35.1% (<65: 32.5% and About 700,000 women veterans receive healthcare at Veterans Health Administration 33.3%; ≥65: 26.6% and 39.9%). Total PMPY incremental costs between VVA women (VA) facilities and their mean age is 48 years. We investigated how women veterans with versus without depression/anxiety was $7,294 (cost ratio [CR]: 1.65) (Figure). receiving primary care at VA obtain menopause information, how they would prefer A larger difference in total PMPY costs was observed among women aged <65 versus to receive it, and their perception of the menopausal care they receive at VA. We also 65 years old (CR, <65: 1.77; ≥65: 1.51, p<.05 for both). The total PMPY incremental examined if these findings vary by race or ethnicity. Design: A postal survey inquiring costs between VVA women with versus without UTI was $6,104 (CR: 1.54) (Figure) about preferred and actual sources of menopause information, symptoms and perceptions (CR, <65: 1.50; ≥65: 1.55, p<.05 for both). Conclusion: Among women with VVA, of menopause care at VA was mailed to all women veterans ages 45-64 who had received those suffering from depression/anxiety and UTI have significantly higher health care primary care at three large VA Healthcare Systems (Miami, West Palm Beach) in the costs. Since a higher incidence of depression/anxiety and UTI is associated with VVA, a previous 12 months. In the 4-page anonymous form, women self-reported their race and well accepted treatment of VVA has the potential for significant health care cost savings. ethnicity, education level, and their menopausal status: premenopause, perimenopause, Sources of Funding: This study was funded by Endoceutics Inc. or postmenopause. The survey also inquired about their usual sources of menopause information, their preferred way to receive this information, if they had hot flashes, night sweats and/or vaginal dryness ever and in the previous 30 days, and present or past menopause symptom management at their VA clinic. Results: Surveys were mailed to 5888 women veterans; 26% returned the completed forms (Orlando 26%, West Palm Beach 25%, Miami 24%). After excluding those who were premenopausal, checked more than one menopause status, or had missing data, we report results of 1293 women: 57% white, 23% black, and 14% Hispanic; 19% perimenopausal and 81% menopausal. There were no differences in baseline characteristics, except white women used email daily significantly more frequently than minority women (p<0.01). Although across race/ ethnicities, most women would have preferred to receive menopause information from their VA doctor, the most common sources were the internet (50%) and friends or family members (48%), which were comparable across racial/ethnic groups. After adjusting for employment, education and site of medical care, compared to white women, the adjusted OR of receiving menopausal information from their physicians was 0.71; 95% CI 0.51- 0.98 (p=0.02) for black women and 0.79; 95% CI 0.50-0.99 (p=0.03) for Hispanic women. Black and Hispanic women were more likely to receive information regarding menopause from magazines than white women, 32% and 28% vs. 21%, respectively (p <0.01). Similarly across race/ethnicities and menopause stage, 68% of women reported being bothered by vasomotor symptoms and 55% by vaginal dryness. Although the proportion of those having a discussion with their VA provider about these symptoms varied significantly across race/ethnicity, there were no significant differences on who received treatment for vasomotor symptoms (whites 40%, blacks 33%, Hispanics 34%) or vaginal dryness (whites 43%, blacks and Hispanics 33%, p= 0.52). Those with past or present menopausal symptoms but who did not receive care for these symptoms at VA, listed various reasons, most commonly and similar across race/ethnicity, was that they P-57. movement activity measured by punctuation, number of correctness, number of errors, Does quality of life differ between women with premenstrual syndrome number of omissions, average touch time, average time of successes and time mean of and those who are menopausal? errors), developed by the Laboratory for Research on Visual Applications of the State Mariko Ogawa, MD, Kiyoshi Takamatsu, Professor. Obstetrics and Gynecology, Tokyo University of Santa Catarina (LARVA - UDESC) and presents independent scores for Dental College Ichikawa General Hospital, Ichikawa, Japan each movement activity. Participants were divided into two groups: the active group Objective: Premenstrual syndrome (PMS) occurs during the premenstrual phase. (GA), consisting of physically active postmenopausal women and the sedentary group Women who suffer from PMS usually have normal menstrual cycles and hormone levels. (GS), with sedentary postmenopausal women. The parameter used for the outcome On the other hand, menopausal disorders occur during the perimenopausal transition. was physical activity, according to IPAQ. Statistical analysis was performed using Menopausal symptoms are caused by hormonal changes, especially estrogen depletion. the SPSS software version 21.0 with homogeneity of the two groups by the Shapiro- Although they seem quite different, PMS and menopause have a lot in common. Wilk test, Mann-Whitney test and Linear Regression Analysis for dependent variables. We investigated quality of life (QOL) differences between women with PMS and Results: The women had a mean age of 68.97±5.18 years (GA) and 76.35±9.10 years menopausal disorders. Design: Participants were 68 female outpatients who presented (GS), of which 58% (n = 36) were physically active postmenopausal (GA) and 42% for PMS or menopausal syndrome treatment. The PMS group consisted of 22 females and (n = 26) were sedentary (GS). There were higher exergame scores in GA compared to the menopause group consisted of 46 females. All participants completed the Short Form GS (p = 0.009), with median 61 points and 51 points for each of the groups, respectively. 36 (SF-36) QOL assessment and their responses were subjected to statistical analysis. As well as in the success number (p = 0.014), where GA reached median 7.25 successes Results: The mean QOL results of the PMS group were physical functioning (PF) 88.6, and GS reached 6 successes, and success mean time (p = 0.026) with median 6.23s role limitations-physical (RP) 65.1, bodily pain (BP) 50.5, general health perceptions in GA and 6.80s in GS (Table 1). The age (β = -0.493, p <0.001) and the depressed (GH) 47.4, energy/vitality (VT) 35.5, social functioning (SF) 64.2, role limitations- mood (β = -0.274, p = 0.012) influenced the exergame score, according to a regression emotional (RE) 54.5, and mental health (MH) 44.3. VT, GH, and MH were lower than the analysis that revealed a significant finding considering F (2, 61) = 15.25 and p <0.001. other factors. Among menopausal females, the mean QOL values were PF 82.6, RP 65.5, The predictive capacity of the outcome was 31.8% (r2 = 0.318) in exergame score in BP 55.2, GH 43.1, VT 34.4, SF 67.9, RE 66.8, and MH 54.0. VT and GH were lower postmenopausal women (Table 2). Conclusion: Postmenopausal women practicing than other factors, like the PMS group, but MH was normal. There were no significant physical activity presented better performance in virtual reality games when compared between-group differences for PMS and menopause groups. Conclusion: We could not to sedentary women. Increased age and depressed mood have a negative influence on the find significant QOL differences between the PMS and menopausal groups; however, performance of virtual activities in postmenopausal women. our results revealed a trend suggestive of MH differences. Thus, future well-powered Sources of Funding: None studies are needed. Table 1: Mann-Whitney test to score every movement activity and average response, its Sources of Funding: None median, minimum, maximum and percentiles 25 and 75.

P-58. Pharmacists with the NCMP Credential: Who, Where, What, Why, and How Sally Rafie, PharmD, APh, BCPS, NCMP1, Veronica P. Vernon, PharmD3, Elizabeth Cook, PharmD, AE-C, BCACP, CDE4, Audra Wilson, PharmD2. 1Pharmacy, UC San Diego Health, San Diego, CA; 2Pharmacy, Boise VA Medical Center, Boise, ID; 3College of Pharmacy & Health Sciences, Butler University, Indianapolis, IN; 4Ben and Maytee Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, TX Objective: To characterize the demographics and practices of pharmacists with the North American Menopause Society (NAMS) Certified Menopause Practitioner (NCMP) credential. Design: Pharmacists with the NCMP credential were identified using the NAMS NCMP list published in February 2018 and contacted to participate in a 24-question online survey in June 2018. Results: Of the 41 pharmacists with NCMP credentials, 26 (63%) responded to the survey. The majority of respondents were female (84%), practicing for at least 10 years (range 5-47 years in practice), based in Canada Teste de Mann-Whitney; p-value (p); seconds (s); active group (GA); sedentary (68%), and practicing in community retail (43%) or compounding (39%) pharmacies. group (GS) Most participants (52%) reported no coverage of menopause care in their pharmacy Table 2: Linear Regression Model using score as the dependent variable. school curriculum or post-graduate training. Nearly all (92%) are current members of NAMS and have attended at least one NAMS meeting in the last five years (58%). Most pharmacists reported pursuing the NCMP credential for credibility with patients (81%), to increase their knowledge about menopause (77%), and for credibility with other Linear regression analysis; Beta(β); p-value (p); seconds (s) healthcare providers (73%). Almost all (88%) respondents plan to renew their NCMP credential. Among these pharmacists, many are presently counseling about treatment options (78%) and educating about selected treatment (78%). To advance their practice, P-60. pharmacists are most interested in initiating systemic hormonal therapy (61%) and Using Mobile Health Technologies to Manage Depression in Midlife modifying or continuing systemic hormonal therapy (57%). Conclusion: Pharmacists Women: A Pilot Study represent 4% of all NCMP credentialed healthcare professionals. Pharmacists find the Claudio Soares, MD, PhD, FRCPC, MBA. Psychiatry, Queen’s University, Kingston, NCMP credential to be valuable. While pharmacists are engaged in counseling and ON, Canada recommendations, they desire prescriptive authority related to menopause care. Future Objective: Mobile health technologies (M-health) are transforming the quality, studies should explore the various pharmacist care models and evaluate the impact of efficiency, and availability of care across many disciplines, including mental health. pharmacist care on organizational operations and patient outcomes. M-health technologies may contribute to patient engagement, symptom management, Sources of Funding: None treatment adherence, and real-time monitoring of wellness, resilience and relapse prevention. Here we present preliminary data on M-health application for monitoring of depression in a longitudinal study of midlife women. The ultimate goal is to leverage P-59. digital phenotyping for relapse prevention and identification of key contributors to The physical activity in postmenopause women and performance at greater resilience. Design: Midlife women with Major Depressive Disorders (N=15) who Virtual Reality had presented with satisfactory response to antidepressants were further enrolled into a Juliana Z. Raimundo, MSc1,2, Rodrigo D. Raimundo, PhD2, Luiz C. de Abreu, PhD2, longitudinal study for monitoring of their wellness. In addition to bi-monthly in-person José M. Soares Júnior, PhD1, Ricardo d. Simões1, Alex R. Norberto1,2, Valdelias X. visits, participants were given access to a mobile application. The application allows the Pereira, PhD1,2, Isabel C. Sorpreso, PhD1,2, Edmund C. Baracat, PhD1. 1Faculdade collection of 33 digital-based, context-sensing outcome measures including fluid changes de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; 2Faculdade de in mood, sleep, and depression severity while analyzing spatial and social dimensions Medicina do ABC FMABC, Santo Andre, Brazil and using embedded smartphone tools such as a GPS tracker, accelerometer, and ambient Objective: To analyze factors associated to performance in virtual reality among active light detector. Results: The mobile application generated more than 15,000 hours of real- and sedentary women after menopause. Design: Cross-sectional study carried out at time, context-sensing data with high acceptabliity among users (97% adherence). There the General Ambulatory of the ABC School of Medicine, from October 2016 to April was a strong correlation between novel, digital-based metrics (i.e., location entropy) and 2017. The study included 62 postmenopausal women (absence of menstruation for 12 traditional measures for depression management (e.g., PHQ-9). At the group data level, months) under a convenience sample. A clinical and sociodemographic questionnaire regression model indicated that sensed measures associated with motor activity, sleep containing the following variables was applied: sex, age, body mass index (BMI), interruptions and inferred decreased social interactions were significantly associated with schooling, and marital status. All participants answered to health questionnaires PHQ-9 scores (p=0.025, 0.023 and 0.017, respectively). At the individual level, mobile validated in Brazil for evaluation of mood and physical activity: International Physical health models/algorythms were predictive of individual’s depression (PHQ-9 scores) Activity Questionnaire (IPAQ) and the Brunel Humor scale. After an interview, all at 85% accuracy - i.e. within an average error margin of 15%. Conclusion: M-Health the patients performed exergame activity - “MoviLetrando” (virtual reality game with technologies may have an important role in quantifying prodromal symptoms prior to a relapse in depressed patients; the information collected may also inform contributing Confidence in Providers factors to a more sustained wellness. This technology also allows us to monitor patient’s real-time behavior in the context of interventions, characterizing digital biomarkers for treatment response across patient segments, and cross-validating novel endpoints against traditional markers that are more burdensome and time-consuming - i.e., clinical scales, in-person visits. Ultimately, innovation and research on m-health may help reduce the burden (personal, societal) associated with depression among midlife women. Sources of Funding: Supported by the Canadian Biomarker Integration Network in Depression (CAN-BIND). Partialfy funded by the Ontario Brain Institute (OBI)

P-61. Patient satisfaction with menopause care Premenopausal – menstruation patterns are as they have always been and no menopause symptoms Sandy Truong, MD1, Jennifer Wolff2, Vicki Gelfeld2, Patty David2, Stephen Perrine2, Perimenopausal – some changes in menstruation patterns and no menopause Wen Shen, MD, MPH1. 1Gynecology/Obstetrics, Johns Hopkins, Baltimore, MD; symptoms 2AARP, Washington, DC Menopausal – menstruation stopped within the past year and regular menopause Objective: As life expectancy increases in the United States, a growing number of symptoms women will face postmenopausal health issues such as cardiovascular disease, cancer, Postmenopausal – menstruation stopped more than a year ago and no longer osteoporosis in addition to key aspects of quality of life such as mood disorders and experience any menopause symptoms vulvovaginal atrophy. Primary care providers should be ready to address these concerns, manage these symptoms and prevent morbidity and mortality. A series of surveys from 2000 to 2012 showed that providers are the most frequent source of information for P-62. menopausal symptoms, but 23 to 72% of women did not consult a provider, and of those Factors associated with preoperative counseling about menopause among who did, 65 to 85% of women had to initiate the discussion. One area of controversy women undergoing bilateral oophorectomy in particular has been the role of menopause hormone therapy (MHT) with providers Lauren Verrilli, M.D1, Jacquelyn Mirr, B.S2, Kole Binger, B.S2, Heidi W. Brown, M.D, offering MHT to about 20% of their patients and about 20% of women reporting current M.A.S.1,2, Makeba Williams1,2. 1Department of Obstetrics and Gynecology, University MHT use. Because of these studies raising awareness to the lack of menopause care, we of Wisconsin Madison, Madison, WI; 2University of Wisconsin School of Medicine and hypothesized that more women should be receiving care for menopause symptoms. This Public Health, Madison, WI study sought to determine how often women discuss symptoms with providers, their Objective: To determine factors associated with preoperative counseling of women about satisfaction with care, and any changes to treatment recommendations in light of recent symptoms and treatment of surgical menopause To characterize menopausal symptoms studies demonstrating the safety of MHT. Design: An online survey was administered and treatment in this population Design: This is a retrospective chart review of patients to 1,509 women between age 40-89 in April 2018 from the AARP’s 5,000 panelists and under the age of 52 who underwent the equivalent of bilateral oophorectomy at a single Toluna’s four million panelists. Descriptive statistics were performed. Results: 81% of academic institution between January 2015 and March 2018, and those who underwent women age 40-89 have experienced menopause symptoms, with 12% describing their unilateral oophorectomy in the setting of prior contralateral oophorectomy. We reviewed symptoms as interfering with their lives “a great deal” or “completely debilitating.” charts to abstract relevant medical and surgical details and ascertain whether patients Despite how common these symptoms are, only 50% of women have discussed received preoperative counseling about symptoms and treatment of surgical menopause. menopause with providers and 31% do not receive information about menopause from We collected data about postoperative menopausal symptoms and receipt of hormonal any sources. Among those who say they need treatment for their symptoms, only 15% therapy (HT) and non-hormonal therapy, when available. We performed descriptive have pursued it but not received it; 25% with symptoms have discussed it with their analyses using SPSS 24.0 to describe the sample and to compare women who did and provider but were not offered treatment and 11% felt their provider was not sympathetic did not receive preoperative counseling about symptoms and treatment of surgical about their symptoms. However, 97% have said that their provider was comfortable menopause. Backwards logistic regression identified factors associated with preoperative and 97% said they were knowledgeable. Regarding treatment options, 61% of women counseling. Results: We identified 154 patients, of whom 66% (n=101) received reported that providers discussed MHT, 34% reported that their provider recommended preoperative counseling about menopausal symptoms and treatment options. Women it, and only 6% of women are currently using it. Conclusion: It is encouraging that who received counseling were more likely to be young and BRCA positive (table 1); the vast majority of women who have pursued menopause treatment are satisfied with in multivariate analysis, peri- or post-menopausal women and those whose surgical their care. However, a quarter of all women who sought treatment were not offered it indication was concern for malignancy were less likely to receive preoperative counseling and half had never been counselled on menopause health. As our data show, there has about surgical menopause (table 1). Data about postoperative symptoms and therapy not been any increase in care offered to women for menopause over the past decade. were available for 81% (125/154), of whom 102 (82%) experienced symptoms and 67% Given the progression of science and knowledge regarding the impact of menopause (83) received therapy. Complaints included vasomotor (72%, n=90) or cognitive/mood on women’s health, this is a deficiency which needs to be addressed. Providers should symptoms (22%, n=28), genitourinary symptoms (18%, n=22), and decreased libido routinely provide counselling on menopause medicine in addition to smoking cessation (6%, n=8). Postoperative symptoms were common in both premenopausal women (84%, and weight control as major public health practices. To address this discrepancy, steps n=62/74) and peri/postmenopausal women (78%, n=40/51), p=.45) and did not differ should be taken to improve provider knowledge and comfort in menopause medicine. by surgical indication (81%, n=74/91 of those undergoing risk-reducing surgery and Sources of Funding: None 82%, n=28/34 of those with concern for malignancy, p=.89). Of women with symptoms, 77% (n=79/102) received therapy; among 23 asymptomatic women, 17% (n=4) received therapy (p<.001). Almost half of women (48%) received non-hormonal therapies, alone (38%, n=48) or in combination with HT (10%, n=13); 18% (n=22) received HT alone. Women with an overt contraindication to HT accounted for 50% (24/48) of those who received non-hormonal therapies alone. Having postoperative menopausal symptoms was strongly associated with receipt of hormonal and/or non-hormonal therapy. Women who had preoperative counseling about surgical menopause were significantly more likely to receive non-hormonal therapies, even when controlling for postoperative symptoms (AOR 2.6, 95% CI 1.0 – 6.5, p=.047). Conclusion: One-third of patients under age 52 do not receive preoperative counseling about menopausal symptoms and treatment options before surgeries that will result in menopause, despite the fact that more than 80% of them will experience menopause symptoms after surgery. Women who are peri- or post-menopausal prior to surgery, and women whose surgical indication is concern for malignancy, are less likely to receive counseling – but are equally likely to experience postoperative symptoms. Postoperative symptoms are the strongest predictor of treatment. Women who use non-hormonal therapies are more likely to HORMONE THERAPY POSTER PRESENTATIONS receive preoperative counseling. Based on these data, we suggest that all women under age 52 planning surgery that will result in surgical menopause be counseled regarding menopausal symptoms and treatment options. P-64. Sources of Funding: None Correlations of Serum Estradiol and Estrone Concentrations with Sample description and factors associated with preoperative counseling about surgical Menopausal Outcomes and Bleeding menopause Colton Biehl, BS, Brian Bernick, MD, Sebastian Mirkin, MD. TherapeuticsMD, Boca Raton, FL Objective: The relationship of reproductive hormones to vasomotor symptoms has been incompletely explored, although an increase in such symptoms at midlife and their reduction with hormone therapy suggest a strong and direct relationship. While demographics such as age, years since menopause, race and BMI have been found to be related to endogenous estrogen levels, correlations of estrogen levels with symptoms associated with menopause are not well characterized. The objective of this analysis was to investigate the correlations between serum concentrations of estradiol (E2) and estrone (E1) and clinical outcomes before and during hormone therapy in a large, randomized clinical trial of menopausal women. Design: Serum concentrations of E2 and E1 were measured from a large cohort (n=1835) of menopausal women enrolled in the REPLENISH trial (NCT01442668), a phase 3, randomized, double-blind, placebo- controlled, multicenter study. The trial evaluated various doses of TX-001HR (E2 plus progesterone) in menopausal women (aged 40-65 with a uterus) seeking treatment for * p<.001; ** p<.01; + age not included in multivariate model due to correlation vasomotor symptoms. Serum E2 and E1 concentrations were measured at baseline and at with menopausal status various time points, including week 12. Throughout the trial, outcome data were obtained via participant self-report diaries that denoted their hot flush frequency and severity and P-63. days with vaginal bleeding or spotting; participants also completed questionnaires for Limitations of Instrumental Osmometry: The Impact of Ingredient Class Menopause-specific Quality of Life (MENQOL) and Medical Outcomes Study (MOS)- Sleep scale scores. Analyses were performed on all treatment groups combined in the on Reported Osmolality modified intention-to-treat population (randomized women who took one study dose). Sammy Wang, Bioengineering. Research & Development, The Procter & Gamble Correlations and predictions were obtained using correlation analysis and logistic Company, Cincinnati, OH regression. The correlation analysis computed the correlation coefficient (r) indicating the Objective: Over the counter lubricants and vaginal moisturizers are commonly used to strength of the relationship, as well as a P-value. For the logistic regression, the odds ratio help alleviate vaginal dryness and sexual discomfort experienced by postmenopausal (OR) of bleeding/spotting ≥4 days/week with respect to the increase in serum E2 and E1 women. In selecting or recommending these products, there are a few important concentrations was computed. A common logarithmic transformation of serum hormone factors to consider, including: pH, ingredients, additives, and osmolality. Osmolality concentrations and frequency and severity of hot flushes was performed to resolve the is an important measure for lubricants and vaginal moisturizers because hyperosmolar skewness of the data distribution. Results: 1833 women were in the modified intention- formulations are believed to cause damage to vaginal epithelium. However, it is not to-treat population; mean age of participants was 54.6 years, and the mean number of widely known that osmolality can only be measured instrumentally via freezing point hot flushes at baseline was 57. Endogenous (baseline) serum E2 and E1 concentrations depression osmometry or vapor pressure depression osmometry. (Vapor pressure were not correlated with hot flush, quality of life, or sleep outcome measures at baseline depression osmometry has been shown to be problematic for lubricants and moisturizers, or at week 12 (except for E1 with hot flush frequency at week 12). Inverse correlations so freezing point depression osmometry was selected for this study). Osmometry (P<0.0001 for all) between serum E2 and E1 concentrations at week 12 and frequency extrapolates osmolality by leveraging the colligative properties of aqueous solutions; of hot flushes, severity of hot flushes, overall MENQOL score, MENQOL vasomotor specifically, freezing point depression osmometry leverages the phenomenon that the domain score, and MOS-Sleep overall score at week 12 were found (Table). Positive freezing point of an aqueous solution will decrease 1.86°C when one mole of non-ionic correlations were found between E2 and E1 levels at baseline and bleeding/spotting solute is added. While this physical phenomenon applies to homogeneous, single-phase days/week at week 12 (P<0.01), and between hormone levels at week 12 with bleeding/ aqueous solutions (such as biological serums, for which osmometry was developed), it spotting days/week at week 12 (P<0.001; Table). At week 12, serum concentrations of does not necessarily apply to multi-phase mixtures that include ingredient classes not E2 and E1 also had a significant (P<0.0001) predictive value for ≥4 vaginal bleeding/ fully soluble in water, which are common in lubricants and moisturizers. The aim of spotting days/week (E2: OR 9.34; 95% CI, 4.02-21.69 and E1: OR 6.96; 95% CI, 2.69- this study was to determine the impact of common lubricant and vaginal moisturizer 18.02). Conclusion: Concentrations of E2 and E1 inversely correlated with outcomes ingredient classes on osmolality as measured by a freezing point depression osmometer. commonly measured in menopausal vasomotor symptom trials, such that higher levels of Design: In this study, serial dilutions of common lubricant and moisturizer ingredients E2 or E1 were associated with improved outcome scores. These hormone concentrations were prepared with distilled water. Osmolality of the dilutions was then measured using were also positively associated with the likelihood of vaginal bleeding or spotting. a freezing point depression osmometer (Advanced Instruments Model 3250 Freezing Further investigation into the etiology of vasomotor symptoms is warranted to develop a Point Osmometer, Norwood, MA). The main functional classes of ingredients evaluated more comprehensive understanding of menopausal clinical outcomes. included: viscosity modifiers (eg: carbomer, hydroxyethylcellulose), pH adjusters (eg: Sources of Funding: TherapeuticsMD lactic acid, citric acid, sodium hydroxide), humectants (eg: glycerin, propylene glycol), Significant Correlations Between Estradiol/Estrone Concentrations at Week 12 and and preservatives (eg: sodium benzoate, phenoxyethanol, benzyl alcohol, parabens). Outcomes at Week 12 (P<0.0001 for all) Percent concentration (by weight) was then plotted against measured osmolality for each ingredient to determine the relationship between concentration and osmolality. Results: It was found that ingredient functional class (viscosity modifier, pH adjuster, humectant, preservative) did not necessarily predict impact on osmolality. Rather, the ingredient chemical class was the most determining factor in predicting impact on osmolality. When grouped by chemical class (eg: aromatic alcohols, organic acids, glycols, ionic salts), ingredients impacted osmolality similarly. Ingredients that had the greatest impact on osmolality included ionic salts and salts of organic acids, whereas aromatic alcohols partitioned in water and maintained a constant osmolality even with increased concentration. It was also found that freezing point depression osmometry *Mild, moderate, or severe hot flushes. resulted in freeze errors when used to evaluate ingredients that were not fully soluble in water (eg: mucoadhesive thickeners, emollients, paraben preservatives). Conclusion: P-65. Common ingredients found in over the counter lubricants and vaginal moisturizers Progesterone Absorption via the Skin: A Comparison of Serum Levels impact osmolality in varying degrees. Ingredient chemical class is the best predictor of after Application of a Cream Formulation and an Alcohol-based Gel impact on osmolality and should be taken into consideration when evaluating reported Formulation in Postmenopausal Women osmolality values of formulated products. Because osmolality is an instrumental measure 1 1 3,4 based on colligative properties of homogeneous aqueous solutions, there are limitations Erica J. Chang, MD , Semara Thomas, MD , Intira Sriprasert, MD , Frank Stanczyk, PhD2, Sharon Winer, MD, MPH2. 1Obstetrics & Gynecology, LAC+USC Medical Center, to this method of measurement, especially when applied to multi-phase mixtures such as 2 lubricants and vaginal moisturizers. Los Angeles, CA; Obstetrics & Gynecology, Keck School of Medicine, University of Southern California, Los Angeles, CA; 3Preventive Medicine, Keck School of Medicine, Sources of Funding: The Procter & Gamble Company, Corporate Research & 4 Development University of Southern California, Los Angeles, CA; Obstetrics & Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand Objective: To compare serum progesterone levels and the extent of bloodstream absorption after application of a topical progesterone cream or alcohol-based gel formulation in postmenopausal women. Additionally, to assess the feasibility of a further study evaluating endometrial proliferation in postmenopausal women using different topical progesterone formulations in addition to estrogen therapy. Design: Pilot, prospective randomized controlled trial of ten hysterectomized postmenopausal women. Participants applied 80 mg of progesterone cream or alcohol- very low systemic absorption.1,2 TX-004HR was designed for the softgel capsule to based gel daily for two weeks in a crossover design with a two-week treatment-free have mucoadhesive properties to facilitate the active ingredient being available in the washout period. Blood samples were drawn prior to treatment and at the end of each body in a site-specific manner. Gelatin was selected as the capsule coat based on its treatment period, for a total of three samples per patient. Samples were analyzed for mucoadhesive properties attributable to its polymeric structure and for its fast-dissolving progesterone levels in the serum using a specific immunoassay approximately 12 to 14 properties. Fast dissolution of the capsule is important, first for release of its contents and hours after the last application of gel or cream. Patients were administered a questionnaire second for full dissolution to minimize messiness. In addition, the contents of the capsule at the end of each treatment period to assess for side effects. Results: Currently, four were developed to be viscous at body temperature to resist flow and allow inclusion of of ten patients have completed the protocol. All participants are of Hispanic ethnicity. ingredients reported to have high mucosal tolerance. The objective of this report is to The average age was 56.3 years with an average BMI of 29.2 and an average duration describe the characteristics of the gelatin coat and the softgel capsule fill as optimized for of menopause of 4.3 years. All participants had a baseline progesterone level of <0.2 ng/ vaginal delivery, and to discuss in vitro and in vivo evidence of the rapid release of E2. mL. Following progesterone alcohol-based gel administration, the mean progesterone Design: In vitro testing for dissolution of the softgel capsule was performed using a USP level (standard deviation) was 1.05 (0.89) ng/mL. Following progesterone cream Dissolution Apparatus Type 3 at 30 dips per minute with the media at 37°C. Samples of administration, the mean progesterone level was 0.40 (0.47) ng/mL. One patient the media were collected at 15, 30, 60, 90, and 120 minutes and analyzed for estradiol by experienced skin irritation as well as headache following administration of the alcohol- high performance liquid chromatography. Two phase 1 studies were conducted to assess based gel. No other side effects were associated with application of the gel. No side the pharmacokinetics (PK) in healthy postmenopausal women following treatment with effects were reported following application of the cream. Conclusion: Further patient TX-004HR 25 µg. Subjects in the first study (n=36) were required to remain in a supine recruitment is needed to determine the absorption of topically applied progesterone cream position for 4 hours after insertion while subjects in the second study (n=16 from the or alcohol-based gel formulations as well as the difference in progesterone serum levels first study), were ambulatory or remained seated for 4 hours after insertion. In a phase 2 between the two formulations. Serum levels of progesterone will then be correlated in study, subjects (n=50) with VVA self-administered TX-004HR 10 µg or placebo daily future studies to evaluate the endometrial effect of these progesterone formulations. This for 14 days. The vaginal vault was visually examined for remnants of the softgel capsule data will help practitioners decide the optimal topical formulation and dose necessary for 6 hours after insertion on day 1. Results: In vitro dissolution testing of the TX-004HR endometrial protection when prescribing hormone therapy. capsule resulted in greater than 80% of the E2 in the dissolution media by the first time Sources of Funding: None point, demonstrating that the soft gelatin capsule shell ruptures and begins to dissolve within 15 minutes, making the solubilized E2 in the capsule available for absorption. In the two phase 1 studies, E2 plasma levels from women in a supine position compared P-66. with women who were ambulatory or in a seated position had no significant difference in TX-001HR is Associated with a Clinically Meaningful Effect on Severity baseline-adjusted Cmax (42.1 vs 34.3 pg/mL), Tmax (2.1 vs 1.9 hr), or AUC (77.6 vs 93.7 of Moderate-to-Severe Vasomotor Symptoms in the REPLENISH Trial pg*hr/mL). In the phase 2 study, visual examination of the vaginal vault on day 1 did Ginger Constantine1, James Simon, MD2, James Pickar, MD3, Brian Bernick, MD4, not detect remnants of the soft gelatin capsule. Conclusion: TX-004HR was specifically Sebastian Mirkin, MD4. 1EndoRheum Consultants, LLC, Malvern, PA; 2IntimMedicine designed to be mucoadhesive and rapidly dissolving to release the drug quickly and Specialists, Washington, DC; 3Columbia University Medical Center, New York, NY; disappear fully with little or no resulting mess. The inclusion of gelatin polymers in the 4TherapeuticsMD, Boca Raton, FL coat together with the high viscosity of the fill material have aided in similar PK being Objective: Severity of vasomotor symptoms (VMS) adversely affects quality of life, observed with both supine and seated/ambulatory positions, allowing for flexible timing in fact, severity of VMS may be more bothersome than frequency of symptoms.1 An with dosing. Furthermore, dissolution of the vaginal capsule within 6 hours of vaginal investigational, oral combination of 17β-estradiol and progesterone (E2/P4) in a single, insertion was confirmed visually. These data, in concert with data showing improvements softgel capsule (TX-001HR; TherapeuticsMD, Boca Raton, FL) significantly reduced in dyspareunia, vaginal dryness, and objective measures of vaginal atrophy, suggest frequency and severity of VMS2 and provided clinically meaningful improvements local adherence and dissolution of TX-004HR. 1. Constantine GD, et al. Menopause in VMS frequency3 in menopausal women in the REPLENISH trial. The objective of 2017;24:409-416. 2. Archer DF, et al. Menopause 2017;24:510-516. this analysis was to evaluate the clinical meaningfulness of four E2/P4 doses versus Sources of Funding: TherapeuticsMD placebo based on improvements in severity of moderate-to-severe VMS in menopausal women from the same study. Design: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated TX- P-68. 001HR in menopausal women with an intact uterus (n=1835). In a VMS substudy, Amino Acid Metabolite Changes with Randomized Hormone Therapy in women aged 40-65 years with frequent moderate-to-severe hot flushes (≥7/day or the Women’s Health Initiative Hormone Therapy Trials. ≥50/week) were randomly assigned 1:1:1:1:1 to daily E2/P4 at 1 mg/100 mg (n=141), Heather Hirsch, MD, MS, NCMP1, JoAnn E. Manson2, Raji Balasubramanian, ScD3, 0.5 mg/100 mg (n=149), 0.5 mg/50 mg (n=147), 0.25 mg/50 mg (n=154), or placebo Olga Demler, Ph.D2, Kathryn Rexrode, MD, MPH2. 1Internal Medicine & Center for (n=135); other women were randomized 1:1:1:1 to active E2/P4 doses only for analysis Women’s health, the Ohio State Wexner Medical Center, Columbus, OH; 2Brigham and of the primary safety endpoint (endometrial hyperplasia). Participants rated VMS using Women’s Hospital, Boston, MA; 3U Mass Amherst, Amherst, MA the Clinical Global Impression (CGI) score with 7 response options ranging from Objective: In the Women’s Health Initiative (WHI), cumulative incidence of type 2 “very much improved” to “very much worse.” CGI responses were then allocated into diabetes (T2D) was decreased by 21% in the combined oral conjugated equine estrogen clinically meaningful response (ratings of “much improved” or “very much improved”), plus medroxyprogesterone acetate (CEE + MPA) treatment arm compared to placebo. minimally improved response (rating of “minimally improved”), and no change or worse A similar 12% nonsignificant effect was seen in the oral conjugated equine estrogen (ratings of “no change” to “very much worse”). Nonparametric discriminant, anchor- (CEE) alone active arm of the WHI compared to placebo. Few studies have examined based analysis was used to define clinical response thresholds for severity according to the effect of randomized hormone therapy (HT) on metabolite levels related to glucose a clinically important difference (CID). Results: Women enrolled in the VMS substudy tolerance or T2D. To understand these findings, we examined the effects of randomized (n=726 modified intent-to-treat population) had a mean age of 55 years and a mean HT on five metabolites that were previously found to be strongly associated with the BMI of 27 kg/m2; 67% were white and 31% were black. Results of the CGI showed development of T2D. These metabolites included three branched-chain amino acids that significantly more women had a clinically meaningful response to E2/P4 with all 4 (BCAAs) (leucine, isoleucine, and valine) and two aromatic amino acids (AAAs) doses (73%-82%) compared with placebo (53%) at week 12 (P<0.01). Nonparametric (phenylalanine and tyrosine). We investigated whether treatment with CEE alone or discriminant analyses determined CID response thresholds for severity as a reduction CEE + MPA in the WHI resulted in a decrease in the concentration of these five in severity score of ≥0.775 at week 12. Significantly more women were responders metabolites compared to placebo, which might help explain the clinical findings with clinically important reductions in severity at week 12 with TX-001HR E2/P4 1 regarding HT and T2D reduction in the WHI. Design: This study utilized data from mg/100 mg (56%) and 0.5 mg/100 mg (48%) versus placebo (29%; P<0.05). Proportion a prior analysis of approximately 370 metabolites that were measured on 1362 women of responders with the lower TX-001HR doses (39% for both lower doses) were not in the WH HT trials. Of these, a total of 934 women had metabolomics profiles at both significantly different versus placebo. Conclusion: Data from the REPLENISH trial baseline and year 1 and did not have cardiovascular disease prior to measurement. We demonstrated that TX-001HR 1 mg/100 mg and 0.5 mg/100 mg provided clinically evaluated changes in the five metabolite levels between CEE versus placebo; and CEE + meaningful improvements in VMS severity in menopausal women. If approved, TX- MPA verses placebo treatment arms (intention to treat). We calculated the mean ratio of 001HR would be the first combined, oral E2/P4 softgel capsule that relieves VMS in each metabolite level at year 1 compared to the metabolite level at baseline, comparing terms of clinically meaningful reductions in both frequency and severity. 1Pinkerton JV, the MFC ratio difference for active compared to placebo treatment. All P values were et al. Menopause 2016;23:1060-1066. 2Lobo RA et al, Obstet Gynecol 2018, in press. corrected for multiple comparisons. Results: For four of the five metabolites studied, 3Constantine G, et al. Menopause. 2017;24:1428. there was a decrease in metabolite levels in active HT treatment compared to placebo. Sources of Funding: TherapeuticsMD Tyrosine and phynylalanine were significantly reduced by both treatment regimens, while leucine and valine were significantly lowered only in the CEE+MPA arm (see table). Conclusion: Four of five amino acids (BCAA’s and AAA’s) which have previously P-67. been found to be associated with increased risk of T2D were decreased by one year of Physical Characteristics of TX-004HR: An Ultra-Low-Dose (4- and HT treatment. Interestingly, this finding was slightly more pronounced with CEE + MPA 10-µg) Estradiol Softgel Capsule Vaginal Insert arm than with CEE alone, paralleling the findings in the WHI incidence of T2D. These Ginger Constantine, MD1, Annette Shadiack, PhD2, Bharat Warrier, BS2, Shelli Graham, changes might help to explain the clinical findings of improved insulin sensitivity and PhD2, Brian Bernick, MD2, James Pickar, MD3, Sebastian Mirkin, MD2. 1EndoRheum reductions in T2D incidence among women on HT in the trial. Additional research on Consultants, LLC, Malvern, PA; 2TherapeuticsMD, Boca Raton, FL; 3Columbia these relationships is warranted. University Medical Center, New York, NY Sources of Funding: NHLBI contract: HHSN268201300008C, as well as Objective: TX-004HR is an investigational ultra-low dose (4- and 10-µg) estradiol (E2) contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, softgel vaginal insert designed for the local treatment of moderate-to-severe dyspareunia HHSN268201600003C, and HHSN268201600004C (NIH, NHLBI, US Department of associated with menopausal vulvar and vaginal atrophy (VVA), with negligible to Health and Human Services). Mean ratio of each metabolite level at year 1 compared to baseline, comparing active to In REPLENISH, single-point serum levels were collected at baseline and months 1, 3, 6, placebo treatment. and 12 for E2 and E1 and months 3 and 12 for P4. In the phase 1, randomized, multi-dose study in postmenopausal women, E2, E1, and P4 serum levels were assessed at multiple times following 7 daily doses of TX-001HR (1 mg E2/100 mg P4 or 0.5 mg E2/100 mg P4). Women from both trials were dosed in the evening with food and hormone levels were quantified using the same validated gas and liquid chromatography-tandem mass spectrometry. Results: Baseline serum P4 levels were below level of quantification (0.05 ng/mL) for the vast majority of subjects in both studies. Mean steady-state serum P4 levels collected 8-18 hours after dosing in REPLENISH was 0.387-0.548 ng/mL for both

100 mg P4 doses. In the phase 1 study, P4 mean Cmax, Cavg, and AUCτ were 7.9 ng/mL, 0.655 ng/mL, and 15.1 ng h/mL, respectively, on day 7 with an accumulation ratio of P-69. ~1.3. Mean baseline serum E2 levels were 6.1 and 7.6 pg/mL in the REPLENISH and Incidence of abnormal uterine bleeding and endometrial hyperplasia in phase 1 studies, respectively. Mean steady-state serum E2 levels in REPLENISH were postmenopausal women treated with Pellet Hormonal Therapy 42.3-45.6 pg/mL and 23.0-27.4 pg/mL for 1 mg E2/100 mg P4 and 0.5 mg E2/100 mg Xuezhi Jiang, MD, PhD1,2, Nathalia Arias-Alzate1, Cassandra Mitchell1, Brian D. P4, respectively, over the 12-month trial. In the phase 1 study, E2 achieved steady-state Novi1, Gregory Bolton, MD1, Kristine Leaman, MD1, Shahab Minassian, MD1, Peter F. within 7 days with an accumulation ratio of ~2 and a mean (SD) Cavg of 38.1 (14.2) and Schnatz1,2, Mark B. Woodland, MD1. 1OBGYN, Reading Hospital of Tower Health, 29.2 (23.7) pg/mL for 1 mg E2/100 mg P4 and 0.5 mg E2/100 mg P4, respectively. Reading, PA; 2OBGYN, Sidnel Kimmel Medical College, Philadelphia, PA Mean baseline serum E1 levels were 23.3 and 30.3 pg/mL in the REPLENISH and phase Objective: The objective of this study was to assess the incidence of abnormal uterine 1 studies, respectively. Mean steady-state serum E1 levels in REPLENISH were 214- bleeding (AUB) and endometrial hyperplasia in postmenopausal women treated with 242 pg/mL and 114-128 pg/mL for 1 mg E2/100 mg P4 and 0.5 mg E2/100 mg P4, non-FDA approved Pellet Hormonal Therapy (PHT) while compared with FDA approved respectively, over the 12-month trial. In the phase 1 study, E1 had an accumulation Hormonal Therapy (FHT). Design: A retrospective cohort study was designed to compare ratio of ~2 and a mean (SD) Cavg of 192 (89.4) and 82.1 (40.8) pg/mL for 1 mg E2/100 two cohorts (PHT vs. FHT). A total of 522 postmenopausal women with menopausal mg P4 and 0.5 mg E2/100 mg P4, respectively, on Day 7. Conclusion: Levels of P4, as symptoms were identified from the Reading Hospital Electronic Medical Record System measured in the REPLENISH study, were associated with endometrial protection from through pharmacy coding, including 367 on PHT (estradiol [E2, 6-37.5mg] and/or estrogens administered at 1 mg or 0.5 mg daily over 1 year; similar P4 levels were testosterone [T,12-137.5 mg] pellets) and 155 on FHT. Data on demographics, initial observed in the phase 1 PK study. Steady state levels of E2 and E1 with TX-001HR menopausal symptoms (i.e. hot flash, vaginal dryness, decreased libido), side effects were achieved within 7 days in the phase 1 PK study. These values were similar to those (i.e. AUB, mood swing, anxiety, breast tenderness, change in hair pattern, acne, weight observed in the REPLENISH trial, which showed improvement in moderate-to-severe gain), and treatment duration were extracted from medical records. Chi-Square test was VMS frequency and severity by week 4. Even though these E2 levels were well above the applied to assess the difference in incidence of side effects between the two cohorts, and postmenopausal range, women in the REPLENISH trial did not experience endometrial a multiple logistic regression was fit with covariates (HT cohort, age at the initiation of hyperplasia or cancer as is commonly seen in women with higher levels of unopposed HT, Body Mass Index, duration of HT), to assess risk profile of the individual covariate. estrogens.3 This evaluation helps to further our understanding of endometrial protective Results: Women on PHT (n=367) were significantly younger than those on FHT (n=155), levels of P4. 1Pinkerton and Santoro, Menopause 2015;22:926-936. 2Lobo et al, Obstet with mean age (SD) of 51.04 (7.52) and 60.61 (9.56) years, respectively (p<.0001). The Gynecol 2018, in press. 3Pickar et al, Fertil Steril 2001;76:25-31. incidence of side effects was significantly higher in PHT while compared with FHT Sources of Funding: TherapeuticsMD (179 [49.5%] vs. 23 [15.3%], p<.0001, odds ratio [95% CI] =5.92[3.42-10.25]). A total of 91 (58.7%) women on FHT had a hysterectomy prior to the initiation of HT, which was significantly higher than the 151 (41.4%) on PHT (p=0.0003). When examining 276 P-71. women with an intact uterus prior to HT initiation, mean (SD) duration of HT treatment Comparison of combined oral contraceptive after gonadotropin-releasing in years were significantly longer in PHT group (3.11 [1.64] vs. 2.15 [2.22], p=.0023). hormone agonist versus dienogest as maintenance therapy to prevent During the treatment, 59.4% (127/214) on PHT vs. 19.4% (12/62) on FHT had at least recurrence after surgery of endometriosis one episode of AUB (p<.0001, odds ratio [95% CI] =7.15[3.00-17.04]). Of those, 54 Hyewon Baek, MD, Jong-Wook SEO, Sung pil Choo, INOK Lee, Sangwon Han, Jae (27%) and 5 (7.8%) had a hysterectomy while on PHT and FHT respectively (p=.0013, Eun Chung. obstetrics & gynecology, National health insurrance service ilsan hospital, odds ratio [95% CI] =3.49[1.22-9.99]), and 87(41.8%) in PHT vs. 10 (16.4%) in FHT Goyang, Korea (the Republic of) had endometrial pathology available either from endometrial biopsy or hysterectomy. No Objective: The aim of this study was to assess the tolerability of combined oral endometrial cancer was identified in either group. There was no significant difference in contraceptive (COC) after gonadotropin-releasing hormone (GnRH) agonist versus incidence of endometrial hyperplasia between the two cohorts (22[25.9%] vs. 4[40.0%]), dienogest (DNG) treatment for long-term medical therapy after laparoscopic surgery for with 3(14%) in PHT vs. 0 in FHT being diagnosed with endometrial hyperplasia with ovarian endometriomas. Design: A prospective cohort study was conducted including atypia. A total of 201 women on PHT had lab monitoring data available, abnormal E2 fifty-two reproductive-aged women who underwent laparoscopic surgery for ovarian and T level were detected in 52 (25.9%) and 133 (66.2%) women, respectively, who endometriomas and received postoperatively medical therapy with either COC after subsequently required dose adjustment. Conclusion: When compared with women on GnRH agonist or DNG treatment for at least twenty-four months. The pre- to post- FHT, women on PHT had a significantly higher incidence of AUB and hysterectomy. treatment changes in quality-of-life (QOL) and menopausal symptoms were measured It may be difficult to assess difference in incidence of endometrial hyperplasia due to by questionnaire. Bone mineral density (BMD) was measured before and after medical relatively rare outcome and short durations of HT treatment in our study. Large scale therapy by using dual energy X-ray absorptiometry, and change in BMD were evaluated. prospective clinical trials are warranted to further investigate the safety of PHT for Results: Baseline characteristics of the study participants did not differ in age, body mass treating menopausal symptoms. index, or menstrual history between the two treatment groups. Physical, psychological, Sources of Funding: None social, and environmental components of QOL were not significantly different between COC after GnRH agonist and DNG treatment. BMD at lumbar spine (-3.5 % change for P-70. GnRH agonist and -2.3 % change for DNG) and femur neck (-1.0 % change for GnRH agonist) declined significantly in both treatment groups after first 6 months of medical Estradiol and Progesterone Bioavailability for Moderate-to-Severe therapy, with no significant difference between the two medical treatment modalities. Vasomotor Symptom Treatment and Endometrial Protection with For DNG treatment BMD at femur neck decreased significantly after 1 year (-1.2 % the Continuous-combined Regimen of TX-001HR (Oral Estradiol and change). There was no significantly additional change in BMD for long-term medical Micronized Progesterone Capsules) therapy (2 years). In addition, visual analogue scale pain score decreased significantly James Liu, MD1, Rogerio Lobo, MD2, Frank Stanczyk, PhD3, Ginger Constantine4, without significant differences between the two treatment groups. No case of pain and James Pickar, MD2, Annette Shadiack, PhD5, Brian Bernick, MD5, Sebastian Mirkin, disease recurrence was reported in either treatment groups. Conclusion: The tolerability MD5. 1University Hospital Cleveland Medical Center, Cleveland, OH; 2Columbia of long-term medical therapy after laparoscopic surgery for ovarian endometriomas University Medical Center, New York, NY; 3University of Southern California, Keck was comparable between COC after GnRH agonist plus add-back therapy and DNG School of Medicine, Los Angeles, CA; 4EndoRheum Consultants, LLC, Malvern, PA; treatment. 5TherapeuticsMD, Boca Raton, FL Sources of Funding: none Objective: Approximately 57-75 million hormone therapy prescriptions containing progesterone (P4) have been estimated to be filled yearly in the US.1 Serum P4 levels required for endometrial protection in a continuous-combined regimen are not well MENOPAUSE SYMPTOMS POSTER PRESENTATIONS established. In the phase 3 REPLENISH trial, no cases of endometrial hyperplasia were observed with 12 weeks of continuous use of TX-001HR (an investigational, oral, combined, 17β-estradiol [E2]/P4, softgel capsule), specifically 100 mg P4 plus 0.5 or P-72. 1 mg E2 and 50 mg P4 plus 0.25 or 0.5 mg E2, while reducing the frequency and/ Factor Analysis of the Menopause Transition Scale (MTS) or severity of moderate-to-severe vasomotor symptoms (VMS) for postmenopausal Diana Bitner, MD, NCMP, FACOG1,2. 1Women’s Health, Spectrum Health, Grand women.2 The objective of this analysis is to describe progesterone levels (dosed 12 Haven, MI; 2Ob/Gyn, Women’s Health, Michigan State University, College of Human weeks continuously) sufficient to counteract the potential endometrial estrogenic effects Medicine, Grand Rapids, MI of 1 or 0.5 mg oral E2. Design: We characterized the pharmacokinetics (PK) of E2, Objective: Healthcare Providers need a streamlined tool to measure the constellation of estrone (E1), and P4 at select TX-001HR doses in 2 separate analyses, one from a single menopause symptoms which an excessive number of women suffer in silence. Each of timepoint in REPLENISH and another from a multi-dose, multi-timepoint phase 1 trial. the 6000 women who enters menopause each day in the US deserves to receive education and treatment options. In order to provide good care to populations of women, it is completed, or prior to it. Summary statistics were calculated at baseline. Differences necessary to screen female patients in order to identify symptoms of the transition as well by race were assessed by ANOVA and chi-squared tests. Linear mixed models were as measure response to therapeutic interventions. Several validated symptom inventory used to assess the longitudinal associations of MHT and CAM with QOL, adjusting for scales exist however each tool is time consuming, phrased in clinical language, and covariates (race/ethnicity, education, medical burden or financial hardship). Results: difficult to adopt for digital use. The Menopause Transition Scale (MTS) is short, written Baseline Characteristics: We included 2470 women. Table 1 displays demographics in terms patients use, designed to be self-administered in a short time, and amenable to (mean [sd] for continuous variables, N [%] for categorical variables) by racial groups. digital use. The MTS was developed by the author with input from patients in several Women averaged 52.5 (3.2) years at baseline and all variables except percentage small clinical focus groups and subsequently used in a clinical pilot study. To ensure reporting menopause symptoms differed by racial group. Overall 91% of women reported psychometric validity and reliability, the MTS must withstand factor analysis to evaluate menopausal symptoms and 50.4% of these women reported ≥ 3 menopausal symptoms. symptom cluster, be evaluated for need of refinement, and undergo study for validation The number of reported menopausal symptoms was inversely associated with SRQOL against other previously accepted symptom tools or scales of subset symptom clusters [β(SE)=-0.185(0.011), p<0.001]. Longitudinal Analysis: The median follow-up was 9.2 such as the Patient Health Questionnaire-9 or Female Sexual Function Index. This study years (IQR=7.5-9.5). CAM use for relief of menopausal symptoms was reported by 1436 describes the factor analysis and lessons learned. Design: The MTS was administered women (58.1%) for 2.9±3.3 years, while MHT use was reported by 677 women (27.4%) in a clinical setting to female patients 45-60 self-identified as having irregular periods for 2.2±2.9 years. For the current analysis, CAM and MHT use each was summarized or amenorrhea and at least one symptoms of the menopause transition. The MTS is as ever used vs never used. Blacks and Japanese reported the highest use of CAM for composed of seven questions each scored on a 3, 2, or 1 rating scale with 3 being least relief of menopausal symptoms, while whites reported the highest use of MHT which bothersome. The symptoms were chosen from Study of Women Across the Nation and remained over time. Women who used CAM to treat menopausal symptoms reported a list of commonly reported symptoms in our clinic in common patient language. The higher SRQOL throughout the study: in both unadjusted [β(SE)=0.246(0.057), p<0.001] MTS was completed by patients at their first visit to the practice before being seen analysis and after adjusting for age, education, economic hardship, and ≥ 2 medical by the practitioner. A power analysis was performed assuming the requirement of at comorbidities [β(SE)=0.226(0.056), p<0.001]. This association was not seen with MHT least ten surveys per question. The data was entered into an Excel spreadsheet from 97 use: [β(SE)=0.087(0.062), p=0.160]. We found no relationship between MHT or CAM completed forms and analyzed using Factor Analysis, a Cronbach’s alpha and a Pearson use for menopausal symptoms with the SF36 components scores. Conclusion: In our Correlation Coefficient. Results: The factor analysis demonstrated the questions 1-6 sample, CAM was used more frequently by symptomatic women from all racial groups were grouped into one factor. A Cronbach’s alpha of 0.66 was produced to determine and was associated with a higher SRQOL that persisted over time. Neither MHT nor that the 6 questions had internal consistency within the factor. Within that factor the CAM use for menopausal symptoms were associated with the SF component scores. The tool demonstrated mood and energy having a positive correlation (r=0.44, p<0.0001) definition of CAM was quite inclusive but the use of any modality to treat menopausal and libido and vaginal dryness also having a positive correlation (r=0.43, p<0.0001). symptoms was low. The SWAN timeframe coincided with the Women’s Health Initiative Question 7 regarding vaginal bleeding, as written, was not correlated with any other Trial (WHI) findings that showed health risks with MHT, which may have resulted in symptom. Conclusion: The MTS is a tool for measuring and tracking symptoms of less use, despite published evidence for their safety and efficacy in managing vasomotor the menopause transition written in patient-centric language and requiring less time and vaginal atrophy symptoms. than other validated symptom inventory tools. The MTS shows promise of being useful Sources of Funding: None to clinical populations of women who might be experiencing such symptoms and is Table 1: Baseline Characteristics amenable to digital use. Minor adjustments will be made to the wording of the question about vaginal bleeding and a question will be added regarding body complaints. Once these adjustments are made, the tool will be reanalyzed with factor analysis and evaluated for construct validity against the factor. When the MTS has proven psychometric qualities it will be compared to other validated tools in populations of women of different cultures and different clinical experiences. Sources of Funding: None

P-73. Effect of porcine placental extract on the menopausal symptoms of Korean postmenopausal women: A randomized controlled trial hoon choi, M.D., Ph.D.1, jiyoung lee, M.D.,Ph.D.2. 1Obstetrics and gynecology, Inje University College of Medicine, Seoul, Korea (the Republic of); 2Obstetrics and gynecology, Konkuk University School of medicine, Seoul, Korea (the Republic of) Objective: To determine the effect of oral administration of (PPE) on the menopausal symptoms of Korean women. Design: This study was multicenter, randomized double-blind placebo-controlled trial. A hundred menopausal Korean women were randomly allocated either to PPE 400 mg per day or control group during 12 weeks of study period. Menopausal symptoms were evaluated using Kupperman Index (KMI). P-75. Results: KMI was decreased after 12 weeks in PPE group which was not statistically Lower expression of prestin and MYO7A correlate with menopause- significant. Among overweight or obese women whose body mass index (BMI) was associated hearing loss 23 kg/m2 or higher, KMI significantly more decreased in PPE group after 12 weeks He Diao, Weipei Bai. 1. Peking University Ninth School of Clinical Medicine, Beijing, (p=0.0230; PPE group -18.52±9.09, p<0.0001; placebo group -11.40±10.68, p=0.0001). China Among 49 early menopausal women whose duration of menopause was less than 3 Objective: To test the hearing function and to investigate the effect of oestrogen on years, KMI significantly more decreased in PPE group after 12 weeks (p=0.0390; PPE prestin and MYO7A expression in hair cells of the cochlea in ovariectomised rats. group -17.29±9.07, p<0.0001; placebo group -11.29±10.68, p=0.0001). Conclusion: Design: We compared the hearing function systematically in normal female SD Oral administration of porcine placental extract 400 mg per day decreases menopausal (Sprague–Dawley) rats, and ovariectomised rats with or without exogenous β-oestradiol symptoms in women with BMI 23 kg/m2 or higher or in early menopausal women. administration by ABR Auditory brainstem response measurement (ABR) and distortion Porcine placental extract may be considered as a short-term complementary treatment product otoacoustic emissions (DPOAE). In addition, a correlation analysis between to reduce menopausal symptoms especially in overweight or early menopausal women. the functional parameters and cochlear histology was carried out. Results: There was Sources of Funding: CellaMedic Korea Co, LTD a loss of outer hair cell cilia accompanied with significant auditory threshold shift in the high-frequency range in the ovariectomised rats. Prestin and MYO7A expression P-74. were lowered in the cochlea of ovariectomised rats. These effects could be recovered Race/Ethnic Variation in Treatment of Menopausal Symptoms: by subcutaneous administration of β-oestradiol. Conclusion: Low oestrogen levels may A Longitudinal Analysis of the Initiation, Duration, and Quality of Life in lead to reduced expression of prestin and MYO7A in cochlea leading to a menopause- related hearing loss. the Study of Women’s Health Across the Nation (SWAN) Sources of Funding: 1. National Natural Science Foundation of China NO. 81571399 Monica M. Christmas, MD1, Imke Janssen, PhD2, Howard Kravitz, DO, MPH2, 2.Research Funding Programof Beijing Municipal Administration NO.PX2018031 3. Hadine Joffe, MD, MSc3, Elizabeth Avery, MS2, Dawn Upchurch4. 1Obstetrics & Excellent Youth Foundation of Peking University Ninth School of Clinical Medicine Gynecology, University of Chicago, Chicago, IL; 2Preventive Medicine, Rush University NO.2016-q26 Medical Center, Chicago, IL; 3Psychiatry, Brigham and Women’s Health Harvard, Boston, MA; 4School of Public Health, UCLA, Los Angeles, CA Objective: Determine if quality of life (QOL) differed over time by treatment (complementary alternative medicine [CAM] or menopausal hormone therapy [MHT]). Design: SWAN is a multi-site, community based, prospective, cohort study of the health of women during the menopause transition. Participants reported menopausal symptoms, medical history, demographics, menopausal treatment, and QOL. QOL was assessed using the SF36 mental and physical components and self-reported QOL (SRQOL). The analysis included all women who reported menopausal symptoms at baseline, defined as the 1st assessment at which the questionnaire on CAM use for a reason was baseline structural and functional scans are completed, imaging will be conducted as stressors are initiated, during any participant identified HF, and during the relaxation period. The experimental exposure to psychological stressors will be identical in Phase 1 and 2 (randomly ordered stressors for 5 minutes followed by 10 minutes of rest). Participants will digitally mark any perceived HF. Upon completion of the experimental period, blood glucose will again be evaluated using the glucometer. Results: Data collection is in process and will be completed in late summer. Linear regression will be used to analyze time to HF after stressor stimulus. Image preprocessing and statistical analyses will be performed using appropriate software such as Statistical Parametric Mapping (SPM), FSL for MRI analysis, and others. The areas of activation will be assessed by analyzing the imaging during the periods of time associated with the hot flash and the various psychological testing parameters Conclusion: In response to the urgent need to explain the increased risk for AD in postmenopausal women, this preliminary study will demonstrate our ability to stimulate HF through cognitive stress, and our ability to image the dynamic changes in glucose metabolism in the brain before, during, and after HF. A large multi-ethnic study is planned to determine if blood glucose level and cognitive activation, or cognitive stress, are one of the mechanisms of menopausal HF, to determine if the relationship is consistent across ethnicities, and detail specific sites of change in glucose metabolism in the brain as a results of HF. Sources of Funding: Texas A&M College of Nursing

P-77. Assessment of Menopausal Symptom Management by a Clinical Pharmacist in a Veterans Affairs Medical Center Margaret C. Meuleman, PharmD1, Veronica P. Vernon, PharmD1,2, Christina A. White, PharmD, MBA1, Sarah M. Lenahan2. 1Indianapolis VA Medical Center, Indianapolis, IN; 2College of Pharmacy and Health Sciences, Butler Universtiy, Indianapolis, IN Objective: There are currently greater than 26,000 veterans who have been diagnosed with menopausal disorders. The average age of menopause onset is 52 years, while the average age of the female veteran population is 49 years. As the number of women veterans and their average age continues to increase, the number seeking treatment of menopausal symptoms will follow. Clinical pharmacists within the Veterans Health Administration (VHA) have advanced scope of practice to manage chronic conditions as part of the care team. In 2013, a clinical pharmacy position focused on women’s health was created. This is the first study of its kind to analyze the efficacy of pharmacist interventions in menopausal patients. The purpose of this study was to assess the management of menopausal symptoms in women veterans seen by a clinical pharmacist. Design: This study is a retrospective chart review of female veterans receiving care for menopausal symptoms by the clinical pharmacist and NAMS Certified Menopause Practitioner (NCMP) in the Gynecology (GYN) Specialty Clinic between August 1, 2013 and August 31, 2017 at the Indianapolis VA Medical Center. Research was approved by the local IRB and VA Research and Development Committee. Patients were identified through ICD codes. Primary endpoints include vasomotor symptoms pre- and post- pharmacy intervention at 6 months, 12 months and end of study period as well as, patients P-76. with genitourinary symptoms of menopause (GSM) resolution pre- and post-pharmacy The Dynamics of Glucose Transport in the Brain during Menopausal intervention. Secondary endpoints include analysis of treatments used and side effects Hot Flashes experienced during treatment. Results: A total of 121 patients were included in the Sharon L. Dormire, PhD, RN, Brandon Schmeichel, PhD, Vidya Sridhar, MD, PhD. analysis. Patients who saw the clinical pharmacist in the GYN clinic had an average of Texas A&M University, College Station, TX 11.9 vasomotor symptoms (VMS) per day at baseline and followed by an average of 1.4 Objective: Menopause is a sex-specific risk factor for Alzheimer’s Disease (AD); VMS per day at end of study period (p<0.001). Patients reported an average of 1.6 VMS specifically, the Alzheimer’s Association reports that of the 5.3 million Americans with per day at 6 months and 1.3 VMS per day at 12 months. Some patients had complete AD, 3.3 million are women and only 2.0 million are men. The physiologic basis for this resolution of symptoms with 36% of patients seeing complete resolution of symptoms at sex difference is unknown. The hot flash (HF), long considered benign but bothersome, is 6 months, 33% of patients seeing complete resolution at 12 months and 40% of patients emerging as a related factor to the sex specific difference. Recent evidence links HF with seeing resolution at the end of pharmacist intervention. Patients were followed for an cognitive decline. However, the basis of this linkage is not clear since causal mechanisms average of 11 months. Additionally, 57% of patients self-reported GSM symptoms at of menopausal hot flashes are not well delineated. Brain imaging studies in women with baseline, while 6.6% reported GSM symptoms at the end of the study period (p<0.001). HF have demonstrated hypo-metabolism and mitochondrial changes similar to those The percentage of patients who self-reported full resolution of vaginal symptoms was observed in AD. Estrogen-related changes in brain glucose transport and metabolism 88.4%. Of those who reported GSM, 44.6% of patients used some sort of vaginal resulting in HF may be the link with postmenopausal risk for AD. The overall goal treatment either alone or in addition to systemic methods. These methods included 52% of this study is to validate cognitive activation via psychological stress as a stimulus of patients using an unmedicated vaginal moisturizer, 20% of patients using vaginal for menopausal hot flashes and to provide preliminary evidence of an estrogen-related estrogen therapy in the form of a cream or tablet and 28% of patients using a combination metabolic HF mechanism: neurobarrier coupling. Specifically, brain neuronal activation of estrogen and moisturizer. Fifty percent of patients used hormone therapy. This can be stimulates both production of glucose transporter 1 (GLUT 1) and vasodilation at the further broken down into type of therapy with 21% of patients using a combination of blood brain barrier. With estrogen decline, we hypothesize that the GLUT 1 response transdermal therapy in a patch and oral tablet, 43% of patients using only a patch, and is hindered, and the neurovascular response overcompensates resulting in the HF. 36% of patients using only an oral method. Other therapies utilized included selective Design: This quasi-experimental study is designed to provide direct evidence of the serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors above described changes during HF. The project goals are to 1) identify cognitive (SNRIs) (20%), gabapentin (10%), clonidine (4%), and non-pharmacologic methods stressors that reliably stimulate HF in symptomatic women (Phase 1), and 2) image the alone (16%). Overall, 24% of patients experienced an adverse effect with the most dynamic changes in brain glucose transport and metabolism before, during and following common being breast tenderness, nausea and fatigue. Conclusion: Patients who saw a a HF in symptomatic women (Phase 2). Two days prior to the psychological testing, the pharmacist regarding reduction in menopausal symptoms had a statistically significant Bahr® Skin Conductance Monitor and the FreeStyle Libre Pro® continuous glucose reduction in vasomotor and GSM. Hormone therapy, specifically transdermal, was the monitor will be applied to establish baseline data. In Phase 1, participants will complete most common therapy utilized. Pharmacists, through their accessibility and placement personality questionnaires. They will then complete cognitive tasks including: a color- in team-based care, serve a unique role in the management of menopausal symptoms. naming task known as the Stroop task, an n-back task, and the attention network task Pharmacists with an advanced scope of practice, especially in the VA setting, can work (ANT) with a 10 minute break between exposures to the stressors. Ten minute breaks will to advance the provision of care for women veterans. be provided between stress exposures. Participants will complete short questionnaires Sources of Funding: none during these breaks pertaining to their subjective experiences during task performance. Participants will next be invited to schedule Phase 2 activities, functional magnetic resonance imaging (fMRI), if they choose to continue. Prior to the fMRI on a 3T MRI scanner, blood glucose level will be determined using a standard glucometer. After P-78. women with and without reported hot flashes during the past two weeks, reported hot The Art of Medicine: Female to Male Transgender Patient with flashes during the study period, and objectively measured hot flashes. PSS scores and Menopausal Symptoms After Oophorectomy cortisol levels were examined in relation to number of reported and objective hot flashes Jenna Sarvaideo, DO. Medicine (Endocrinology), Medical College of Wisconsin, during the study period by Spearman correlation analyses. Separate logistic regression Whitefish Bay, WI analyses were used to examine factors associated with objective or subjectively reported Objective: - To acknowledge hot flashes and other bothersome symptoms of menopause hot flashes (yes/no). Independent variables included cortisol levels, menopausal status, after gender-affirming surgery - Estrogen replacement may be necessary after gender- PSS score, sleep quality, Global Sleep Score, BMI, smoking, alcohol use, and parity. affirming surgery to treat bothersome hot flashes - Menopause treatment should be Finally, hot flash events 20 minutes before, during, and 20 minutes after the CAR were considered and not denied to female-to-male transgender patients Design: Patient was a examined to see if women with a CAR ≥50% above the cortisol level at awakening 48-year-old female-to-male transgender patient seen for worsening moodiness and hot were more likely to have a hot flash compared to women with flatter levels of cortisol. flashes. He reported approximately five hot flashes daily. These hot flashes would wake Results: Seventy-two percent of participants reported hot flashes during the past two him from sleep. He would stand in front of the air for relief. He also complained of weeks, 67% demonstrated objective hot flashes with the monitor, and 70% pushed the difficulty concentrating, brain fog, memory less and breast tenderness. He says that all monitor buttons to record a subjective hot flash. There were no associations between of these symptoms worsened after total laparoscopic hysterectomy and bilateral salpingo- self-reported hot flashes in the past two weeks and PSS scores or salivary cortisol levels oophorectomy, which was 2.5 months prior to visit. These symptoms were considered at awakening, 30 minutes later, or 3 hours after that. Women were not more likely to severe to patient and he stated that he could not live with them. Medications included, have hot flashes just before, during, or after a strong cortisol awakening response (CAR). but were not limited to: vaginal estradiol 1 gram three times per week, coenzyme Q10, There was a suggestion that self-reported hot flashes may be more likely with a flatter fish oil, DHEA 50 mg daily, pregabalin 50 mg BID and testosterone cypionate IM 40 mg CAR (p=0.09). There were no significant correlations between any measures of cortisol twice weekly. His vitals were 139/78, pulse 98, BMI 20.51 kg/m2 and LMP 4/5/2012. level or PSS score and the number of subjective hot flashes reported or objective hot Patient was thin, had masculine qualities, frontal hair loss, no acne, normal mood, affect flashes measured during the study period. Finally, in logistic regression analyses, after and behavior. Labs revealed estradiol 12.5 pg/mL, vitamin D, 25(OH) 47.6 ng/mL, total controlling for relevant variables, neither salivary cortisol levels nor PSS score was a testosterone 728 ng/dL, hematocrit 46%, TSH mildly low to 0.372 uIU/mL (0.450-4.5 predictor of hot flashes. Conclusion: In conclusion, this study of subjectively reported uIU/mL) and normal free T4 1.15 ng/dL (0.82-1.77 ng/dL) and normal free T3 3.5 pg/ and objectively measured stress did not support the hypothesis that stress is associated mL (2.0-4.4 pg/mL). Results: Patient was started on an estradiol 0.025 mg patch twice with self-reported or objectively measured hot flashes. In addition, an elevated CAR was weekly. He was seen two months later and said that he was feeling some relief with not associated with concurrent hot flashes. systemic estrogen therapy. Mood was better, but he was still getting approximately two Sources of Funding: UMass Amherst, Center for Teaching hot flashes daily and still waking up from sleep with them. Estradiol patch was increased to 0.0375 mg twice weekly. When he was seen three months later, he said that he was P-80. satisfied with treatment and hot flashes had resolved. Estradiol by liquid chromatography Health After eaRly Menopause due to Oophorectomy: the HARMOny tandem mass spectrometry was 34.5 pg/mL. Hot flashes later returned and estradiol was increased to 0.05 mg twice weekly. Given slightly elevated hematocrit, we discussed study A protocol Lara Terra, MD1, Flora v. van Leeuwen, prof.dr.ir1, Angela Maas, prof.dr.2, decreasing the IM testosterone dose, but patient wished to try a topical treatment instead. Maartje Hooning, dr.3. 1Epidemiology, Dutch Cancer Institute, Amsterdam, Netherlands; Patient used a compounded testosterone temporarily and hematrocrit normalized to 2Cardiology, Radboud UMC, Nijmegen, Netherlands; 3Epidemiology, Erasmus MC, 44%. However, total testosterone was 15.1 ng/dL, which is low when trying to achieve Rotterdam, Netherlands a normal male testosterone range. Patient was switched to topical testosterone gel 40.5 Objective: Risk-reducing salpingo-oophorectomy (RRSO) at the age of 35 to 45 years mg daily. His total testosterone increased to 452.5 ng/dL, but hematocrit continues to is recommended for women with a high genetic risk for ovarian cancer. This procedure stay mildly elevated at 48%. Patient was also found to have subclinical hyperthyroidism decreases the risk of ovarian cancer by 80-96% but also results in an immediate with a mildly low TSH, but this normalized without any treatment. Conclusion: The two menopause. Current research on potential adverse effects of premenopausal risk-reducing major goals of hormonal therapy in transgender medicine are (1) to reduce endogenous salpingo-oophorectomy, such as increased risk of cardiovascular disease, compromised sex hormone levels, and thus reduce the secondary sex characteristics of the individual’s bone health, cognitive dysfunction and reduced quality of life, is limited, mostly due to designated gender, and (2) to replace endogenous sex hormone levels consistent with the short follow up. Design: We will conduct a multicenter cross-sectional study nested in individual’s gender identity by using the principles of hormone replacement treatment a cohort of BRCA mutation carriers from 8 Dutch centers for hereditary cancer. Eligible of hypogonadal patients (1). However, it is important to recognize that female-to-male patients are women who underwent RRSO before the age of 45. They will be frequency- transgender patients may have menopausal symptoms especially after gender-affirming matched on current age with women above the age of 55 without RRSO or with RRSO surgery and these symptoms should be addressed. Management of menopausal after the age of 55. Participants will complete an online questionnaire containing various symptoms does not have to be significantly different from our cisgender population and questions about lifestyle, medical history, risk factors for cardiovascular disease, will not necessarily prevent us from achieving our transgender medicine goals. Patient bone health, cognition and quality of life. Participants will be asked to visit one of the preferences along with hormonal and non-hormonal therapies for menopause should participating hospitals for a blood test, a cardiovascular assessment and a DEXA scan for be clearly discussed. Estrogen is our most effective treatment to alleviate symptoms of determining bone mineral density. Afterwards participants will be requested to perform menopause and it can be given along with testosterone therapy. the online Amsterdam Cognition Scale. Results: Since this is a design protocol we do Sources of Funding: None not have results yet. Conclusion: The long-term health effects of premenopausal RRSO are not known. Therefore, this study will provide crucial results to better inform women P-79. about the long-term effects of early surgical menopause on cardiovascular disease, bone Is stress associated with hot flashes? Ambulatory hot flashes in relation health, cognition and quality of life. to subjective and objective measures of stress Sources of Funding: Dutch Cancer Society (KWF) Lynnette L. Sievert, PhD1, Gennifer Greenberg2. 1Anthropology, UMass Amherst, Amherst, MA; 2Public Health, UMass Amherst, Amherst, MA Objective: The evidence for a relationship between stress and hot flashes has been SEXUAL, OVARIAN AND UTERINE HEALTH inconsistent across studies. Both stress and hot flashes can be assessed by self-report POSTER PRESENTATIONS and physiological measures. For example, stress can be assessed by the Perceived Stress Scale (PSS) and also by cortisol levels. Most studies of cortisol levels in relation to hot flashes have failed to look at cortisol levels concurrent with hot flashes. The P-81. purpose of this study was to examine the relationship between PSS scores, cortisol The effects of soybean isoflavones and 17β estradiol in the proliferation levels, and hot flashes. We hypothesized that (1) higher PSS scores and higher salivary uterine endocervix of type 1 diabetic rats cortisol levels would be associated with an increased likelihood of self-reported and Adriana F. Carbonel, Post Doctoral1,2, Ricardo S. Simões, Post doctoral fellow2,1, Jose M. biometrically measured hot flashes, and (2) women with an elevated cortisol awakening Soares Junior, Professor2,1, Edmund C. Baracat, Professor2,1, Manuel d. Simões1,2. response (CAR) would be more likely to report or demonstrate a concurrent hot flash 1Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil; in the morning compared with women with a flatter CAR. Design: Sixty women living 2Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil in western Massachusetts and southern Vermont, aged 43 to 59 years, participated in Objective: To evaluate the histomorphometric and immunohistochemical alterations in face-to-face semi-structured interviews and anthropometric measures. Participants the uterine endocervix of ovariectomized type 1 diabetics rats (DM1) treated with soybean answered questions for demographic, reproductive, physical activity, stress, sleep, isoflavones (ISO). Design: Fifteen adult Wistar rats were bilaterally ovariectomized and biobehavioral information. Women were asked “Thinking back over the past two (Ovx) and divided into three groups: Group I (Ovx + DM1) – received vehicle solution weeks, have you ever been bothered by …” followed by a list of 29 symptoms, including (propilenoglicol); Group II (OVX-ISO + DM1) - received with concentrated extract of hot flashes. Answers were “not at all,” “a little,” “somewhat,” and “a lot.” BMI was ISO (150 mg/kg) and Group III (OVX-E2+DM1) - treated with 17β-estradiol (10 µg/kg), computed from height and weight (kg/m2). A stress score was computed from the PSS. by gavage for 30 consecutive days. Afterwards, the uterine endocervix was collected, A Global Sleep Score was computed from the Pittsburg Sleep Quality Index. Participants fixed in 10% formaldehyde buffered solution and processed for paraffin embedding. wore a Biolog ambulatory hot flash monitor for about 19 hours, overnight. Individual Sections (4µm) were stained with Hematoxilin and eosin for morphological and hot flash graphs were scored for subjective hot flashes (button pushes) and objective hot morphometric studies, or subjected to immunohistochemistry for detections of Ki-67 flashes (an increase in sternal skin conductance of 2 µmho within 30 seconds). Saliva and vascular endothelial growth factor (VEGF) The obtained data were subjected to was collected at awakening, 30 minutes later, and 3 hours after awakening. Saliva was statistical analysis (p ≤ 0.05). Results: We noted an atrophic uterine endocervix in the kept frozen and analyzed for cortisol by Salimetrics. PSS scores and log-transformed GI (Ovx+DM1), whereas it was more voluminous in the GII (Ovx+DM1+ISO) and even cortisol levels (three time points, mean, and CAR) were compared by t-test between more voluminous in the GIII (Ovx+ DM1+E2). The thickness of the cervical mucosa was significantly higher in GIII, as compared to GI and GII. The cell proliferation (Ki-67) was P-84. significantly elevated in the estradiol and soybean isoflavones treated groups, whereas Study Prevalence of Hypoactive Sexual Desire Disorder in Brazilian the VEGF immunoexpression was significantly higher in the GIII, as compared to GII Postmenopausal Woman with Metabolic Syndrome and GI groups. Conclusion: Soybean isoflavones causes less trophic and proliferative Gustavo M. Dutra da Silva, PhD student1,2, SONIA MARIA ROLIM ROSA LIMA, effects in the uterine endocervix of Ovx + DM1 rats, as compared to estrogen. PhD1, BENEDITO F. DOS REIS, PhD1, SOSTENES POSTIGO, MD1, Carolina F. Sources of Funding: This study was funded by Fundacão de Amparo à Pesquisa do Macruz1. 1Obstetrics and Gynaecology, Santa Casa of Sao Paulo Medical School, São Estado de São Paulo (FAPESP) Number: 2014/17077-9 Paulo, Brazil; 2São Francisco University, Bragança Paulista, Brazil Objective: To evaluate the prevalence of Hypoactive Sexual Desire Disorder in brazilian P-82. postmenopausal women with the diagnosis of Metabolic Syndrome and to compare them Effects of melatonin, metformin, clomiphene citrate in the endometrium to women without this diagnosis. Design: A cross-sectional, prospective, case-controlled study was carried out by interviewing 1,100 postmenopausal women at the Climacteric of rats in the permanent estrous phase Outpatient Clinic of the FCMSCSP and at the HMLMB. Women are regularly seen Adriana F. Carbonel, Post Doctoral1,2, Leandro S. Mattos, Master2,1, Gisela R. Sasso, in these institutions to perform routine climacteric exams. After performing care and postdoctoral fellow2,1, Ricardo S. Simões, Post doctoral fellow3, Manuel d. Simões1,3, evaluation of inclusion and exclusion criteria, 291 women were invited to participate Clélia R. Bertoncini, Professor2,1. 1Morphology and Genetics, Universidade Federal de in the study. All participants signed the Free and Informed Consent Form. The women São Paulo, São Paulo, Brazil; 2Gynecology, Universidade Federal de São Paulo, São considered as being postmenopausal were those with amenorrhea ≥ 1 year and FSH Paulo, Brazil; 3Obstetrics and Gynecology, University of São Paulo, São Paulo, Brazil ≥30mUI/mL (1). Sexual function was assessed by completion of the Female Sexual Objective: Evaluate the metabolic syndrome effects can cause in the uterus Function Index (FSFI). A score of 5 or less on the combination of items comprising histomorphometry of rats in permanent estrus, treated with melatonin. Thickness and the desire domain of the FSFI questionnaire was used to define the diagnosis of HSDD number of glands, as well as quantify the number of eosinophilic cells, the percentage of in postmenopausal women. We consider that a score of 6 or more the woman does not birefringent collagen fibers and to evaluate Ki67 and VEGF. Design: Eighteen rats were present with HSDD. The types of diagnosis based on the DSM -IV- TR. The diagnosis of divided into 3 groups with 6 animals each. Control group with rats exposed to continuous sexual dysfunctions was established by a sexology specialist experienced and trained in light for 60 days, causing permanent estrous (GCtrl). Experimental groups were divided diagnosing FSD using structured clinical interviews. The Beck Depression Inventory was in 2 experiments. Experiment 1 consisted of animals exposed to continuous light for used to exclude depression in patients with a history of the disease. The MetS diagnosis 60 days receiving melatonin (GM1). Experiment 2 had the same group configuration, was determined by following the guidelines defined by the Adult Treatment Panel (ATP from Experiment 1, but animals were exposed for 60 days before treatment to induce III) (8): (1) Abdominal circumference (AC) ≥88cm; (2) HDL-cholesterol ≤50mg/dL; permanent estrous (GM2). At the end of each experiment, all animals were anesthetized (3) triglycerides ≥150mg/dL; (4) arterial blood pressure (SAH) ≥130/85mmHg; and (5) and uterine portion were processed for paraffin inclusion. Three histological sections were fasting glucose ≥110mg/dL. The women considered as carrying MetS were those with collected and submitted to H.E, Picro Sirius Red staining and Immunohistochemistry. at least three of the components described. All of the women underwent the standard Results: The study showed histomorphometric results regarding endometrial thickness anamnesis of the service. Blood pressure (BP) readings were taken, waist circumference were no trophic results for both GM1 and GM2 when compared to the Ctrl group. The (WC) measured and body mass index (BMI) calculated, gynecological exams conducted quantity of glands showed trophic results for groups GM1 in relation to the Ctrl group. and cytology collected for the Papanicolaou smears. Subsequently, laboratory exams For the eosinophils evaluation, the results were trophic for both GM1 and GM2 when (total cholesterol and fractions, triglycerides and fasting glucose) were ordered, along compared with GCtrl. In regard of collagen percentage, GM1 showed a decreased with bilateral mammography and transvaginal ultrasound exams, in line with the basic expression when compared with GCtrl. However, GM2 showed trophic results propedeutics of the service. The study was carried out in compliance with the protocol when compared with GCtrl. For immunohistochemical results, Ki67 expression was and principles established in the Declaration of Helsinki (1996 version), the International significantly lower in GM1 and GM2 when compared with GCtrl. Regarding VEGF, Conference on Harmonisation Harmonised Tripartite Guideline and with the Guidelines there was a similar result, with a lower expression in GM1 and GM2 when compared for Good Clinical Practice and applicable regulatory requirements. The protocol was with GCtrl. Conclusion: Melatonin do not promote proliferative and angiogenic effects approved by the Research Ethics Committee of the FCMSCSP and of the HMLMB in the endometrium of rats in the permanent estrous phase (CAAE Permit 40594814.4.0000.5479) and under the Clinical trials ID NCT02430987. Sources of Funding: None Results: The diagnosis of HSDD was statistically higher in women diagnosed with MetS (p = 0.001) than in women without this diagnosis (p = 0.01). Overweight (N = 126) P-83. and obesity (N = 101) also had this ratio when compared to the control group (normal The effects of Lepidium meyenii Walp (Peruvian maca) on the sexual BMI, N = 64) (p = 0.036). Women with a diagnosis of SAH (p <0.01) (N = 146) and function of postmenopausal women increased triglycerides (p = 0.03) (N = 115) also presented more diagnosis of HSDD BENEDITO F. DOS REIS, PhD1,2, SONIA MARIA ROLIM ROSA LIMA, PhD2, compared to women without these conditions. All scores of the FSFI domains of desire, GUSTAVO MAXIMILIANO D. SILVA, MD2, SOSTENES POSTIGO, MD2, ANTONIO arousal, lubrication, orgasm, satisfaction, total score, diagnosis of FSD by both cut- MARCOS C. FRANCISCO, PhD1, LYLIANA COUTINHO R. BARBOSA, PhD1, offs were statistically lower in postmenopausal women with MetS (N = 153) (p < 0.05) LUCAS DE OLIVEIRA FERRER1, ORLANDO BRUNET FILHO1. 1GYNECOLOGY, when compared to women without this diagnosis (N = 138), except for the pain score Vale do Sapucai University - UNIVAS, Pouso Alegre, Brazil; 2GYNECOLOGY, Faculty (p = 0.913). The presence of FSD was statistically higher in women with MetS, regardless of Medical Sciences of Santa Casa de Sao Paulo - FCMSCSP, Sao Paulo, Brazil of the diagnostic criteria used (p <0.05). Conclusion: Through our study we can conclude Objective: The objective was to evaluate the effects of Lepidium meyenii Walp that postmenopausal women diagnosed with MetS present higher rates of HSDD when (Peruvian maca) on the sexual function of postmenopausal women Design: It was a compared to women without this diagnosis. clinical, prospective, randomized, double blind trial in which 40 postmenopausal women Sources of Funding: None were attended at the Climacteric clinic of Vale do Sapucai University (UNIVAS) in Brazil. The diagnosis of sexual dysfunction was made by a physician with experience P-85. and through the Female Sexual Function Index Questionnaire (FSFI) and after signed Ophiopogon japonicus selectively inhibited cell proliferation and induced the Informed Consent Term. Then they were allocated in two groups with 20 women apoptosis in human uterine leiomyoma cells each: Maca (one capsule of 875 mg of Lepidium meyenii extract ingested 12/12 h) Minhyung Jung. Kyunghee university, Seoul, Korea (the Republic of) and Control (one capsule of placebo ingested 12/12 h). The questionnaires were Objective: To investigate the anti-proliferative effect of the Ophiopogon japonicus in applied at the first visit, after 90 days and 180 days of medication use or placebo. cell proliferation and apoptosis in primary cultured human uterine leiomyoma cells. Results: The healthy women allocated had a mean age range of 49.2 ± 2.3 years, post- Design: IRB approved this study and we obtained infromed consent from the patients. menopausal age of 1.3 ± 0.9 years, whose origin was Caucasian. The study was concluded The myoma and myometrium were obtained from the patients who were underwent with 25 women, 15 women in the maca group and 10 women in the control group. Where hysterectomy. Cell viability was measured by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- six FSFI’s domains were evaluated: Desire, Excitation, Lubrication, Orgasm, Satisfaction diphenyltetrazolium bromide) assay. Caspase-3 activity assay and DNA fragmentation and Pain. Results were obtained with significant difference in the domains of: Desire, assay were performed to determine the effect of apoptosis. The expression of apoptosis Excitation, Orgasm and Pain in the Maca group compared to the Control with 90 days. regulatory-related proteins was evaluated by western blot. Results: The cell viability After 180 days, the domains of: Desire, Excitation, Lubrication and Orgasm presented a and proliferation of uterine leiomyoma cells were significantly reduced by Ophiopogon significant difference for the Maca Group compared to Control. Conclusion: The use of japonicus treatment rather than myometrium cells in a dose-dependent manner. DNA Lepidium meyenii Walp (Peruvian Maca) in postmenopausal women showed significant fragmentation assay results showed apoptotic cell death after Ophiopogon japonicus improvement in the FSFI domains: Desire, Excitation, Orgasm and Pain in 90 days and incubation. Ophiopogon japonicus activated caspase-3, -8, and -9, causing apoptosis in after 180 days in the domains: Desire, Excitation, Lubrication and Orgasm. uterine leiomyoma cells. Down-regulation of Bcl-2, XIAP, and FLIP with a concomitant Sources of Funding: None increase in Bax, Fas, and DR5 were observed. Conclusion: These results provided the first evidence that Ophiopogon japonicus induce both intrinsic and extrinsic apoptosis. Therefore, Ophiopogon japonicus may be a promising chemopreventive and therapeutic agent against human uterine leiomyoma. Sources of Funding: None characteristics. Therefore, new strategies for the development (maturation) of remaining follicles are essential for menopausal women who want to be pregnant. In this study, we tried to develop in vitro follicular maturation condition with vitamin C (L-ascorbic acid) for remaining follicles of menopausal stage, aged mice and to establish the proper time point of vitamin C for the follicle maturation. Design: Secondary follicles of 24-week-old mice were isolated using mechanical direction and cultured in the presence of 100 nM L-ascorbic acid (vitamin C) or not. The treatment was stated from early (day 0) or late (day 9) period of development. Growths of follicles were daily observed and the diameter was calculated. The expressions of specific genes, BMP15, GDF9 and figla, were evaluated by qPCR. Results: As the results, treatment of vitamin C significantly enhanced in vitro development of follicles from 24 week-old-mice in comparison with 2 week-old mice. The growth of follicles from early treatment was significantly enhanced than those of late treatment. In addition, the expression of development related genes upregulated in vitamin C treated group. Conclusion: In conclusion, we suggest that vitamin C could be used as co-factor for preserving ovarian reserve of menopausal stage of female. P-86. Sources of Funding: 2016R1E1A1A01943455 Milli™; the Only Patient Controlled Expanding Dilator Results from the Initial Launch P-88. Michael Krychman, MD1, Alyssa Dweck, MS MD FACOG2, Stephanie Prendergast, MPT3, Susan Kellogg-Spadt, PhD4, Sheryl Kingsberg, PhD5, mark Jurvic6. 1Southern Women’s Views on Hypoactive Sexual Desire Disorder: A Survey Aisha M. Van Pratt Levin1, Percy Yeung, PhD1,2, Nancy Phillips, MD1,2. 1Rutgers Robert California Center for Sexual Health, Newport beach, CA; 2OBGYN, CareMount, mount Wood Johnson Medical School, New Brunswick, NJ; 2Women’s Health Institute, New Kisco, NY; 3PT, Pelvic Health and Rehabilitation Center, Los Angeles, CA; 4Center for Brunswick, NJ Pelvic Medicine, Rosemont, PA; 5Department of obgyn, University Hospitals Cleveland Objective: Decreased sexual desire is estimated to affect up to 41% of women globally medical center, Cleveland, OH; 6Fogarty Institute of Innovation, Materna, Mountain (1,2). Hypoactive sexual desire disorder (HSDD), which requires that the decrease View, CA in desire causes distress occurs in about 10-12% (3). Studies generally agree that the Objective: Dilators are poorly characterized in the scientific literature yet may facilitate incidence of HSDD increases after menopause, but are higher in the younger menopausal reconditioning the brain body reconnection for anticipatory anxiety. Some post- women (less than 65 years of age) (3). There is little data which assesses women’s menopausal women experiencing dyspareunia use vaginal dilators to facilitate penetrative knowledge of HSDD as a recognized medical disorder or of the availability of treatment, intercourse with less pain. However, women often report of decreased compliance, especially differentiated by menopausal status. Design: An IRB approved survey on burdensome regimes, and excessive time commitments as well as concern about stepwise HSDD was distributed to women aged 18 and over presenting to a general gynecology abrupt transitioning from one size to another. Milli is a patient controlled electronically practice. Demographics related to age and menopausal status were collected. The purpose dilator that expands 1 mm at a time that attempts to rectify many of these dilemmas. of this analysis was to compare the incidence of decreased desire and HSDD between The secondary launch (n=130) of this novel dilator is reported here. Design: The Milli pre-and post-menopausal women, and also to see if there was a difference between device was available for a selected group of patients and used in conjunction with diverse these 2 groups in their recognition of this as a disorder, or their awareness of an FDA group of sexual medicine specialists. Each Milli patient participated in a phone interview, approved medication for its treatment. Results: 310 women completed the survey. introduction survey (n=130) and 3-month follow-up survey (n=80 collected). Patients (190 premenopausal, 87 post, and 33 who preferred not to answer) 23% of premenopausal were offered the device at a 50% discounted retail price for anonymous participation and 36.8% of postmenopausal reported decreased desire (p<0.05), with 52.3% of pre and Results: Milli is designed to be inserted at the smallest diameter (15mm), and expand 43.7% of postmenopausal women reporting distress (p=0.51). The incidence of HSDD in 1 mm slow patient-controlled increments and can expand to a maximum diameter of was 12.1% in pre and 16.1% in post- menopausal women (p=0.5). 25% of all respondents 40mm. The most common goals for patients were: return to penetrative intercourse and were aware that HSDD was a medical condition, (24.74% pre and 28.74% post, p<0.05), pain reduction during coitus. Patients saw their clinician on average every 13 weeks but only 12.5% were aware of an FDA approved medication for its treatment (11.17% pre (range 1-52 weeks) Outcomes monitored included: 1) return to intercourse (27% of non- and 15.66% post (p=0.3). In the women who reported having HSDD the overall number active returning to intercourse) 2) reduction in pain scores 0-10 (1.5 point reduction) aware of its designation as a disorder dropped to 17% in the premenopausal women, but 3) Increase in Milli Diameter (7.1mm) and 4) subjective feedback regarding progress rose to 28.6% in the postmenopausal population (p=0.42). Yet only 7% with the disorder toward goals (89% reported progress). 60% of patients had suffered from their medical (none of whom were premenopausal) were aware of an FDA approved medication for condition for >2 years, 25% haven’t been sexually active for >5 years, and 73% engaged its treatment. Conclusion: In this survey, postmenopausal women reported significantly in penetrative sex despite experiencing pain. Patients used Milli on average 3 days/week. more decreased desire than premenopausal women, and better knowledge of HSDD as The most common emotions patients to describe their treatment were “anxious”, a medical condition, but there was no difference in the rate of HSDD between the two “frustrated”, yet “empowered” and “optimistic”. The average dilatory session was groups. Overall knowledge of HSDD as a medical disorder and availability of FDA 15 minutes, mostly in the evening /bedtime (75%), in the bedroom (90%). Adjunctive approved medication was low in both groups, and even lower in women self-identified treatment included moisturizers, local estrogen products and physical therapy. Women as having HSDD. Better health care professional-patient communication is needed to most often watched TV, videos, read, listened to soothing music while dilating. Only improve awareness of HSDD. Although no FDA approved medical treatment is available 27% have used their dilators with their partners before coitus, 83% of those patients for post-menopausal women, interventions may be available to improve their symptoms. were post-menopausal. There were no serious adverse events reported. All participants A strength of our study was the total number of participants. A weakness of our study reported that Milli was superior to conventional dilators because of the ability to expand was the number of women who did not identify their menopausal status. Our data may while already inserted and smaller increments resulted in improved confidence. The yield different results if stratified by age. References: McCool ME, Zuleke A, Thourich optional vibration feature (used by 87% of patients) and esthetically pleasing silicone MA, Knuettel H, et al. Prevalence of Female Sexual Dysfunction Amoug Premenopausal cover design (soft, easy to clean) were also positive attributes. Factors that showed women: A systemic review and meta-analysis of Observational Studies. Sex Med rev trends to improved patient outcomes were use of vibration, length of Milli treatment 2016;4(3):197-212. Kingsberg, SA, Rezaee, RL. Hypoactive sexual desire in women. (>3 months), dilation sessions >15min, dilating with their partners prior to intercourse, Menopause. 2013: 20(12): 1284–1300. Shifren, Jan L. Monz, Brigitta U, etal. Sexual and use of candles and soothing music. Factors not associated with improvement trends Problems and Distress in United States Women: Prevalence and Correlates Obstetrics & were: when/where patients dilated, and other patient demographics including condition, Gynecology 2008: 112(5);970-978. race, or religious views. Conclusion: Milli ™ shows excellent promise in a limited Sources of Funding: None launch for safety and efficacy with high patient satisfaction and compliance. Slow incremental dilation, with vibration, every other day for 15-30 min, prior to intercourse may optimize returning to intercourse with less pain. Larger long-term interventions P-89. investigating a standardized dilation program are also planned post marketing. Sexual Function in Afro-Descendant Women in Climacteric with Severe Sources of Funding: This research is funded by Materna Medical Deterioration of the Urogenital Domain Alvaro Monterrosa-Castro1,2, Sally Parra-Almeida1,2, Katherin Portela-Buelvas1,2, María P-87. Fernanda Mercado-Lara1,2. 1Grupo de Investigación Salud de la Mujer, Cartagena, 2 Vitamin C enhances in vitro development of ovarian follicles in aged mice Colombia; Universidad de Cartagena. Colombia, Cartagena, Colombia Seung-Yup Ku1,2, Yoon Young Y. Kim, PhD2, Young Jae Ryu*2, Hoon Kim, MD,PhD1, Objective: The estrogen deprivation own of climacteric produces changes in the Chang Suk Suh, MD, PhD1. 1Dept of OBGYN, Seoul National University Hospital, urogenital tract: weight loss of the mucosa with loss of the rough folds and of the Seoul, Korea (the Republic of); 2Biomedical Research Institute, Seoul National elasticity of the vaginal, urethral and vesicle epithelium; increase of the ph., cervical University Hospital, Seoul, Korea (the Republic of) and vaginal fragility, with loss of the adipose tissue of the vulva, laxity of the labia Objective: Ovarian reserve of women is critically related to contents of follicles majora, decrease of the elasticity and turgor. The objective to assess the sexual function, in ovaries. As the declining of ovarian reserve in aged or menopaused women, in afro-descendant women in Colombia, with severe deterioration of the urogenital major populations of follicles are altered from pre-antral to primordial follicles. domain Design: Cross-sectional study, which is part of the CAVIMEC (Calidad de Considering that the current application of ART (e.g. IVF) is mainly based on the use Vida en la Menopausia y Etnias Colombianas) project, carried out in afro-descendant of hormones, the primordial follicles are not suitable for its hormone-independent women resident in municipalities of the Urabá Antioqueño, to the west of Colombian, with age between 40-59 years old, who participated voluntarily. A questionnaire of socio-demographic characteristics, the Menopause Rating Scale (MRS) to identify the college or postgraduate training (88% vs. 9.7%, p<0.01), had health insurance (100% urogenital deterioration and the 6-item Female Sexual Function Index (FSFI-6), to study vs. 66%, p<0.01), and self-reported excellent health more often (39% vs. 22%, p<0.01) the sexual function, were applied. A punctuation lower to 19 with the FSFI-6 defined compared to the Texas cohort. GCS scores were higher overall in the Arizona cohort sexual dysfunction. A scoring ≥ 4 of the urogenital domain of the MRS was considered (GCS total mean 32.9 vs. 17.8, p <0.01), consistent with more menopausal symptoms. severe urogenital deterioration. Women with sexual activity in the last four weeks were Statistically significant differences were seen by overall FSFI score (AZ mean 18.9 considered. The analysis was carried out with the statistical program Epi-Info 7. This was (SD=7.08) vs. TX mean 16.7 (SD=6.45), p<0.01), lubrication (AZ mean 3.4 (SD=0.89) a non-impact study in the integrity of the participants; it was anonymous and developed vs. TX mean 3.6 (1.46), p<0.01) and satisfaction (AZ mean 3.9 (SD=1.71) vs. TX mean in their own communities. It was guaranteed by the ethic committee of the Universidad de 3.3 (1.41), p<0.01). Sexual dysfunction did not significantly differ (AZ 96% vs. Texas Cartagena Results: 369 women with sexual activity were included, with average age of 93%, p=0.30). When evaluating the whole cohort by Hispanic descent status, Hispanic 49.6±5.3, with global score of the FSFI-6: 21.4±5.0 and prevalence of sexual dysfunction women had lower FSFI scores compared to non-Hispanic women (mean 16.1 (5.94) of 30.8%. Of the total of participants, 99 (26.8%) had severe deterioration of the vs. 18.2 (7.06), p<0.01), as well as lower GCS scores overall (17.5 (SD=11.78) vs. urogenital domain. These had greater age, greater number of children, greater presence 27.8 (SD=11.72), p<0.01). Conclusion: Differences in self-reported sexual function of arterial hypertension and greater proportion of women in postmenopause. There were were seen in two geographically and socially distinct groups of menopausal women. not differences between the two groups in terms of body mass index, education, coffee In spite of higher rates of menopausal hormone therapy, health insurance and self- consumption, smoking, presence of diabetes mellitus or hypothyroidism. Significant reported excellent health, Arizona participants reported more menopausal symptoms on difference was found in all the items and in the total score of the FSFI-6, the greater the GCS, and higher scores on the FSFI consistent with better sexual function compared deterioration was found between women with severe urogenital deterioration. Women to the Texas cohort. Hispanic women had lower menopausal symptoms overall, as well as with severe urogenital deterioration had significantly greater presence of low sexual more sexual function concerns compared to non-Hispanic women. Multivariable analysis desire, low sexual excitation, poor genital lubrication, low frequency of orgasms, to evaluate if differences between the cohorts could be explained by the differences in inadequate sexual satisfaction and more presence of pain. The prevalence of sexual socioeconomic and demographic variables will aid in identifying the role geographic dysfunction was significantly greater in women with severe urogenital deterioration than location may be playing in these findings. in those who did not have it, 73.7% [CI95%: 63.9-82.0] and 15.1% [CI95%:11.1-20.0], Sources of Funding: None respectively p<0.001. To have severe deterioration of the urogenital domain was risk factor for sexual dysfunction OR: 6.8 [CI95%:1.4-33.1] Conclusion: The presence of severe urogenital deterioration increased significantly the risk of sexual dysfunction in a P-91. group of afro-descendant women in the west of Colombia Soy Isoflavones Protect Against Oxidative Stress and Diminsh Apoptosis Sources of Funding: None in Ovary of Female Rats Assessment of the sexual function with the FSFI-6 Cristiane d. Teixeira1, Rinaldo Florencio-Silva, Post Doctoral1, Gisela R. Sasso, postdoctoral fellow2, Ricardo d. Simões3, Manuel d. Simões1. 1Morphology and Genetic, Universidade Federal de São Paulo, SP, Brazil; 2Ginecology, Universidade Federal de São Paulo, SP, Brazil; 3Ginecology, Universidade de São Paulo, São Paulo, Brazil Objective: Menopause results from quantitative and qualitative declines in follicular reserve. Oxidative stress seems to increase apoptosis and has been implicated in aging process. Soy isoflavones have antioxidant activity. We here investigated follicular reserve, apoptosis and oxidative stress in the ovary of 3 and 12-month-old rats treated with soy isoflavones. Design: Twenty-six female rats at 3 and 12-month-old were divided into groups and daily treated by gavage with soy isoflavone extract or propylene glycol vehicle. After 8 weeks, rats were euthanized and ovaries removed. Ovaries were processed for histomorphometric analysis (% follicles) and apoptosis (cleaved-caspase-3 and BCL2). Ovaries were subjected to reactive oxygen species levels, total antioxidant (*) Mann Whitney U test (**) Chi-Square test capacity and lipid peroxidation assays. Results: A significant decrease in atretic follicles was noticed in 12-month-old isoflavonestreated rats compared to age-matched controls. In isoflavone-treated groups, there was a decrease in cleaved-caspase-3 positive cells at P-90. 3- and 12-month-old rats, and an increase in BCL2-positive cells only in 12-month-old Differences in Female Sexual Function by Region and Ethnicity: A rats compared to age-matched controls. Isoflavones promoted an increase in total Cross-sectional survey of menopausal women in West Texas and Central antioxidant capacity as well as a decrease in reactive oxygen species levels and in lipid Arizona peroxidation in both 3- and 12-month-old. Conclusion: Soy isoflavones can decrease Beth Prairie, MD MPH3, Juliana Kling, MD MPH1, Matthew Buras, Masters Degree, follicular atresia, apoptosis and oxidative stress, as well as increase total antioxidant Applied Sciences2, Marjorie R. Jenkins4. 1Women’s Health Internal Medicine, Mayo capacity in ovarian tissue of rats. The anti-apoptotic effects of soy isoflavones are, at least Clinic, Scottsdale, AZ; 2Divison of Health Sciences Research, Mayo Clinic, Scottsdale, in part, related to the antioxidant capacity of these compounds. AZ; 3Obstetrics, Gynecology and Reproductive Sciences, Lewis Katz School at Sources of Funding: NONE Temple University, Pittsburgh, PA; 4Texas Tech University Health Sciences Center, Lubbock, TX P-92. Objective: Sexual complaints are frequently reported during menopause and women Effects of Korean red ginseng on endometrium: in vitro and human data with sexual dysfunction report lower health-related quality of life. Factors such as 1 1 1 1 ethnicity and socioeconomic status may impact sexual function but research is limited. Jisun Yun, M.D. , Young Bin Won, M.D. , Inha Lee, M.D. , Jae Hoon Lee, M.D. , Bo Hyon Yun, M.D.1, Si Hyun Cho, MD., Ph.D.2, Young Sik Choi, MD., Ph.D.1, Byung Our study aim was to evaluate differences in sexual function in menopausal women 1 1 1 of different geographic locations with diverse socioeconomic and ethnic backgrounds. seok Lee, MD., Ph.D. , Seok kyo Seo, MD., Ph.D. . Department of Obstetrics and Gynecology, Severance hospital, Yonsei University College of Medicine, Seoul, Korea Design: A cross-sectional, anonymous survey study was conducted by mail and online to 2 evaluate self-reported sexual function in menopausal women aged 40-60 years old who (the Republic of); Department of Obstetrics & Gynecology, Gangnam Severance spoke English or Spanish. Surveys were distributed in 2012 in West Texas, and 2016 in Hospital, Yonsei University College of Medicine, Seoul, Korea (the Republic of) Scottsdale, AZ. The survey included the Greene Climacteric Scale (GCS), Female Sexual Objective: In order for Korean red ginseng (KRG) to be widely used by women, the safety Function Index (FSFI) and patient demographic and socioeconomic questions. Lower of KRG on endometrium have to be proven. The aim of this study was to investigate the FSFI scores are consistent with worse sexual function and sexual dysfunction is defined effects of KRG on endometrium. Design: Endometrial stromal cells (ESCs) were isolated as an FSFI < 26.55. Higher GCS scores signify more menopausal symptoms, and can be and cultured from endometrial tissue of patients with fibroids undergoing hysterectomy. broken into symptom clusters (psychological, anxiety, depression, somatic, vasomotor). ESCs and Ishikawa cells were treated with different concentrations of KRG extracts for Surveys were mailed to 1,000 women in each community. Post mailing, community 48h. Cell proliferation and apoptosis were assessed by CCK-8 assay and flow cytometry, group outreach was conducted to attempt to collect additional data to achieve recruitment respectively. Western blot analysis was used to quantify the expression of apoptosis- goals set by power analysis. In Texas, an online questionnaire option was made available associated proteins. In addition, we performed a randomized controlled trial for human post mailings. All data were de-identified and analyzed in SAS. Descriptive statistics data. Results: KRG extract was found to inhibit proliferation and induced apoptosis in were used to assess all variables. The Wilcoxon Rank-Sum test was used to compare both ESCs and Ishikawa cells with the effects dependent on its concentrations. KRG the GCS and FSFI score differences between the two sites. Chi-square tests were used extract increased the activities of caspase-3, -8 and -9 in both cells. KRG extract also to compare menopausal and socio-demographic characteristics differences between triggered pro-apoptotic signals including increase of BAD, BAK and BAX, and decrease Hispanic and Non-Hispanic women. Results: One hundred and ninety nine women of Bcl-2 and Bcl-XL in both cells. Serum hormone levels and endometrial thickness were completed surveys in West Texas, and 163 in Scottsdale. Women on average were 51.5 not influenced by KRG supplementation in postmenopausal women. Conclusion: KRG (SD=7.25) years of age, non-Hispanic (70%), menopausal (62 % with no menstrual extract is a potent proliferation inhibitor in ESCs and Ishikawa cells. In addition, KRG period in last 12 months), and equal numbers were married (43%) and single (43%). Fifty supplementation had no effect on the endometrium of postmenopausal women. These percent had completed college or postgraduate degrees, 81% had health insurance and results suggest that KRG may be safely used in postmenopausal women. 6% reported sexual dysfunction (FSFI>26.55). Many differences were seen between the Sources of Funding: None two cohorts. Women in Arizona were older (mean age 54 vs. 50, p<0.01), on menopausal hormone therapy more (24% vs. 9%, p<0.01), married (76% vs. 10%, p<0.01), completed SLEEP AND MOOD POSTER PRESENTATIONS SPSS-21. Categorical data was expressed as percentages with confidence interval of 95% (CI95%) and continuous data was expressed as median (Me) with interquartile range (IR). The differences of percentages were evaluated with χ2 test and differences P-93. of medians with Mann Whitney. Association, Odds ratio (OR), was established between Depression, anxiety and stress in women with premature ovarian sleep disorders and the other variables by means of logistic regression. A p value insufficiency using Hormone Therapy - a comparative study of age- <0.05 was considered as statistically significant. This study was approved by the ethics matched women with preserved ovarian function committee of the Universidad de Cartagena. Results: 90,3% [CI95% 87,5-97,5] of Helena P. Giraldo, Doctorate, camila menezes, Daniela A. Yela, phd, Cristina L. Benetti- the studied women presented sleep disorder. There were no significant differences in Pinto. Obstetrics and Gynecology, University of Campinas, Campinas, Brazil the age between women with sleep disorder, Me=47 [IR:6,5], and those who were not Objective: To evaluate some psychological aspects of women with premature ovarian presenting it, Me=48 [IR:6,0], p=0,51. The presence of sleep disorder was higher in insufficiency (POI) receiving multidisciplinary treatment with medical, nutritional, mestizos [91,5% [CI95% 88,8-93,7], followed by afro-descendants and indigenes, 73,9% psychological and physiotherapeutic support and using hormone therapy (HT). [CI95% 51,6-89,8] and 75% [CI95% 50,9-91,3], respectively, p=0,001. 92,7% [CI95% Design: A cross-sectional study of 61 women (between 18 and 45 years of age) with 89,1-95,1] of postmenopausal women presented sleep disorders, different from women POI using HT and receiving multidisciplinary care (POI group), and 61 women with in perimenopause and premenopause, 90,0% [CI95% 82,4-95,1] and 85,4% [CI95% 79, preserved ovarian function, matched one by one by age ± 2 years (control group). Age, 0-90,5], respectively, p=0,04. The median of the punctuation of the MRS was greater single sexual partner, number of children, number of abortions, time of diagnosis and time in those women with sleep disorder, Me=18 [IR:10], than in those without it, Me=11,0 of treatment were evaluated (the last two for the POI group). The tools used to evaluate [IR;18,5], p=0,003. To have clinically meaningful depressive symptoms (Goldberg) depression, anxiety and stress were Beck Depression Inventory (BDI), Beck Anxiety increased more than five times the risk of presenting sleep disorder. To have symptoms Inventory (BAI) and LIPP Stress Symptom Inventory (LSSI) respectively. The study of anxiety, urinary incontinence, eating disorders, perceived stress, loneliness was approved by the Ethics Committee of the Institution (CAEE 61821516.0.000.5404). and deterioration of the quality of life, were not factors associated significantly. Statistical analysis: Chi-square or Fisher’s exact tests for qualitative variables, and Mann- Conclusion: The prevalence of sleep disorder, especially in postmenopause, was high. Whitney or Kruskal-Wallis for comparison of numerical variables were used. Spearman Clinically meaningful depressive symptoms were identified as risk factor to develop correlation or logistic regression analysis with Stepwise criteria was also used. (p=0,001). sleep disorder in a Colombian population. Results: Women with POI and the control group presented 35.0 ± 7.6 and 34.4 ± 7.5 Sources of Funding: None years, respectively (p = 0.63). Women with POI had been diagnosed 10.4 ± 7.4 years Factor associated with sleep disorder in women in climacteric n=585 beforehand (median 8 years); treatment time with HT was 7.8 ± 6.0 years (median 7 years). The number of children was 0.4 ± 0.9 for the patients who had POI, 75% were nulliparous, whereas in the control group it was 1.2 ± 1.3 children (p = 0.001). In the IOP and control groups, total BDI, BAI and LSSI scores were 15.7 ± 11.6 and 13.6 ± 8.4, (p = 0.64); 17.5 ± 13.1 and 17.2 ± 11.0 (p=0.90), 19.3 ± 12.0 and 18.9 ± 11.2 *Adjusted by age, ethnic group, labor activity, civil status, sexual partner, wine (p = 0.945) respectively, with no difference between the groups, however 30 and 28% consumption, use of hormonal therapy, climacteric status, urinary incontinence, for POI and control (p=0.17) respectively, presented moderate to severe depression, and probable anxiety, probable depression, total score of the loneliness scale, total 41 and 47% presented moderate to severe anxiety (p = 0.78) respectively. In women score of the MRS, severe urogenital deterioration and for the 11 climacteric with POI, depression was positively correlated with the number of children (each child symptoms of the MRS, **Wald test, ***Significant presented a 2.3 times increased risk of depression) and anxiety, while anxiety and stress were also positively correlated. The other variables were not correlated with the P-95. psychological aspects evaluated. Conclusion: Although literature associates receiving Impact of Depressive Symptoms on Acute Stress Response in Midlife the diagnosis of POI to different psychological disorders, the long-term repercussions are not evaluated. Our results show that women with POI undergoing hormone treatment Women Margo Nathan, MD2, Kathleen McCormick, BS2,1, Aleta Wiley, MPH2, and receiving multidisciplinary care have depression, anxiety and stress indexes similar Akanksha Srivastava2, Kathryn Sullivan2, Kimberly Albert, PhD3, Paul Newhouse, MD3,4, to those of women with normal ovarian function, but depression and anxiety may be Hadine Joffe, MD, MSc2,1. 1Department of Psychosocial Oncology and Palliative Care, underdiagnosed in both groups. Dana Farber Cancer Institute, Boston, MA; 2Women’s Hormones and Aging Research Sources of Funding: None Program, Department of Psychiatry, Brigham and Women’s Hospital, Boston, MA; Comparison of depression, anxiety and stress indexes among women with premature 3Department of Psychiatry and Behavioral Sciences, Vanderbilt University School of ovarian failure and women with preserved gonadal function (control) matched by age Medicine, Nashville, TN; 4GRECC, Veterans Affairs Tennessee Valley Health System, (± 2 years). Nashville, TN Objective: Depression and PTSD are associated with altered perceived stress and hypothalamic-pituitary-adrenal (HPA) axis responsivity, manifesting as an underactive stress response. We have shown that frequent hot flashes and night sweats, or vasomotor symptoms (VMS), are associated with a blunted psychological and physiological acute stress response in midlife women. As VMS are strongly linked with depressive symptoms, we examined whether current depressive symptoms also correlate with a smaller anxiety and cortisol response to an acute stressor in women with VMS and without VMS. Design: 37 unmedicated midlife women without a current major depressive episode completed the Montreal Imaging Stress Task (MIST), an acute stress provocation paradigm involving a computerized arithmetic task combined with a social evaluative BDI: Beck Depression Inventory/ BAI: Beck Anxiety Inventory /LSSI LIPP Stress threat. Women with and without VMS were included and subthreshold depressive Symptom Inventory symptoms were allowed. All subjects completed questionnaires assessing depressive symptoms over the past 2 weeks on the Patient Health Questionnaire (PHQ-8). Before and 20 minutes after the task, acute anxiety response on a Visual Analog Scale (VAS) P-94. and salivary cortisol were measured. Spearman correlations were used to relate within- Factors Associated with Sleep Disorders in Women in Climacteric person depressive symptoms (PHQ-8) with change in stress (VAS, cortisol) during the Alvaro Monterrosa-Castro2,1, Liezel Ulloque-Caamaño2,1, Camila Buelvas-de-laRosa1,2, task. Results: The median PHQ-8 score was 6, the median increase in anxiety was 6.2 Estefana Ordosgoitia-Parra1,2. 1Universidad de Cartagena. Colombia, Cartagena, on the 10-point VAS scale, and the median change in cortisol was 0.02 µg/dl. Higher Colombia; 2Grupo de Investigación Salud de la Mujer, Cartagena, Colombia levels of depressive symptoms on the PHQ-8 correlated with a smaller anxiety response

Objective: Sleep is a physiological process of vital importance for the integral health to the stress task (rs=-0.47, p<0.01). Similarly, higher levels of depressive symptoms of human beings. It could present alterations and to produce cognitive, organic and correlated with a blunted cortisol response to the task (rs=-0.38, p=0.02). Depressive psychosocial dysfunction. There are different factors that could affect it. The hormonal symptoms correlated with baseline anxiety (rs=-0.40, p=0.01), but not with baseline changes during climacteric provoke the apparition of sleep disorders. The objective cortisol (rs=-0.07, p=0.67). Conclusion: Results of this analysis show that subthreshold to establish the factors associated with sleep disorders in Colombian women in depressive symptoms are linked with a diminished acute anxiety response and reduced climacteric, who live in the Caribbean. Design: Cross-sectional study, which is part HPA reactivity in midlife women. These findings suggest that depressive symptoms of the CAVIMEC (Calidad de Vida en la Menopausia y Etnias Colombianas) project, contribute to an altered stress response in midlife women with VMS. carried out in Colombian women in climacteric, with age between 40-59 years old. Sources of Funding: None Pregnant women, those who did not want to participate, those with psychiatric history, mental deficiency or physical disorders that made difficult the participation in the study, were excluded. An anonymous survey was applied, which included general socio-demographic questions and the Jenkins Sleep Scale (JSS), the Menopause Rating Scale (MRS), the International Consultation on Incontinence Questionnaire Short-Form (ICIQ-SF), Perceived Stress Scale (PSS), the Goldberg Anxiety and Depression Scale (GADS), the SCOFF questionnaire, a screening tool for eating disorders, and the short loneliness scale. A sample of 585 women was calculated. The population was divided in two groups according to the JSS: Women with sleep disorder (with scoring greater than or equal to 1) and without it (scoring equal to 0). The analysis was carried out with P-96. Sources of Funding: Bedjet, (Rhode Island, USA) provided the bedjet units used in the Dietary Intake of Insoluble Fiber is Negatively Associated with Subjective study and funding for this project. Night Sweats Tamami Odai1, Masakazu Terauchi, MD, PhD2, Asuka Hirose1,2, Kiyoko Kato2, 1 1 1 P-98. Mihoko Akiyoshi , Naoyuki MIyasaka . Obstetrics and Gynecology, Tokyo Medical A proprietary maca blend (Maca-JDS) improves cognitive function in and Dental University, Tokyo, Japan; 2Women’s Health, Tokyo Medical and Dental University, Tokyo, Japan postmenopausal women Ellen Manos, MD2, Sara Perez Ojalvo1, Sarah Sylla1, James Komorowski1. 1Scientific & Objective: This study was undertaken to investigate the nutritional factors positively Regulatory Affairs, JDS Therapeutics, Purchase, NY; 2Obstetrics & Gynecology, Ellen or negatively associated with vasomotor symptoms in middle-aged women. Design: Manos, MD, New York, NY The baseline data collected in a previous study that examined the effects of a dietary Objective: Lepidium meyenii, commonly known as maca, is a Peruvian root vegetable supplement on a variety of health parameters in 88 Japanese women aged 40 to 60 years that has been used as a food and therapeutic ingredient for many centuries due to its were analyzed cross-sectionally. Participants had been assessed for age, menopausal high nutrient content and various biological effects. Numerous studies support the use status, lifestyle factors, and body composition. Their vasomotor symptoms were of maca to enhance libido, fertility, energy, endurance, and mood. More recently, maca rated as 0 (none) to 3 (severe) according to their responses to the items “hot flush” has been studied for its neuroprotective effects and has been shown to improve memory and “night sweats” on the Menopausal Health-Related Quality of Life (MHR-QOL) function. Postmenopausal women often report problems with cognitive performance Questionnaire. Dietary habits were assessed using the Brief-type self-administered including difficulty remembering, concentrating and thinking clearly. This may be due to Diet History Questionnaire (B-DHQ), which provided information on the amounts of a decline in estrogen levels. Although hormone replacement therapy (HRT) may improve 97 nutritional factors consumed during the previous month. Results: The average age cognitive function, the various health concerns associated with HRT point to the need of the participants was 49.7±5.1 years (mean±standard deviation). The percentage of for alternative approaches to treat cognitive impairment associated with menopause. women who rated their hot flush and night sweats as mild to severe was 28.4% and Therefore, Maca-JDS, a proprietary blend of maca, was studied for its effect on cognitive 20.5%, respectively. None of the 97 nutritional factors were significantly associated function in postmenopausal women. Design: In a randomized, double-blind, placebo- (Pearson’s r > 0.3, p<0.05) with hot flush score, whereas insoluble and total dietary fibers controlled trial, 80 postmenopausal female subjects (35 to 60 years, BMI 18.0-34.9 kg/m2) were negatively associated with night sweats score (insoluble, r=-0.369, p<0.001; total, were randomly assigned to receive 4 capsules/day of Maca-JDS (2.6 g) or placebo. r=-0.351, p<0.001). The average dietary intake (g/1,000 Kcal) of insoluble and total Subjects were dosed for 12 weeks. To assess cognitive function, Trail Making Test parts dietary fibers were significantly different between the women who were and were not A and B (TMT-A and TMT-B) were completed by subjects at baseline and at weeks 4, bothered by night sweats (insoluble, 4.3±1.1 vs. 5.8±1.9; total, 6.1±1.7 vs. 8.2±2.7). 8, and 12. TMT measures mental acuity, focus, and processing speed, with an increase Multiple logistic regression analysis revealed that dietary intake of insoluble fiber in time indicating a decline in cognitive function, and a decrease in time indicating an (g/1,000 Kcal) was negatively associated with mild to severe night sweats after improvement in cognitive function. Subjects were timed while connecting an ascending adjustment for age, menopausal status, body mass index, insomnia, exercise, smoking, sequence of 25 numbers for TMT-A and an alternating sequence of numbers and alcohol, and coffee consumption (adjusted odds ratio, 0.39; 95% confidence interval letters for TMT-B, the more complex measure of cognitive function and flexibility. 0.19-0.68). Conclusion: Dietary intake of insoluble fiber was negatively associated with Results: After 12 weeks, mean TMT-B time significantly decreased in the Maca-JDS subjective night sweats in middle-aged women. Consumption of fruits and vegetables group compared to the placebo group. TMT-B time decreased by 22 seconds in the rich in insoluble dietary fibers including cellulose might alleviate night sweats. Maca-JDS group and by 11 seconds in the placebo group (p < 0.05). At weeks 4 and Sources of Funding: None 8, there was a significant decrease in TMT-B time in the Maca-JDS group compared to baseline (p < 0.05), while there was no significant change in the placebo group, though P-97. a practice effect was evident. There were no differences between groups in TMT-A Efficacy of BedJet for Peri-Menopausal Night Sweat and Hot Flash time at any measured timepoint. There were no serious adverse events reported, and no Symptoms and Corresponding Impact on Sleep Quality differences were seen in side effects between the Maca-JDS and placebo groups. Serum Jordan C. Stern, MD1, Stephanie Zhu2, Iman A. Blow, NY2, Darlyne Johnson, MD3. estrogen levels did not differ between groups. Conclusion: The results of this clinical 1Otolaryngology, New York Eye & Ear Infirmary of Mount Sinai, New York City, study show that Maca-JDS, a proprietary maca blend, doubles the effect on cognitive NY; 2Columbia University, New York, NY; 3OB/GYN, South Shore Hospital, function compared to placebo, as demonstrated by a significant reduction in TMT-B time Weymouth, MA after 12 weeks of supplementation. The reduction in TMT-B time indicates enhanced Objective: Hot flashes are a major source of sleep disruption during menopause and executive functioning, which is important for focus, organization, memory, and flexible perimenopause affecting up to 80% of women. Few non-hormonal effective treatments thinking. Therefore, Maca-JDS can provide postmenopausal women with a safe and exist to control nocturnal hot flashes and improve sleep quality during the climacteric. effective treatment option to improve cognitive function and overall mental clarity in This study evaluates a novel treatment: the BedJet® (a climate controlled air flow everyday life without affecting estrogen levels. bed cover); in a group of women naïve to this treatment. The goal of the study was Sources of Funding: This study was funded by JDS Therapeutics, LLC. to determine the clinical efficacy of the BedJet Climate System in relieving various symptoms; including poor sleep quality with night sweats and/or hot flashes; and other P-99. non-sleep related symptoms, in a group of perimenopausal and menopausal women. Subjective dizziness in Peri- and Postmenopausal Women is Associated Design: We evaluated the BedJet’s efficacy using four validated pre and post-treatment surveys, the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), with Anxiety Masakazu Terauchi, MD, PhD1, Tamami Odai2, Asuka Hirose1,2, Kiyoko Kato1, the Functional Outcome of Sleep Questionnaire (FOSQ), and the Greene Climacteric Mihoko Akiyoshi2, Mikako Masuda2, Reiko Tsunoda3, Hiroaki Fushiki3, Scale. This was a prospective study consisting of 36 women with an average age of 49.8. Naoyuki MIyasaka2. 1Department of Women’s Health, Tokyo Medical and Dental We examined the data collected from the PSQI, ISI and FOSQ for 36 of the subjects University, Tokyo, Japan; 2Department of Obstetrics and Gynecology, Tokyo Medical that completed the study; and the Greene Climacteric Scale for 34 of these 36 subjects. and Dental University, Tokyo, Japan; 3Department of Speech, Language, and Hearing Subjects were shipped a BedJet unit that was used in their home for a period of at least Therapy, Mejiro University, Saitama, Japan 3 weeks. Answers to questionnaires were obtained before using the bedjet, and then Objective: This study aimed to investigate the prevalence of, and risk factors associated again after using the BedJet for one to 2 weeks, after a one week acclimation period. with, subjective dizziness in peri- and postmenopausal women. Design: The records Results: We performed a paired t-test analysis comparing the pre and post treatment of 471 women aged 40–65 who enrolled in a health and nutrition education program scores from subject questionnaires. Results showed significant improvement in sleep at a menopause clinic were analyzed in a cross-sectional manner. Subjective dizziness quality and daytime function according to results of the PSQI (n=36, t=5.965, p <.0001), was evaluated according to responses for the corresponding item on the Menopausal ISI (n=36, t=8.742, p <.0001), FOSQ (n=36, t=-9.126, p <.0001), and improvement in Health-Related Quality of Life Questionnaire. Age, menopausal status, body symptoms from the Greene Climacteric Scale (n=34, t=6.336, p <.0001). Individual composition, cardiovascular parameters, basal metabolism, physical fitness, physical question analysis from the Greene Climacteric Scale indicates a statistical significance and psychological symptoms of menopause, and lifestyle factors were assessed for in reduction of anxiety or panic (p = .0054), lack of energy (p <.0001), irritability associations with subjective dizziness. Results: The percentage of women who were (p = .0017), muscle and joint pain (p = .0028), hot flashes (p <.0001), and night sweats bothered by dizziness once a week or more was 35.7%. The variables that significantly (p <.0001). Individual question analysis of the ISI indicates significant improvement differed between the groups of women with and without subjective dizziness at the in: falling asleep (p = .0048), staying asleep (p <.0001), and waking up too early univariate level included age, body weight, body mass index, muscle mass, waist-hip (p <.0001). Individual question analysis of the FOSQ indicates improvement regarding ratio, systolic pressure, reaction time, vasomotor, insomnia, depressive, and anxiety the effect of sleepiness on relationships with family, friends, and work colleagues symptoms, exercise, and alcohol consumption. Multivariate logistic regression analysis (p =.0005) and improvement in subjects’ mood (p <.0001). The effect size between the revealed that the anxiety symptom evaluated by the Hospital Anxiety and Depression pre and post-treatment scores on the PSQI (r=.138), ISI (r=.597), and FOSQ (r=.535), Scale was the sole independent predictor for subjective dizziness (adjusted odds ratio Greene Climacteric Scale (r=.670) all indicated an overall improvement in sleep quality. (OR) 1.14; 95% confidence interval (CI) 1.08–1.20). Conclusion: Subjective dizziness The PSQI results indicated improvement in sleep quality in 83% of the subjects. is highly prevalent in peri- and postmenopausal women, and is associated with anxiety. The ISI results indicated that 94% of subjects’ sleep quality improved. The FOSQ results Sources of Funding: M. T. received an unrestricted research grant from Kikkoman indicated that 89% of the subjects demonstrated an improvement in daytime activity Corporation. related to improved sleep, and the Greene Climacteric Scale results improved in 85% of subjects. Conclusion: The results of this study suggest that BedJet may be a new and useful non-hormonal treatment for the relief of menopausal sleep disturbances including: increasing overall sleep quality, improving daytime function, and decreasing other non sleep related symptoms of menopause.