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POSTER PRESENTATIONS P-3. Cognitive Dysfunction Among Women with a History of P-1. Experiencing Frequent and Longer Sleep Duration John S. Bark2,3, Jessica S. Fogel2,3, Ece Kilic3, Shannon Dowty3, Rachel Horwitz2, Targeting Enhancer of Zeste Homolog 2 (EZH2) with Methyl Jasmonate, David R. Walega1, Suzanne Banuvar1, Pauline M. Maki, PhD2,3. 1Department of a Promising Natural Compound against Human Uterine Fibroids Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL; 1,2 1 Mohamed Ali, Masters of clinical pharmacy , Ayman Al-Hendy, MD, PhD , Qiwei Yang, 2Department of Psychology, University of Illinois at Chicago, Chicago, IL; 3Department 1 1 PhD . Obstetrics and Gynecology, University of Illinois at Chicago, Chicago, IL; of Psychiatry, University of Illinois at Chicago, Chicago, IL 2 Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt Objective: Vasomotor symptoms (VMS) (i.e., daytime hot flashes and night sweats Objective: Uterine Fibroids (UFs) are the most common benign tumors in women of [NS]) represent a hallmark of and contribute to sleep deficits. VMS can be reproductive age with a prevalence increases with age, peaks during the fifth decade of measured objectively with ambulatory conductance monitors. Previous research from and tends to decline after menopause. UFs have subsequent significant quality of life our group has demonstrated that objective VMS are associated with decreased memory, and economic impact. They are characterized by excessive deposition of extracellular raising the possibility that NS may be a modifiable risk factor for cognitive decline during matrix (ECM) as well as an increase in proliferation, which explains accompanied menopause. Here we extend this working hypothesis to women with a history of breast bleeding and bulk symptoms. Current treatment options for UFs are primarily surgical cancer to examine how objective NS and objectively measured sleep relate to cognition and no FDA approved medical treatment is available so far. Natural compounds may among this population. Design: We conducted secondary analyses of baseline data from be beneficial for UFs patients as a safe long-term cost effective therapeutic option. a feasibility study of Stellate Ganglion Blockade (SGB) for the treatment of VMS among EZH2 is linked with many including reproductive diseases such as UFs. Methyl women with a history of (n=33) who reported ≥4 daily VMS. Participants Jasmonate (MJ) is a natural compound isolated from jasmine with a potent anti-EZH2 completed neuropsychological testing, ambulatory skin conductance assessments of activity. In this study, we determine the effect of MJ on UFs. Design: Human uterine VMS, and actigraphy-based sleep monitoring (i.e., total sleep time). Three women were leiomyoma (HuLM) and normal uterine cell (UTSM) cells were treated excluded from the final analysis for invalid data and/or having <4 daily VMS. Using with concentration ranges (100 µM-3 mM) of MJ and the growth inhibitory effect was linear models, we examined the main effects of NS and daytime hot flashes on TST, the assessed by MTT assay after 24 and 72 hr. treatment. Total cell lysates from MJ treated main effects of TST and NS on cognition, as well as interactions between NS and TST or untreated HuLM cells for 24 hr. were examined by (WB) and RT-qPCR on cognition. Results: More frequent NS were associated with greater sleep duration for measurement of and expression of the following; fibrosis related markers (β=9.16;p<.05), while daytime hot flashes were unrelated to TST (β=-3.20;p=.17). { type 1 (COLL1A) and Fibronectin (FN)}, proliferation markers {Cyclin D1 Controlling for NS, TST was not significantly associated with performance in any (CCND1) and proliferating cell nuclear antigen (PCNA)}, tumor related marker (P21, cognitive domain. However, there were significant interactions between NS and TST EZH2 and β-catenin). Since activated Wnt/β-catenin pathway has been identified to be on semantic fluency (β=-0.02,p=.01), digit span forward (β=-.01,p=.003), and digit span involved in UF pathogenesis, we determined the alteration of in WNT backward (β=-.004,p=.01). Specifically, the association between TST and cognition signaling pathway using Prime-PCR array containing 84 related . Unpaired student depended on the number of NS such that the association between TST and cognitive t-test was used to measure statistical significance. (P< 0.05) is considered significant. performance was positive among women with fewer NS. Furthermore, the association Results: Using MTT assay, MJ showed a potent, statistical significant, concentration and between TST and cognitive performance was negative or neutral among those with more time dependent anti-proliferative effect on HuLM cells (P< 0.05) reaches 80% growth frequent NS (Figure 1). TST alone or in combination with NS was unrelated to memory inhibition at doses over 1mM at 72 hr. Interestingly, dose ranges between 100-500 µM performance. Conclusion: Results suggest that sleep duration was associated with showed selective growth inhibitory effect on HuLM cells, but not on normal UTSM improved attention and fluency in women without NS, but that paradoxically women who cells. At molecular level, MJ treatment at 500 µM for 24 hr. significantly decreased both experience NS may be vulnerable to prefrontal cortex deficits (i.e., decreased attention protein and gene expression of EZH2, along with decreased expression of COLL1A, and executive function) as their sleep duration increases. This work presents novel FN, CCND1, PCNA, and β-catenin while increased p21 in HuLM cells as compared insights into the influence of menopausal symptoms on cognitive performance among to untreated control using WB and qPCR respectively (P< 0.05). PCR array data women with a history of breast cancer and raises the possibility that VMS treatments showed that MJ treated cells exhibited downregulation of 35 genes including CTNNB1, could benefit cognition in these women through effects on sleep. CCND1, Wnt3, Wnt5A, Wnt5B and upregulation of 36 genes including Wnt antagonist Sources of Funding: The Donald Kirk Foundation. genes WIF1, PRICKlE1 and DKK1 while 13 genes remain unchanged as compared to untreated control. Conclusion: Our studies demonstrate for the first time that MJ, via EZH2 downregulation, promotes the anti-UFs effect by decreasing cell proliferation through suppression of activated Wnt/ β-catenin pathway. In addition, MJ exhibited an anti-fibrotic effect through downregulation of the expression levels of ECM related markers. MJ might offer promising therapeutic option as safe non-hormonal and cost- effective treatment against UFs with favorable long term clinical utility especially for women seeking future in addition to women at perimenopause who suffer from the anti-hormonal side effects of current available short-term treatment options. Sources of Funding: NIH grants: RO1 ES028615, U54 MD007602.

P-2. Vulvar fusion as a late complication of Genitourinary Syndrome of Menopause Dr. Dominguez Bali, MD1, Guarina Molina, MD1,2, Sindhuri Gollamudi, MD1,3. 1Miami Center for Obstetrics Gynecology and , Miami, FL; 2Universidad Iberoamericana, Santo Domingo, Dominican Republic; 3American University of Antigua, Miami, FL Objective: Genitourinary syndrome of menopause (GSM) comprises of the vulvovaginal, bladder, and urethral changes associated with decreased levels. These changes include genital dryness, recurrent urinary tract infections, and atrophic changes to the labia, introitus, and . Although these changes are common in menopausal P-4. women, they may occur at any age if the patient presents a decrease in estrogen levels. An Efficacy of (7.5 mg) in the treatment of menopause-associated uncommon manifestation of genitourinary syndrome of menopause is vulvar fusion (also vasomotor symptoms known as labial fusion, labial agglutination, labial adhesion and vulvar synechiae) which Maria A. Belardo. Climacteric Section, Italian , , has been defined as the total or partial adherence of the labia minora and/or majora. Two Objective: Primary: describe the results obtained with the use of paroxetine for the of the main etiologic factors for vulvar fusion include low estrogen levels and cessation of treatment of menopause-associated vasomotor symptoms. Secondary: evaluate the sexual activity. This pathology can be congenital or acquired, and although common in the impact on body weight and on sexual function as well as on the overall quality of life pediatric population, few cases have been reported in post-menopausal women. Design: Design: Prospective that evaluates the impact of the use of paroxetine 7.5 Discussion of 3 cases of labial agglutination in women of marked advanced age Results: mg in the treatment of vasomotor symptoms. 52 peri and postmenopausal women were This study presents 3 cases of labial agglutination in women of marked advanced age, included at the Climacteric Section of the Italian Hospital of Buenos Aires between who presented with complaints of urinary incontinence and dribbling, , January 2018 and March 2019, 18 of 52 women (34.64%) had contraindications to difficulty voiding, dysuria, and urodynia due to urethral outlet obstruction by the labia Menopausal Therapy (MHT); 6 (11.54%) rejected the use of ; minora and majora, urocolpos, bilateral hydronephrosis and bilateral megaloureters. 1 (1.92%) had not responded to MHT, 4 women (7.69%) had other motives. Patients These cases didn’t respond to the use of local estrogen application and two of them had with were excluded. The women were evaluated at the first visit and after 8 to have surgical incision of the fusion and then vaginal local applications of estrogen weeks of treatment. The basal evaluation comprised: Initial weight in kg as well as the along with continual and regular use of dilators. Conclusion: Based on the 3 cases we weight during the follow-up period; and the presence of daily hot flashes within a week have discussed in this study, vulvar fusion is an uncommon manifestation but one that is classified according to their severity in mild, moderate, severe and night sweats. Mild worthy of notable discussion with the patient in the beginning stages of GSM allowing hot flashes were defined as the feeling of warmth, moderate hot flashes were defined them to avoid the fusion. as the feeling of warmth associated with sweating and severe hot flashes as the feeling Sources of Funding: None of intense warmth along with profuse sweating that interferes with everyday activities. All women filled in a basal hot flashes diary and another one at 8 weeks of treatment. The total Score was calculated by dividing the total number of hot flashes in a week by 7. In addition the Sexual Function Index (FSFI) and the Menopause Rating Scale (MRS) was calculated. Results: 52 patients were included, with a mean age of 55.05 years old. 3 patients (5.76%) suspended the treatment within the first week due to adverse effects (mainly somnolence). 49 women (94.23%) completed the treatment at 8 weeks. It was observed that at 1 week the hot flashes score had decreased in 92.59% of the patients and a reduction of more than 50% was reported by 31.58% of the patients. Mild hot flashes improved in 82.61% women and a decrease by more than 50% was observed in 52.63%. Moderate hot flashes were reduced in 86.11% of the women and a reduction of more than 50% presented in 51.51%. Severe hot flashes improved in 95% of patients and more than 50% reduction occurred in 84.21%. Night sweats diminished in 80.95% of P-6. women and more than 50% in 72.22% of them. At 8 weeks there was a decrease in the hot E2/P4 Capsules Effectively Treat Vasomotor Symptoms Irrespective of flashes score in 92.59% of patients and an improvement of more than 50% in 61.54% of Age and BMI women. Mild hot flashes improved in 83.33% and more than 50% in 76%. Moderate hot Diana Bitner, MD1, Rebecca Brightman, MD2, Shelli Graham, PhD3, Brian Bernick3, flashes decreased in 94.59% of patients, more than 50% in 72.97% of them. Severe hot Sebastian Mirkin3. 1Spectrum Health, Grand Rapids, MI; 2The Icahn School of Medicine flashes improved in 100% of women and a reduction of more than 50% was observed in at Mount Sinai, New York, NY; 3TherapeuticsMD, Boca Raton, FL 95.24%. Lastly, night sweats improved in 82.61% of patients, more than 50% in 73.68%. Objective: TX-001HR is a combined hormone therapy (HT) of bioidentical 17β- Variations in weight were analysed and found that the mean deviation value was 200 g. and (E2/P4) available in the US as a single, oral softgel capsule An improvement in the MRS scale was observed in 76.47% of women with a statistically as Bijuva™ (1 mg/100 mg; TherapeuticsMD, Boca Raton, FL). In the REPLENISH significant difference (p=0.0006). The FSFI improved in 53.33% of patients but the trial, doses of E2 mg/P4 mg 1/100 and 0.5/100 significantly improved frequency and difference was not statistically significant (p=0.77). Conclusion: According to this study, severity of moderate to severe hot flushes at weeks 4 and 12 from baseline vs placebo low-dose Paroxetine (7.5 mg) could be a good therapeutic option for the management (all co-primary endpoints met; Lobo et al, Obstet Gynecol 2018;132:161-170). The of menopause-associated vasomotor symptoms which does not cause significant weight objective of this study was to further analyze the 4 co-primary efficacy endpoints by variations as well as improves quality of life scales. age and (BMI). Design: REPLENISH (NCT01942668) was a phase 3, Sources of Funding: None randomized, double-blind, placebo-controlled, multicenter trial evaluating the safety and efficacy of E2/P4 for the treatment of vasomotor symptoms (VMS) in postmenopausal women with a (n=1835; 40−65 years). Women with moderate to severe hot flushes (≥7/day or ≥50/week) were randomized 1:1:1:1:1 to E2 mg/P4 mg 1/100 (n=141), 0.5/100 (n=149), 0.5/50 (n=147), 0.25/50 (n=154), or placebo (n=135) in the VMS substudy. Percent changes in the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 vs placebo were analyzed by age (<55 and ≥55 years) and BMI (<25, 25 to <30, and ≥30 kg/m2) in these women. Results: Baseline frequency of moderate to severe VMS, but not severity, was numerically higher in the younger group; BMI subgroups had similar baseline values. When analyzed by age, percent changes from baseline in frequency with E2/P4 were similar at weeks 4 (43-56%) and 12 (64-78%) between age groups. While subgroup analyses were not powered for statistical P-5. significance, significant differences between E2/P4 doses and placebo were observed Pregabalin use for the management of menopause-associated vasomotor at week 12 (FigA). For severity, percent change from baseline with E2/P4 ranged from symptoms, a new alternative? 16-22% at week 4 and 24-51% for either age group at week 12 (FigB). When analyzed Maria A. Belardo. climacteric section, italian hospital, Buenos Aires, Argentina by BMI, larger percent reductions in VMS frequency and severity were observed with Objective: Primary; Evaluate the response to low dose pregabalin as treatment of hot E2/P4 vs placebo, with some groups meeting statistical significance at weeks 4 and 12 flashes in menopausal women Secondary: Evaluate the quality of life of the women (Fig). Conclusion: This oral, combined, bioidentical E2/P4 improved VMS frequency that use pregabalin Design: A case series clinical study using the data base from the and severity regardless of age or BMI. Subgroup analyses reported here demonstrate a Climacteric Section of the Italian Hospital of Buenos Aires in a period comprised consistency of effect of this E2/P4 among different populations. between September 2015 and April 2019. 23 postmenopausal women were included Sources of Funding: TherapeuticsMD and 20 were eligible for the first evaluation. The inclusion criteria used was women with moderate and/or severe hot flashes and/or night sweats (more than 21 weekly in total) and/or had contraindication to and/or refused the use of hormonal treatment and/or had had unsatisfactory response to other nonhormonal treatments. Patients with previous pregabalin treatments were excluded. Moderate hot flashes were defined as the feeling of warmth associated with sweating and severe hot flashes as the feeling of intense warmth along with profuse sweating that interferes with everyday activities. All women filled in a basal hot flashes diary and another one at 8 weeks of treatment. The final score was calculated by dividing the total number of hot flashes in a week by 7. Each patient received an initial pregabalin dose of 25 mg per day during the first week, followed by an increase in dose of 50 mg per day for the remaining 7 weeks. The data was analysed evaluating the clinical response to the use of pregabalin, defined as a 50% reduction in the total amount of hot flashes or night sweats. In addition, the quality of life scale MenQol (The Menopause-Specific Quality of Life), Female Sexual Function Index (FSFI), BMI (Body Mass Index) and the presence of adverse effects was evaluated. Results: 23 patients were recruited, 3 of them (13.04%) suspended the drug intake behore 8 weeks of treatment due to the presence of adverse effects such as somnolence. Thus, 20 women with a mean age of 55 years old (RIC25-75 45-61) and a mean BMI of 26.3 (SD 5.29) were analysed. From these women, 16 patients (69.57%) had contraindications to Menopausal Hormone Therapy (MHT). Among them, 9 had a history of prior breast cancer; 1 patient had a history of previous ; 2 presented a history of a thromboembolic episode; other 2 were outside the MHT therapeutic window; and 2 had a history of . Besides this, 9 patients (39.13%) had had therapeutic failure to other nonhormonal treatments and 3 patients (13%) had refused MHT. Among 85.1% of patients that improved their total score of hot flashes, 77.7% decreased mild hot flashes, of which 66.67% were reduced in more than 50%; moderate hot flashes improved in 72.7% of women, of which 36.3% reduced the total amount in more than 50%. In addition, severe hot flashes were reduced in 71.43% of patients, of which 71.43% did it Mean percent change from baseline to week 12 in weekly (A) frequency and (B) in more than 50%. Night sweats improved in 70% of women, of which 50% decreased severity of VMS by age and BMI more than 50%. Likewise, an improvement in sexual function was achieved from 22.16 to 26.1 and quality of life with a baseline score in MenQol from 94.47 to 86.75 at follow-up. Conclusion: According to the results obtained by the study, pregabalin 50 mg could be a nonhormonal therapeutic option for postmenopausal women with vasomotor symptoms. Sources of Funding: none P-7. obstructive sleep dyspnea syndrome (OSA), restless legs syndrome (RLS), Thai Hosipital The factors associated with frontal lobe cognitive impairment in surgical Anxiety and Scale (Thai HAD) score > 11 and had used for sleep menopausal women disorders in the past month were excluded. All elegible participants were evaluated for Sukanya Chaikittisilpa, MD, MSc2, Malika Kengsakul, MD1, Solaphat Hemrungrojn, sleep efficiency by wearing Actiwatch2™ on their non-dominant wrist all day for 7 days. MD3, Nalina Orprayoon, MD2, Chanakarn Suebthawinkul, MD2, Phanupong Phutrakool4, Sleep and food diary were recorded. After one week, the Actiwatch2™ was taken off Unnop Jaisamrarn, MD, MHS2. 1Department of Obstetrics and Gynecology, Faculty and the recorded data was retrieved, displayed as Actighraph. Good sleep effeciency was of Medicine, Chulalongkorn University, Bangkok, Thailand; 2Menopause Research defined as sleep efficiency ≥ 85%. Total sleep time (TST), sleep latency (SL) and wake Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn after sleep onset (WASO) were recorded. The visceral rating scale was measured by University, Bangkok, Thailand; 3Department of Psychiatry, Faculty of Medicine, bioelectrical impedance analyzer (BIA) technique. for plasma , Chulalongkorn University, Bangkok, Thailand; 4Chula Data Management Center, total , and HDL-cholesterol levels were collected. Mann Whitney Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand U test, binary logistic regression analysis and Spearman’s rank correlation coefficient Objective: To determine the percentage and factors associated with frontal lobe analysis were performed in this study. Statistical significance was taken as p-value cognitive impairment in women with surgical menopause Design: Design: This study < 0.05 for all tests. Results: Ninety-five peri or early postmenopausal women with is a post hoc analysis of a cross-sectional study between October 2013 and July 2014. vasomotor symptoms were enrolled into this study. The severity of vasomotor symptoms Method: Data from 180 surgical menopausal women were used for analysis. The were 84.2% mild, 11.6% moderate and 4.2% severe symptoms. There were 52 women information was obtained by self-reported questionnaire which included age, year since with good sleep efficiency and 43 women with poor sleep effeciency. The difference menopause, education, medical and surgical history, history of menopausal hormone of sleep parameters in good sleep and poor sleep was showed in table 1. Women with therapy (MHT), exercise, sleeping disorder, family history of , and self- high risk visceral fat were 69.8% and 44.2% in poor SE group and good SE group, awareness of forgetfulness. The Montreal Cognitive Assessment Thai version (MoCA-T) respectively (OR 1.577, 95% CI 1.097, 2.268, p=0.013). After adjusted for age and time test was administered by well-trained psychologist. Outcome measures: MoCA-Global since menopause, the difference between groups was showed as OR = 2.991 95%CI cognitive function, MoCA-Frontal lobe cognitive function (included visuospatial/ 1.213, 7.378, p=0.017), table 2. SE and TST were significantly negative correlation with executive, language fluency and abstraction scores) and MoCA-Visuospatial/Executive visceral fat rating. Conclusion: Menopausal women with vasomotor symptoms who had score Statistical analyses: Pearson correlation was performed to determine the clinical poor sleep efficiency had higher risk for visceral fat deposition than good sleep efficiency variables associated with MoCA test values. Multivariate Linear Regression was used group. to explore the influence of different variables on MoCA test values including age, Sources of Funding: Ratchdapiseksompotch Fund, Faculty of Medicine, Chulalongkorn education, body mass index, year since menopause, menopausal hormone therapy, Univarsity, Bangkok, Thailand family history of dementia and other independent variables. Statistical significance was Table 1 Difference of sleep parameters between good sleep and poor sleep taken as P-value < 0.05 for all tests. Results: The mean age was 55.4 ± 7.7 years and nearly half of the participants were menopause for more than 10 years. The percentage of mild cognitive impairment (MCI) in the present study was 43.5%. The difference of frontal lobe cognitive impairment between normal group and MCI group are shown in table 1. There was 73.9% of surgical menopausal women showed frontal lobe cognitive impairment in this study. Even in normal MoCA-total group, the frontal lobe cognitive impairment was 59.8% and individual domain was 19.6%, 37.3% and 23.5%, Statistical significance was taken as p-value < 0.05 in visuospatial, language fluency and abstraction impairment, respectively. Pearson Table 2 Comparison high risk visceral fat between good SE and poor SE group correlation showed significant negative associations between MoCA- Global Cognitive Function with Year since menopause (r=-0.165, p-value=0.027), but no association between MoCA-frontal lobe and clinical variables was shown. A multiple regression was run to predict MOCA Frontal Lobe score from all independent variables. These variables statistically significantly predicted MOCA score, F (14, 115) = 6.40, p < .001, R2 = 0.4381. The regression coefficient associated with Education > 6 Year is 2.92 and the patient with family history of dementia is associated with a 0.72 score increase in MOCA-Frontal lobe score (p-value=0.040) after all adjustment. Conclusion: Almost Statistical significance was taken as p-value< 0.05 three-fourth of the surgical menopausal women had impaired frontal lobe cognitive function, 92.3% in MCI group and 59.8% in normal group. Menopausal hormone therapy P-9. showed no association with frontal lobe cognitive function, only year of education and family history of dementia were associated with MoCA-frontal lobe score. Discussion of Vulvovaginal Health at Postmenopausal Well Woman Visit – Sources of Funding: Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn Patient Characteristics and Visit Experiences 2,1 2 University, Bangkok, Thailand Amanda L. Clark, MD, MCR, NCMP , Joanna E. Bulkley, PhD , Alaina T. Bennett, 1 2 1 Table 1 Frontal lobe cognitive impairment between normal and MCI group (n=180) MD, MS , Kimberly K. Vesco, MD, MPH . Obstetrics and Gynecology, Female Pelvic Medicine and Reconstructive Surgery, Oregon Health & Science University, Portland, OR; 2Center for Health Research, Kaiser Permanente Northwest, Portland, OR Objective: Determine patient and visit characteristics associated with discussion of postmenopausal vulvovaginal symptoms (VVS) at well woman exam among women who had at least one vulvovaginal symptom at the time of the visit. Design: We performed a secondary analysis of a 2015 survey of postmenopausal women conducted to assess the impact of a health system intervention on genitourinary syndrome of menopause (GSM). In this clinic-based, cluster-randomized trial, primary care and gynecology clinics were randomized to intervention, which included clinician education and computer support tools, or to no intervention. Patients were surveyed within 2 weeks of a well-woman visit via REDCap. Our primary outcome for this analysis was self-report of discussion of VVS at the visit. Vulvovaginal, sexual and urinary symptoms with bother were elicited using a format adapted from the Pelvic Floor Distress Inventory–20. Among women *Frontal lobe cognitive function by MoCA-frontal lobe score = Visuospatial + with at least one VVS, women who did and did not discuss VVS were compared using language fluency + abstraction score independent two-sample t-tests (continuous variables) and chi-square tests (categorical variables), with α<0.05. Results: The survey response rate was 26% (1546/5915). We excluded 13 women who were patients of the study’s clinician investigators P-8. (N= 1533). Our study cohort was comprised of the 45% (695/1533) who reported ≥1 Effect of sleep efficiency on high risk visceral fat in menopausal women VVS by survey. Of these symptomatic women, only 39% (272/695) discussed their with vasomotor symptoms symptoms at their well woman visit. Symptom bother varied from “not at all” to “quite Pimpagar Chavanaves, MD3, Nattapong Jaimchariyatam, MD2, Tassawan Rungruxsirivorn, a bit” and on average was between “somewhat” and “moderately.” Bivariate analyses MD3, Nalina Orprayoon, MD1, Chanakarn Suebthawinkul, MD1, Unnop Jaisamrarn, MD, (Table) showed discussion of VVS was associated with the presence of most VVS’s, MHS1, Sukanya Chaikittisilpa, M.D., M.Sc.1. 1Menopause Research Unit, Department of but not vaginal dryness or odor. Discussion of VVS was not associated with study Obstetrics and Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, intervention or the presence of lower urinary tract symptoms other than dysuria. Women Thailand; 2Excellence Center for Sleep Disorders, Department of Medicine, Faculty of initiated discussions more often than clinicians (59% vs. 22%), with 16% reporting that Medicine, Chulalongkorn University, Bangkok, Thailand; 3Department of Obstetrics and both started the discussion. Eighty-three per cent were satisfied or very satisfied with the Gynecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand discussion. Of women who didn’t have a discussion, 18% wished that they had. Having Objective: To compare the proportion of high risk visceral fat between good and poor a discussion was positively associated with clinician actions to address VVS—providing sleep efficacy in menopausal women with vasomortor symptoms Design: Method: written educational materials, suggesting lubricants or , and referral to A cross-sectional study was performed in King Chulalongkorn Memorial Hospital, a class or specialty clinician. Conclusion: Nearly half of these postmenopausal women Bangkok, Thailand. Peri- or early postmenopausal women with vasomotor symptoms, reported having VVS, yet a minority discussed their symptoms at a well woman visit. serum FSH ≥ 20 IU/L and literate were recriuted. The women with history of chronic Discussion of VVS led to helpful interventions, suggesting a role for greater clinician- medical diseases, psychiatric disorders, drug or abuse, had high risk criteria for initated screening for GSM. Sources of Funding: An Independent Grant for Learning and Change (Grant knowledge improved, 28.6% (N=8) knowledge reduced, and 32.1% (N=9) demonstrated #10319749), Pfizer, Inc, in collaboration with the North American Menopause Society no change in knowledge. In the multiple regression model, baseline scores (p < .001) Characteristics of patients and care experienced among patients with ≥1 VVS at the time and race (p = .039) were significantly related to improvement. Age, menopause status, of well woman visit, by vulvovaginal symptom discussion status , and hormone therapy were not significantly related. Participants with lower initial knowledge were more likely to improve and no measurements in the EOG were significantly related to improved knowledge. Conclusion: This 4-week pilot study provided a menopause education course in a group care format. There were significant gains in knowledge. Race and lower baseline scores were associated with gaining the most knowledge. Limitations were non-randomization and a small sample size. Sources of Funding: “None”

P-11. Baseline Estradiol Levels in Postmenopausal Women D. Constantine, MD1, James Liu, MD2, James A. Simon, MD3, Shelli Graham, PhD4, Brian Bernick, MD4, Sebastian Mirkin, MD4. 1EndoRheum Consultants, LLC, Malvern, PA; 2University Cleveland Medical Center, Cleveland, OH; 3George Washington University School of Medicine, IntimMedicine Specialists, Washington, DC; 4TherapeuticsMD, Boca Raton, FL Objective: Estradiol (E2) is a key hormone of the female , and exogenous administration may be utilized to treat menopausal vasomotor symptoms (VMS) and symptoms associated with vulvar and vaginal (VVA). A generally accepted normal range for E2 determined from a well-defined population of postmenopausal women using an accurate, standardized, analytical method is needed. Our objectives for this analysis of two phase 3 trials were to report E2 levels from a large database of postmenopausal women and to assess normal E2 ranges based on varying demographic parameters using such an analytic method. Design: The REPLENISH (NCT01942668) study is a phase 3, randomized, double-blind, placebo-controlled, multicenter trial that evaluated postmenopausal women with a uterus seeking treatment for VMS (VMS population; aged 40−65 years, body mass index [BMI] ≤34 kg/m2). The REJOICE (NCT02253173) trial is a phase 3, randomized, double-blind, placebo- controlled, multicenter study that examined postmenopausal women with VVA (VVA population; aged 40-75 years; BMI ≤38 kg/m2). Serum E2 levels were measured in both trials using chromatography/tandem with a lower limit of quantification of 2.0 pg/mL and sensitivities for estradiol of 4.83% for precision P-10. and -8.00% for accuracy on the LLOQ samples. Mean E2 levels were summarized A Pilot Study Measuring the Effectiveness of an Educational Group descriptively by factors that might impact endogenous E2 levels (i.e., age, BMI, race, Model to Increase the Menopause Knowledge Base of Pre, Peri- and Post- , alcohol use, and number of and live ). Results: Mean E2 Menopausal Group Participants levels at screening were available from 1905 women (n=1835 VMS population and Danette Conklin, PhD1,4, Corinne A. Bazella, MD2,3, Sarah DeLozier, PhD5, n=72 women VVA population). The overall mean E2 level at screening was 5.6-6.5 Brittany Brownrigg, BS1, Sheryl A. Kingsberg, PhD2,6, Jean M. Marino, APRN-CNP, pg/mL in the VMS population and 3.6-4.9 pg/mL in the VVA population. Mean levels NCMP, IF2. 1Psychiatry, University Hospitals Cleveland Medical Center, Cleveland, OH; of E2 decreased with increasing age, ranging from 8.2 pg/mL in women 40-45 years to 2 3 3.5 pg/mL in women ≥70 years of age (Figure). E2 concentrations also increased with Ob/Gyn, University Hospitals Cleveland Medical Center, Cleveland, OH; Reproductive 2 2 Biology, Case Western Reserve School of Medicine, Cleveland, OH; 4Psychiatry and increasing BMI from 4.8 pg/mL for BMI <25 kg/m to 7.8 pg/mL for BMI ≥30 kg/m Reproductive Biology, Case Western Reserve University, Cleveland, OH; 5Clinical (Figure). Black women had the highest E2 levels, followed by White and Asian women Research Center, University Hospitals Cleveland Medical Center, Cleveland, OH; (Figure). Smoking, alcohol use, and numbers of pregnancies or live births did not appear 6Reproductive Biology and Psychiatry, Case Western Reserve University, Cleveland, OH to influence screening E2 levels. Conclusion: This stratification of E2 concentrations Objective: There have been limited studies conducted on menopause education delivered by demographic characteristics found that serum E2 decreased with older age and lower in a group care model. These studies showed improvements in overall quality of life and a BMI, and was highest in Black women and lowest in Asian women. These data will reduction in menopause symptoms. There were no studies found that examined increased contribute toward an understanding of the differences in endogenous E2 among women fund of knowledge using a menopause education course in a group care model format. This based on age, BMI, and race, and potential differences in hormone treatment responses. study aimed to measure the increase of knowledge acquired by participants in a 4-week Sources of Funding: TherapeuticsMD menopause, education group course developed by the Menopause Clinic team at University Hospitals Cleveland Medical Center. Design: This pilot study enrolled 38 pre-, peri- and postmenopausal 34-65 year old women of various races and ethnicities. The intervention was for 4 consecutive weeks (5 groups of 3 to 10). The Fund of Knowledge questionnaire developed by the National Institute on Aging (2001) was used to evaluate Knowledge Improvement and was collected pre and post. Demographics and an Evaluation of Groups (EOG) questionnaire (developed by Myra Hunter and colleagues) were collected at baseline (BL) and end of study (EOS), respectively. The EOG is rated from “a little” to “very” in the categories of useful, upsetting, supportive, influence, and coping. A 4-week menopause education course was developed based on clinical providers’ expertise and guidelines by the North American Menopause Society on How to Develop Menopause Discussion Groups. Content included: changes leading up to menopause, exploring women’s feelings toward menopause, vasomotor symptoms, genitourinary syndrome of menopause, sexual function, mood, depression, sleep, cognitive changes, surgical menopause, hormonal therapy, cardiovascular and cancer risks, , non-hormonal options (cognitive behavioral therapy, non-evidence based- /exercise, herbal supplements, and psychotropic ), and growth and acceptance of menopause. Participants were recruited from a University Hospital outpatient setting. Non-English speaking and people who could not give informed consent were excluded. This study was non-funded. Descriptive statistics Mean Serum Estradiol Levels Stratified by Age, BMI, Race, and Smoking were used to analyze clinical and demographic variables and chi-square for categorical variables. Fund of Knowledge scores were calculated out of a possible 13 points (1 point P-12. for each correct answer). Univariate linear regressions were conducted, followed by a multiple linear regression model to determine factors predictive of improved knowledge. Nonsmokers May Benefit From Lower Doses of an Oral 17β-Estradiol/ Univariate and multiple regressions were conducted to determine whether participants’ Progesterone Capsule—Data from the REPLENISH Trial 1 2 3 perceptions of group sessions (EOG) were predictive of participants’ improved knowledge Ginger D. Constantine, MD , Nanette Santoro, MD , Shelli Graham, PhD , Brian Bernick, 3 3 1 2 at EOS. Results: Mean age was 50.84±5.69, 18.9% (N=7) black; 73.7% (N=28) white; MD , Sebastian Mirkin, MD . EndoRheum Consultants, LLC, Malvern, PA; Department 5.4% (N=2) other. Menopause status was 18.4% (N=7) premenopausal; 31.6% (N=12) of Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO; 3 peri-menopausal; 36.8% (N=14) post-menopausal. Menopause status was undetermined TherapeuticsMD, Boca Raton, FL 1-3 for 13.2% (N=5) participants. Of the 38 participants, 34.2% (N=13) were taking hormone Objective: Smoking has been reported to alter exogenous estradiol and 2,3 therapy. 28 (73.7%) completed the study. Average scores improved significantly between reduce the effectiveness of hormone therapy (HT) efficacy in postmenopausal women. BL (10.89±1.50) and EOS (11.21±1.17), p=.001. In 39.3% of participants (N=11) In the REPLENISH trial, the three highest doses of an oral 17β-estradiol/progesterone softgel capsule (TX-001HR; E2 mg/P4 mg: 1/100, 0.5/100, 0.5/50; 1/100 approved by the FDA as BijuvaTM; TherapeuticsMD, Boca Raton, FL) were shown to significantly improve moderate to severe vasomotor symptom (VMS) frequency and severity at week 12 in menopausal women with a uterus.4 The 0.5-mg dose is the lowest oral E2 dose that showed efficacy for VMS treatment. The objective of this analysis was to determine the impact of smoking on E2/P4 treatment efficacy and systemic hormone levels. Design: The REPLENISH trial (NCT01942668) was a 12-month, phase 3, randomized, double- blind, placebo-controlled, multicenter trial that evaluated 4 doses of E2/P4 combined in a single, oral softgel capsule vs placebo in 1835 postmenopausal women (40−65 y; intact uterus) seeking relief from VMS. Women with moderate to severe hot flushes (≥7/day or ≥50/week) were enrolled in a VMS substudy and randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo; women with fewer VMS were randomized to E2/ P4 doses only. An exclusion criterion of the study was smoking ≥15 cigarettes per day or any electronic cigarettes; therefore, current smokers were defined as those reporting smoking <15 cigarettes/day and nonsmokers were never or past smokers. Mean change from baseline for VMS frequency and severity and ≥50% and ≥75% reductions in VMS frequency (responder analysis) were calculated at weeks 4 and 12 for E2/P4 vs placebo and analyzed by smoking status in the VMS substudy population. Hormone levels were measured at baseline, weeks 4 and 12, and months 6, 9, and 12, using validated gas chromatography-tandem mass assays. Median estradiol and levels of nonsmokers were compared with smokers in the safety population using a two-sample median test. Results: Approximately one quarter of women in the REPLENISH trial reported smoking <15 cigarettes per day. In nonsmokers, all E2/P4 doses significantly reduced the weekly frequency and severity of moderate to severe VMS from baseline to weeks 4 (except 0.5/50 for VMS severity) and 12 compared with placebo (all, P<0.05). Nonsmokers receiving the lowest (0.25/50) dose had ≥14 reduction of hot flushes per week compared with placebo beginning at week 4 and through to week 12. Additionally, significantly more nonsmokers had ≥50% and ≥75% reductions in VMS frequency with E2/P4 vs placebo at week 4 (except 0.5/50 at ≥75% level) and week 12 (all, P<0.001). Current smokers in any E2/P4 group had no significant VMS improvements from baseline to weeks 4 and 12 compared with placebo and proportions of smokers who responded to treatment (at both ≥50% and ≥75% levels) were not different from placebo at weeks 4 and 12. Baseline estradiol (3.8-4.7 pg/mL) and estrone (19.5-22.3 pg/mL) levels were similar between current smokers and nonsmokers for all treatment groups. Current smokers had significantly lower median levels of estradiol (19%-38%, all P<0.05) and estrone (25%-42%, all P<0.01) compared with nonsmokers for all E2/P4 groups, but not with placebo, at all timepoints. Conclusion: Nonsmokers taking E2/P4 showed a significant and clinically meaningful reduction in VMS frequency (≥14 hot flushes P-14. per week) and severity compared with placebo beginning at week 4 and maintained to WomanLab: A Multi-Modal Web-based Platform Co-Designed with week 12 (except for 0.5/50 at week 4 for severity). Current smoking (<15 cigarettes/day) had a significant impact on the efficacy of E2/P4 treatment and on systemic estradiol Patients to Address a Gap in Public Knowledge about Women’s Sexual and estrone concentrations with treatment. These data suggest that nonsmokers may Function in the Contexts of the Menopause Transition, Aging and Illness 1 1 1 1 benefit more from lower E2/P4 doses than current smokers. 1. Jensen J, et al. NEJM. Megan DePumpo, AM , Monica Christmas, MD , Leilani Douglas, BA , Kelly Boyd, BS , 1 1,2 1 1985;313:973-975. 2. Tansavatdi B, et al. Minerva Ginecol. 2004;56:105-114. 3. Chenab Navalkha, BA , Stacy T. Lindau, MD, MAPP . Obstetrics and Gynecology, 2 Ruan X and Mueck AO. Climacteric. 2015;18:38-46. 4. Lobo RA, et al. Obstet Gynecol. University of Chicago, Chicago, IL; Medicine-Geriatrics, University of Chicago, 2018;132:161-170. Chicago, IL Sources of Funding: TherapeuticsMD Objective: WomanLab aims to serve all women by providing access to scientifically accurate and consumable information about female sexual function. Research shows women regard sexual function as a key aspect of health and knowledge about their sexual P-13. function as important for their agency. Public health messaging about female sexuality Do additional clinical risk factors improve the performance of Fracture and overall health in midlife and beyond is heavily focused on prevention of Risk Assessment Tool (FRAX) Among Postmenopausal Women? and STIs, not sexual function. Design: WomanLab.org, co-designed with a diverse Findings from The Women’s Health Initiative Study patient advisory board, disseminates content driven by women’s priorities. WomanLab Carolyn J. Crandall, MD, MS1, Joseph Larson2, Jane Cauley3, John Schousboe4, implemented a multi-modal social media strategy, including Twitter, Facebook and Andrea LaCroix5, John Robbins6, Nelson B. Watts7, Kristine Ensrud8. 1University YouTube and impact was tracked using the analytics functionality of each platform. of California, Los Angeles, Los Angeles, CA; 2Fred Hutchinson Cancer Research Engagement trends informed content development and delivery strategies. Cost was Center, Seattle, WA; 3University of Pittsburgh, Pittsburgh, PA; 4Park Nicollet Clinic, estimated as total funding/# of users. Website search was introduced in July of 2018 Minneapolis, MN; 5University of California, San Diego, La Jolla, CA; 6UC Davis in response to requests from the WomanLab patient advisory board. Results: Between Medical Center, Sacramento, CA; 7Mercy Health Osteoporosis and Health 8/2017 and 4/2019 womanlab.org published 8 self-care tools, 60 educational blogposts Services, Cincinnati, OH; 8University of Minnesota Medical School, Minneapolis, MN and 13 videos, reaching more than 80K users from 200 countries and all U.S. states. Objective: To determine the ability of the Fracture Risk Assessment Tool (FRAX) to Among womanlab.org visitors for whom data were available (36%), 31% were male, discriminate between women who do and do not experience major osteoporotic fractures 32% were 45-64 and 9% were 65+ years old. The most frequently-viewed menopause (MOF), and whether adding common clinical risk factors may improve discrimination. blogs explained the cognitive and psychology changes associated with menopause (2.4K), Design: We used data from the Women’s Health Initiative, a study of postmenopausal menopause self-care strategies (930), and general information about menopause (766). women aged 50-79 at baseline (n = 99,413). Incident MOF were assessed annually during For all content, visitors spent an average of 2:35 minutes/page; 8% visited 3+ pages/ 10 years’ follow-up. For prediction of incident MOF, we examined the area under the session. Access to womanlab.org varied among users: 75% used a search engine, 18% receiver operatic characteristic curve (AUC) and net reclassification index (NRI) of the went to womanlab.org directly, and 6% used social media. Approximate cost was $6/ FRAX model alone and FRAX plus additional risk factors: type 2 mellitus, user and declined with time. Since the search function was implemented, “menopause” frequent falls [≥2 falls in the past year], vasomotor symptoms, self-reported physical or related terms (ie: hormone therapy) have been searched for 50 times. Conclusion: function score, and lumbar spine bone mineral . For NRI calculations, high risk WomanLab has the potential to all women with an internet connection. WomanLab was defined as predicted MOF risk ≥ 20%. Results: The AUC value for FRAX without is attracting geographically broad engagement and demonstrates the feasibility of using a BMD information was 0.65 (95% confidence interval [CI] 0.65-0.66). Compared with the web-based platform to disseminate knowledge about female sexuality in aging women. FRAX model, the AUC value was not improved by the addition of vasomotor symptoms, Sources of Funding: University of Chicago Women’s Board and The Ellie Fund at the diabetes, or frequent falls but was minimally increased by adding physical function score Jewish Women’s Foundation (AUC 0.66, 95% CI 0.66 to 0.67). The NRI of FRAX + additional variables vs. FRAX alone was 5.7% (p <0.001) among MOF cases and -1.7% among non-cases (p>0.99). Conclusion: Additional variables (diabetes, frequent falls, vasomotor symptoms, physical function score, or lumbar spine BMD) did not yield meaningful improvements in NRI or discrimination of FRAX for MOF. Tools other than FRAX may provide superior discrimination for prediction of MOF. Sources of Funding: National Institutes of Health HHSN268201600018C P-16.

Withdrawn by Author

P-15. Remodeling of High-density Lipoproteins Subclasses and Their Contents of Phospholipid and over the Menopause Transition: The SWAN HDL Ancillary Study Samar R. El Khoudary, PhD, MPH3, Xirun Chen3, Alexis Nasr3, Jeff Billheimer1, Dan McConnell2, Maria Brooks3, Trevor Orchard3, Sybil Crawford4, Dan Rader1, Karen Matthews3. 1University of Pennsylvania, Philadelphia, PA; 2University of Michigan, Anarbor, MI; 3University of Pittsburgh, Pittsburgh, PA; 4University of Massachusetts, Worcester, MA Objective: Higher levels of high-density lipoproteins cholesterol (HDL-C) may not always be cardio-protective in postmenopausal women. Novel metrics that quantify HDL subclasses and their phospholipid and triglycerides contents have shown strong associations with CVD risk beyond HDL-C promising a better determination of HDL clinical utility. Changes in these metrics have not been characterized over the menopause transition (MT). Our objective was to characterize trajectories of HDL subclasses and HDL phospholipid (HDL-PL) and triglycerides (HDL-Tg) contents relative to time of the final menstrual period (FMP). Design: The Study of Women’s Health Across the Nation (SWAN) HDL ancillary study measured HDL subclasses (total, large, medium and small HDL particles [HDL-P]) using nuclear magnetic resonance (NMR) spectroscopy and HDL-PL and HDL-Tg contents among a subset of midlife women over a maximum of 5 time points across the MT. LOESS plots and splines were used to assess whether changes in HDL metrics over time, in relation to the FMP, were not linear and had inflection points, consistent with an ovarian aging effect. Piecewise linear mixed-effects models were used to estimate and compare yearly changes in each HDL metrics at LOESS-identified time segments adjusted for age at FMP, race and study site. Results: We evaluated 558 women (at first visit: mean age ± SD 49.86 ± 2.7 years; 80.3% still menstruating). Consistent with menopause-induced changes, LOESS curves suggested a non-linear trajectory for HDL-C, total, large, and small HDL-P, and HDL-PL, and HDL-Tg over the MT. The trajectory for medium HDL-P was linear. HDL-C, HDL-PL and HDL-Tg trajectories had one inflection point within 1.5 years of the FMP resulting in 2 time segments, while total, large and small HDL-P trajectories had 2 inflection points; one at or before the FMP and one after the FMP resulting in 3 time segments (Table). HDL-C and HDL-PL steeply increased over the MT with increases decelerated P-17. or stabilized in segment 2. In contrast, HDL-Tg was relatively stable in segment 1 Anti-Mullerian Hormone (AMH) Decline in Women with Hysterectomy but significantly increased in segment 2. Total HDL-P increased over the MT with or Natural Menopause: Data from the Study of Women’s Health Across the steepest rise occurring in segment 2. Large HDL-P declined while small HDL-P the Nation (SWAN) increased in segment 2. Conclusion: Although HDL-C significantly increased over the 2 2 3 4 5 MT, HDL subclasses and contents of phospholipid and triglycerides showed a dramatic Anne Davis , Rebecca Flyckt, MD , Joel Finkelstein , Janet Sun, MS , Sybil Crawford , Carol A. Derby6, Anthony Morrison7, Patrick Sluss7, Heping Zhang4, Nanette Santoro, adverse remodeling during this time. Declines in large HDL-P and increases in small 1 1 HDL-P and HDL-Tg contents around or after the FMP may contribute to increase risk of MD . Obstetrics and Gynecology, University of Colorado School of Medicine, Aurora, CO; 2Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH; 3Medicine, CVD in postmenopausal women. Our results support efforts to identifying novel targets 4 for HDL-based therapies and better HDL of CVD risk in women. Massachusetts General Hospital, Boston, MA; Yale University, New Haven, CT; 5University of Massachusetts Medical Center, Worcester, MA; 6Albert Einstein College Sources of Funding: The Study of Womenʼs Health Across the Nation (SWAN) HDL 7 ancillary study has grant support from National Institute on Aging (NIA) AG058690. The of Medicine, Bronx, NY; Ansh Laboratories, Webster, TX SWAN has grant support from NIH, DHHS, through NIA, NINR and ORWH. Objective: The definition of the onset of menopause is based upon the occurrence of Segment-specific slopes for years before/after the FMP for HDL metrics with non-linear a final menstrual period (FMP). Women who have undergone hysterectomy have no trajectories over the MT menstrually based ‘anchor’ to determine their timing of menopause. Data are scant and not in agreement about whether women undergoing hysterectomy with ovarian conservation have an earlier menopause than those who transition naturally. Design: Prospective, observational cohort study, SWAN, in which 3302 women at baseline have been followed for 25 years. Women undergoing hysterectomy with conservation of at least one (N=74) were compared to women undergoing natural menopause with an observed FMP (N=1536). Anti-mullerian hormone (AMH) was measured using an ultrasensitive ELISA (picoAMH, Ansh Labs, Webster, TX) annually in the naturally menopausal women from the early perimenopause up to one year after the FMP. Women with hysterectomy had at least one pre-operative AMH measured, and were measured a Inflection points vary by analyte: HDL-C at 0.5 years after FMP; HDL-PL at annually thereafter until AMH was undetectable (<3 pg/mL). Cox proportional hazard 1.5 years after FMP; HDL-Tg at 0.5 years after FMP; total HDL-P at 3.5 years and linear mixed modeling was used to compare the age at which each group had their before and 0.5 years after FMP; large HDL-P at FMP and 2.5 years after FMP; first undetectable AMH determination, before and after adjusting for age, BMI, race/ small HDL-P at 3.5 years before and 2 years after FMP. NA: not applicable since ethnicity, study site, self-reported presence of fibroids at basline, and smoking status. one inflection point was identified resulting in only two segments. AMH was log transformed for the mixed modeling analysis. Results: The median b Models adjusted for age at FMP, race and study site age (95% CI) at which AMH became undetectable was 50.2 (49.5, 50.7) for women c Significantly differs from segment 1 estimate at P<0.05 undergoing hysterectomy with ovarian conservation and 50.2 (50.1, 50.3) for women d Significantly differs from segment 3 estimate at P<0.05 undergoing natural menopause, p=0.343 before and p=0.220 after adjustment. Current smokers reached an undetectable AMH at an earlier age (HR 1.221, p<0.001). Being Japanese-American, or having a higher BMI were associated with later age at reaching undetectable AMH (HR 0.825, p=0.003 for race; HR 0.883 and 0.882 for BMI of 25-30 and 30 or more versus referent BMI of <25, p<0.001 for both). Conclusion: There is P-19. no difference in the age at which AMH becomes undetectable in women undergoing (E4) is a unique native estrogen that does not modify hysterectomy with ovarian conservation compared to women undergoing natural markers in postmenopausal women and maintains sensitivity to activated menopause. These data suggest that there is not significant ovarian damage occurring at protein C (APC) the time of hysterectomy with ovarian conservation. Jean-Michel Foidart, MD, PhD2,1, Rogerio Lobo, MD3, Jan Rosing4, Mélanie Taziaux1, Sources of Funding: The Study of Womenʼs Health Across the Nation (SWAN) Maud Jost1, Céline Bouvy5, Jonathan Douxfils, PharmD, PhD5,6, Ulysse Gaspard, MD, has grant support from the National Institutes of Health (NIH), DHHS, through the PhD, OB/GYN2. 1Mithra Pharmaceuticals, Liege, Belgium; 2University of Liège, Liege, National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) Belgium; 3Columbia University Medical Center, New York, NY; 4Maastricht University, and the NIH Office of Research on Women’s Health (ORWH) (Grants U01NR004061; Maastricht, Netherlands; 5Qualiblood sa, Namur, Belgium; 6University of Namur, U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, Namur, Belgium U01AG012553, U01AG012554, U01AG012495) and the SWAN Repository Objective: Compared to non-users, the risk of venous thromboembolism (VTE) has (U01AG017719). This publication was supported in part by the National Center for been reported to be increased several fold in women using combined oral contraceptives Research Resources and the National Center for Advancing Translational Sciences, (COC) or hormonal replacement therapy (HRT). This increase in risk is explained, at National Institutes of Health, through UCSF-CTSI Grant Number UL1 RR024131. The least in part, by activated protein C resistance (APCr) induced by the estrogenic moieties content of this abstract is solely the responsibility of the authors and does not necessarily [1–2]. APCr has also been observed in carriers of the factor V Leiden mutation, where represent the official views of the NIA, NINR, ORWH or the NIH. This study was also heterozygosity imparts an approximately 8-fold increased risk of VTE [1]. Factor Va supported by R25 HD075737 (to NS). inactivation by APC is crucial in down-regulating formation. Impaired factor Va inactivation increases the risk of VTE both in carriers and in non-carriers of the P-18. factor V Leiden mutation [3]. A global measure of the clotting capacity of plasma is the Estetrol (E4) has specific activity with a that is endogenous thrombin potential (ETP), which is determined by the thrombin generation different from Selective Estrogen Modulators (SERMs). test (TGT). The TGT quantifies thrombin generation after triggering the extrinsic Jean-Michel Foidart, MD, PhD2,1, Jean-François Arnal3, Françoise Lenfant, Ph.D.3, pathway of the coagulation cascade with tissue factor in the presence of phospholipids. Mélanie Taziaux1, Céline Gérard1, René Houtman4, Maud Jost1, Rogerio Lobo, MD5. To assess APC resistance, the amounts of thrombin generated in the absence and presence 1Mithra Pharmaceuticals, Liege, Belgium; 2University of Liège, Liege, Belgium; 3Inserm, of exogenous APC are compared. The relative resistance compared to that of individuals Toulouse, France; 4PamGene International, s-Hertogenbosch, Netherlands; 5Columbia without and who are not receiving COCs or HRT, provides the normalized University Medical Center, New York, NY APC sensitivity ratio (nAPCsr). Estetrol (E4) acts as an estrogen in stimulating Objective: The effects of are based on genomic mechanisms mediated by the , and when administered to postmenopausal women, reverses vaginal nuclear estrogen receptors (ERα and ERβ) activation and by non-genomic mechanisms atrophy while decreasing vasomotor symptoms [4-5]. Unlike other estrogens, E4 involving cell membrane receptors. Nuclear and membrane ER are biochemically blocks the membrane α (ERα), has tissue specific activity, and acts identical and act in concert. ERα is a member of the large steroid receptor superfamily and differently than Selective Estrogen Receptor Modulators (SERMs). Crystalline structure is expressed in a variety of reproductive tissues. Estetrol (E4) acts as a typical estrogen studies confirm that E4 interacts with the nuclear ERα in a fashion similar to other agonist in stimulating the endometrium, and when administered to postmenopausal estrogens and not SERMs [6]. In contrast to other estrogens administered orally, E4 women in various doses, reverses vaginal atrophy and decreases vasomotor symptoms. exhibits only minimal first-pass metabolism and hepatic effects on triglycerides, However, in contrast to other estrogens administered orally, E4 demonstrates a minimal hormone-binding globulin, -binding globulin, and angiotensinogen. In this hepatic effect and only moderately stimulates breast proliferation. Data in pre and study, we sought to determine the effects of E4 on coagulation factors, including the postmenopausal women show that E4 has minimal stimulatory effects on triglycerides, ETP-based nAPCsr in postmenopausal women. Design: In this multicenter, randomized, binding globulin, corticosteroid-binding globulin, and angiotensinogen. placebo-controlled, double-blind, dose-finding study, changes from baseline of Similarly, E4 exerts minimal effects on coagulation markers, and does not increase the coagulation factors, biomarkers and ETP-based nAPCsr were assessed in generation of thrombin as measured by the activated protein C resistance ratio, unlike 257 postmenopausal women who received 2.5; 5; 10; or 15 mg E4, or placebo once . Previous research has shown that E4 activates the nuclear ERα, but is daily for 12 weeks. Results: During E4 use in postmenopausal women, the hemostasis an antagonist of the membrane ERα [1]. In this study, we sought to further delineate markers including fibrinogen, prothrombin, prothrombin fragment 1+2, D-, the molecular mode of action of E4, and specifically probed whether the tissue factor VIII activity, protein C, antithrombin, and tissue factor pathway inhibitor, did selectivity of E4 may be explained by selective estrogen (SERM)- not show significant changes from baseline. A small statistically significant, but non- like mechanisms. Design: We performed a functional characterization of ERα clinically meaningful decrease of free protein S (5.9%) was observed at the highest E4 through coregulatory-based recruitment. We compared the binding pattern of ERα to 154 dose. Relative changes from baseline of the ETP-based nAPCsr were -27.6% (n=34) coregulator motifs induced by estradiol (E2), (E3) and E4 in a specific MARCoNI for placebo, and -12.3% (n=39), 14.0% (n=35), 11.1% (n=32), and 40.0% (n=32) for assay (PamGene International, the Netherlands) [2]. Human breast carcinoma cell pellets 2.5, 5, 10, and 15 mg E4, respectively. This was similar to the 30% increase observed (INSERM, Toulouse, France) containing ERα were processed and total protein and ERα in younger women receiving 15 mg E4/DRSP, but is in marked contrast to the increases content of cell lysate were quantified. Known amounts of ERα were exposed to 154 on EE/DRSP (219%) and EE/LNG (165%). Conclusion: The observed changes with binding motifs derived from nuclear hormone receptor coregulators immobilized on a E4 and E4/DRSP in the old and younger populations included in postmenopausal and microarray platform and in the presence of different doses of E2, E3 or E4. Receptor contraceptive trials can be considered as clinically non-significant. These hemostasis interaction with each coregulatory motif was detected by a fluorescently labelled changes were less than those observed with other HRT products containing estradiol or antibody. For each ERα-coregulator motif interaction, dose-response curves, conjugated equine estrogens. These data on ETP-based nAPCsr and the other hemostasis graphs and heatmaps were created. Comparison of compound potency of E2, E3, and data from previous trials support the notion that E4 may be associated with a lower risk E4 was performed by ANOVA. Results: In the absence of , ERα bound poorly of strengthening the position of E4 as a promising new treatment option for to the immobilized coregulator motifs. In the presence of increasing concentrations of postmenopausal women. 1-Lidegaard, Acta Obstet Gynecol Scand 2012 2-Rosing, Br J E2, E3, or E4, the ERα-ligand complex bound to the immobilized and induced Haematol 1997 3-De Visser, Blood 1999 4-Mithra, data on file 5-Foidart, Abstract IMS a binding signature. The pattern of coregulator recruitment induced by E4 was identical 2018 6-Abot, EMBO Mol Med 2014 to that elicited by E2 and E3, but E4 potency was 50-fold lower than the potency of E2 Sources of Funding: Financial support was provided by Mithra Pharmaceuticals (p<0.001). Conclusion: These data, together with previously published studies of the Belgium. crystal structures of ERα bound to E2, E3 or E4 confirm that E4 interacts with nuclear ERα in a manner identical to that of the other estrogens [1]. E4 inhibits the activity of P-20. the membrane ERα, and blocks the stimulatory action of E2 in this membrane ERα Vaginal Microbiome of Women with Premature Ovarian Insufficiency: subpopulation. Based on the results, it can also be concluded that the E4 interaction with Descriptive cross-sectional study the nuclear ERα is distinct from that observed with SERMs, such as 4-hydroxytamoxifen. Helena P. Giraldo, PHD, MD, Paulo C. Giraldo, São Paulo, Ticiana A. Mira, Daniela A. SERMs exhibit specific cell and tissue estrogenic, neutral or anti-estrogenic activities and Yela, PhD, Rose Gomes do Amaral, Cristina L. Benetti-Pinto, Associate professor. interact with the ligand binding domain of the ERα in a way that is distinct from that of OBSTETRICS AND GYNECOLOGY, CAMPINAS UNIVERSITY, Campinas, estrogens [3]. By preventing the kinking of helix 12, SERMs recruit other co-receptor Objective: To describe the vaginal microbiome of women with premature ovarian activators and inhibitors that are responsible for SERMs action. In conclusion, E4 is insufficiency (POI) receiving systemic hormone therapy (HT). Design: Descriptive a unique estrogen with specific actions in tissues, demonstrating absence of specific cross-sectional study. Results: Women had a mean age of 37.13 (± 7.27) years and membrane receptor effects, and no interaction with ERα in the way characteristic of POI diagnosis at 27.90 (± 8.68) years, a mean HT duration of 8.20 (± 8.73) years. It SERMs. 1)Abot et al. EMBO Mol Med. 2014; 6:1328 2)Broekema et al. . was observed that 33.4% of the women presented group I flora, with a predominance of 2018; 159:2397 3)Fanning et al. Elife. 2018 Nov 29;7 L. crispatus; 9% group II flora, with a predominance of L. gasseri; 33.4% group III flora, Sources of Funding: Financial support was provided by Mithra Pharmaceuticals with a predominance of L. iners; 15.2% group IV flora, with a predominance of anaerobic Belgium. bacteria; and 9% group V flora, with a predominance of L. jensenii. Conclusion: Women with POI receiving HT presented a vaginal microbiome with a predominance of lactobacilli in the composition of the vaginal flora, specifically L. crispatus and L. iners when evaluated by molecular biology through the pyrosequencing of 16S rRNA. Sources of Funding: The São Paulo Research Foundation (http://www.fapesp.br/) Grant # 2015/08334-0. P-21. P-23. Positive False Cervical Dysplasia in Perimenopausal Years: An Early Do Menopausal Symptoms Affect Job Performance in ? Keiko Sign of Genitourinary Syndrome of Menopause Hashimoto; Mikako Yoshida, PhD; Yasuka Nakamura, PhD; Yoko Dr. Dominguez Bali, MD1, Sindhuri Gollamudi, 3rd year Medical Student1,2. 1Miami Takeishi, PhD; Toyoko Yoshizawa, PhD Tohoku University Graduate Center for Obstetrics Gynecology and Human Sexuality, Miami, FL; 2American School of Medicine, Women’s Health Nursing & Midwifery University of Antigua, New York, NY Keiko Hashimoto. Tohoku University, Sendai, Japan Objective: As recently demonstrated, dysplastic cells have morphological similarities to Objective: Menopausal symptoms have been reported to reduce job performance in atrophic cells in the vagina and . (reference) Because of this, we find an increase in foreign countries. However, this has not been clarified in Japan. is the present study abnormal pap smears (dysplastic cells with or without HPV) in women >40 years old. We aims to clarify the relationship between menopausal symptoms and job performance in realize that this confusion is due to the misinterpretation of atrophic vaginal and cervical Japanese working women. Design: An online survey was completed by working women cells with dysplasia of vaginal and cervical cells. In general practice of OBGYN, physicians aged 45-65 years, excluding those who had a diagnosis of mental illness or who had who confront this issue, following the ASCCP guidelines, will subject these women to become menopausal due to surgery. Self-reported data were collected on demographics, colposcopy, biopsy and with subsequent persistent positive results; cryotherapy, LEEP menopausal status (pre-, peri-, post-menopausal), work-related variables, menopausal excision, and possible total abdominal hysterectomy. However, a recent study showed that symptoms, and job performance. Menopausal symptoms were assessed using the even after an abdominal hysterectomy, follow up Pap smear continues to be abnormal. Greene Climacteric Scale (GCS). The GCS contains 21 items, divided into four clusters (reference) Thus, we suggest that a local (vaginal) estrogen be started immediately after (psychological, somatic, vasomotor, and sexual). Job performance was evaluated using a the finding of an abnormal Pap smear in women over 40 years, especially if she has had single item (“absolute presenteeism”)from the Japanese version of the WHO Health and a stable relationship with her partner and previous negative pap smears results. Estrogen Work Performance Questionnaire (WHO-HPQ). Results: For the 564 participants, the therapy will cause the cellular abnormalities to disappear if the changes are benign due median age was 54.2 years (SD 5.8). The participants comprised 40.2% regular employees. to genitourinary syndrome of menopause. For this reason, we propose that abnormal pap The participants were classified based on menopausal status as follows: pre-menopausal smears include ASCUS, LSIL, and HSIL with HPV or without HPV be included in to (26.6%), peri-menopausal (15.2%), post-menopausal (58.2%). The mean (SD) total GCS the sign and symptoms of genitourinary syndrome of menopause. Measures will be taken score was 10.2 (0.9) in pre-menopausal, 13.3 (1.2) in peri-menopausal, and 10.0(0.5) in to assure that we are not in the presence of a real dysplasia. Design: Retrospective study post-menopausal participants. Peri-menopausal GCS score was significantly higher than of 400 female patients >40 years old with abnormal pap smears categorized as ASCUS post-menopausal (p=0.034). The psychological score was higher than the scores of the (atypical squamous cells of undetermined significance), LSIL, or HSIL, with or without other subscales in the three groups (p=0.00) (Figure.1). The presenteeism scores were as HPV, treated with a local estrogen course of at least 4-6 months with repeat pap smears. follows: 61.2(1.5) for pre-menopausal,59.5(1.7) for peri-menopause, and 62.4(1.0) for Results: Among the 400 patients that have come in with abnormal Pap smears, 29 women post-menopausal, with no difference between the three groups (p = 0.4). We examined the out the 43 (67%) we have analyzed thus far have improved and had no abnormal Pap smears correlation between menopausal symptoms and presenteeism. The correlation coefficient after treatment of Estrogen Vaginal for 6 months. 1 out of the 43 women (2.3%) had of the psychological scores (r = -0.232) was higher than that of the vasomotor scores no clinical improvement after the treatment and therefore had to go on to further testing. 13 (r = -0.122) (Table 1). Conclusion: The menopausal symptoms of Japanese women were out of the 43 women (30.2%) had undergone treatment however discontinued treatment or the most severe among the psychological symptoms, which reduced their presenteeism. switched providers due to insurance coverage issues. Conclusion: Having analyzed 43 of There is a need for health support interventions for psychological symptoms. the 400 women up to now, we found 67.4% of the abnormal Pap smears were due to benign Sources of Funding: “None” changes proper of genitourinary syndrome of menopause. This approach prevents a lot of Association between menopause symptoms and presenteeism time, unnecessary procedures/treatments and millions of dollars spent on what has been up to now, the normal guidelines to approach these kinds of problems. Sources of Funding: None ** p=0.00 P-22. Differences in Presentations of Women Presenting to the Menopause Units with Premature Ovarian Insufficiency or Menopause at the Expected Age. Hala Gomaa, MD1, Catherine Kelly2, Iliana Lega2, Ola Shaltout3, Wendy Wolfman1. 1Obstetrics and , University of Toronto, Toronto, ON, ; 2Women’s College Hospital, Toronto, ON, Canada; 3Medicine, Royal College of Surgeons in Ireland - MUB, Manama, Bahrain Objective: Menopause is defined as the cessation of for 12 months. When menopause occurs before the age of 40 years, whatever the (spontaneous or iatrogenic), it is defined as premature ovarian insufficiency [POI]. The decline in estrogen around the time of menopause is associated with physical, mental and emotional symptoms that may affect women’s quality of life in different ways. The most common symptoms are vasomotor symptoms, sleep disturbance, symptoms of depression and anxiety, joint and muscle pain, vaginal dryness and sexual disorders. The aim of our study is to assess the differences in menopausal symptoms and their severity among the two groups. Design: We conducted a cross-sectional study of women who initially presented with menopausal symptoms at two clinics at Mount Sinai Hospital, University of Toronto, Canada - the Mature Women’s clinic and the Premature Ovarian Insufficiency clinic from 2013 to 2018. We administered validated questionnaires to new patients during their first visit that measured the type and P-24. severity of menopausal symptoms. We also collected data on patient demographics, the nature of menopause, past medical history and family history. Results: We included data Effect of hormone therapy on associated with diabetes in the from 334 older postmenopausal women and 187 women with POI. The mean age of the Women’s Health Initiative Hormone Therapy Trials. 1 2 2 women from the Mature women’s clinic [perimenopausal and postmenopausal] [Group 1] Heather Hirsch, MD , Kathryn Rexrode , JoAnn E. Manson, MD, NCMP , 3 1 was45.38 y old and average age of symptoms was 46.53 y old. While the mean age in POI Raji Balasubramanian, ScD . Internal Medicine, The Ohio State University Medical 2 [Group 2] was 36.5 y old. Irritability, anxiety and mental exhaustion were significantly Center, Columbus, OH; Internal Medicine, Brigham and Woman’s Hospital, Boston, 3 higher in POI patients [67.53%vs 52.09%, p value = 0.01], [75.53%% vs 53.29%, p MA; University of Massachusetts, Amherst, MA value = 0.002] and [78.66%vs 58.98%, p value = 0.001]. Sexual disorders and vaginal Objective: In the Women’s Health Initiative (WHI), cumulative incidence of type 2 dryness were also notably higher in patients with POI compared to older postmenopausal diabetes (T2D) was decreased by 21% in the combined oral conjugated women [64% vs 50%, p value = 0.002] and [60.25%vs 46.10%, p value = 0.02]. Although plus acetate (CEE + MPA) treatment arm compared to placebo. there was a remarkable difference in symptoms of anxiety between the two groups, the A similar 12% non-significant effect was seen in the oral conjugated equine estrogen difference was not notable in regard to symptoms of depression [49.35%vs 52.69%, p (CEE) alone active arm of the WHI compared to placebo. To our knowledge, there have value = 0.5]. Hot flushes were insignificantly higher in women with POI [70.5%vs 59.88%, been no previous investigations of the effect of randomized hormone therapy (HT) on p value = 0.08], whereas joint and muscular discomfort was insignificantly higher in older levels related to glucose tolerance or T2D. To understand these findings, postmenopausal patients [56.88%vs 44.87%, p value = 0.055]. Conclusion: Our results we selected nine metabolites that were previously found to be strongly associated with concluded that the symptoms of irritability, mental exhaustion and anxiety are more the development of T2D, to see if they were affected by randomized hormone therapy. prevalent in the POI group. Furthermore, women with POI are also more affected by sexual Metabolites included three branched-chain amino (BCAAs; , , disorders and vaginal dryness. There was no significant difference found between both and ), two aromatic amino acids (AAAs; and ), , groups in the other symptoms including vasomotor symptoms, sleep disturbance, depressive , C3 and C5 . We investigated whether treatment with CEE alone or mood and bladder problems. Given a higher prevalence of irritability, mental exhaustion, CEE + MPA in the WHI showed a decrease in the concentration of these metabolites anxiety, sexual disorders and vaginal dryness in POI compared to older postmenopausal compared to placebo, which in turn might help explain the clinical findings regarding women, more emphasis should be placed on optimizing their mental and sexual health HT and T2D reduction in the WHI. Design: This study utilized data from a prior study, needs. which measured approximately 370 metabolites on 1362 women in the WHI in the Sources of Funding: Funded by non restricted grant support of Pfizer, no input. HT trials. Of these, a total of 1072 women had metabolomics profiles at both baseline and year 1. We evaluated changes in levels of the nine selected metabolites between in EQL-N (r=-0.228, P=0.018), but not in EQL-P (P=0.825). In addition, a correlation CEE alone versus placebo; and CEE + MPA versus placebo treatment arms. Within between months after menopause and percentage of thin hairs was found in EQL-N each HT trial, metabolite changes due to treatment relative placebo were evaluated in (r=0.243, P=0.012), but not in EQL-P (P=0.420). There was a significant interaction linear models considering metabolite change from baseline as outcome and adjusting between production status and months after menopause (P=0.017). Perceptions of for age and BMI. All P values were corrected for multiple comparisons. Results were “hair collectability, tension and elasticity”, and “shiny hair” in their hairs compared with further stratified by age (50-59, 60-69, and 70-70) and BMI (<24, 25-30, and 30+) to those during pre-menopause period did not worse in EQL-P than in EQL-NP (P=0.043, see if these sub-groups modified the response. Results: Of the nine metabolites, five and P=0.098, respectively). Conclusion: This cross-sectional study suggested that equol were significantly decreased by CEE alone and seven were significantly decreased with could attenuate in decreasing hair density, thinning and graying hair with menopause in CEE+MPA. For five of these metabolites, C3 and C5 carnitine, glycine, phenylalanine Japanese postmenopausal women. This is the first study showing a potential of equol for and tyrosine, there was a significant decrease seen in both CEE and CEE + MPA arms. attenuating the hair aging. For two metabolites, leucine and valine, only the CEE+MPA arm showed a significant Sources of Funding: None decrease. No significant changes with HT were observed for glutamine and isoleucine. Glycine had the largest decrease due to active HT in metabolite change over time with -0.95 (95% CI: -1.09, -0.80) SD unit change for CEE alone versus placebo; and -1.05 P-26. (95% CI: -1.22, -0.88) SD unit change for CEE+MPA versus placebo, with FDR adjust p Preventive Ovarian Cancer Clinic: A Model for Care of Women at Risk values < 10-27. In the CEE + MPA arm vs. placebo, the changes of the seven metabolites for Hereditary Ovarian Cancer were significantly modified by age, with strongest association in older ages (i.e., largest Michelle R. Jacobson1,2, Gabrielle E.V. Ene3, Mara L. Sobel1,2, Lisa M. Allen1,2, changes seen in 70 – 79, then 60 – 69, and then 50 – 59). Conclusion: Seven metabolites Melissa Walker2,4, Marcus Q. Bernardini1,3. 1Women’s College Hospital, Toronto, ON, which have previously been found to be associated with increased risk of T2D were Canada; 2Sinai Health System, Mount Sinai Hospital, Toronto, ON, Canada; 3University decreased by randomized HT at year one in both active arms compared to placebo in the Health Network, Toronto, ON, Canada; 4University of Toronto, Toronto, ON, Canada WHI. Interestingly, this finding was slightly more pronounced with CEE + MPA than Objective: The gynaecologic care for women with hereditary breast and ovarian cancer with CEE alone, paralleling the findings in the WHI incidence of T2D. These changes syndrome is complex. These women have unique challenges throughout their reproductive might help to explain the clinical findings of improved sensitivity and reductions . The Preventive Ovarian Cancer and Aftercare Clinic has been established to address in T2D incidence among women on active HT in the trial. these needs through expert and evidence based care. The aim of this study was to examine Sources of Funding: NHLBI contract the outcomes of our clinic two years after its inception. Design: A retrospective chart Table 1: Mean ratio of each metabolite level at year 1 compared to baseline, comparing review was performed on women with confirmed BRCA1/2 mutations referred to the active to placebo treatment. POCC at Women’s College Hospital, Toronto, Canada. Patient demographics, diagnostic codes, preoperative investigations, intraoperative and pathology findings were recorded. Results: Following referrals from genetic counsellors in Toronto, in 2017 our clinic expanded to 175 new patients visits, 75-85 outpatient procedures (i.e. bilateral salpingo- , bilateral salpingectomy), 20 inpatient procedures (total laparoscopic hysterectomy or medically complex BSO), and 130 aftercare (menopause management) visits. A total of 183 women were included in our cohort; 132 (72.1%) underwent RRS and 51 (27.9%) deferred or declined surgery. In women who underwent RRS (mean age 46 [30-72] years), 115 (87.1%) underwent RRSO and 17 (12.9%) chose risk initial reducing bilateral salpingectomy with delayed oophorectomy. Three occult malignancies were detected (2 serous tubal intraepithelial carcinoma, 1 invasive ovarian cancer; 2.3%). Preoperative investigations were normal in all women with abnormal pathology. Visit codes included contraception counselling, liaison with fertility specialists, counselling An asterix represents a p value <= 0.01 on risk reduction, risk reducing surgery, and menopause management. Conclusion: The Preventive Ovarian Cancer and Aftercare Clinic is providing comprehensive clinical P-25. care to women at a risk of hereditary ovarian cancer. This unique model encourages Equol status affects hair aging in postmenopausal women. A cross- comprehensive management and continued research collaboration and advancement. sectional study. The program also offers further management to those experiencing surgical menopause following their risk-reduction surgery. Ongoing goals include collection of patient Soh Iwashita1, Haruna Miyakawa2, Tomomi Ueno2, Shigeto Uchiyama2, satisfaction data and integrative care with the breast centre. Keisuke Hamamoto1, Rie Ueki3. 1Nutraceuticals Division, Otsuka Pharmaceutical Co., Sources of Funding: None Ltd., Tokyo, Japan; 2Saga Nutraceuticals Research Institute, Otsuka Pharmaceutical Co., Ltd., Yoshinogari, Japan; 3Dermatology, The Juntendo Tokyo Koto Geriatric Medical Center, Tokyo, Japan P-27. Objective: Hair loss and gray hair in women are typical hair aging. It becomes more Fractional CO2 Laser Treatment as Adjunctive Therapy to High-Potency serious quality of life issue in postmenopausal women with increasing aging population Topical for Managing Vulvar Lichen Sclerosus: Preliminary in the developed countries. A type of hair loss in women refers to as female pattern Findings of a Pilot Study hair loss (FPHL), which is characterized by diffuse reduction in the number of hairs, Sunbal Javaid, MD1,2, Sarah E. Bartlett, MD FACOG1, Kristen Stewart, MD FAAD3, especially in the central, frontal, and parietal scalp regions. On the other hand, aging of Konika Patel Schallen, MD4,2. 1Somi Javaid MD and Associates, Cincinnati, OH; melanocyte stem cells, which is affected by aging, induces gray 2Candela, Bethlehem, PA; 3Total Dermatology Care Center, Jacksonville, FL; 4Center hair. Thus, hair follicle stem cells could be a consistent cause of both hair loss and gray for Modern Aesthetic Medicine, Jacksonville, FL hair. Although the reason for the stem cell aging has not been well understood to date, Objective: Background and Objective: Skin conditions such as vulvar lichen sclerosus the decrease in estrogen concentration could be a candidate of the causes because hair (VLS) often go untreated until advanced signs of skin damage occur. Treatment with aging is markedly accelerated after menopause. Equol, which is an intestinal bacterial potent topical steroids is aimed at relieving symptoms and preventing further damage. metabolite of soy , shows estrogen-like bioactivity. Approximately Fractional CO lasers have been shown histologically to improve vaginal tissue and to 20-30% of Westerns and ~50% of Asians can produce equol in their body. We have 2 alleviate self-reported vulvar symptoms of itching and . The objective of demonstrated that an equol-containing has an efficacy of alleviating this study was to evaluate a series of fractional CO laser treatments to improve clinical menopausal symptoms, reducing bone loss, improving metabolic parameters such as 2 signs and architectural changes associated with VLS and, as an adjunctive therapy, to hemoglobin A1c and LDL-cholesterol and cardio-ankle vascular index, and inhibiting maintain symptomatic control of the . Design: Methods: Female participants, skin aging in postmenopausal women. Therefore, we studied the relation between hair with a diagnosis of VLS supported by histologic findings on biopsy and/or clinical aging and equol status in postmenopausal women in a cross-sectional study. Design: signs on physical examination and recalcitrant to high-potency therapy, The 200 postmenopausal women aged 45 to 64 years from the 277 eligible participants received up to 5 monthly treatments to the vulvar area with a fractional CO laser. were chosen for this study based on the rating of hair loss (FPHL scale). Microscopic 2 Subjects maintained their existing topical steroid and exogenous hormone treatment, if images of cropped hair area in all subjects were taken for the hair analysis. Hair any, during the study. Investigators assessed severity (0=not present, 1=mild, 2=moderate density, percentage of gray hair, and percentage of thin hair defined as less than 40µm or 3=severe) of clinical signs and architectural changes following treatments. Subjects in diameter was calculated for evaluating the objective hair parameters. The subjects reported the presence of symptoms and impact on quality of life and sexual function on also completed a questionnaire about change of hair condition with menopause. Equol 5-point scales. Clinical assessments, self-reported symptoms and sexual function, using status was determined using samples after soy challenge. Results: Number of equol the validated Female Sexual Function Index (FSFI), will be reported at the 3-, 6- and producers was 93 (47%) in the total 200 subjects. All 22 smokers were consisted 12 12-month follow-ups after the final treatment. Biopsies were taken from three subjects in the equol non-producers (EQL-N, 11%) and 10 in the producers (EQL-P, 11%). In at baseline, and histological markers (degree of hyperkeratosis, epidermal atrophy and FPHL scale, 117 (59%) subjects were evaluated as normal with scale-1. Then, the rest dermal ) will be evaluated with repeat biopsies at follow up. Results: of subjects were judged as FPHL and the number of scale-2, -3, -4 and -5 was 74, 7, 2 Results: Currently, 11 with a mean age of 57±10 years and postmenopausal and 0 subjects, respectively. Ages, months after menopause, body mass index, blood status (10/11 women) of 2-19 years received a total of 48 treatments (mean of 4). At pressure and soy isoflavone consumption were not different between EQL-N and EQL- baseline, the prevalent clinical signs observed were whitening, parchment-like skin, P. Density and percentage of gray hair were lower in EQL-P than in EQL-N (P=0.025 lichenification, sclerosus and loss of elasticity, as well as labial fusion. Subjects and P=0.078, respectively). Then, other objective hair parameters calculated from the predominantly reported superficial (introital) dyspareunia, skin tearing/bleeding, number or diameter of the hair as well as FPHL scale were not different between groups. negative impact on quality of life, and decrease in sexual function. Following the last A negative correlation was found between months after menopause and hair density treatment, 89% (8/9) of subjects showed at least one-point improvement compared to P-29. baseline in sclerosus, 82% (9/11) in whitening, 73% (8/11) in parchment-like skin, 70% Apoptotic activity of R. verniciflua Stockes and its extracts on uterine (7/10) in elasticity and 63% (5/8) in lichenification. Moderate to severe labial fusion myomas improved in only four of the 11 subjects (36%). Ulcerations present in three subjects Min Hyung Jung. Obstetrics and Gynecology, School of Medicine, Kyung Hee Medical were completely resolved with treatment. The greatest impact of treatment was on Center, Kyung Hee University, Seoul, Korea (the Republic of) quality of life and decrease in sexual function; 91% (10/11) and 88% (7/8) of subjects, Objective: To investigate the potential of natural medication, Rhus verniciflua Stockes respectively, reported 1 to 4 points’ improvement. Good improvement was also reported (RVS), as a new therapeutic agent of the uterine leiomyomas. Design: After IRB for dyspareunia (78%, 6/8). Skin tearing worsened in some subjects but did improve in approval, the uterine myoma and normal myometrium cells were collected from the 50% (3/6). Mild to moderate erythema and were present immediately following patients underwent hysterectomy with benign gynecologic diseases. To evaluate the treatment. No adverse events were reported with treatment. Conclusion: Conclusion: cytotoxic effect of RVS, uterine leiomyoma and myometrium cells were inoculated into Preliminary findings support improvement in predominant clinical a 60 mm culture dish at a density of 2.5 × 105 cells/dish. The cells were treated with of VLS following a series of fractional CO2 laser treatments. Long-term follow-up will RVS by varying concentrations (50, 100, 200, 400, and 600 µm/mL), and then cultured indicate whether this treatment effect is maintained. A larger population is warranted to for 24, 48, and 72 h, respectively. To further determine the mechanism of cell death of further explore the role of laser therapy in managing VLS. leiomyoma and myometrium cells induced by RVS, the method of Annexin V-ITC/PI Sources of Funding: Candela Corporation provided partial funding for the study. Study double staining was conducted. To identify causative factors of selective cytotoxicity devices were not provided as compensation for research. on leiomyoma, the principal components of RVS were analyzed via HPLC. The RVS component was confirmed by comparison with the HPLC results of the reference standard P-28. of fustin, fisetin and sulfuretin. Results: The viability of leiomyoma cells was decreased with increasing concentration of RVS after 24 h treatment, and similar cytotoxic effects were observed in the groups treated for 48 and 72 h. The viability of myometrium cells Withdrawn by Author were also decreased by RVS and showed a dependency on the RVS concentration in all

groups of 24, 48, and 72 h treatment. In leiomyoma cell, the IC50 values were estimated to be 343.1 μg/mL (24 h), 309.1 μg/mL (48 h), and 261.9 μg/mL (72 h), respectively.

In Annexin V-ITC/PI double staining result, the number of myoma cells entering G0/G1 phase increased as the concentration of RVS increased. Comparing the cytotoxic effects of leiomyoma and myometrium cells at each concentration of RVS, it was confirmed that the cell death rate in leiomyoma cells was statistically significant than that in normal myometrium cells under certain conditions. Compare to myometrium, RVS was selectively induced cell cycle arrest and inhibited the cell proliferation of leiomyoma at concentrations of 200 μg/mL (24 h), 50 μg/mL (48 h), and 50 μg/mL and 200 μg/mL (72 h), respectively. Conclusion: , RVS, could be a candidate for new therapeutic agent of the uterine myoma treatment. Sources of Funding: None

P-30. Examination about the influence that hormone replacement therapy gives to breast density of mammography Takeshi Kato, Ph.D., Yuri Kadota, Ph.D, Takako Kawakita, Ph.D., Otgontsetseg Erdenebayar, Ph.D. student, Kanako Yoshida, Minoru Irahara, Ph.D. Obstetrics and Gynecology, Tokushima University, Tokushima, Japan Objective: With the increasing interests of health care, the number of women undergoing hormone replacement therapy for menopausal disorder is increasing. While hormone replacement therapy is known to affect density, dense in mammography have become an issue. Here, we examined the relationship between hormone replacement therapy and breast density in mammography. Design: We retrospectively examined breast density of mammography in 89 patients who underwent breast cancer screening at our department during the year from August 2016 to July 2017. Measurement of mammary gland densitywas performed using imageJ. Results: The subjects were 89 people, 44 underwent examinations during hormone replacement therapy and 45 underwent no hormone replacement therapy. The median age was 54 (29-81). Breast density were elevated in 15 (20.4%) of the 44 patients in the group receiving hormone replacement therapy, but not in the groups not receiving it. Conclusion: It has also been reported that elevated mammary gland density affect breast cancer risk during hormone replacement therapy. In the future, we plan to conduct analysis taking into consideration the regimen of hormone replacement therapy and the administration period. Sources of Funding: None

P-31. Oral 17β-Estradiol/Progesterone (E2/P4) Improved Sleep Outcomes in the REPLENISH Trial Andrew M. Kaunitz, MD1, Risa Kagan, MD2,3, Shelli Graham, PhD4, Brian Bernick4, Sebastian Mirkin4. 1University of Florida, College of Medicine-Jacksonville, Jacksonville, FL; 2University of California, San Francisco, CA; 3Sutter East Bay Medical Foundation, Berkeley, CA; 4TherapeuticsMD, Boca Raton, FL Objective: Postmenopausal women often complain about having difficulty sleeping. In the REPLENISH trial, the oral 17β-estradiol/progesterone (E2/P4) softgel capsule (TX-001HR; 1 mg E2/100 mg P4 FDA approved as BijuvaTM; TherapeuticsMD, Boca Raton, FL) was shown to reduce moderate to severe vasomotor symptoms (VMS) frequency and severity and improve quality of life outcomes in menopausal women with a uterus, while protecting the endometrium. The objective of this report is to present the effects of E2/P4 on sleep outcomes, including pertinent data from the Medical Outcomes Study (MOS)-Sleep and the Menopause-specific Quality of Life (MENQOL) questionnaires, and their correlations with VMS using mediation models. Design: REPLENISH (NCT01942668) was a phase 3, randomized, double-blind, placebo- controlled, multicenter trial that evaluated E2/P4 in menopausal women (40-65 years) with VMS and a uterus (n=1835). Women with moderate to severe hot flushes (≥7/ day or ≥50/week) were enrolled in a VMS substudy and randomized to E2/P4 (mg/mg) 1/100, 0.5/100, 0.5/50, 0.25/50, or placebo; women with fewer VMS were randomized to active E2/P4 doses only. All subjects self-administered the MOS-Sleep and MENQOL questionnaires at baseline, week 12, and months 6 and 12. The MOS-Sleep was a 12- P-33. item questionnaire measuring 6 sleep dimensions and MENQOL included a difficulty The Human Theca Cells expressed Müllerian Inhibiting Substance/Anti- sleeping item. Changes from baseline were analyzed for each treatment versus placebo Müllerian Hormone Type II Receptor at each timepoint. Somnolence was also reported as a treatment-emergent adverse event. Jang Heub Kim, Professor. Obstetrics & Gynecology, Catholic Kwandong University, Mediation models were constructed using data from the VMS substudy to evaluate the International St. Mary’s Hospital, Incheon, Korea (the Republic of) effect of E2/P4 versus placebo on sleep disturbance from MOS-Sleep mediated through Objective: Müllerian inhibiting substance/anti-Müllerian hormone (MIS/AMH) is the MENQOL hot flush bother item (model 1) or VMS frequency and severity diary produced in the ovarian granulosa cells and it is believed to inhibit ovarian scores (model 2). Results: Women treated with E2/P4 reported significantly better and steroidogenesis in women of reproductive age. However, the mechanism of MIS/ change in the MOS-Sleep total, sleep problems index II subscale and sleep disturbance AMH activity in human has not been elucidated. We aimed to investigate the subscale scores compared with those treated with placebo at week 12, and months 6 and expression of MIS/AMH type II receptor (MISRII/AMHRII) that binds MIS/AMH in the 12 (all, P<0.05), except those treated with 0.25/50 at week 12. Better improvements ovaries of women of reproductive age, to identify the exact targets of MIS/AMH. Design: were observed in the sleep problems index I subscale score for all E2/P4 doses versus Tissue samples from 25 patients who had undergone ovarian surgery were included in placebo at all timepoints (all, P<0.05). The MENQOL difficulty sleeping score also this study. The segregation of ovarian granulosa and theca cells by laser microdissection significantly improved from baseline with the three highest E2/P4 doses (1/100, 0.5/100, was followed by RT-PCR, analyzing MISRII/AMHRII mRNA expression. Afterward, 0.5/50) versus placebo at all timepoints (all, P<0.05), except for 0.5/50 at month 6. in situ hybridization and were performed to determine the Incidence of somnolence was low (0.2%-1.2%) with E2/P4. Mediation models showed localization of MISRII/AMHRII mRNA and protein expression. MISRII/AMHRII were that E2/P4 had an indirect effect on sleep via VMS improvement. In model 1, E2/P4 had expressed in granulosa and theca cells of preantral and antral follicles. Results: The a direct effect on the MENQOL hot flush bother item, which in turn directly affected granulosa cells showed stronger MISRII/AMHRII expression than theca cells. MISRII/ the MOS-Sleep disturbance scale; in model 2, E2/P4 had a direct effect on both VMS AMHRII mRNA staining of granulosa and theca cells in large antral follicles, early frequency and severity scores, which in turn directly affected the MOS-Sleep disturbance atretic follicles and waned, but were still detected weakly, showing higher scale. Conclusion: In REPLENISH, women with VMS treated with E2/P4 capsules expression in theca cells than in granulosa cells. However, MISRII/AMHRII protein in experienced significant and sustained improvements in sleep parameters versus placebo. granulosa layer of atretic follicle and corpus luteum could not be assessed. Conclusion: Sleep mediation models showed that E2/P4 improved MOS-sleep disturbances indirectly Since MISRII/AMHRII is expressed in both granulosa and theca cells, this indicates that through improvements in VMS. In women taking oral E2/P4 capsules to treat moderate MIS/AMH, produced in the granulosa cells, is active in the theca cells as well. MIS/AMH to severe VMS, E2/P4 may also improve sleep. is most likely actively involved not only in the autocrine and endocrine processes, but in Sources of Funding: TherapeuticsMD the paracrine processes involving theca cells. Sources of Funding: None P-32. Effects of Ristela supplementation on female sexual satisfaction: an open- label trial Susan Kellogg-Spadt, PhD, CRNP, IF1,2, Ellen Manos, MD3, Michael Krychman, MD4, Alyssa Dweck, MS, MD FACOG5,6, Sharon J. Parish, MD7. 1Drexel University College of Medicine, Philadelphia, PA; 2Center for Pelvic Medicine, Bryn Mawr, PA; 3Physician Department of Obstetrics and Gynecology, Lenox Hill Hospital division of Northwell Health, New York, NY; 4Southern California Center for Sexual Health and Survivorship Medicine Inc, Newport Beach, CA; 5CareMount Medical Group, Mount Kisco, NY; 6Northern Westchester Hospital, Mount Kisco, NY; 7Weill Cornell Medical College, New York, NY Objective: An open-label experience trial was conducted to determine the effects of a proprietary supplement, JDS-PACR (RistelaTM), on female sexual satisfaction in pre, peri and postmenopausal women. JDS-PACR has been shown in multiple controlled trials to be a well-tolerated, effective, hormone-free treatment for improving female sexual satisfaction. JDS-PACR is made from a unique blend of amino acids and that work synergistically to increase female genital circulation, thereby enhancing a critical component of the female sexual response. JDS-PACR has been shown to significantly improve overall sexual function, as measured by the Female Sexual Function Index (FSFI), in three randomized controlled trials involving pre, peri and postmenopausal women (n=263). In these trials, JDS-PACR significantly improved arousal, lubrication, orgasm, satisfaction, pain and desire. Improvements were seen in as early as four weeks, with continued improvement at eight weeks. Design: The current study involved forty women (Age: 30 – 76 years, BMI: 19.2 – 44.8 kg/m2) who completed an eight week, open-label experience trial. This study included pre, peri and postmenopausal women who were in monogamous heterosexual or homosexual relationships for at least three months prior to study enrollment. Participants were required, at baseline, to self-report their sexual function/satisfaction as “low” or “very low or none at all”. During the trial, participants were allowed to remain on any preexisting medications, which included: local and systemic hormone therapy, combined hormonal contraceptives, , antihypertensives, statins, medications, IBS medications and vaginal lubricants. Participants were not precluded from social alcohol intake. Participants were recruited from five general gynecology or sexual medicine practices across the US. They were instructed to take JDS-PACR, two tablets daily, for eight weeks and provide on their experience via online questionnaires. Questionnaires consisted of nine specific questions about sexual satisfaction taken from the validated Female Sexual Function Index (FSFI) and additional questions related to relationship quality and distress related to sexual function. Questionnaires were sent out to participants at baseline and after P-34. taking JDS-PACR for two, four, and eight weeks. After completion of each questionnaire, Menopausal experience in women with a history of in subjects were compensated with a $25 gift card. Results: JDS-PACR improved response pregnancy: is there an association? scores to all FSFI questions after eight weeks. Questions related to arousal and orgasm Amanda N. King, MD1, Andrea Kattah, MD2, Stephanie Faubion3, Kristin Mara, improved in as early as two weeks, with continued improvements over eight weeks. At Statistics4, Ekta Kapoor3. 1OBGYN, Mayo Clinic, Rochester, MN; 2Nephrology, Mayo eight weeks, JDS-PACR improved (over baseline levels) arousal in 84% of women, Clinic, Rochester, MN; 3Internal Medicine, Mayo Clinic, Rochester, MN; 4Statistics, orgasm in 63% of women and desire in 85% of women. Overall, sexual function/ Mayo Clinic, Rochester, MN satisfaction improved by 40%. In addition, women reported greater emotional closeness Objective: Approximately 15% of pregnancies are affected by hypertensive disorders with their partners and lower distress about their sex lives, suggesting improvements in which can lead to increased cardiovascular (CV) risk and complications later in general quality of life. Seventy-five percent of respondents indicated that they would life. Pregnancy and menopause are conditions unique to women, in which there are continue taking JDS-PACR on a daily basis after trial completion. No adverse effects hormonal changes affecting vascular tone and blood flow. Emerging evidence suggests were noted. Conclusion: These experience trial data are consistent with results from that vasomotor symptoms associated with estrogen deprivation at menopause may be prior controlled clinical studies that demonstrate JDS-PACR (Ristela) has positive associated with CV risk. The relationship between hypertensive disorders of pregnancy effects on female sexual function, specifically in the domains of arousal, orgasm and and menopausal symptoms are unknown. This study assessed the association between desire. JDS-PACR decreased sexual distress and enhanced women’s overall relationship self-reported history of hypertension during pregnancy and presence and severity of satisfaction and quality of life. menopausal symptoms. Design: We performed a cross-sectional study of peri and Sources of Funding: This study was funded by JDS Therapeutics, LLC, the parent postmenopausal women seen in the Mayo Clinic Women’s Health Clinic from 5/2015 company of Bonafide® to 6/2018 who completed questionnaires for the Data Registry on Experiences of Aging, Menopause and Sexuality (DREAMS). We excluded women with surgically-induced Milli. Most felt anxious or frustrated when using static dilators, whereas 91% of those menopause and included 1367 women in the study. By self-report, there were 214 women surveyed reported that using Milli was a an optimistic (71%), empowering (26%) and a with no pregnancy (NP), 1038 women with pregnancy and no hypertension (PNHTN), and confidence boosting experience. Almost 63% used the vibration feature frequently of the 115 women with pregnancy complicated by hypertension (PHTN). The MRS was used device and over 90% of users were satisfied with the cost of this advanced technological to assess the presence and severity of psychological symptoms (4 symptoms: depressed, device. 84% of users report an easier dilation experience over time and most have irritable, anxious, exhausted), somato-vegetative symptoms (4 symptoms: sweating/flush, gained an increased diameter of 9 mm. Pain scores reduced on average by 3.3-points cardiac complaints, sleeping disorders, joint and muscle complaints), and urogenital (0-10 scale), coupled with a 3-point reduction in anxiety after 3 months of use. Forty symptoms (3 symptoms: sexual problems, urinary complaints, vaginal dryness) with five percent of women in a relationship who were not able to have intercourse, were scoring: none 0; mild 1; moderate 2; severe 3; very severe 4. Subjects were stratified now able to resume coital relations after 3 months. Conclusion: Women with GSM, into two groups based on total MRS scores: none to mild (0-1) vs. moderate to very dyspareunia and vestibulodynia often use dilators but are anxious, and frustrated with the severe (2-4). Results: The mean age of menopause was not statistically different between step wise drastic changes between sizes of dilators. Milli™ is a novel expanding dilator groups (p-value=0.09) (Table 2). MRS total score (p-value 0.032) and somato-vegatative under patient control which can be increased in increments of 1 mm. Milli ™ shows symptoms (p-value 0.026) were found to be statistically different between PHTN, NP and excellent promise for safety and efficacy with high patient satisfaction and compliance. PNTHN (table 2), with MRS score higher for PTHN. Hot flashes were not found to be Milli’s ability to expand while inserted at the users control, dilating for >15min per significant. Multivariable analysis demonstrated that PHTN group had significantly higher session, use of vibration, and using Milli immediately prior to intercourse appear to help MRS total scores as compared to reference NP group (difference=2.34, 95% CI 0.67- patients achieve their goal sooner. Future studies are underway with prospective design 4.01, p =0.006). Conclusion: There was an association between self-reported hypertension to confirm these data. in pregnancy and severity of menopausal symptoms in general, and somato-vegetative Sources of Funding: Materna Medical symptoms in particular. These results suggest that hypertensive pregnancy disease maybe associated with severity of menopausal symptoms. Additional studies are needed to confirm these findings, particularly in relation to prediction of future CV risk in women. P-36. Sources of Funding: None Use in a Sexual Medicine Oncology Clinic Table 1: Menopause Severity Michael Krychman, MD. Southern California Center for Sexual Health, Newport beach, CA Objective: Prasterone is a novel intravaginal sex steroid that is FDA approved and indicated for moderate to severe dyspareunia a symptom of vulvovaginal atrophy (VVA) due to menopause. It has clinical utility in a diversity of menopausal patients who have a variety of medical conditions. Oncological patients are often ignored when it comes to quality of life considerations and many health care professionals neglect discussing and treating sexual dysfunctions. There are many newly approved medications that are both safe and effective for the treatment of these impactful symptoms in the oncological cancer survivor. Prasterone, and ultra-low dose intravaginal estradiol inserts are safe and effective and after appropriate counseling should be considered when treating this patient population. These results presented here represent one aspect of an on-going study of the treatment options for moderate to severe dyspareunia a symptom of VVA due to menopause in an oncological sexual medicine setting. Design: Current prasterone users were surveyed on paper for this retrospective descriptive study. The researcher has 4 clinical sites which span a diversity of patient populations who have varied insurances and diverse ethnicities. All patients had a sexual medicine and gynecological evaluation and had confirmed genitourinary syndrome of menopause (GSM) and painful intercourse. Participants were not financially compensated. Results: Thirty female participants were surveyed with a mean age of 53.5 (range 27-74). There was a diversity of patients on prasterone including 43% who Table 2: Multivariate Analysis had a malignancy (23% and 17% with breast cancer); and 13 % had endocrinopathies. Treatment duration was on average for 6.5 months and all applied the medication at nighttime. Eighty-three percent of participants used the applicator however 57% had problems opening up the inserts packaging. Most (80%) rated the effectiveness and symptomatic improvement at very good to excellent and the overall rating of dryness was 2.3 (where 10 is no change from baseline and 0 is no dryness whatsoever). Most *Estimates are adjusted for age, BMI, hormone therapy, SSRI/SNRI, diabetes, patients had a previous diagnosis of pain and dryness. Conclusion: Prasterone is a safe high cholesterol, high blood pressure, abuse in the last year, anxiety, and and effective treatment option for a diversity of patients including the breast and cervical depression. cancer survivor. It is well tolerated and has excellent patient satisfaction. Future studies that are currently underway include the use of low dose estradiol teardrop vaginal insert and ospemifene in this specialized oncological center. A comparative analysis is planned. P-35. Sources of Funding: THis research was not funded by industry The Milli™; the Only Patient Controlled Expanding Dilator: Interim Follow Up Survey Experience P-37. Michael Krychman, MD1, Susan Kellogg-Spadt, PhD2, Stephanie Prendergast, MPT3, Mark Jurvic4. 1Southern California Center for Sexual Health, Newport beach, CA; Menopausal hormone therapy and fracture risk in Korean population Dae-Hui Kwon1, Ikjin Chang1, Kyong Wook Yi1, Si Hyun Cho2, Tak Kim, MD, 2Center for Pelvic Medicine, Rosemont, PA; 3Pelvic Health and Rehabilitation Center, Ph.D1, Jun Young Hur1, Jang Heub Kim3, Jung-Ho Shin1. 1Department of Obstetrics Los Angeles, CA; 4Materna, Mountain View, CA and Gynecology, Korea University College of Medicine, Seoul, Korea (the Republic Objective: Pelvic floor hypertonus and vaginismus are downstream genitopelvic medical of); 2Department of Obstetrics and Gynecology, Gangnam Severance Hospital, complications of vaginal and vulvar atrophy (VVA) a component genitourinary syndrome Yonsei University College of Medicine, Seoul, Korea (the Republic of); 3Department of menopause (GSM). Aggressive vaginal rehabilitation includes moisturizers, lubricants, of Obstetrics and Gynecology, Seoul St. Mary’s Hospital, College of Medicine, The dilator guidance and pelvic floor physical therapy. Dilators are poorly characterized in the Catholic University of Korea, Incheon, Korea (the Republic of) scientific literature. Although vaginal dilators may help decrease pelvic spasm, and may Objective: We aimed to assess the fracture risk among contemporary menopausal facilitate reconditioning the body reconnection for anticipatory anxiety, women hormone therapy (MHT) users in Korean. Design: A nationwide Korean population- report decreased compliance, due to with burdensome regimes, and strong concern about based cohort study including all 143,194 women aged ≥ 45 years having used systemic stepwise abrupt transitioning from one size to another. Milli is a novel, patient controlled MHT during the study period (Jan 2003 and Dec 2006), compared with the Korean electronically expanding dilator (that is capable of expanding 1 mm at a time Design: The female background population. MHT ever-use (all MHT, estrogen-only MHT [E-MHT] initial launch recently took place whereby the device was available to the general public and estrogen plus progestin MHT [EP-MHT]) and fracture diagnoses were based on and used in conjunction with sexual medicine specialists (sexual medicine gynecologist/ the nationwide Health insurance review & assessment service. For fracture diagnoses, therapist, generalist in OBGYN, pelvic pain nurse practitioner, physical therapist) of standardised incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated. diverse background, training and geographical location. We report results on the first 99 Results: The SIR of femur neck fracture was 0.84 (95% CI: 0.73-0.98) following ever women who have used milli consistently for at least 3 months duration. Results: Milli MHT, 0.95 (95% CI: 0.69-1.30) for E-MHT and 0.27 (95% CI: 0.14-0.55) for EP-MHT is designed to be patient controlled and expand in 1 mm slow controlled increments and 0.79 (95% CI: 0.64-0.98) for and 0.87 (95% CI: 0.68-1.11) for EP-MHT (Figure 1,2,3). Patients were offered the device with a partial rebate of the retail price for (except tibolone). The lowest SIR was found for EP-MHT (including tibolone) among anonymous participation in an electronic 3-month follow up survey. Ninety-nine surveys users aged 55~65 years (SIR Z 0.18, 95% CI: 0.03-1.31). The risk of spine facture was were received. 45% of patients were diagnosed with GSM/VVA, and 42% participants decreased following EP-MHT (SIR Z 0.85, 95% CI: 0.64-1.11). The SIR of total fracture had suffered from their pain syndrome for over 5 years before using Milli. 93% were (femur neck, spine, wrist) was 0.83 (95% CI: 0.68-1.00) following EP-MHT. Conclusion: cisfemale whereas 7% were post-operative transwomen. 49% had seen 3 or more MHT, especially EP-MHT, was associated with a decrease in total fracture risk. clinicians for their condition. 54% of Milli patients were prior sequential dilator susers. Sources of Funding: None Ninety five percent of Milli users claim to have either achieved or are making progress toward their goals (within 3 months), and 98% of past sequential dilator user prefer using P-38. Sources of Funding: Geriatric Research, Education and Clinical Center (GRECC) Oncologists’ Perceptions of Sexual Intimacy Issues in Metastatic Breast Clinical Demonstration Project, Veterans Health Administration Cancer: An Opportunity to Address Patients’ Concerns and Improve Baseline and follow-up characteristics and measurements Quality of Life Lisa Larkin, MD1, David Portman, MD2, Elizabeth Attias2. 1Ms. Medicine, Cincinnati, OH; 2Sermonix Pharmaceuticals, Columbus, OH Objective: Research on women’s sexual well- being and partner intimacy issues in women with breast cancer consistently demonstrates a large gap in sexual health care in these women. Despite the well-established prevalence of sexual health issues in women with breast cancer, especially in women on extended endocrine therapy, sexual health concerns remain undiagnosed and untreated in the majority of women, even in survivorship clinics at major cancer centers. Recently a NAMS/ISSWSH consensus guideline on the management of GSM in women with breast cancer was developed and published to inform clinicians of available data and present management strategies in order to address the unmet sexual health needs of survivors. However, there is little data to guide clinical care of sexual health concerns in women living with metastatic disease. and consensus on management in this patient population is lacking. Given the significant advancements in the treatment of metastatic breast cancer (mBC) and the evolution of treatments such as the CDK 4/6 inhibitors and their widespread use and Results are expressed as mean ± standard deviation (median). BMI, Body Mass doubling of progression free survival from 12 to 24 months to over 2 years, many patients Index; WC, waist circumference; BP, blood pressure. are now living with metastatic disease for extended periods of time. We conducted a survey of medical oncologists to better understand their perceptions of the importance P-40. of sexual health and intimacy, and their discussions with their patients living with Effect of phytopharmaceutical composition based on glucosinolates, metastatic disease about sexual health and intimacy. Design: Seventy 60-minute web- assisted, telephone interviews were conducted with medical oncologists. Each physician β-sitosterol and citroflavonoids (Warmi®) over the proliferation of the was prescreened prior to being interviewed to ensure board certification and adequate human mammary adenocarcinoma cell line MCF-7: a pilot study 1,3 2 2 practice experience and breast cancer patient volume. Results: Efficacy continues to Edward Mezones-Holguín, MD MSc , Teresa Barreto , Patricia Herrera-Velit , 2 2 3 6 be primary driver and concern for the oncologists in this survey, with quality of life Maxy De los Santos , Percy Rojas , Percy Soto-Becerra, MD , Gabriela Lugo-Martinez , 5 4 1 benefits such as vulvovaginal atrophy not featured as prominently important in contrast Luis Danckers, MD , Peter Chedraui . Centro de Excelencia en Investigaciones to documented literature which finds sexual concerns are of widespread concern among Económicas y Sociales en Salud, Universidad San Ignacio de Loyola, Lima, Peru; 2 3 breast cancer patients in the metastatic setting. Physicians largely dismissed vaginal Universidad Peruana Cayetano Heredia, Lima, Peru; Epi-gnosis Solutions, Piura, Peru; 4 5 atrophy as clinically meaningful limitations in the metastatic setting although they do Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador; Instituto Peruano 6 acknowledge that they are relevant in the adjuvant setting. A few physicians did associate de Paternidad Responsable (INPPARES), Lima, Peru; Instituto Politécnico Nacional, vaginal atrophy with current treatment unaided, and all of the physicians did confirm its DF, Mexico potential relevance when prompted, however did not place it as a high priority in the Objective: Several controversies and potential health risks related to menopausal metastatic setting. Reasons for this lack of priority include: availability of lubricants hormone therapy (MHT) have caused a growing interest in the use of alternative to help with vaginal dryness, few patients complain, perception that patients are not therapies for menopausal symptoms (MS). In Peru, Warmi® has been developed sexually active, quality of life issues are deprioritized when focus is keeping the patient as a phytopharmaceutical composition containing: glucosinolates and β-sitosterol alive. Conclusion: As medical advances continue in the mBC arena and new treatments supplemented with citroflavonoids, all from sources. The three previous compounds add years to patients’ lives, quality of life considerations with respect to sexual intimacy have potential benefits over MS, and several of their effects could be complemented. In will increase in importance. MBC patients’ concerns and solutions will be important addition, the estrogenic activity, efficacy and safety of Warmi® over MS have been tested considerations for health care practitioners to address to ensure that patients are able to in pre-clinical and clinical studies, showing that these components have a better action enjoy satisfying relationships and benefit that these relationships can provide. There is when they work in conjunction rather than isolated. Human mammary adenocarcinoma need for further research and education to incorporate the appropriate tools and guidelines cell line MCF-7 has widely been used as an cellular model that proliferates in to bridge from the survivorship population into the metastatic setting so that providers response to estrogens such as 17β-estradiol. However, to our knowledge there are no can facilitate discussions with patients to optimize quality of life. studies regarding the effects of Warmi® over this cell line. Therefore, the objective Sources of Funding: Sermonix Pharmaceuticals of our study was to evaluate the proliferative activity of Warmi® on MCF-7 cell line. Design: We carried out an analytical experimental study. MFC-7 cells were cultivated in M24 plaques. Four mains treatment groups were defined: without intervention as P-39 - Featured Poster. control; and rising doses of 17-β-estradiol (E2) as positive control (1 nM,10 nM, and The Impact of Lifestyle Health Coaching on Central Obesity Varies 100 nM), tamoxifen/ as negative control (1 nM, 10 nM, 100 nM, 1 µnM, 2 According to Menopausal Status µnM and 5 µnM), and Warmi® (20 ng/ml, 50 ng/ml, 100 ng/ml, 200 ng/ml, 500 ng/ Silvina Levis2,1, Otmara Soberanes2, Jason Dahn2, Fei Tang2, Ana Palacio2,1. 1University ml, 1µg/ml, 2µg/ml, 5 µg/ml, 10 µg/ml). Each intervention was applied for seven days. of Miami, Miami, FL; 2GRECC, Miami VA Healthcare System, Miami, FL Cells were counted through counting by field and MTT coloration. The assessment of Objective: Central obesity has a greater detrimental effect on proliferative short and long-term effect was made with 24 - 48 hours dose-response (CVD) risk than general obesity. Most women gain body weight in the peri- and curves and by comparison of cell proliferation in the four study groups. Results: At postmenopausal years. Average is 4.6 lb. ± 11.2 (SD), predominantly as all concentrations, estradiol produced the expected cell proliferation that was greater central abdominal fat. A healthy and increased physical activity can reduce central after six days of treatment. Contrary to this, tamoxifen and Warmi® did not show any obesity and decrease CVD risk. We compared the response in reducing central obesity proliferative effect, yet a contrary tendency to decrease the proliferation of MCF-7 cells, of women of premenopausal vs. peri/postmenopausal age after participation in a Health also greater at the sixth day. The proportion of cellular proliferation at all 17β-estradiol Coaching Program offered free of charge at a primary care clinic. Design: Women age (average: 250%) dosages was higher than the rate of other interventions (average: 100%). ≥18 years receiving primary care at Miami Veterans Affairs’ Women’s Clinic who chose In the dose-response curves we observed the highest proliferative effects of the 10 nM of to enroll in the program received health coaching via phone and/or video conference for 17β–estradiol at 48 hours. In short-term, Warmi® produced a two-phase growth effect, up to 4 months. The same individual coached all participants on how to set and maintain stimulating cell proliferation at a concentration of 100 ng/ml and inhibiting growth in goals for healthy eating habits and increased physical activity. Body Mass Index (BMI), a dose-dependent way at high doses of 500 ng/ml. In the long-term proliferation assay, body composition and waist circumference were obtained in clinic at baseline and at 17β–estradiol showed the highest cell proliferation, but a stable cell concentration, even a follow-up clinic visit scheduled for a time when women wished to return. Statistical antiproliferative effects in tamoxifen/fulvestrant and Warmi® groups were observed. In Analysis: Characteristics at baseline were described with means, standard deviations and the comparative analysis of proliferative effect between groups, we observed a statistical medians for continuous variables. To evaluate for differences between premenopausal difference being greater in 17β–estradiol group. Conclusion: This pilot study suggests and peri/ postmenopausal women, we used T-Test for continuous variables and Chi that Warmi® does not have proliferative effects on MCF-7 cells in short and long-term; square for categorical variables. Results: At baseline, peri/postmenopausal women had and presented weak estrogenic capacity. Based on these exploratory findings, Warmi® a trend to larger waist circumference despite similar proportion of fat mass and lower seems a safe option for patients with contraindication to MHT, although, it would be BMI than premenopausal women. Both groups had similar participation rates. After the interesting to perform future studies to complement this breast cancer safety profile. program, peri/ postmenopausal women had similar decrease in BMI and mass than Sources of Funding: This study was partialy financed by HERSIL ® Laboratorios premenopausal women, but a trend towards smaller decreases in waist circumference Industriales Farmaceúticos and FONDECYT (Peruvian National Fund for Science and and percent body fat. See Table. Conclusion: Results from the initial group of women Technology). participating in a primary care clinic-based health coaching program show that lifestyle coaching resulted in decreases in BMI, body fat and waist circumference in all women, however peri/postmenopausal women experienced smaller reductions in percent body fat and waist circumference than premenopausal women, suggesting that a longer, more aggressive, or differently tailored program might be needed for women in peri/ postmenopause. This observation is significant as the CVD benefit of lifestyle change could be blunted in the absence of reduction of central obesity. P-41. Factors associated with sarcopenia among studied women (n = 403) Efficacy and safety of menopausal hormone therapy on women with Human Immunodeficiency Virus Infection: a systematic review Edward Mezones-Holguín, MD MSc1,2, Luis M Helguero-Santin3,2, Jhacksson S. Cordova-Agurto3,2, José Arriola-Montenegro4, Luis Danckers5, Juan E. Blümel, MD PhD6, Faustino Pérez-López7, Peter Chedraui8. 1Centro de Excelencia en Investigaciones Económicas y Sociales en Salud, Universidad San Ignacio de Loyola, Lima, Peru; 2Epi-gnosis Solutions, Piura, Peru; 3Facultad de Ciencias de la Salud, Sociedad Científica de Estudiantes de Medicina (SOCIEMUNP), Universidad Nacional de Piura, Piura, Peru; 4Sociedad Nacional de Capacitación (SONACAP SAC), Lima, Peru; 5Instituto Peruano de Paternidad Responsable (INPPARES), Lima, Peru; 6Universidad de Chile, Santiago, Chile; 7Universidad de Zaragoza, Zaragoza, Spain; 8Universidad Católica de Santiago de Guayaquil, Guayaquil, Ecuador Objective: Human immunodeficiency virus (HIV) infection is a relevant worldwide public health issue. Current, due to highly active antiretroviral therapy (HAART), most infected women reach mid-age, stage were estrogen deficiency changes occurs. An important proportion of these women develop premature menopause. Several series have described a higher intensification of menopausal symptoms (MS) observed in this population and its effect over important clinical outcomes as HAART adherence, viral load, CD4 count levels and quality life. Nevertheless, general management of these women is mainly provided by infectious disease physicians and problems related to the menopause are not usually explored. Menopausal hormone therapy (MHT) is the first line option for menopausal symptoms, although there are several clinical conditions where its use is not indicated or controversial. Moreover, the evidence supporting recommendations for the treatment of MS in HIV infected women is not clear. Therefore, the objective of our study was to synthesize the scientific evidence about the efficacy and safety of MHT in women with HIV infection and MS. Design: We carried out a systematic review based on the Preferred reporting items for systematic review and meta-analysis (PRISMA). Protocol was recorded in the International prospective register of systematic reviews (PROSPERO). PICOS question was delimited as follow: Women with HIV infection and menopausal symptoms (Participants), Menopausal hormone therapy (Intervention), Placebo or other interventions (Comparison), Efficacy and safety (Outcomes), and randomized clinical trials (Study design). Primary search was performed in Pubmed- P-43. MEDLINE, EMBASE, WEB OF SCIENCE, SCOPUS, CINALH, y CENTRAL CONSISTENCE AND INTERNAL STRUCTURE OF ATHENS without language restriction. In addition, we searched in the clinical trials register of INSOMNIA SCALE IN COLOMBIAN CLIMACTERIC WOMEN the of America (www.clinicaltrials.gov), European Union (https://www. Alvaro Monterrosa-Castro1,2, Adalberto Campo-Arias3,4, Edwin Herazo4. 1Universidad de clinicaltrialsregister.eu) and the International Clinical Trials Registry Platform (ICTRP) Cartagena. Colombia, Cartagena, Colombia; 2Grupo de Investigacion Salud de La Mujer, (http://www.who.int/ictrp/en/). Also, we examined in the electronic registers of the Cartagena, Colombia; 3Universidad del Magdalena, Santa Marta, Colombia; 4Instituto de International Menopause Society (IMS), North American Menopause Society (NAMS) Investigación del Comportamiento Humano, Bogotá, Colombia and European Menopause and Andropause Society (EMAS) congresses. The process of Objective: To study the internal consistency and structure of the Athens Insomnia selection of studies was made by two independent and blind reviewers with participation Scale (AIS) in women in the climacteric of the Colombian Caribbean. Design: A of a third author as diriment. We delineated the risk of bias assessment (Cochrane tool) methodological study was carried out involving 1358 women between 40-59 years old and data extraction under the same strategy. Results: We identified 383 records from (M=40, SD=5,8), 70,3% were mestiza, 18,2% were Afro-Colombian and 11,6% were the primary search, and none from other sources. After screening by title and abstract Amerindian. 55,5% postmenopausal. The AIS is an eight-item instrument based on the evaluation, all records were excluded because none of them answered the research criteria for insomnia of the International Classification of Mental Disorders (World question. Therefore, we could not assess the risk of bias and nor perform data extraction. Health Organization, 1992). The internal consistency was estimated with the coefficients Conclusion: We did not find randomized clinical trials evaluating the efficacy and safety of Cronbach alpha and McDonald omega and internal structure (dimensionality) was of MHT in HIV infected women. Future primary studies are required to explore the tested by confirmatory factor analysis and the calculation of goodness-of-fit indicators: causes of this, as well as, explore the use of alternative therapies in this population. Root Mean Square Error of Approximation and 90%CI (RMSEA), Comparative Fit Index Sources of Funding: None (CFI), índice of Tucker-Lewis (TLI), Standardized Mean Square Residual (SMRM). RMSEA (<0,06); CFI (>0,90); TLI (>0,90) SMRM (<0,05). Results: The AIS showed both Cronbach alpha and McDonald omega of 0.93. The internal structure showed a P-42. dimension with Eigen value of 5,43 which explained 67.9% of the total variance. The SARCOPENIA AND CLIMACTERIC WOMEN OF THE COLOMBIAN commonality between 0,538 and 0,733. The coefficients between 0,774 and 0,880. CARIBBEAN RMSEA=0,111 [90%CI: 0,101-0,121): CFI=0,96; TLI=0,94 and SMRM=0,03. These Alvaro Monterrosa-Castro1,2, Mauricio Ortiz-Banquez, Médico1,2, María Mercado-Lara1,2. findings need to be corroborated in other Colombian and American populations. 1Universidad de Cartagena. Colombia, Cartagena, Colombia; 2Grupo de Investigación Conclusion: The ASI presents high internal consistency with a one-dimensional structure Salud de la Mujer, Cartagena, Colombia in Colombian climacteric women. Objective: To determine the prevalence of sarcopenia and associated factors in Sources of Funding: None climacteric mid-aged women. Design: Methods: This was a cross-sectional study carried ATHENS INSOMNIA SCALE out in Colombian Caribbean women (40-59 years, n=403) who were surveyed with a form that included sociodemographic information and two validated tools (the Menopause Rating Scale and the SF-36 Health questionnaire). Calf circumference, hand grip and gait speed were measured. Low muscle mass (calf circumference < 31 cm), reduced muscle strength (<20 kg in hand grip) and lower physical performance (<0.8 m/s gait speed) were estimated. Criteria of the European Working Group on Sarcopenia in Older People were used to identify sarcopenia. Association between sarcopenia (dependent variable) and menopausal symptoms and health perception (independent variables) was estimated. Results: Results: Median age of surveyed women was 48 years, with 44.5% being postmenopausal. A 9.6% had low muscle mass, 18.1% reduced muscle strength and 6.9% had lower physical performance. Pre-sarcopenia was identified in 9.6% and sarcopenia in 7.9% (non-severe sarcopenia 7.1% and severe sarcopenia 0.8%). Most P-44. important factors associated with sarcopenia were: feeling full of life only sometimes, COMPARISON OF SARCOPENIA PREVALENCE ACCORDING TO feeling a lot of energy only sometimes, having joint/muscular discomfort, history of AGE GROUP IN CLIMACTERIC WOMEN FROM THE CARIBBEAN hysterectomy, hot flashes, mestizo ethnic group, age 50 or more, being postmenopausal, OF COLOMBIA sleep problems. Conclusion: Sarcopenia was present in this mid-aged female Colombian Alvaro Monterrosa-Castro1,2, Mauricio Ortiz-Banquez, Médico1,2, Angelica Monterrosa- Caribbean sample and associated to various factors such as ethnicity, age and menopausal Blanco3,2. 1Universidad de Cartagena. Colombia, Cartagena, Colombia; 2Grupo de symptoms and status. Investigación Salud de la MUjer, Cartagena, Colombia; 3Universidad de la Sabana, Chia, Sources of Funding: none Cundinamarca., Colombia Objective: To compare sarcopenia prevalence according to age group in middle aged women. Design: Cross-sectional study in caribbean women from Colombia between 40-59 years, healthy in their communities, who participated voluntarily and anonymously with prior signature of informed consent. Sociodemographic form and anthropometric measurements: muscle mass (calf circumference), muscle strength (hand grip) and P-46. physical performance (gait speed) were measured. The Working Group criteria on Vasomotor symptoms and /lipoproteins in midlife women: Does Sarcopenia in Older People were used to identify sarcopenia: low muscle mass (<31 cm), level of endogenous estradiol matter? The SWAN HDL Ancillary study reduced muscle strength (<20kg) and lower physical performance (<0,8m/s). Statistic Alexis Nasr1, Karen Matthews2, Maria Brooks1, Dan McConnell3, Jeff Billheimer4, analysis with EPI-INFO-7. Results: 403 women were studied, aged 48 years and 40.4% Trevor Orchard1, Dan Rader4, Samar R. El Khoudary, PhD, MPH1. 1Epidemiology, en postmenopause. 9.6% had low muscle mass, 18.1% reduced muscle strength and 6.9% University of Pittsburgh, Pittsburgh, PA; 2Psychiatry, University of Pittsburgh, lower physical performance. Pre-sarcopenia was identified in 9.6% and sarcopenia in Pittsburgh, PA; 3Epidemiology, University of Michigan, Ann Arbor, MI; 4Perelman 7.9% (non-severe sarcopenia 7.1% and severe sarcopenia 0.8%). Sarcopenia prevalence School of Medicine at the University of Pennsylvania, Philadelphia, PA is shown in the graphic, distributed by age range, with a significant increase from 4,1% Objective: Greater vasomotor symptoms (VMS) frequency in midlife women is in the group of 40 - 44 years to 16,4% in the group of 55 - 59 years (p<0.05). Taking as associated with higher low density lipoprotein cholesterol (LDL-C), but association a reference the group of 40 - 44 years of age, being 45 - 49 years had OR: 1,13 [95% with high density lipoprotein cholesterol (HDL-C) remains unclear. Endogenous CI: 0,31-4,13], p = 0.84; being 50 - 54 years old had OR: 1,88 [95% CI: 0,51-6,92], estradiol (E2), known to contribute to VMS occurrence and profile, may explain or p = 0.33 and being 55 - 59 years old: OR: 4,59 [95% CI: 1,47-14,29], (p<0.05). modify the association between VMS and lipids. Lipoprotein subclasses as assessed by Conclusion: There was difference in sarcopenia prevalence in age groups that are part nuclear magnetic resonance (NMR) spectroscopy have been linked to CVD risk beyond of of the climacteric life stage. traditional lipid measures and may provide better understanding of the relation between Sources of Funding: None VMS and lipids. We assessed the association of VMS frequency with each of LDL-C, HDL-C and lipoprotein subclasses (LDL particles [LDL-P] and HDL particles [HDL-P]) and sizes in midlife women over time, and evaluated whether these associations were modified by E2. Design: LDL-P and HDL-P concentrations (total, large, medium, and small) and sizes were measured by NMR in the Study of Women’s Health Across the Nation (SWAN)-HDL ancillary study up to 5 times over the menopausal transition. Self- reported VMS (hot flashes and/or night sweats) frequency categorized into none, 1-5 days (moderate) or ≥6 days (severe) within the past 2 weeks. Multivariable linear mixed effects models were used for analyses. Results: The study included 556 women (mean age 49.9(±2.7 SD) years; 80% premenopausal; 55% White), of whom 30% reported moderate and 15% reported severe VMS at first time point. Adjusting for confounders except log-E2, severe VMS was associated with higher LDL-C and smaller HDL size compared to no VMS (Table-Model 1). Additional adjustment for log-E2 explained these associations (Table-Model 2). E2 significantly modified the association between VMS and LDL-C, large LDL-P, small HDL-P and HDL size. Compared to no VMS, women with moderate VMS whose log-E2 level was 1SD higher had lower LDL-C and total LDL-P levels, lower small HDL-P levels and larger HDL size in final model (Table-Interaction Model). Conclusion: Higher endogenous E2 level may play a protective role in the association between VMS and lipids/lipoproteins, particularly among women with moderate VMS. Future studies should evaluate role of exogenous estrogen preparations on lipid/lipoproteins in women with moderate levels of VMS. Sources of Funding: SWAN HDL ancillary study has grant support from National Institute on Aging (NIA) AG058690. P-45. Multivariable linear mixed effect models of associations of VMS and each lipid/ Oxidative stress in the visceral fat is elevated in postmenopausal women. lipoprotein measure Megumi Narumi1, Kazuhiro Takahashi2, Hizuru Yamatani3, Satoru Nagase3. 1Obstetrics and Gynecology, Hamamatsu University School of Medicine, Hamamatsu, Japan; 2Akanegaoka Takahashi Ladies’ Clinic, Yamagata, Japan; 3Obstetrics and Gynecology, Yamagata University, Yamagata, Japan Objective: This study aimed to evaluate differences in oxidative stress of visceral fat between premenopausal and postmenopausal women, and to clarify the effect of estrogen on adipocytes. Design: Abdominal subcutaneous and omental visceral adipose tissues were obtained from 38 patients who underwent gynecological surgery. We measured the sizes of the adipocytes and evaluated the lipid peroxidation levels in the adipose tissues. We investigated whether estrogen inhibited the intracellular reactive

species (ROS) production that was induced by peroxide (H2O2) in 3T3- L1 adipocytes. Results: The visceral adipocytes were 1,162.4 µm2 and 1,881.9 µm2 in the premenopausal and postmenopausal women, respectively; hence they were significantly larger in the latter (P < 0.05). The lipid peroxidation levels were 46.7 nmoL/mg protein in the premenopausal women and 99.6 nmoL/mg protein in the postmenopausal women; hence the lipid peroxidation levels were significantly higher in the latter (P < 0.05). Estradiol (E2) significantly reduced the intracellular ROS levels that were induced by H2O2 in 3T3-L1 adipocytes (P < 0.01). We determined that E2 significantly increased the expression of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent antioxidant genes, oxygenase-1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO-1), and the glutamate- ligase modifier subunit (GCL) genes in 3T3-L1 adipocytes (P < 0.01). Conclusion: Oxidative stress in the visceral fat is higher in postmenopausal women. The expression of the antioxidant genes HO-1, NQO-1, and GCL was upregulated by estrogen a in 3T3-L1 adipocytes. Hence, estrogen may act as an antioxidant in the adipose tissues Adjusted for age, site, race, education, menopausal status, physical activity, of premenopausal women. alcohol use and BMI b Sources of Funding: Grants-in-Aid for Scientific Research No. 19K18629 from the Model 1+ log-E2 + day of blood collection c Ministry of Education, Culture, Sports, Science and Technology of Japan. Compared to none d Log-transformed * P-value<0.05

Lipid peroxidation is elevated in the visceral of postmenopausal women. P-47. enrolled in the KEEPS (Kronos Early Estrogen Prevention Study) RCT of menopausal The factors associated with amnestic mild cognitive impairment (aMCI) hormone therapy who also participated in the ancillary KEEPS-Cognitive study (n=621). in surgical menopausal women Baseline information on presence and severity of menopausal symptoms was captured Nalina Orprayoon, MD2, Malika Kengsakul, MD1, Solaphat Hemrungrojn, MD3, on a scale of 0-3 (none, mild, moderate and severe). Serum levels of E2 and T were Chanakarn Suebthawinkul, MD2, Phanupong Phutrakool4, Unnop Jaisamrarn, MD, available as part of the parent study. FSH and LH were analyzed utilizing a well MHS2, Sukanya Chaikittisilpa, MD, MSc2. 1Department of Obstetrics and Gynecology, validated two sided immunoenzymatic assay (Beckman Instruments, Chaska, MN) in Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 2Menopause stored baseline samples in 369 women who completed KEEPS-Cog. Performance on Research Unit, Department of Obstetrics and Gynecology, Faculty of Medicine, 3MS (higher score reflecting better cognition) was the outcome of interest. Stepwise Chulalongkorn University, Bangkok, Thailand; 3Department of Psychiatry, Faculty of multivariable linear regression analyses assessed relationships between menopausal Medicine, Chulalongkorn University, Bangkok, Thailand; 4Chula Data Management symptoms and specified with 3MS score at study baseline. Results: After Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand adjusting for potential confounders including demographics (age, time since menopause, Objective: To determine the percentage and factors associated with amnestic mild race, socioeconomic status, education, partnered status, exercise, exposure to , cognitive impairment in women with surgical menopause Design: This study is a post , tea), and comorbid or biological traits (obesity, blood pressure, depression) hoc analysis of a cross-sectional study between October 2013 and July 2014. Method: variables, statistically significant inverse relationships were observed between 3MS Data from 178 surgical menopausal women were used for analysis. The information score and menopausal symptom of vaginal dryness. Worsening vaginal dryness was was obtained by self-reported questionnaire which included age, year since menopause, associated with decreasing 3MS scores (β coefficient 0.99, SE 0.33), and this relationship education, medical and surgical history, history of menopausal hormone therapy was statistically significant (p=0.003). No relationships were observed between 3MS (MHT), exercise, sleeping disorder, family history of dementia, and self-awareness of score and vasomotor symptoms or insomnia. Individual levels did not forgetfulness. The Montreal Cognitive Assessment Thai version (MoCA-T) test and relate to 3MS. However, after adjusting for above specified confounders, an inverse Montreal Cognitive Assessment Memory Index score (MoCA-MIS) were administered relationship of statistical significance was observed between 3MS and the FSH: LH ratio by well-trained psychologist. Outcome measures: Montreal Cognitive Assessment (i.e. higher FSH: LH ratio related to worse cognitive performance, β coefficient -0.80, SE Memory Index Score (MoCA-MIS). Amnestic mild cognitive impairment (aMCI) was 0.39, p=0.042). An inverse relationship was similarly observed between 3MS score and defined when MoCA-MIS score < 7. Statistical analyses: Pearson correlation was log-normalized E2 (i.e. higher E2 related to worse cognitive performance, β -0.44, SE performed to determine the clinical variables associate with aMCI. Multivariate Logistic 0.18, p=0.017) on analyses that adjusted for BMI and waist:hip ratio. Conclusion: In a Regression was used to explore the influence of different variables on aMCI including population of menopausal women within 3 years of their final menstrual period, we report age, age at menopause, year since menopause, body mass index (BMI) and duration novel findings on relationships between symptomatology (specifically vaginal dryness) of menopausal hormone therapy (MHT). Statistical significance was taken as P-value and endocrine biomarkers (specifically FSH: LH ratio and E2 levels) with cognitive < 0.05 for all tests. Results: The mean age was 55.5 ± 7.7 years and nearly half of the performance in early menopause. participants were menopause for more than 10 years. 75.8 % of all participants had ever Sources of Funding: -Funding for the KEEPS core investigation was be provided by the used MHT and the median of duration was 5 years. The percentage of mild cognitive Kronos Longevity Research Institute of Phoenix, Arizona, and the Aurora Foundation, impairment (MCI) in the present study was 43.5%. There was only 14.6% of all surgical Phoenix, Arizona. -The KEEPS-Cog project was supported by grants from the National menopausal women showed amnestic cognitive impairment which was lower than Institutes of Health (NIH) R01 AG029624, P50AG033514, R01AG031790, grant frontal lobe cognitive impairment (73.9%) in another study, 22 % of surgical menopausal 1UL1RR025011 from the Clinical and Translational Science Award (CTSA) program women with MCI had amnestic MCI. Pearson correlation between MIS score and related of the NIH National Center for Research Resources and the Wisconsin National Primate variable showed the significant negative associations between MIS score with Year since Research Center base grant, NIH NCRR000167. Funding for FSH:LH assays was made menopause (r=-0.156, p-value=0.038). The Multivariate Logistic Regression after all available through funding by Department of Obstetrics, Gynecology & Reproductive adjusted showed the odds of the aMCI is 82% lower in women who had duration of Sciences and the Benneck-Polan Family Foundation education > 6 year than in the duration of education ≤ 6 year, and the result is statistically significant (95% CI 0.04,0.86). Conclusion: As MCI with amnestic impairment (MIS P-49. <7) have a higher risk to develop Alzheimer’s disease, we found 14.6% of amnestic MCI Higher prevalence of low mass with obesity especially in in all surgical menopausal women, and 22% in surgical menopausal women with MCI. Menopausal hormone therapy showed no association with amnestic MCI, only duration elderly population: A nationwide study in Korea women Hyoung Moo Park, MD, Ph.D2, Youngnam Kwon, MD, Ph.D3, Tak Kim, MD, Ph.D1. of education was associated with amnestic MCI. 1OBGYN, Korea University Anam hospital, Seoul, Korea (the Republic of); 2OBGYN, Sources of Funding: Ratchadapiseksompotch Fund, Faculty of Medicine, Chulalongkorn Grace Woman’s Hospital, Goyang, Korea (the Republic of); 3Neurology, Seoul National University, Bangkok, Thailand University Bundang Hospital, Sungnam, Korea (the Republic of) Table 1 Multivariate Logistic Regression with aMCI (n=178) Objective: Sarcopenia causes loss of muscle mass in the elderly and is associated with development of in those with obesity. This study evaluated the prevalence of low skeletal muscle mass index (SMI) with obesity in elderly population compared to young population in healthy Korean elderly women. Design: This study was based on data from the Korea National Health and Examination Survey IV and V, 2008-2011. Whole body dual energy X-ray absorptiometry and body mass index measurement were performed for all participants. SMI was calculated as appendicular skeletal muscle mass (ASM)/height2. SMI lower than 5.4kg/m2 was defined as low SMI, and body mass index ≥ 25kg/m2 was defined as obesity. Results: Of total 11,625 women, 2,396 (20.6%) women were elderly (aged 65 years or older). The prevalence rates of obesity were 37.8% (905/2,396) in elderly women, and 25.0% (2,311/9,229) in young women. Among the obese population, the prevalence of low SMI was significantly higher in elderly women compared to young women [respectively, 6.1 % (55/905) vs. 2.2% (51/2311), p < 0.001]. Conclusion: The prevalence rates of low SMI and obesity were different among age groups. In the elderly population, the skeletal muscle mass could be *Significant level at 0.05 (2-tailed) lower than young population, even with the similar BMI. The fatty tissue might replace the skeletal muscle with aging. Therefore, the prevalence rate of low SMI with obesity (sarcopenic-obesity) as well as the prevalence of obesity were significantly higher in P-48. elderly women compared to young women. Furthermore, sarcopenic-obesity, a new Examining relevance of menopausal symptoms and reproductive category of metabolic disease in older adults with high adiposity coupled with low endocrine milieu for cognitive performance in early menopausal women. muscle mass, could emerging clinical issue in elderly population Lubna Pal, MBBS, FRCOG, FACOG, MS1, Juliana M. Kling, MD, MPH2, Virginia M. Sources of Funding: none Miller, PhD2, Nanette Santoro, MD3, Hugh Taylor, MD1, JoAnn E. Manson, MD, 6,7 4 5 1 NCMP , Rogerio Lobo, MD , Carey Gleason, PhD . Obstetrics, Gynecology & P-50. Reproductive Sciences, Yale University, New Haven, CT; 2Division of Women’s Health Internal Medicine, Mayo Clinic, Scottsdale, AZ; 3Obstetrics & Gynecology, University Equol status and changes in fecal microbiota in menopausal women of Colorado, Denver, CO; 4Obstetrics & Gynecology, Columbia University, New York, receiving treatment for menopause symptoms with soy-isoflavone NY; 5University of Wisconsin, Madison, WI; 6Internal Medicine, Brigham & Women’s associated with probiotics: results from a randomized controlled trial. Hospital, Boston, MA; 7Harvard Medical School, Boston, MA Naice S. Monteiro, PhD2, Gabriela A. Macedo, Full Professor2, Ana E. Ribeiro, Objective: To examine relationships between cognitive performance as assessed MSc1, Adriana O. Pedro1. 1GYNECOLOGY, UNICAMP, Campinas, Brazil; 2FOOD by modified mini mental status (3MS) examination, with : a) common menopausal ENGINEERING, UNICAMP, Campinas, Brazil symptoms including vasomotor symptoms (hot flushes and night sweats), insomnia, and Objective: To evaluate the influence of a treatment with soy isoflavone, either in vaginal dryness, and b) endocrine profile (serum levels of FSH, LH, ratio of FSH:LH, conjunction with probiotic use or not, on equol production status and changes in estradiol-E2, and -T) in recently menopausal women within 3 years of their intestinal microbiota profile in symptomatic postmenopausal women, in comparison to last menstrual period. We hypothesized an inverse relationship of cognitive performance low-dose hormone therapy. Design: A randomized controlled trial including 60 healthy with menopausal symptom burden and with circulating gonadotropin levels. Design: postmenopausal women aged 40–60 years was performed for 16 weeks. The women Retrospective analysis of baseline data from recently postmenopausal women who were randomized into three groups: (150 mg/day), isoflavones plus probiotics (150 mg/day plus 2 g/day of probiotic) or hormone therapy (1 mg of estradiol plus 0.5 mg metabolism of isoflavones after 16 weeks of treatment. This study compared the effects of acetate). All treatment was by . Vasomotor, of isoflavones, their association with probiotics and HT for the relief of menopausal urogenital, and psychological complaints were evaluated using the Menopause Rating symptoms. Although HT has been considered the most effective treatment for relief Scale. All demographic and reproductive variables were evaluated before and after the climacteric symptoms, our findings show that isoflavones plus probiotics and isoflavones study. Gas-chromatography-mass spectrometry (GC-MS) was used to measure equol, alone were also effective in improving climacteric symptoms, for all subscales of MRS, equol intermediate, O-dimethylangolensin, and aglycones. Sequencing of 16S rDNA with different magnitude effect among treatment. The total, psychological, somatic, and amplicons was performed on fecal samples taken at baseline and after 120 days of urogenital scores were significantly decreased over time, with a delta difference and treatment. Changes in fecal communities were analyzed with respect to the women’s percent of change before and after intervention that demonstrated the effectiveness of equol-producing phenotype. The trial was registered in the Brazilian Clinical Trials the three treatments in relieving climacteric symptoms. Registry (ReBEC; RBR-83wwpx). This clinical trial was performed in accordance Sources of Funding: Financial support: grant #2016/08089-9, São Paulo Research with the Consolidated Standards of Reporting Trials 2010 statement (CONSORT). Foundation (FAPESP) Results: A total of 58 women (96.67%) completed the study. All three groups had a statistically significant improvement of somatic, psychological and urogenital symptoms over time (p<0.001). There was not statistical difference among the three P-52. groups (inter-group analyses). The performance of isoflavones plus probiotic group was Metabolic profile of postmenopausal women treated with isoflavones and more favorable in produce equol and its intermediates. Microorganisms known to be probiotics in comparison to hormone therapy: results from a randomized involved in the metabolism of dietary , as Bifidobacterium adolescentis, controlled clinical trial Faecalibacterium prausnitzii, Bifidobacterium sp., Ruminococcus sp., were found in all Naice S. Monteiro, PhD2,1, Adriana O. Pedro3, Ana E. Ribeiro, MSc3, Gabriela A. groups. Faecalibacterium prausnitzii, an intestinal health marker associated with equol Macedo, Full Professor2. 1Gynecology, CLINICA LANE, Campinas, Brazil; 2SCHOOL production, was found in significant greater quantity in the group that used hormonal OF FOOD ENGINEERING, UNICAMP, Campinas, Brazil; 3GYNECOLOGY, therapy (13.36%) than in the Isoflavone (10.07%) and Isoflavone plus probiotics (7.85%) UNICAMP, Campinas, Brazil groups (p<0.04) after the intervention. Conclusion: The metabolism of soy isoflavones, Objective: Evaluate the influence of soy isoflavone administration, either in conjunction and therefore their and activity in humans, strongly depends on the activity with probiotic use or not, on metabolic profile in postmenopausal women compared to of the intestinal microbiota. The underlying interactions between microbial populations hormone therapy, on habitual dietary intake. Design: A randomized, controlled trial with and isoflavone metabolites, however, remain poorly understood. The composition of sixty healthy postmenopausal women of 40-60 years of age was performed. The women the fecal bacterial communities was modified by the presence of phenolic compounds, were allocated to use (ISO: 60 mg of isoflavone/capsule), phytoestrogen including increases in equol-producing taxa associated to this microbial community. associated to probiotics (ISO+PROB: 60 mg of isoflavone/capsule associated with 2 g Variations in the microbial communities over the 4-month period of treatment were of probiotics product containing Lactobacillus and Bifidobacterium strains) or hormone higher and the equol production status did appear to be associated with the presence or therapy (HT: 1 mg estradiol and 0.5 mg ). Biochemical plasma increase in the gut microbial diversity. Even if, women with an equol-producer phenotype levels of glucose, insulin, total cholesterol, HDL, LDL, triglycerides, estradiol and FSH were primary benefited, equol non-producer also developed the ability to produce this were assessed at baseline and after 16 weeks of treatment, as well as the production compound after the intervention. Our findings corroborate that the ability to convert status of urinary equol. Equol, equol intermediate, O-dimethylangolensin, and aglycones daidzein to equol can be induced in nonproducers, through the modulation of the gut were measured using gas chromatography coupled to mass spectrometry. Over the study, microbiota. dietary assessment was performed by a mean of three-day food records in allowing the Sources of Funding: Financial support: grant #2016/08089-9, São Paulo Research estimation of energy, carbohydrate, total fiber, protein, cholesterol, total fat, saturated Foundation (FAPESP) fatty acids (SFA), monounsaturated fatty (MUFA) and polyunsaturated fatty acids (PUFA) intake. Food consumption frequency questionnaire (FFQ) was used to access average phenolic intake. Statistical analyses were carried out using the chi-square test, P-51 - Featured Poster. Fisher’s exact test, the Kruskal–Wallis non-parametric test and analysis of variance Phytoestrogens associated with probiotics as an alternative for alleviating (ANOVA). The trial was registered in the Brazilian Clinical Trials Registry (ReBEC; climacteric symptoms in postmenopausal women. Results from a RBR-83wwpx). This clinical trial was performed in accordance with the Consolidated randomized controlled trial. Standards of Reporting Trials 2010 statement (CONSORT). Results: The mean age of Adriana O. Pedro, PhD1, Naice S. Monteiro, PhD2, Ana E. Ribeiro, MSc1, Anna the women was 52.4 years, and the mean age at menopause was 48.6 years; the mean time Valeria G. Moraes, MSc1, Lucia S. Costa-Paiva, Full Professor1, Gabriela A. Macedo, Full since menopause was 46.5 months. The treatment groups were homogeneous for most Professor2. 1Gynecology, UNICAMP, Campinas, Brazil; 2School of Food Engineering, characteristics, except for the HT group participants who had higher social class (p=0.03) UNICAMP, Campinas, Brazil and the majority were non-smokers (p = 0.04), providing greater reliability of intragroup Objective: To evaluate the effect of soy isoflavone administration, either in conjunction and intergroup comparisons. The groups were similar at baseline in relation to all with probiotic use or not, on climacteric symptoms, and compare the effects with metabolic profiles. No statistically significant differences were found between the groups those of hormone therapy. Design: A randomized clinical trial was conducted on 60 with respect to baseline clinical and sociodemographic characteristics. Comparison postmenopausal women aged 40 to 60 years, randomly assigned to receive oral isoflavone between groups revealed a non-statistically significant improvement in glucose, insulin, (150 mg dry extract of glycine max) alone or isoflavone plus probiotic (Lactobacillus total cholesterol, HDL-c, LDL-c and triglycerides when isoflavone or isoflavone plus acidophilus, Lactobacillus casei, Lactococcus lactis, Bifidobacterium bifidum, and probiotic are used, but an important decrease in total cholesterol (p=0.0077) and LDL-c Bifidobacterium lactis) or hormone therapy (1 mg estradiol and 0.5 mg norethisterone (p=0.0102) was observed in HT group. The average consumption of total / acetate). Vasomotor, psychological and urogenital symptoms were evaluated using the portion (mg) was 43.23 mg in ISO group, 100.75 mg in ISO+PROB group and 57.52 Menopause Rating Scale (MRS). Equol, equol intermediate, O-dimethylangolensin and mg in HT group participants. The concentrations of equol (ug/mL) among groups over aglycones were measured using gas chromatography coupled to mass spectrometry. time were 7.69 µg/ml in ISO group, 7.39 µg/ml in ISO+PROB group and 2.46 µg/ml Transvaginal sonography was performed to evaluate endometrial thickness. A written in HT intervention (p=0.005). Conclusion: Hormone therapy may constitute a good symptom questionnaire for adverse effects was administered at baseline, and after therapeutic approach in postmenopausal women with dyslipidemia, in detriment to the 8 and 16 weeks to determine new onset or aggravation of symptoms associated with use of phytoestrogens. medications. All variables were evaluated before and after the study (16 weeks). Data Sources of Funding: Financial support: grant #2016/08089-9, São Paulo Research were analyzed on an intention-to-treat basis, including all participants enrolled in each Foundation (FAPESP) group. The intragroup analysis of climacteric symptoms was performed by comparing the means over time using ANOVA followed by the Mann-Whitney U test, while the intergroup analysis was performed using only ANOVA. The trial was registered in P-53. the Brazilian Clinical Trials Registry (ReBEC; RBR-83wwpx). This clinical trial was RISK FACTORS ASSOCIATED WITH GENITOURINARY performed in accordance with the Consolidated Standards of Reporting Trials 2010 SYNDROME OF MENOPAUSE IN BRAZILIAN MIDDLE-AGED statement (CONSORT). Results: A total of 58 women (96.67%) completed the study. The WOMEN: A POPULATION-BASED HOUSEHOLD SURVEY. mean age of women was 52.4 years, and the mean age at menopause was 48.6 years; the Jeffrey F. Lui-Filho, PhD2, Lucia S. Costa-Paiva, Full Professor2, Adriana O. Pedro1. mean time since menopause was 46.5 months. The treatment groups were homogeneous 1Gynecology, CLINICA LANE, Campinas, Brazil; 2gynecology, Unicamp, Campinas, for most characteristics, except for the HT group participants who had higher social class Brazil (P=0.03) and the majority were non-smokers (p = 0.04), providing greater reliability of Objective: To determine the factors associated with genitourinary syndrome of intragroup and intergroup comparisons. The groups were similar at baseline in relation menopause (GSM), among middle-aged women in the Metropolitan Region of Campinas, to total MRS and all subscales. Over 16 weeks, menopausal symptoms were evaluated by Brazil. The association between vulvovaginal atrophy and urogenital symptoms was the total score of the Menopause Rating Scale, and delta of -10.94 (±10.09) reduction was analyzed as a unique condition and also as an individualized condition. Design: A cross- observed in the isoflavone group, followed by -12.95 (±8.87) reduction in the isoflavone sectional population-based household survey was conducted with 749 women aged plus probiotic group, compared with the -16.42 (±8.72) reductions in the hormone 45-60 years. The dependent variable was the presence of GSM assessed by a pre-tested therapy group (p<0.001). There was a significant increase in the daidzein, , equol structured questionnaire. The independent variables were sociodemographic data, health- intermediate, and O-dimethylangolensin contents after 16 weeks in the isoflavone plus related habits and problems, self-perception of health, and gynecological background. probiotic group. The performance of isoflavones plus probiotic group was more favorable To assess which variables were independently associated with GMS, multiple Poisson than isoflavones alone, possibly because of the higher bioavailability of aglycones regression models were created. Prevalence ratios (PRs) and 95% confidence intervals achieved after biotransformation by probiotic microorganisms. Statistically significant (95% CIs) were calculated using backward selection of the significant variables. The differences in the adverse effects evaluated were observed for mastalgia and bleeding, level of statistical significance was set at 5% and the sampling clusters (census tracts) only for post-intervention analysis in the HT group. Conclusion: Probiotics improved the were considered in the multivariate analyses. Results: The mean age of the women was 52.5±4.4 years, and the mean age at onset of menopause was 46.5±5.8 years. GSM was P-55. defined as the presence of one or more symptoms among genital symptoms of dryness, Uterine Bleeding Rates with Hormone Therapies in Menopausal Women burning, and irritation; sexual symptoms of lack of lubrication, discomfort or pain, and with Vasomotor Symptoms impaired function; and urinary symptoms of urgency, dysuria and recurrent urinary tract James H. Pickar, MD1, David F. Archer, MD2, Steven R. Goldstein, MD4, Risa Kagan, infections. Women may present with some or all of the signs and symptoms, which must MD3,6, Brian Bernick, MD5, Sebastian Mirkin, MD5. 1Columbia University Medical be bothersome and should not be better accounted for by another diagnosis. GSM was Center, New York, NY; 2Eastern Virginia Medical School, Norfolk, VA; 3University of prevalent in 49.5%. Poisson multiple regression for GSM, genital and urinary symptoms California, San Francisco, CA; 4New York University School of Medicine, New York, NY; showed a variety of associated factors to GSM and each specific symptom. Factors 5TherapeuticsMD, Boca Raton, FL; 6Sutter East Bay Medical Foundation, Berkeley, CA associated with GSM were depression/anxiety (p<0.001), marital status (p=0.002), Objective: Women often discontinue the use of hormone therapy (HT) taken for osteoarticular diseases (p=0.009) and topical menopause treatment (p=0.032). Factors menopausal vasomotor symptoms (VMS) because of bleeding and spotting. The associated with urinary symptoms of GSM were depression/anxiety (p=0.015), vaginal REPLENISH trial (NCT01942668) evaluated a single oral capsule combining deliveries (p=0.034) and hypertension (p=0.043). Factors associated with genital bioidentical 17β-estradiol and progesterone (E2/P4; TherapeuticsMD, Boca Raton, FL) symptoms of GSM were marital status (0.001), depression/anxiety (p=0.003), topical in postmenopausal women with a uterus seeking relief of moderate to severe VMS. The menopause treatment (p=0.006) and seeking information about menopause with doctors 1 mg E2/100 mg P4 dose was FDA approved as BijuvaTM. This systematic review reports (p=0.025). Conclusion: GSM is a highly prevalent medical condition, impacting midlife on the incidence of amenorrhea with this E2/P4 and other commercially available in the women’s health, sexual function and quality of life. It was related to a broad set of US, continuous-combined HT for the treatment of VMS in postmenopausal women with factors, that may be differently associated with urinary and genital symptoms. A better a uterus. Design: PubMed was searched using these following keywords: menopause understanding of these factors may help to not only reduce the impact of genitourinary and bleeding and ( [CEE] or estradiol or ethinyl estradiol) and symptoms on the quality of life of middle-aged women, but also to define groups of (medroxyprogesterone [MPA], norethindrone acetate or norethisterone acetate [NETA], women who will need multidisciplinary health care. The results highlight the importance [NGM], , ). Bleeding data from separate of carrying out interventions aimed at reducing modifiable factors and to individualize randomized controlled trials of continuous-combined oral or HT (estrogen approach to women with vulvar, vaginal or urinary symptoms. plus ) with at least 25 women per treatment group and bleeding data Sources of Funding: Financial Support: Funded by São Paulo Foundation for the over 12-13 cycles were summarized and compared with those of E2/P4. Only studies Support of Research (FAPESP – Fundação de Amparo à Pesquisa do Estado de São reported in the were included. Results: The proportion of women Paulo) grant 2011/14526-9. with cumulative amenorrhea (no bleeding or spotting) and amenorrhea at cycle 12/13, and mean bleeding/spotting days are shown in the Table. E2/P4 (1 mg/100 mg) had the P-54. highest cumulative amenorrhea rate from cycle 1 to 13 among the oral HT, similar to that Hormonal Therapy in patients with Premature Ovarian Insufficiency: reported for EE/NETA (0.025/0.5). Lower cumulative amenorrhea rates were observed with E2/NGM (1/0.09), followed by CEE/MPA (higher doses) and E2/NETA (2/1). effects in body composition and correlation with markers of The amenorrhea rate at cycle 13 was also high with E2/P4 (90%), similar to oral E2/ cardiovascular risk. NETA and CEE/MPA. No cumulative amenorrhea data were found for Alberto Freitas, MD, Andrea D. Giraldo, Gabriela P. Rezende, MD, Daniela A. Yela, (E2V)/, E2V/,1 and E2V/NETA. Compared with transdermal HT, E2/ PhD, Adriana O. Pedro, Cristina L. Benetti-Pinto, Associate professor. Gynecology, P4 capsules had a somewhat similar amenorrhea rate from cycle 1 to 13 and at cycle 13 UNICAMP, Campinas, Brazil to that with the lowest transdermal E2/NETA (0.025/0.125) system; other transdermal Objective: To evaluate the body composition of women with POI and use of HT in systems reported lower amenorrhea rates. Overall, the mean number of bleeding/spotting comparison to women with preserved gonadal function matched by age and Body Mass days decreased over time. Mean bleeding days per cycle observed from cycle 1 to 13 Index (BMI). To correlate the body compostion parameters with cardiovascular disease were the lowest with oral E2/P4 and EE/NETA. Conclusion: Compared with published markers in POI women. Design: Cross-sectional study at the Endocrine Gynecology bleeding data from other continuous-combined HT reported in separate studies, E2/P4 Outpatient Clinic of the Department of Obstetrics and Gynecology, Faculty of Medical appears to have a favorable bleeding profile. Given its good amenorrhea and bleeding Sciences, University of Campinas (UNICAMP), with the inclusion of 70 women with POI profiles, Bijuva can be an alternative FDA-approved option for the millions of women diagnosis using HT for at least 12 months, matched by age (± 2 years) and BMI to women seeking bioidentical HT. with preserved gonadal function (control group). For all women, the measurements Sources of Funding: TherapeuticsMD of waist, hip and BMI were obtained, in addition to the study of dual-energy X-ray Amenorrhea rates and number of bleeding days with continuous HT Absorciometry (DXA densitometry) of total body, For POI women, were obtained laboratory tests to evaluate metabolic parameters, in addition to ultrasound measures of the thickness of the intimal layer of the right and left carotid . STATISTICAL ANALYSIS: The variables obtained from DXA were compared between two groups using the Wilcoxon test for paired samples. For the POI group, Spearman’s correlation analysis was performed to evaluate the correlation between clinical, densitometric variables and laboratorial parameters. Results: The age and BMI of POI women were 36.33 ± 7.51 years old and 26.30 ± 4.19 kg/m2. They were using HT for 6.53 ± 7.57 years. Those with preserved ovarian function had age of 36.27 ± 7,30 years old and BMI of 26.15 ± 4,06 kg/m2 (p = ns). The body composition was similar for the groups for the total mass parameters (66,88 ± 11.77 and 67.47 ± 12.12 kilograms, (p = 0,681), percentage of total fat (43.02 ± 7.63 and 42.03 ± 8.30%, p = 0.311) and percentage of lean mass (56.97 ± 7.62 and 57.97 ± 8.30%, p = 0.309). The android/ginoid (A/G) fat ratio (0.93 ± 0.15) was similar between then. For the group with POI, the waist-hip ratio was 0.84 ± 0.08 cm and in the densitometric evaluation, they showed higher lean mass index (14.19 ± 1.63) than fat mass index (11.04 ± 3.58), besides higher percentage of ginoid fat (51.17 ± 6.71%) In relation to android fat (47.74 ± 9.19%). Age, waist-hip ratio and age at diagnosis of POI showed a positive correlation with blood glucose levels. In the analysis of correlation between body composition parameters obtained by DXA and laboratory parameters, the increase in total mass correlated to increase in blood glucose levels (R = 0.263 and P = 0.03) and ALT (R = 315 and P = 0.041), being negative the association with HDL-Cholesterol (R =-0.358 and P = 0.004). A/G ratio was positively associated with glycemia (R = 0.464 and P = 0.0002), insulin (R = 0.367 and P = 0.03), total cholesterol (R = 0.274 and P = 0.03), triglycerides (R = 0.288 and P = 0.02), LDL- cholesterol (R = 0.299 and P = 0.02), VLDL cholesterol (R = 0.295 and P = 0.025) and ALT (R = 0.574 and P = < 0.0001), in addition to negatively correlate to HDL (R =-0.191 and P = 0.139). The Visceral Adiposity Index (VAI) was positively correlated with glycemia (R = 0.370 and P = 0.028), triglycerides (R = 0.911 and P = < 0.0001), total cholesterol (R = 0.373 and P = 0.02), LDL-cholesterol (R = 0.350 and P = 0.03), VLDL-cholesterol (R = 0.926 and P = < 0.0001) and ALT (R = 0.455 and P = 0.019), in addition to being correlated inversely with HDL-cholesterol (R =-0.440 and P = 0.007). Conclusion: Women with POI in the use of HT have body composition similar to women of the same age and preserved gonadal function. The centralization of fat and visceral adiposity were associated with worsening of some markers of cardiovascular risk. Sources of Funding: None P-56. was selected. The dependent variable was calculated by measuring PREVALENCE OF SELF-REPORTED DIABETES AND waist circumference, performed with a flexible, non-elastic tape measure and evaluated ASSOCIATED FACTORS IN CLIMACTERIC WOMEN in an orthostatic position, with the arms alongside the body, a relaxed abdomen and the Joao Pedro B. Rocha1, Maria Clara B. Rocha2, Maria Fernanda S. Brito3, Lucineia Pinho3, individual looking at a fixed point in front of them. Abdominal obesity was considered Marcelo S. Rocha4, Selen Jaqueline Souza3, Fernanda Piana5, Josiane B. Rocha3,5, as waist circumference ≥ 88 cm. The independent variables were age, marital status, Nathalia Magalhaes4. 1UFMG, Belo Horizonte, Brazil; 2Medicina, Faculdade Ciencias schooling, work, family income, religion, eating habits (consumption of fatty meat, Medicas, Montes Claros, Brazil; 3Mestrado Cuidado Primario, Unimontes, Montes skin, , soda, fruit), smoking, alcohol consumption, level of physical activity, Claros, Brazil; 4Medicina, Unimontes, Montes Claros, Brazil; 5Medicina, Unifipmoc, climacteric stages, climacteric symptoms, depression, anxiety, sleep quality, glycemia, Montes Claros, Brazil triglycerides, HDL cholesterol, blood pressure, body mass index. The associated data Objective: To identify the prevalence of self-reported diabetes and associated factors were tabulated using the Predictiv Analytics Software 18.0 package. Bivariate analysis in climacteric women assisted in Primary Health Care Design: This is a cross-sectional, using the Pearson chi-squared test was applied to analyze the association between waist analytical study conducted in 2014 and 2015 in the Family Health Strategies of Montes circumference and the independent variables. Those associated up to a level of 25% Claros, Minas Gerais, Brazil. We adopted a probabilistic sample by conglomerates in (p≤0.25) were selected for Poisson multiple regression analysis with robust variance, two stages, consisting of 867 women aged 40 to 65 years. Data were collected through from which the prevalence ratios were obtained. A significance level of 5% (p ≤0.05) was questionnaires (sociodemographic, behavioral, reproductive, gynecological and clinical), adopted for the final model. The participants signed a Free and Informed Consent Form anthropometric evaluation and blood collection. The dependent variable was the presence and the project was approved under approval 817.166. Results: a total of 817 women, of self-reported diabetes. For statistical analysis, the absolute and relative frequency was aged 38-73 years, with a mean age of 51.1 years (SD ± 7.25) and a median age of 50 estimated. The association between the variables was analyzed by the chi-square test years were evaluated. The prevalence of women with abdominal obesity was 62.5%. and the associated variables up to the level of 20% were analyzed together by means of Bivariate analysis identified the variables age, marital status, schooling, work, family Logistic Regression, with only the associated variables up to the 5% level being assumed income, level of physical activity, fat intake, climacteric stage, intensity of climacteric in the final model. Results: The prevalence of diabetes was 14.9% in the analyzed group. symptoms, Body Mass Index, triglycerides and arterial hypertension as associated Among the climacteric women, diabetes was associated with comorbidities: hypertension with abdominal obesity, and these were selected for Poisson regression analysis with (OR = 4.333, p = 0.001), hypercholesterolemia (OR = 3.005, p = 0.001) and nephropathy robust variance. The variables sedentarism (PR=1.49), overweight/obesity (PR=3.39), (OR = 1.694, p = 0.047); as well as with altered abdominal circumference (OR = 1.695, arterial hypertension (PR=1.31) and changes in triglyceride levels (PR=1.10) remained p = 0.041). Conclusion: The prevalence of self-reported diabetes was high and associated associated with abnormal abdominal obesity in the final model. One limitation of the with other health conditions in climacteric women, which may contribute as risk factors present study was its cross-sectional design, which did not allow conclusions to be drawn for further complications in the future, increasing morbidity and mortality in this group. in terms of causality. The study remains relevant, however, as it features a representative It is necessary to invest in educational actions to prevent this disease and to control the sample of the population and allows the inference that waist circumference measurement risk factors and their complications in the context of Primary Health Care. is a good indicator for climacteric women, as it was associated with four markers of Sources of Funding: No cardiovascular diseases. Conclusion: waist circumference measurement should not be Bivariate and adjusted analysis of self-reported diabetes and associated factors in overlooked by FHS professionals, and physical exercises should be encouraged. climacteric women. Sources of Funding: None

P-58. Prevalence of suicidal ideation and associated factors in climacteric women Joao Pedro B. Rocha1, Maria Clara B. Rocha2, Lucineia Pinho3, Thalita Bahia Ferreira4, Mariane Silveira Barbosa4, Marcelo S. Rocha4, Daniela Rodrigues5, Dorothéa Schimidt França6, Carolina Ananias Meira Trovão6, Josiane B. Rocha3,6, Maria Fernanda S. Brito3. 1UFMG, Belo Horizonte, Brazil; 2Medicina, Faculdades Ciencias Medica, Montes Claros, Brazil; 3Mestrado em cuidados Primarios, Unimontes, Montes Claros, Brazil; 4Unimontes, Montes Claros, Brazil; 5Funorte, Montes Claros, Brazil; 6Medicina, UnifipMOC, Montes Claros, Brazil Objective: To identify the prevalence of suicidal ideation and associated factors in climacteric women. Design: This is a cross-sectional, analytical, population-based study conducted in 2014 and 2015, with a sample of 836 climacteric women registered in 73 Primary Care Teams in the city of Montes Claros, Minas Gerais, Brazil. Sampling was of the probabilistic type. Data were collected through questionnaires (sociodemographic, behavioral, reproductive, gynecological and clinical), anthropometric evaluation and blood collection. Its dependent variable is suicidal ideation and independent variables: sociodemographic characteristics, lifestyle, health conditions, climacteric profile and obstetric characteristics. For statistical analysis, the absolute and relative frequency was estimated. The association between the variables was analyzed by the chi-square test and the associated variables up to the 5% level. Results: A total of 836 climacteric women participated in the study. The prevalence of suicidal ideation was 10.5% in the analyzed group. Among those with suicidal thoughts, 42.5% are between 52 and 65 years old; 86.9% do not currently smoke; 72.6% do not consume alcoholic beverages; 51.8% do not have mood disorders; 43.7% have finished Elementary School I; 62.8% do not have financial compensation; 41.4% have mild climacteric symptoms; 54% have a low risk for cardiovascular diseases; 50.6% are postmenopausal; 88.9% have sleep disorders; 59.3% have a partner; 63.1% had the first with more than 18 years. Among these variables, a statistically significant association between mood disorder (p = 0.000), symptoms of climacteric (p = 0.000), sleep (p = 0.000) and age at first (p = 0.021) with suicidal ideation was identified Conclusion: There was a high prevalence of suicidal P-57. ideation among climacteric women. Suicidal ideation is associated with mood disorder, Prevalence and associated factors of abdominal obesity in climateric climacteric symptoms, age of first birth, and sleep disturbances. Early assessment and women identification favor adequate behavior and a better prognosis for climacteric women. Josiane B. Rocha1, Maria Clara B. Rocha2, Joao Pedro B. Rocha3, Marcelo S. Rocha1, Sources of Funding: No Wiviane Costa Pimenta1, Maria Fernanda S. Brito1, Dorothéa Schimidt França4, Fernanda Piana4, Daniela Velloso1, Luiza Augusta Rossi-Barbosa1. 1mestrado cuidado primario, unimontes, Montes Claros, Brazil; 2Medicina, Faculdades Ciencias Medica, Belo Horizonte, Brazil; 3Medicina, UFMG, Belo Horizonte, Brazil; 4UnifipMOC, Montes Claros, Brazil Objective: to evaluate the association between abdominal obesity, measured through waist circumference, and sociodemographic, behavioral and clinical data Design: an analytical, cross-sectional, population-based study was carried out in the city of Montes Claros, Minas Gerais, Brazil. Probabilistic sampling was performed in two stages. Firstly, Family Health Strategy (FHS) units were selected by a single draw. Next, the participants were randomly selected from each FHS unit, respecting the proportionally of stratification according to climacteric stage (pre, peri and post-menopause). The sample size was calculated based on a confidence level of 95%, a margin of error of 5% and an estimated prevalence of this event of 50%. A final sample of 817 women Bivariate and adjusted analysis of prevalence of suicidal ideation and associated factors pains differed by study group (period prevalence: post = 35%; peri = 45%; pre = 80%, in climacteric women. p= 0.03). Surprisingly, frequency was similar, but fever/chills/sweats varied across menopause stage (period prevalence: post=42%; peri=15%; pre=0%, p=0.01). By regression, “having my period today” predicted a greater likelihood of attributing , muscle aches and pains, fatigue, and cramps as reproductive symptoms. Compared to postmenopause women, the peri group was more likely to endorse fatigue and cramps, but less likely to attribute headaches, and muscle/joint pain to reproductive status. Conclusion: This exploratory study suggests that in women living with HIV, multiple symptoms including fatigue, muscle aches/pains, depression, and fevers/chills/ sweats are perceived as common attributes of both HIV infection and reproductive status, but with distinct condition-specific symptom profiles that are dependent on menopause stage. A better understanding of how women assign and discriminate between symptom causes has important implications for clinical care. Sources of Funding: NIH RO1NR015737, RO1NR015737-02S1, and NCATS UL1TR001873

P-60. Effect of hormone therapy on in older adults: Possible relevance to Alzheimer’s? Rachel Schroeder, BS1, Leah H. Rubin, PhD, MPH2, Pauline M. Maki1. 1Psychology, University of Illinois at Chicago, Chicago, IL; 2Neurology, Johns Hopkins University, Baltimore, MD Objective: Personality changes often precede cognitive decline in Alzheimer’s disease (AD) and are considered in the diagnosis of AD. Hormone therapy (HT) in older postmenopausal women increases the risk of dementia, but in early postmenopausal women may confer protection. Similarly, raising testosterone to supraphysiological levels in older men induced memory declines and reductions in hippocampal glucose metabolism, whereas high endogenous levels of testosterone were associated with a reduced incidence of AD, increased hippocampal volume, and improved memory. Design: Here we evaluated the effects of hormone treatment on personality in 59 older adults (40% female, mean age=75.14) enrolled in a double-blind, placebo-controlled, cross-over study of HT. The counterbalanced design involved HT for 3 months, a 3-month washout period, and placebo for 3 months. Seven women without a uterus received oral conjugated equine estrogen (CEE 0.625 mg/d) and 15 women with a uterus received CEE plus 2.5 mg medroxyprogesterone acetate (2.5 mg/day). Thirty-eight men received (200 mg IM every 2 weeks). Fifty participants completed the NEO-PIR after each treatment. Linear mixed-effect models were conducted to assess HT effects on personality, controlling for treatment order in the overall sample and stratified by biological sex. Results: In women, HT was related to decreases in conscientiousness P-59. and increases in neuroticism, the two domains found to be most related to AD. Overall An Ecological Momentary Assessment (EMA) to Compare HIV vs conscientiousness decreased t(2,20)= -3.33, p<.01, conscientiousness subdomain C4, Reproductive Health Symptoms in Women of Differing Menopause achievement striving, decreased t(2,20)=-3.13, p<.01, and neuroticism subdomain N6, Stages Living with HIV (WLHIV) vulnerability, increased t(2,20)=2.22, p<.05. Conclusion: Overall these results show that interventions that induce negative cognitive effects in older adults, including hormone Rebecca Schnall, PhD, MPH, RN-BC, FAAN, Jianfang Liu, Nancy Reame, MSN, PhD. therapy, can also induce negative changes in personality. Personality measures may be School of Nursing, Columbia University, New York, NY useful additions to studies of cognitive interventions. Objective: In people living with HIV, symptom experiences and management influence Sources of Funding: This work was supported by National Institutes of Health (NIH) disease progression and clinical outcomes. Whether menopause impacts HIV symptoms Grant 1Z01AG000192-01; the Intramural Research Program of the National Institute on is unclear as few studies have simultaneously examined both conditions for their Aging, NIH; and the General Clinical Research Centers at Johns Hopkins and the Johns interaction. This pilot study documented and compared frequency and attributions Hopkins Bayview Medical Center, which are funded by NIH Grants 5M01RR000052 and of self-identified HIV and reproductive health symptoms in women living with HIV 5M01RR002719; and the National Science Foundation Graduate Resesearch Fellowship using ecological momentary assessment. EMA is an approach for repeated sampling Program 1842398 of experiences in real time, while volunteers are in their natural environments. Design: Women were recruited from urban HIV clinics, and screened on the following: over age 18, a confirmed HIV diagnosis, self-identified Black/Latina, cis-gender, taking P-61 - Featured Poster. antiretroviral therapy and virally suppressed, a past history of regular menstrual cycles Comparison of adherence to Zoledronic Acid verses Denosumab Taryn at some point after menarche, not using steroid contraceptives or post-hysterectomy and Smith, MD, Kenneth Edelman, MD, Holly L. Thacker, MD Women’s able to read/write English or Spanish to provide written informed consent. At study start, Health Institute, Center for Specialized Women’s Health, Cleveland participants completed demographic and health questionnaires for grouping into one of 3 menopause stages (pre, peri, post) using STRAW criteria (Staging of Reproductive Aging Clinic, Cleveland, OH in Women). A blood sample for FSH and E2 (timed between cycle day 1-7 in those with Taryn Smith, MD. Specilaized Women’s Health, Clevelnd Clinic, Cleveland, OH menses) confirmed menopause stage. Using text messenging 3x weekly across a 46-day Objective: As a women’s health specialist it is imperative to identify women at increased study interval (timed to cycle day 1 in those with menses), participants responded to risk of osteoporotic fracture and ensure that they receive the proper treatment. Both the following questions: 1) did you have your period today?; 2) what were your top Zoledronic acid and Denosumab are frequently used in the Center for Specialized 3 menstrual cycle/menopause symptoms today?; 3) what were your top 3 HIV-related Women’s Health (CSWH) due to their ease of use, efficacy, safety profiles and symptoms today? Results: 74 women (mean± SD age = 51± 8 yrs, range= 24-67 yrs) convenient administration. The objective and primary outcome of this study is to completed the study (10 pre-, 20 peri, 44 post-menopause). Mean age differed across determine if treatment regimen affects patient adherence rates among patients with the 3 study groups (36± 8 yrs vs 49±4 yrs vs 56±4 yrs for the pre, peri, post groups osteoporosis receiving yearly Zoledronic acid infusions verses biannual Denosumab respectively, p=<0.001). The majority of volunteers were Black, non-Hispanic (74%), injections in a retrospective cohort of patients treated at the CSWH. The secondary non-smokers (61%), with some high school (68%) and reporting <$20,000 annual outcome of this study is to compare change in bone mineral density (BMD) over time income. Of 25 symptoms attributed to HIV over the 46-day EMA, fatigue (59%), in patients who received yearly Zoledronic acid infusions compared to those who muscle aches and pains (44%), and depression (40%) were most commonly reported received biannual denosumab infusions. The third outcome of this study is to identify for the total sample, along with /vomiting, change, fevers/chills, sweats, barriers affecting adherence to /infusion administration schedule. Design: The diarrhea and (35-30%), but only headache differed by menopause sub-group electronic medical record system, Epic, was used to conduct a retrospective chart review. (period prevalence: post = 23%; peri = 25%; pre = 70%; p = <.05). After controlling for Women ages 50-80 with documented osteoporosis who received their first infusion of co-factors, multilevel Cox regression models revealed that “having my period today” did Zoledronic acid or Denosumab at the CSWH between January 2010 and July 2016 not predict any of these HIV-endorsed symptoms, but HIV symptom profiles differed were included in the study. Adherence rates were monitored from the time of initial by menopause stage: the postmenopause stage predicted a greater likelihood for fatigue, infusion until July 2018. Non-adherence is defined as failure to receive treatment within muscle aches and pains, nausea/vomiting and diarrhea (vs peri or premenopause). 30 days of scheduled dose unless otherwise instructed by the prescribing physician. HIV-related depression was predicted by the peri (vs post) stage, while change in appetite Dosing schedules were as follows: annual Zoledronic acid infusion and Denosumab was predicted by both peri and pre (vs post) menopause. Women also simultaneously injection every six months. Available T-scores were extracted from up to two DXA bone endorsed fatigue (58%), depression (49%), muscle aches and pains (44%), fevers,/ density reports along with self-reported demographics and risk factors for osteoporosis. chills/sweats (29%) as common reproductive symptoms; but only muscle aches and For patients with two or more DXA scans performed on the same machine during the study period, significant changes in bone mineral density (BMD) were documented as P-63. “no significant change,” “statistically significant increase” or “statistically significant Determinants of attained estradiol levels in response to oral estradiol plus decrease” in BMD for each of the following available sites: femoral neck, total hip, progesterone therapy spine, distal 1/3 of the radius. Reasons for non-adherence were extracted from office Intira Sriprasert1,2, Howard Hodis3,4, Brian Bernick5, Sebastian Mirkin5, Wendy Mack1,4. visit documentation. Results: Sixty five patients were included in this study, 29 of them 1Preventive Medicine, Keck School of Medicine, University of Southern California, received Zoledronic Acid treatment and 36 received Denosumab. Of patients receiving Los Angeles, CA; 2Department of Obstetrics and Gynecology, Faculty of Medicine, Denosumab 61.1% were compliant with treatment regimen compared to only 31.0% Chiang Mai University, Chiang Mai, Thailand; 3Department of Medicine, Keck School of patients receiving Zoledronic Acid (P=0.002). After adjusting BMI and age, there of Medicine, University of Southern California, Los Angeles, CA; 4Atherosclerosis is no significant difference between the two treatments on BMD change at the spine Research Unit, Keck School of Medicine, University of Southern California, Los (P=0.33) or the femoral neck (P=0.12). Reasons for non-adherence were not identified in Angeles, CA; 5TherapeuticsMD, Boca Raton, FL most patients. Conclusion: Among patients being treated for osteoporosis in the CSWH Objective: Among postmenopausal women taking hormone therapy (HT), we found that patients are more likely to remain adherent to twice yearly Denosumab compared to estradiol (E2) dose and E2 levels were differently associated with change in metabolic yearly Zoledronic acid. Between treatment groups there was no significant difference in measures. As we found a weak correlation between E2 dose and E2 levels, we aimed to changes in BMD at the spine or femoral neck. More studies are need to identify barriers evaluate determinants of attained E2 levels in response to HT using REPLENISH trial to medication adherence. data. Design: REPLENISH was a randomized, double-blinded trial of an oral combined Sources of Funding: None E2 and progesterone (1/100 mg, 0.5/100 mg, 0.5/50 mg, 0.25/50 mg) agent or placebo for the treatment of postmenopausal vasomotor symptoms (The 1 mg E2/100 mg P4 dose was TM P-62. FDA approved as Bijuva ). Among women taking HT with at least 80% compliance, Determinants of estradiol level among postmenopausal women using mixed-effects linear models assessed characteristics associated with E2 levels adjusted for E2 dose and baseline E2 level. Serum E2 levels were assessed every 3 months over hormone therapy a 12-month follow-up. Potential correlated measures at baseline were age, time-since- Intira Sriprasert1,2, Naoko Kono1, Roksana Karim, PhD1,3, Howard Hodis3,4, menopause, weight, body mass index (BMI), , creatinine clearance, aspartate Wendy Mack1,3. 1Preventive Medicine, Keck School of Medicine, University of Southern aminotransferase(AST), aminotransferase(ALT), current smoking status, current California, Los Angeles, CA; 2Department of Obstetrics and Gynecology, Faculty of alcohol use, and dyslipidemia, antihypertensive, , diabetic and Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Atherosclerosis Research medications. Results: The analysis included 1173 postmenopausal women with mean Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA; (SD) age 55 (4.3) years and 5.2 (4.8) years-since-menopause. Race was significantly 4Department of Medicine, Keck School of Medicine, University of Southern California, associated with E2 levels. Higher E2 levels were significantly related to younger age, Los Angeles, CA more recent menopause, and current alcohol use, while lower E2 levels were related to Objective: The beneficial effect of hormone therapy (HT) on among current smoking. In the multivariable model, either age and time-since-menopause were postmenopausal women is related to achieved estradiol (E2) levels. Our prior analysis significantly inversely associated with E2 levels; time-since-menopause had a stronger from the Early versus Late Intervention Trial with Estradiol (ELITE) showed that E2 association with E2 levels. In the final multivariable model, E2 levels were positively levels were higher among early than late postmenopausal women. We aimed to identify associated with recent year-since-menopause and current alcohol use, and inversely determinants of E2 level among healthy women using HT. Design: ELITE was a associated with current smoking. Conclusion: Adjusting for E2 dose and baseline E2 randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy level, on-trial E2 levels were significantly associated with time-since-menopause, current postmenopausal women stratified by time-since-menopause. In ELITE participants who smoking and current alcohol use. As E2 levels were associated with beneficial metabolic were at least 80% compliant to the HT intervention, we used mixed-effects linear models effects in REPLENISH, other factors may enhance or limit the HT effect on metabolic to identify factors associated with on-trial serum E2 levels assessed every 6 months measures. over a median follow-up of 4.8 years adjusted for baseline E2 level. Possible correlates Sources of Funding: TherapeuticsMD unrestricted research grant were age, time-since-menopause, race, weight, body mass index (BMI), menopause type Univariate and multivariate association of on-trial estradiol level with demographic and (natural vs surgical), creatinine, creatinine clearance, aspartate aminotransferase(AST), clinical characteristics alanine aminotransferase(ALT), glucose, smoking status, alcohol use, physical activity, multivitamin use and dyslipidemia, antihypertensive, anticonvulsant, antifungal and diabetic medication. Results: The analysis included 1039 E2 measurements in 256 postmenopausal women (118 early and 138 late postmenopause). Mean age (SD) was 55.4 (3.9) vs 64.4 (5.5) years and mean time-since-menopause was 3.6 (1.8) vs 16.0 (5.6) years for early vs late postmenopausal women, respectively. Univariate analysis showed higher E2 levels with higher BMI, higher weight, higher creatinine, lower ALT, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower E2 levels. In the multivariable model, higher BMI, higher creatinine, lower ALT, surgical menopause and alcohol use were associated with higher E2 level while current smoking and antifungal medication use were associated with lower E2 level. The determinants of E2 level were similar between early and late postmenopausal women. Conclusion: Among postmenopausal women taking HT, E2 level was associated with BMI, creatinine, ALT, surgical menopause, smoking, alcohol use and antifungal medication use. These determinants of E2 level are similar in both early and late postmenopausal women. Achievement of desirable E2 levels should consider these factors in individual women. Sources of Funding: This work was supported by the National Institute on Aging, National Institutes of Health (R01-AG024154 and R01-AG059690) Multivariable association of on-trial estradiol level with demographic and clinical characteristics

Beta estimates and p-values are from mixed-effects linear model, adjusted for estradiol dose and baseline estradiol level; SE=Standard error

P-64. Modifying effect of time-since-menopause and age on the association of estradiol dose and estradiol level on coagulation measures Intira Sriprasert1,2, Howard Hodis3,4, Brian Bernick5, Sebastian Mirkin5, Wendy Mack1,4. 1 Beta estimates and p-values are from mixed-effects linear model, adjusted for Preventive Medicine, Keck School of Medicine, University of Southern California, 2 baseline estradiol level; SE=Standard error Los Angeles, CA; Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 3Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA; 4Atherosclerosis Research Unit, Keck School of Medicine, University of Southern California, Los Angeles, CA; 5TherapeuticsMD, Boca Raton, FL Objective: Hormone therapy (HT) differently affects cardiovascular risk among early or young postmenopausal women compared with late or older postmenopausal women. This study aimed to explore the modifying effect of time-since-menopause and age on the association of estradiol (E2) dose and serum E2 levels from HT on coagulation measures among postmenopausal women using data from the REPLENISH trial. Design: REPLENISH was a randomized, double-blinded, placebo-controlled, multi- and premenopausal women. Cervico-vaginal IL-1β levels were highest at baseline, center trial testing safety and efficacy of an oral combined E2 and progesterone (P4) decreased on day 14 and remained stable (postmenopausal women) or increased on day (1/100 mg,0.5/100 mg, 0.5/50 mg, 0.25/50 mg) agent or placebo in postmenopausal 28 (premenopausal women). Postmenopausal women treated with hormone therapy women (1/100 mg is approved by the FDA as BijuvaTM; TherapeuticsMD, Boca Raton, and premenopausal women had similar cervico-vaginal IL-8 and IL-1β levels (p>0.05) FL). Mixed-effects linear models tested the modifying effect of time-since-menopause (See Table). In postmenopausal women, rising serum E2 level were correlated with or age on the association of E2 dose and serum E2 level with the changes in coagulation decreases in IL-8 level from baseline to day 14 (r=-0.72, p=0.03). Conclusion: Higher parameters; prothrombin time (PT), activated partial thromboplastin time (APTT), E2 levels achieved with hormone therapy significantly decreased cervico-vaginal IL-8 antithrombin (AT), fibrinogen (FIB), protein C (PROTC), and protein S (PROTS) from level mirroring similar findings in premenopausal cycling women. Exogenous hormone 6 visits over 12 months adjusted for baseline measures and serum P4 level. Results: therapy had no effect on cervico-vaginal IL-1β concentration. Cervico-vaginal IL-8 A total of 1835 postmenopausal women with mean age (SD) of 54.6(4.3) years and changes with hormone therapy mimic those found in cycling premenopausal women. mean time-since-menopause of 5.3(4.9) years were included in the analysis. Baseline As cervico-vaginal cytokines reflect vaginal immunity, changes of cervico-vaginal characteristics among women across E2 dose groups were similar. Pearson correlation cytokines from hormone therapy may reduce risk for vaginal inflammation and infection coefficient between time-since-menopause and age was 0.54, p<0.001. With longer time- in postmenopausal women. since-menopause, higher E2 dose was associated with lower levels of all coagulation Sources of Funding: TherapeuticsMD unrestricted research grant measures tested. After adjustment for age, the significant modifying effect of time- Comparison of cervico-vaginal IL-8 level and IL-1β level by menopause status and study since-menopause on E2 dose only remained for PT, ATHRM and PROTC. With longer visit time-since-menopause, higher E2 level was associated with lower levels of PT, APTT, PROTC and PROTS. After adjustment for age, the significant modifying effect of time-since-menopause on E2 level remained only for PT. With older age, higher E2 dose was associated with lower levels of PT and FIBRINO. After adjustment for time- since-menopause, the significant modifying effect of age on E2 dose remained. With older age, higher E2 level was associated with lower levels of all coagulation measures tested. After adjustment for time-since-menopause, the significant modifying effect of age on E2 dose remained for all measures. Conclusion: Time-since-menopause significantly modified the association between E2 dose and level with coagulation measures. However, the time-since-menopause modifying effect was reduced after adjustment for age. Age significantly modified the association between E2 dose and level with coagulation measures and the significant effect remained after adjustment p-values from mixed effects model for repeated measures comparing levels for time-since-menopause. Age may be a stronger chronological parameter than time- between premenopausal women and postmenopausal women at each visit since-menopause to indicate the effect of HT on risk. Sources of Funding: TherapeuticsMD unrestricted research grant Beta estimate for interaction terms testing the modifying effect of time-since-menopause P-66. (TSM) or age on the association between estradiol (E2) dose and level with coagulation Evidence-based clinical success of treating vulvovaginal atrophy measures symptoms with a non-hormonal oil-in- cream Susana Garciadearriba, Dr.1, Manuel Häuser, Dr.1, Lisa König, Dr.1, Clarissa Masur, Dr.1, Christoph Abels, Prof.1, Petra Stute, Prof.2. 1Medical Affairs, Dr. August Wolff, Bielefeld, ; 2Department of Obstetrics and Gynecology, Frauenklinik Inselspital, Bern, Switzerland Objective: The vulvovaginal atrophy (VVA), also known as genitourinary syndrome of menopause (GSM) is a silent epidemic that occurs at any age with the prevalence being significantly higher in postmenopausal women (50%) and women treated for breast cancer (63%). With increased life expectancy, the impact of GSM on quality of life is becoming more evident in the day-to-day practice of medicine. Women are reluctant to discuss their vaginal concerns for several reasons: embarrassment, cultural taboos and especially they are unaware of the availability of non-hormonal successful treatments. According to NAMS guidelines, the primary aim of GSM treatment is to alleviate subjective symptoms (vaginal dryness, itching, burning, pain independent of sexual intercourse). All these symptoms are interrelated with the vulvovaginal level of dryness. Design: Three clinical studies and more than 10 years of post-marketing experience have provided enough information for evaluating the efficacy and safety of an oil-in-water emulsion (non-hormonal cream), whose emollient properties supplying moisture and soothing lipids to the dry and sensitive skin of the vagina and external genital area, seem to relevantly benefit GSM symptoms. Results: The efficacy of the oil-in-water cream was first compared to a non-hormonal, water-based vaginal in Beta estimates of interaction term are from mixed effect model adjusted for a 12-week study with a cohort of 92 postmenopausal women suffering from GSM. baseline measure and progesterone level; Interaction p value tests interaction Subjective and objective GSM symptoms (thinning of vaginal , redness, between E2 dose or E2 level with TSM or age petechiae, and discharge) were reliably and safely reduced by both non-hormonal topical products. However, regarding GSM symptom relief, not only the non-inferiority of the P-65. cream was confirmed, but the results even indicated superiority of the cream over gel. Effect of Estradiol and Progesterone on Cervico-Vaginal Cytokines in Secondly, the efficacy of this non-hormonal vaginal cream was compared to a vaginal estriol cream (0.1%) in a clinical study of 172 postmenopausal women with GSM. All Premenopausal and Postmenopausal Women 1 2 2 2 3 subjective symptoms as well as the daily life impairment significantly improved with Intira Sriprasert , Tarita Pakrashi , Akhil Shah , Terry Jacot , Brian Bernick , both treatments (p<0.001). Non-inferiority of the non-hormonal cream with regard to Sebastian Mirkin3, David F. Archer, MD2. 1Department of Obstetrics and Gynecology, 2 the daily life impairment due to vaginal dryness was shown. Thirdly, the efficacy of Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of this non-hormonal vaginal cream was tested in 117 women undergoing breast cancer Obstetrics and Gynecology, Jones Institute for , Eastern Virginia 3 treatment. The frequency and intensity of all subjective GSM symptoms as well as the Medical School, Norfolk, VA; TherapeuticsMD, Boca Raton, FL sum score for all four objective findings significantly improved from baseline after 28 Objective: Cervico-vaginal cytokines relate to vaginal inflammation and infection as days of treatment (p<0.0001). The excellent overall safety and of this vaginal vaginal epithelial cells express many pro and anti-inflammatory mediators. This study cream was proven by less than 700 documented adverse events, which corresponds to compared the cervico-vaginal cytokine level changes between normal menstruating a rate of 0.041‰ of sold packages during the vigilance reporting period from 2008 to premenopausal women and postmenopausal women using hormone therapy; oral 2018. The most reported event was initial local burning sensation at the application. No estradiol (E2) and progesterone (P4). Design: Premenopausal women were followed serious adverse events were documented in the three studies. Conclusion: In conclusion, during one menstrual cycle with serum E2 and P4 levels and cervico-vaginal cytokines data from three clinical studies and more than 10 years of post-marketing experience measured at baseline, day 14 and day 28. Postmenopausal women were treated with guarantee the satisfaction with the efficacy and safety of the treatment with this oil- oral estradiol 1 mg/d for 14 days followed with oral E2 1 mg/d plus P4 100 mg/d for 14 in-water emulsion (non-hormonal cream), whose emollient properties efficiently days. Serum hormones and cervico-vaginal cytokines levels were measured at baseline contribute to the reduction of subjective GSM symptoms, while having an excellent and day 14 and 28 of treatment. IL-8 and IL-1β levels in cervico-vaginal lavage were safety profile. quantified by ELISA and normalized to the protein concentration. Comparison of serum Sources of Funding: None E2, serum P4, cervico-vaginal IL-8 and IL-1β levels between premenopausal and postmenopausal women were assessed with mixed effects model for repeated measures. Correlation between changes in serum E2 and P4 level with changes in cervico-vaginal cytokines levels were assessed by Pearson correlation. Results: The analysis included 9 postmenopausal and 7 premenopausal women. Cervico-vaginal IL-8 levels were highest at baseline, decreased on day 14 and remained stable thereafter for both postmenopausal P-67. year after surgery. Those who underwent surgery <45yr significantly used MHT more than those ≥45yr (90.5% vs 79.3%, respectively, (P <0.001, OR2.48; 95% CI=1.72-3.57), Withdrawn by Author but with less compliance until ≥50yr (34.4% vs 70.7%, respectively, P <0.001, OR4.69; 95% CI=3.49-6.31). The median time of long-term follow-up after surgery for MHT non-user (145 cases), MHT user until <50yr (435 cases), and MHT user until ≥50yr (420 cases) were 14yr, 8.0yr and 15.0yr, respectively (P<0.001). The median time of MHT duration in the users until <50yr and until ≥50yr was 4.0 and 7.0 years, respectively (P<0.001). After age adjustment at the follow-up time, the only significant adverse health consequence was osteopenia (32.4%, 10.6% and 21.4% in the MHT non-user, MHT user until <50yr, and MHT user until ≥50yr, respectively, P<0.001). Prevalence of breast cancer among groups was not significantly different (P =0.548). Conclusion: The majority of women used MHT with low compliance until age ≥50yr. Age at surgery <45yr or ≥45yr was a significant factor determining use and compliance of MHT. Early MHT after surgical menopause significantly prevented osteopenia. Interestingly, when comparing with MHT non-user, no significant increase risk of breast cancer among MHT users was observed in this study. Sources of Funding: None. Table 1. Long-term new health consequences of all 3 subgroups.

*P<0.001 compared with MHT non-user, **P<0.001 compared with MHT non- user (both after age-adjustment at F/U) HT = Hypertension, DM = Diabetes mellitus, DLP = Dyslipidemia, TIA = Transient ischemic attack, HD = Ischemic disease, MI = , BrCA = Breast cancer Neurological = Cognitive impairment + Dementia + Alzheimer’s disease + Parkinsonism

P-69. A Randomized Controlled Clinical Trial on Comparing the Efficacy of Soy Isoflavones and Evening Primrose Oil in Improving the Symptoms of Menopausal Filipino women seen at the Outpatient Department of a Tertiary Medical Center in Quezon City Maria Kathrina S. Timbol, Doctor of Medicine, Anna Belen I. Alensuela, Doctor of Medicine, Lylah D. Reyes, Doctor of Medicine. Obstetrics and Gynecology, Far Eastern University-Dr. Nicanor Reyes Medical Foundation, Angeles, Philippines Objective: To compare the efficacy of Soy Isoflavones and EPO in Improving the Symptoms of Menopausal Filipino women seen at the Outpatient Department of a Tertiary Medical Center in Quezon City Design: This is an Open-Label Randomized Controlled Clinical Trial involving 180 naturally menopause women randomized into two groups. There were 91 women who received 60mg isoflavones and 89 who took EPO 1,000mg per day for 6 months. Symptomatology was assessed using the Menopause Rating Scale P-68. (MRS) at baseline, first, third and six months of treatment. Results: The mean age of Menopausal hormonal therapy after surgical menopause: A retrospective the participants is 48 years old with a mean gravidity and parity of 2 and average of 1 study of compliance, long-term health consequences and breast safety to 4 years of menopause. However, after 3 months of treatment, the isoflavone group from Thailand. showed a significantly lower MRS score for the somatic symptoms as compared to Kitirat Techatraisak, MD,Ph.D, Surasak Angsuwathana, MD, Manee Rattanachaiyanont, those in the EPO group (7.0 versus 8.0, p= 0.03). The MRS score for somatic remained Prasong Tanmahasumut, MD, Suchada Indhavivadhana, MD, Thanyarat Wongwananurak, significantly lower for those who took isoflavones as compared EPO up to the 6th month MD, Pichai Leerasiri, MD, Preyaporn Jirakittidul, MD. Department of Obstetrics and of treatment (6.89 versus 7.92; p=0.02). In the same period, a significantly lower score for Gynecology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, the urogenital symptoms was also observed among women in the isoflavones arm (6.73 Thailand versus 7.60; p= 0.01). But when categorized according to severity of symptoms, there Objective: The primary objectives of this research were to study percentage of MHT was no significant difference in the proportion of participants distributed per category in Thai surgical menopause and compliance until age ≥50yr (according to Global between the 2 treatment arms. Conclusion: Soy isoflavones at 60mg per day was found Consensus Statement on MHT (2013) and NAMS hormonal therapy position statement to be more effective than EPO in improving somatic and urogenital symptoms. (2017). The secondary objective was to compare new long-term health consequences Sources of Funding: Primary Author among MHT non-users, users until age <50yr and until age ≥50yr for possible health benefits and breast safety. Design: A retrospective study of 1,000 consecutive surgically P-70. menopausal women who underwent premenopausal surgery between 1996-2012. The inclusion criteria were: women who underwent premenopausal surgery before age 50yr. Prevalence of endometrial cancer and endometrial atypical hiperplasia in If registered after age 50yr, age at surgery and pre-surgically menopausal status must be patients with postmenopausal bleeding (PMB) confirmed with a clear documented medical history of MHT use, including date starting Marta I. Tutzer, asociada. ginecologia, hospital Italiano de buenos Aires, Caba, Argentina and stopping MHT. Hospital electronic medical records as in- or out-patients must be Objective: Postmenopausal bleeding is a prevalent consultation in gynecological available for access. The exclusion criteria were: patients with initial contraindication for clinics. The most frequent etiology is endometrial atrophy, being other diagnoses MHT use were excluded. Patients with known history of cancer of any organ or system polyps, and myomas. But according to the bibliography, 90% of including borderline cancer or carcinoma in situ were also excluded. Known cases of women with endometrial cancer present with PMB and women with PMB have a 5-10% ischemic heart disease (IHD)/myocardial infarction (MI) or other major cardiovascular % (between 1-25% according to risk factors) of chance of having endometrial cancer, disorders documented at the time of preoperative evaluation were also excluded. Patients Transvaginal ultrasound is used as the initial diagnostic test and an undergoing prophylactic bilateral oophorectomy eg. BRCA1/2 carrier, familial ovarian is indicated when the thickness is greater than 4mm (as cutt off), is heterogeneously cancer etc. were also excluded. Main data analysed were: age at surgery, indication for thickened or presents with persistent bleeding. When endometria is thinner (< 4 mm) surgery, use of MHT, duration of MHT, major health consequences [HT, DM, DLP, in women with PMB is associated <1% risk of endometrial cancer; therefore, these cognitive impairment/dementia/Alzheimer disease/Parkisonism, osteopenia/osteoporosis, women are usually reassured without the need for further investigations Objectives: To IHD/MI, and breast cancer(BrCA)] during long-term follow-up. MHT non-user served assess the prevalence of malignant, pre malignant and benign pathology in those women as the control group. Results: The average age at surgery of 1,000 cases was 42.6±5.1yr. who present postmenopausal bleeding. Design: We evaluated 3439 hysteroscopies at The overall average age at follow-up was 55.1±8.9yr with the median follow-up time the Hospital Italiano de Buenos Aires Gynecology unit for postmenopausal bleeding of 12.0yr. The three most common single surgical indications were: myoma (49.8%), in a period of 18 years from 12/28/2000 until 09/25/2018. Results: Our findings were: endometriosis (13.5%) and benign ovarian cyst/tumor (8.6%). 85.5% of cases used MHT. Malignant lesions:312 endometrioid adenocarcinoma (5 endometrial carcinoma with Among MHT users, 49.1% used until age ≥50yr. Almost 90% started MHT witnin the first squamous differentiation),1 Mucinous carcinoma, 54 Papillary serous carcinoma,10 clear cell adenocacinoma,7carcinosarcomas, 8 sarcomas,6 mixed Mullerian tumor, and in a 4-week randomized cross-over study. The intervention included 2-weeks of ohers 1 3 Cervical adenocarcinoma, 16 cervical Squamous cell carcinoma 2 vaginal nighttime use of an Embr Wave, a warming and cooling device worn on the wrist, and adenocarcinoma Premalignant lesions: Atypical polips 53 Atypical hyperplasia 26 (22 was compared to a baseline period of 2 weeks (no device). All participants completed a Atipical complex hyperplasiawith, and 4 atypical simplex atypical) Malignant lesion battery of self-report questionnaires at the end of each two-week period, including the prevalence was 12,03%, endometrial carcinoma 11,3% and premalignant lesions 2,29% Insomnia Severity Index, the PROMIS Sleep Disturbance and Sleep-Related Impairment Conclusion: In patients with postmenopausal bleeding, a prevalence of malignant scales, Epworth Sleepiness Scale, and the Hot Flash Daily Interference Scale. Results: pathology similar to that reported in the international literature was found. We emphasize Wearing the Embr Wave resulted in a 28% reduction (47 vs 34 minutes, p<.05) in sleep the importance of performing diagnostic hysteroscopies in postmenopausal metrorrhagia onset latency compared to baseline as well as an increase in nighttime sleep on weekdays since it is of great value for the diagnosis of various pathologies, mainly endometrial (6.2 vs 6.7 hours) and weekends (7.0 vs 7.4 hours), p<.05. There was a significant adenocarcinoma. improvement of scores on the Insomnia Severity Index, with 28% fewer women meeting Sources of Funding: None criteria for moderate to severe insomnia while using the Embr, p<.05. Similarly, fewer women scored high (1+ SD above the mean on published norms) on the PROMIS Sleep Disturbance scale (28% vs 8%), and improvements were found on the Epworth P-71. Sleepiness Scale (7.3 vs 5.4), p<.05. Significantly fewer women also reported that hot A Phase 3 Protocol to assess the Efficacy and Safety of Estetrol (E4), a flashes interfered with their sleep (90% vs 70%) and approximately half felt control over Promising New Treatment for Menopausal Vasomotor Symptoms their nighttime hot flashes while using the Embr (5% vs 49%), p<.05. The majority of Wulf H. Utian, MD, PhD, DSc(Med), FRCOG, FACOG, FICS1, Rogerio Lobo, MD2, participants reported a positive experience, with two-thirds of women reporting that the Marie Mawet3, Mélanie Taziaux3, Maud Jost3, Ulysse Gaspard4, Jean-Michel Foidart3,4. Embr improved their thermal comfort and their ability to return to sleep after a night 1Case Western Reserve School of Medicine, Cleveland, OH; 2Columbia University waking. Conclusion: Overall, this study suggests that the Embr Wave may offer sleep Medical Center, New York, NY; 3Mithra Pharmaceuticals, Liège, Belgium; 4University benefits for perimenopausal- and menopausal-aged women who experience disruptive of Liège, Liège, Belgium nighttime hot flashes, particularly in terms of falling asleep at bedtime and perception of Objective: Estetrol (E4) is a promising natural estrogen in development by Mithra control over nighttime hot flash interference. Additional research is needed to evaluate Pharmaceuticals. Unlike other estrogens, E4 blocks activation of the membrane the benefits relative to placebo in a larger subject population. estrogen receptor α, which confers E4 a tissue specific activity with a mechanism of Sources of Funding: Johnson & Johnson Consumer Inc., Skillman, NJ, USA. action different from Selective Estrogen Receptor Modulators (SERMs). Data in pre- and postmenopausal women show that E4 alone or in combination with a progestin has minimal stimulatory effects on triglycerides, sex hormone binding globulin (SHBG), P-73. corticosteroid-binding globulin, and angiotensinogen. E4 also had minimal effects on Transitioning to the Transition: Results of a Scoping Review of the Late hemostasis markers used as surrogate markers of venous thromboembolism risk. A Reproductive Stage multicenter, randomized, placebo-controlled, double-blinded, dose-finding Phase 2 study Nancy F. Woods, BSN, MN, PhD1, Ellen S. Mitchell, BSN, PhD2. 1Biobehavioral showed that among the tested doses E4 15 mg is effective for the treatment of menopausal Nursing and Health Informatics, University of Washington, Seattle, WA; 2Family and vasomotor symptoms (VMS). Hemostasis, adrenal, lipid, and glucose parameters were Child Nursing, University of Washington, Seattle, WA not significantly affected. No unexpected adverse events were noted. Our objective is Objective: Midlife women report changes in their menstrual cycles and symptom to present the design of a Phase 3 trial to be conducted in USA and Canada. Design: experiences prior to experiencing the STRAW markers for the early menopausal Advice on the design of the planned Phase 3 program of E4 for treatment of VMS was transition. To date researchers have directed little attention to events that precede the early obtained from several experts, investigators, institutional review boards, and regulatory menopausal transition stage, the late reproductive stage. STRAW conferees defined the bodies including the FDA. Protocols for two trials have been developed, one protocol late reproductive (LR) stage as the time when fecundability begins to wane and when a for , Russia, and Latin America (E4Comfort Study I). The full protocol of the woman may begin to notice changes in her menstrual cycles. Our purpose was to examine one for the USA and Canada, presented here (E4Comfort Study II), has been submitted the scope of published peer reviewed research on the late reproductive stage, including to the FDA. Feedback is expected by Q3 2019. Results: The E4Comfort Study II is a bleeding patterns, symptoms, and women’s related experiences. Design: We employed placebo-controlled, multicenter, randomized trial to evaluate the efficacy and safety of PubMed, CINAHL, and PsychInfo searches in which the phrase “late reproductive stage” E4 for the treatment of moderate to severe VMS in postmenopausal women age 40 to 65 and “human” were used as search terms for the period from 2000-2019. We subsequently years. The trial will start with washout and screening phases including an up to 4-week completed a hand search of publications cited in articles identified by the searches and period for the assessment of VMS. Hereafter, the trial will split in two parts: an Efficacy also searched for publications from longitudinal studies of the menopausal transition Study and a Safety Study. In the Efficacy Study, approximately 600 hysterectomized or such as the Melbourne Midlife Women’s Health Project, Penn Ovarian Aging Study, non-hysterectomized subjects with ≥7 daily or ≥50 moderate to severe bothersome VMS Study of Women Across the Nation, and the Seattle Midlife Women’s Health Study. in the week before randomization will be included and receive (double blind) E4 15 mg, Two investigators reviewed each report for consensus on the summary of design, E4 20 mg, or placebo in a 1:1:1 ratio for 12 weeks, followed by long term continuous methods, and findings with respect to the late reproductive stage. Results: The PubMed treatment (40 weeks). After the end-of-trial procedures, all non-hysterectomized subjects search identified only 11 unique articles meeting search criteria. Searching PsychInfo will receive Progesterone (P4) 200 mg for 14 days. Efficacy in terms of VMS reduction and CINAHL resulted in identifying no additional published research reports. Articles (primary objective) will be assessed using the mean change in weekly frequency of identified in the search provided data related to changes in menstrual cycle length, days of moderate to severe VMS and the mean change in severity of moderate to severe VMS, both flow, amount of flow, and regularity. Identified articles included data about the prevalence from baseline to week 4 and week 12. Beyond primary objective, impact on hemostasis, and severity of symptoms such as hot flashes, anxiety, sleep disruption, incontinence, and bone turn-over, lipid and glucose metabolism, general safety, treatment satisfaction, and clusters of these symptoms. Results also included studies of inflammatory cytokines quality of life will be assessed through the 52 weeks treatment. Efficacy assessments and gene polymorphisms (AMH and AMHR2) and characteristics of the menopausal will be recorded daily in a paper diary. For non-hysterectomized subjects, endometrial transition stages and late reproductive stage. Publications of the executive summary of thickness will be measured after 3, 6, and 12 months by transvaginal ultrasound (TVUS) the Staging Reproductive Aging Workshops and a review of neuroendocrine changes and daily recordings of events. Endometrial biopsy will be performed during the late reproductive stage and the menopausal transition were also identified. with a bi-layer endometrial thickness >10 mm or persistent and/or recurrent bleeding Hand searches of publications from the longitudinal studies of the menopausal transition after 4 weeks of treatment. If endometrium is proliferative, treatment with a progestin such as the Melbourne Midlife Women’s Health Project, Penn Ovarian Aging Study, will start according to local practice/guidelines and the subject will be withdrawn. A Data Seattle Midlife Women’s Health Study and Study of Women Across the Nation included Safety Monitoring Board will monitor endometrial safety. In the Safety Study, up to 400 limited data available to promote women’s understanding of their experiences such as hysterectomized subjects seeking treatment for menopausal VMS with ≥1 moderate to bleeding patterns and symptoms in the years immediately preceding the menopausal severe VMS in the week before randomization will receive (open label) 20 mg E4 for a transition (early and late MT stages). Instead, the late reproductive stage has been studied period of 52 weeks. Safety will be assessed for up to 52 weeks. Treatment satisfaction and predominantly as a source of comparison to early transition, late transition, and early quality of life will be assessed after 4, 12, and 52 weeks. Conclusion: The E4Comfort postmenopause events. Because some of the larger longitudinal studies included women Study II is expected to start in the USA and Canada in 2019. With the expectation that as young as 35 years (vs 45 years and older), there were findings related to menstrual good efficacy and safety data will be available from the E4Comfort Study I and II trials, cycle changes as well as symptpoms in these resports. Nonetheless most of these research E4 offers a novel treatment for symptomatic postmenopausal women. reports considered the late reproductive stage as a comparison to women’s experiences Sources of Funding: Mithra Pharmaceuticals in the menopausal transition stages. Conclusion: Women who are still experiencing fairly regular menstrual cycles often report noticing subtle changes in their cycles and experience symptoms that they attribute to menopause, yet when they present these P-72. concerns to health care providers, they report being advised they are not “in menopause” Thermal comfort intervention for hot-flash related insomnia in or are not “perimenopausal,” challenging their attributions. Not surprisingly, women menopausal-aged women: A pilot study reporting these experiences indicate dissatisfaction with health care when providers Jordana Composto1,2, Erin Leichman, PhD1, Kathryn Luedtke3, Matthew Smith4, invalidate or minimize their concerns. Enlarging the scope of research about the late David Cohen-Tanugi4, Russel M. Walters, PhD3,2, Jodi Mindell, PhD1. 1Saint Joseph’s reproductive stage and translating this information to health care providers and women University, Philadelphia, PA; 2Somn, Philadelphia, PA; 3Johnson & Johnson Consumer, presents a significant challenge. Skillman, NJ; 4Embr Labs, Somerville, MA Sources of Funding: National Institute of Nursing Research Objective: To examine the effects of Embr Wave, a commercially available wrist worn device, on the nighttime thermal comfort and sleep of menopausal-aged women who experience hot flashes/night sweats and insomnia. Design: 39 women (ages 45-58, M = 52.1 years) who experienced sleep disrupting hot flashes and insomnia participated P-74. The Development and Evaluation of a Patient Decision Aid for Managing Early Surgical Menopause Nese Yuksel, BScPharm, PharmD1,2, Tasneem Siyam1, Alisha Shivji1, Sue Ross2,3. 1Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada; 2Lois Hole Hospital for Women Royal Alexandra Hospital, Edmonton, AB, Canada; 3Department of Obstetrics & Gynecology, University of Alberta, Edmonton, AB, Canada Objective: To develop and evaluate an evidence-based patient decision aid (PDA) to support women making decisions on hormone therapy (HT) to manage early surgical menopause. Design: The PDA development was guided by the Ottawa Decision Support Framework and the International Patient Decision Aid Standards and involved 3 phases: an exploratory phase to identify women’s decisional needs; a development phase to identify evidence related to treatment options and draft initial prototype; and an evaluation phase to evaluate the prototype and elicit views on acceptability in women. For exploratory and evaluation phases, we recruited women from the Edmonton Menopause Clinics. We searched Medline, TRIP, Dynamed, and others for evidence to inform the content of the PDA. Data on HT outcome probabilities were evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). A convenience sample of women who had participated in the initial focus group conducted during the exploratory phase of the decision aid were contacted to participate in one- on-one semi-structured interviews about the acceptability of the PDA. Women who agreed attended an interview between May 31 and July 19, 2018 to review the tool and Figure. Cox cumulative hazard for oxidative stress during the postmenopausal answer questions on its acceptability using a validated 9-item acceptability questionnaire. period. All phases were driven by a multidisciplinary group of researchers, clinicians and patient stakeholders to ensure women priorities were met. Results: Informed by identified needs from the exploratory phase, a prototype was drafted. The PDA has five domains: Information on surgical menopause and HT; HT outcome probabilities; patient stories; values clarification; and guidance in deliberation. Of the 31 women approached for participation, twelve participants were interviewed. Overall, participants rated the acceptability of different sections of the PDA as good or excellent (83%). Themes related to the value of the tool, context of use, dissemination and other expectations of support were identified when women were asked to share views on strengths of the PDA and areas for improvement. Conclusion: Through our systematic approach, the SheEmpowers PDA was developed to help women overcome deterrents to decision- making related to lack of knowledge, decision-making skills and involvement in therapy decisions. Evaluation of decisional effectiveness of the PDA is planned. Sources of Funding: Lois Hole Hospital through the Women and Children's Health Research Institute, Philip Cash Pharmacy Research Excellence Endowment

P-75. The relationship between postmenopausal years and oxidative stress is affected by the chronological age Martha A. Sanchez-Rodriguez, PhD1, Mariano Zacarias-Flores2, Victor Manuel Mendoza-Nuñez1. 1Unidad de Investigación en Gerontología, Facultad de Estudios Superiores Zaragoza, UNAM, Mexico City, Mexico; 2Hospital Gustavo Baz Prada, Instituto de Salud del Estado de México, Nezahualcoyotl, Mexico Objective: To determine the relationship between the postmenopausal years and the oxidative stress. Design: We carry out a longitudinal study with 93 community-dwelling women (40-69 y) from Mexico City (healthy or with controlled diabetes or hypertension) without oxidative stress (OS), divided in three groups: a) 28 premenopausal women [PRE] (48±3 y); b) 28 early postmenopausal women [early POS] (52±3 y), and c) 37 late postmenopausal women [late POS] (61±4 y). We measured plasma malondialdehyde level (MDA) by the TBARS assay, erythrocyte superoxide dismutase (SOD) and peroxidase (GPx), levels and total plasma antioxidant status (TAS) with Randox kits, also we calculated SOD/GPx ratio and antioxidant gap, as oxidative stress markers. We computed a stress score (SS) ranging from 0 to 7. All the women completed Spanish versions of the Zung Self-Rating Depression Scale or Geriatric Depression Scale, the Athens Insomnia Scale, and a structured questionnaire about pro-oxidant factors that included an item about the date of menopause, if this was the case. All evaluations were carried out every 6 months up to 2 years. The postmenopausal years after the follow-up were the underlying time scale, and the primary outcome was OS considerate as a SS ≥ 4. The women that dropout were censured. When any woman had OS, she was considerate positive, and was eliminated from the follow-up. Results: The dropout number was 8 (9%). We observed that 5 (18%) PRE women went to the early POS group, and 1 (4%) early POS passed to the late POS group after 2 years. We found a global incidence of OS of 46% (39/85); 8 (31%) of PRE women, 10 (40%) of early POS, and 21 (62%) of late POS, (p< 0.05). The Kaplan-Meier estimate of cumulative hazard indicates that the 50% of women have had OS after 11 years in postmenopausal period. The Cox proportional hazard analysis that included smoking, insomnia, sedentarism, dysthymia/depression and age, shows the age as only risk factor (p< 0.0001). The cumulative hazard indicated that the risk for OS increases after 16 years of menopause, what happens around 66 years old in Mexico (Figure). Conclusion: Our findings suggest that the OS increases with the postmenopausal years and is affected by the age, more noticeably over 65 years old. We propose that this could be mitigated with the use of lower doses of estrogen in early postmenopausal period. Sources of Funding: None