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STUDY QUESTIONAre menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk?SUMMARY ANSWERIrregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers.WHAT IS KNOWN ALREADYLong and irregular menstrual cycles have been associated with lower risk of pre-menopausal breast cancer and higher risk of endometrial cancer, but associations with other malignancies are less clear.STUDY DESIGN, SIZE, DURATIONProspective cohort study. Prospective follow-up of 78 943 women participating in the Nurses’ Health Study II between 1989 and 2015.PARTICIPANTS/MATERIALS, SETTING, METHODSWe followed 78 943 pre-menopausal women without cancer history who reported the usual length and regularity of their menstrual cycles at different ages (14–17, 18–22 and 29–46 years). Cancer diagnosis was confirmed through medical record review and classified as obesity-related (colorectal, gallbladder, kidney, multiple myeloma, thyroid, pancreatic, esophageal, gastric, liver, endometrial, ovarian and post-menopausal breast) or non-obesity-related. We fitted Cox proportional hazards models to estimate hazard ratios (HRs) and 95% CIs of the association between menstrual cycle characteristics and cancer incidence.MAIN RESULTS AND THE ROLE OF CHANCEWe documented 5794 incident cancer cases during 1 646 789 person-years of follow-up. After adjusting for BMI and other potential confounders, women reporting irregular cycles at age 29–46 years had an 11% (95% CI: 2–21%) higher risk of total invasive cancer than women reporting very regular cycles at the same age. This association was limited to obesity-related cancers, with a 23% (95% CI: 9–39%) higher risk and was strongest for endometrial cancer (HR = 1.39; 95% CI: 1.09–1.77). Findings were comparable for cycle characteristics earlier in life and for menstrual cycle length. Very irregular cycles at age 14–17 years were associated with significant increase in risk of colorectal cancer (HR = 1.36; 95% CI: 1.02–1.81).LIMITATIONS, REASONS FOR CAUTIONOur study might be subject to recall bias for findings pertaining to cycle characteristics in adolescence and early adulthood, as these were retrospectively reported. Generalizability to non-White women may be limited, as 96% of participants were White.WIDER IMPLICATIONS OF THE FINDINGSWomen with irregular or long menstrual cycles in mid-adulthood had a statistically significantly higher risk of developing cancer, especially obesity-related cancers. This association was not limited to gynecological cancers. Obesity-related cancers may need to be added to the spectrum of long-term health consequences of long or irregular cycles, possibly warranting targeted screening among women who experience long or irregular cycles in mid-adulthood.STUDY FUNDING/COMPETING INTERESTThis work was supported by grants U01 CA176726, U01 HL145386 and R01 HD096033 from the National Institutes of Health. The authors have no conflicts of interest to declare.TRIAL REGISTRATION NUMBERN/A.

Genitourinary syndrome of menopause (GSM) affects nearly 50% of postmenopausal women. Yet women fail to recognize GSM as a chronic condition and are reluctant to discuss their vaginal or sexual complaints with a health care provider. This quality improvement project implemented the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire to improve the identification and diagnosis of GSM in women ≥ 45 years of age presenting for an annual wellness examination or a vulvovaginal/genitourinary complaint.From October 2019 to February 2020, the DIVA questionnaire was distributed in a large women's health practice setting to women ≥ 45 years of age, for completion before their annual wellness visit or for evaluation of a GSM-related complaint. GSM diagnosis rates during the implementation period were compared with diagnosis rates during a 4-month period immediately preceding the implementation. Data collected during the implementation period were examined to evaluate if GSM diagnosis was more likely in patients who completed the DIVA questionnaire when compared to those women who did not complete the questionnaire.Of the 175 women who met the inclusion criteria, 113 completed the DIVA questionnaire. Completion of the DIVA questionnaire demonstrated a relative percentage increase in GSM diagnosis by 30.7% when compared to the 4-month preimplementation period (10.1% to 13.2%, P = 0.231). This change was not statistically significant. During the implementation period, a statistically significant difference in GSM diagnosis was observed for patients who completed the DIVA questionnaire when compared to those patients who did not complete the questionnaire (37.2% vs 9.7%, P 0.001). When results were stratified by visit type, women presenting for an annual wellness visit who completed the DIVA questionnaire had a higher GSM diagnosis rate than those who did not complete the questionnaire (37.2% vs 10%, P 0.001). When results were stratified by menopausal status, GSM diagnosis rates were also more likely for postmenopausal women who completed the DIVA questionnaire when compared to those who did not complete the questionnaire (44.2% vs 8.5%, P 0.001).The DIVA questionnaire is a brief, but comprehensive screening tool that can increase GSM identification and treatment, particularly for postmenopausal, and midlife women presenting for an annual wellness visit in a busy women's health practice setting. : Video Summary:http://links.lww.com/MENO/A655.Video Summary:http://links.lww.com/MENO/A655.

Objective Genitourinary symptoms, such as vaginal dryness and pain with sex, are commonly experienced by postmenopausal women. Comparing treatments for these genitourinary symptoms are restricted by the use of different outcome measures in clinical trials and the omission of outcomes, which may be relevant to women. The aim of this project was to develop a Core Outcome Set (COS) to be reported in clinical trials of treatments for genitourinary symptoms associated with menopause. Methods We performed a systematic review of randomized controlled trials of treatments for genitourinary symptoms associated with menopause and extracted their outcomes. This list was refined and entered into a two-round modified Delphi survey, which was open to clinicians, researchers, and postmenopausal women from November 2019 to March 2020. Outcomes were scored on a nine-point scale from "not important" to "critically important." The final COS was determined following two international consensus meetings. Results A total of 26 unique outcomes were included in the Delphi process, which was completed by 227 participants of whom 58% were postmenopausal women, 34% clinicians, and 8% researchers. Predefined thresholds were applied to the Delphi scores to categorize outcomes by importance, which informed the e consensus meetings, attended by 43 participants from 21 countries. The final COS includes eight outcomes: (1) pain with sex, (2) vulvovaginal dryness, (3) vulvovaginal discomfort or irritation, (4) discomfort or pain when urinating, (5) change in most bothersome symptom, (6) distress, bother or interference of genitourinary symptoms, (7) satisfaction with treatment, (8) side effects of treatment. Conclusion These eight core outcomes reflect the joint priorities of postmenopausal women, clinicians, and researchers internationally. Standardized collection and reporting of these outcomes in clinical trials will facilitate the comparison of different treatments for genitourinary symptoms, advance clinical practice, and ultimately improve outcomes for symptomatic women.

Large‐scale studies have not addressed the knowledge level of US resident physicians regarding osteoporosis management. We gauged the knowledge level of family medicine, internal medicine, and obstetrics and gynecology resident physicians regarding osteoporosis management. In 2019, we sent an anonymous survey via e‐mail to all program directors of Accreditation Council for Graduate Medical Education–accredited residency programs in family medicine, internal medicine, and obstetrics and gynecology for distribution to resident physicians. Knowledge items assessed osteoporosis screening, diagnosis, and treatment. We received responses from 182 family medicine, 275 internal medicine, and 122 obstetrics and gynecology programs. Of 582 resident physician respondents, 31% were family medicine residents, 47% were internal medicine residents, and 21% were obstetrics and gynecology residents. Although 77% of respondents correctly selected the T‐score threshold for the diagnosis of osteoporosis among persons aged 50 years and older (−2.5), only 20% of respondents correctly identified minimal‐trauma hip fracture as being diagnostic of osteoporosis. One‐third of respondents correctly identified which medications were demonstrated in clinical trials to decrease hip fracture risk. Fifteen percent of respondents correctly identified that denosumab and alendronate are associated with osteonecrosis of the jaw; and 40% of respondents correctly identified that decline in bone density is more rapid after discontinuation of denosumab than after discontinuation of bisphosphonates. Less than half of resident physicians knew that bisphosphonate‐associated atypical femoral fractures are duration‐dependent. One‐quarter of respondents felt not at all prepared to manage osteoporosis. In this nationwide survey of resident physicians, knowledge regarding osteoporosis diagnosis and treatment was poor, with a striking lack of knowledge regarding the two most serious adverse effects of osteoporosis pharmacotherapy (osteonecrosis of the jaw and atypical femoral fractures). The undertreatment of osteoporosis is unlikely to improve without increased education of resident physicians. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain.This is a post-hoc analysis of data from a 12-week double-blind placebo-controlled trial that randomized postmenopausal women (ages 45-70 years) with moderate-severe genitourinary discomfort to vaginal 10 μg estradiol tablet plus placebo gel (n = 102), placebo tablet plus vaginal moisturizer (n = 100), or dual placebo (n = 100). Outcomes were proportion of sexually active women at 12 weeks, frequency of sexual activity, and pain severity with sexual activity (0-3 scale). Consistent with the original study design, comparisons were made between each active arm and the dual placebo arm.Most women enrolled in the trial, 294/302 (97%), had sufficient data to be included in this analysis. Mean age of participants was 61 years, most were white (88%), college educated (66%), and most reported sexual activity in the month before enrollment (81%). After 12 weeks of treatment, a similar proportion of women in the vaginal estrogen and dual placebo groups reported sexual activity in the past week (50% and 40%; P = 0.10) and the past month (78% and 84%, P = 0.52). Mean (standard deviation) pain with sexual activity scores at 12 weeks were similar between vaginal estrogen (1.0 [1.0]) and placebo (0.9 [0.9], P = 0.52] groups. The proportion sexually active at 12 weeks (35%) and mean (standard deviation) pain severity in the vaginal moisturizer group (1.1 [0.9]) did not differ from placebo (P = 0.36).Compared to placebo, neither low-dose vaginal estradiol nor vaginal moisturizer treatment over 12 weeks resulted in significantly greater increases in the proportions of women reporting sexual activity or improvement in pain scores with sexual activity.Clinical trials.gov: NCT02516202.

Objective This study describes women's experiences of the genitourinary syndrome of menopause (GSM) elicited through focus groups and cognitive debriefing sessions during development of a novel patient-reported outcome measure (PROM) designed for use in both clinical care and research. Methods A draft questionnaire to identify and assess bothersome genitourinary symptoms associated with estrogen deficiency in menopausal women was developed in five discrete phases from multiple sources of information in accordance with standards for PROM development. GSM was confirmed by report of symptoms in conjunction with a confirmatory pelvic examination and laboratory assessments. Results Qualitative content interviews were completed in 36 menopausal women with GSM. Cognitive testing of draft PROM items was performed in nine focus groups, including 26 menopausal women with and 15 without GSM. Participants reported a range of symptoms and described associated impacts on more than 15 quality-of-life domains. The majority of women reported that their symptoms impacted their sexual functioning and had a negative effect on their overall quality of life. GSM affected many aspects of menopausal women's lives beyond sexual function, with descriptions of pain when walking, urinating, wearing tight clothes, and with other activities of daily living. Conclusions Women's own words methodically recorded and analyzed during qualitative interviews and cognitive debriefing focus groups illuminate the subjective experience of women with GSM. It is hoped that the PROM currently in development will provide an effective tool for increasing our understanding of the prevalence, predictors, and impact of GSM in menopausal women's lives.

OBJECTIVE: To examine the associations between vaginal estrogen use and multiple health outcomes including cardiovascular disease (total myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal cancer), and hip fracture. METHODS: We included postmenopausal women from the Nurses’ Health Study (1982–2012) who were not current users of systemic hormone therapy at the start of the study or during follow-up. Vaginal estrogen use was self-reported on the biennial questionnaires. Information on incident health outcomes were self-reported and confirmed by medical records. We used Cox proportional hazards regression to model the multivariable adjusted hazard ratios and the 95% confidence intervals for vaginal estrogen use and multiple health outcomes. RESULTS: Over 18 years of follow-up, after adjusting for covariates, risks for cardiovascular disease, cancer, and hip fracture were not different between users and non-users of vaginal estrogen. No statistically significant increase in risk of any health outcome was observed with vaginal estrogen use. In sensitivity analyses, when we examined associations by hysterectomy status, the stratified results were generally similar to those for the total cohort. CONCLUSIONS: Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use, a highly effective treatment for genitourinary syndrome of menopause.

Genitourinary syndrome of menopause (GSM) describes a collection of exam findings and bothersome symptoms associated with estrogen deficiency involving changes to the labia, introitus, clitoris, vagina, urethra, and bladder. Vulvovaginal atrophy is a component of GSM. GSM is a highly prevalent medical condition with adverse effects on the health and quality of life of midlife women. There are many effective treatment options, including nonhormonal lubricants and moisturizers, physical therapy, low-dose vaginal estrogen therapy, vaginal dehydroepiandrosterone, and oral ospemifene. Despite the availability of safe and effective therapies, GSM often remains unrecognized and untreated.

There is significant interest in the use of androgen therapy for postmenopausal women. This review provides background on endogenous androgens in women, describes factors that affect circulating androgen concentrations, and examines the relationship between low levels of androgens and sexual problems. Possible effects of androgens in postmenopausal women beyond sexual function also are discussed. Clinical trials of androgen therapy for the treatment of hypoactive sexual desire disorder are reviewed, with a discussion of potential risks. A practical approach to using androgens to treat low sexual desire with associated distress is presented, accompanied by an illustrative case.

The 2017 Hormone Therapy Position Statement of The North American Menopause Society (NAMS) updates the 2012 Hormone Therapy Position Statement of The North American Menopause Society and identifies future research needs. An Advisory Panel of clinicians and researchers expert in the field of women's health and menopause was recruited by NAMS to review the 2012 Position Statement, evaluate new literature, assess the evidence, and reach consensus on recommendations, using the level of evidence to identify the strength of recommendations and the quality of the evidence. The Panel's recommendations were reviewed and approved by the NAMS Board of Trustees. Hormone therapy (HT) remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM) and has been shown to prevent bone loss and fracture. The risks of HT differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. Treatment should be individualized to identify the most appropriate HT type, dose, formulation, route of administration, and duration of use, using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of the benefits and risks of continuing or discontinuing HT. For women aged younger than 60 years or who are within 10 years of menopause onset and have no contraindications, the benefit-risk ratio is most favorable for treatment of bothersome VMS and for those at elevated risk for bone loss or fracture. For women who initiate HT more than 10 or 20 years from menopause onset or are aged 60 years or older, the benefit-risk ratio appears less favorable because of the greater absolute risks of coronary heart disease, stroke, venous thromboembolism, and dementia. Longer durations of therapy should be for documented indications such as persistent VMS or bone loss, with shared decision making and periodic reevaluation. For bothersome GSM symptoms not relieved with over-the-counter therapies and without indications for use of systemic HT, low-dose vaginal estrogen therapy or other therapies are recommended. This NAMS position statement has been endorsed by Academy of Women's Health, American Association of Clinical Endocrinologists, American Association of Nurse Practitioners, American Medical Women's Association, American Society for Reproductive Medicine, Asociación Mexicana para el Estudio del Climaterio, Association of Reproductive Health Professionals, Australasian Menopause Society, Chinese Menopause Society, Colegio Mexicano de Especialistas en Ginecologia y Obstetricia, Czech Menopause and Andropause Society, Dominican Menopause Society, European Menopause and Andropause Society, German Menopause Society, Groupe d’études de la ménopause et du vieillissement Hormonal, HealthyWomen, Indian Menopause Society, International Menopause Society, International Osteoporosis Foundation, International Society for the Study of Women's Sexual Health, Israeli Menopause Society, Japan Society of Menopause and Women's Health, Korean Society of Menopause, Menopause Research Society of Singapore, National Association of Nurse Practitioners in Women's Health, SOBRAC and FEBRASGO, SIGMA Canadian Menopause Society, Società Italiana della Menopausa, Society of Obstetricians and Gynaecologists of Canada, South African Menopause Society, Taiwanese Menopause Society, and the Thai Menopause Society. The American College of Obstetricians and Gynecologists supports the value of this clinical document as an educational tool, June 2017. The British Menopause Society supports this Position Statement.

Supplemental Digital Content is available in the text, Objective: Sexual well-being can contribute significantly to the overall quality of women's lives. This qualitative study aimed to examine sexual activity, functioning, and satisfaction in a large sample of postmenopausal women from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) Methods: Thematic analysis was used to evaluate the free-text data of the Fallowfield Sexual Activity Questionnaire (FSAQ) completed by UKCTOCS participants at baseline before annual screening. Results: A total of 24,305 women completed the baseline FSAQ and 4,525 (19%) provided free-text data, with 4,418 comments eligible for analysis. Median age was 64 years; 65% had a partner and 22.5% were sexually active. Four interrelated themes were derived: partner availability, physical and sexual health, mental well-being, and interpersonal relationships. Primary reason for absence of sexual activity was lack of a partner, mainly due to widowhood (n = 1,000). Women discussed how partner's medical condition (27%) or sexual dysfunction (13.5%), their own physical health (18%) or menopause-related symptoms (12.5%), and prescribed medication (7%) affected sexual activity. Impact of low libido in self (16%) or partner (7%), relationship problems (10.5%) or logistics (6%), and perceptions of ageing (9%) were also mentioned. Few (3%) referred to positive sexual experiences or had sought medical help for sexual problems (6%). Conclusions: This qualitative analysis explored postmenopausal women's perspective on their sexual functioning. Having an intimate partner and good physical health are key factors for continuation of sexual activity and satisfaction. Further sexual education for healthcare professionals is needed to raise awareness about sexuality and sexual difficulties in later life., Video Summary: Supplemental Digital Content 1.

A national survey was conducted to determine the extent of use of compounded hormone therapy (C-HT) and to characterize the differences between C-HT users and users of hormone therapy approved by the US Food and Drug Administration (FDA-HT users).This Internet survey enrolled 3,725 women aged 40 to 84 years who were postmenopausal or experiencing the menopause transition. The sample was weighted slightly by age, region, education, and race to reflect population attributes based on US Census data.Overall, 9% of women were current users of HT, and 28% of all respondents were ever-users of HT. C-HT users represented 31% of ever-users of HT, 35% of current users of HT, and 41% of ever-users aged 40 to 49 years. Approximately 13% of ever-users indicated current or past use of testosterone. The most cited reason for using HT was vasomotor symptoms (∼70%). Nonapproved indications for using HT were selected more often by C-HT users. There were four reports of endometrial cancer among the 326 C-HT users compared with none reported among the 738 FDA-HT users. Significance was not determined because of small numbers.This survey indicates substantial use of C-HT across the country and the possibility of higher rates of endometrial side effects with such products. There is a need for standardized data collection on the extent of use of compounded hormones and their potential risks.

Objective HIV-infected women are burdened by depression and anxiety, which may impact adherence to antiretroviral therapy and overall quality of life. Yet, little is known about the scope of psychological symptoms in the growing number of HIV-infected women reaching menopause, when affective symptoms are more prevalent in the general population. We conducted a longitudinal study to compare affective symptoms between perimenopausal HIV-infected and non-HIV-infected women. Methods The Center for Epidemiologic Studies Depression Scale (CES-D), and the Generalized Anxiety Disorder scale (GAD-7) were completed at baseline and 12 months among 33 HIV-infected and 33 non-HIV-infected perimenopausal women matched by race, age, menstrual patterns, and BMI. Linear regression models estimated the relationship of baseline GAD-7 and CES-D scores with clinical factors. Results All women were perimenopausal at baseline, and the vast majority remained perimenopausal throughout follow-up. HIV status was associated with higher baseline CES-D scores (median [interquartile range] 21 [12, 29] vs 10 [5, 14]; P = 0.03) and GAD-7 scores (7 [5, 15] vs 2 [1, 7]; P = 0.01), controlling for smoking, substance use, and antidepressant use. Depressive symptoms and anxiety remained significantly higher in the HIV-infected women at 12 months (P ≤ 0.01). Significant relationships of depressive symptoms (P = 0.048) and anxiety (P = 0.02) with hot flash severity were also observed. Conclusions Perimenopausal HIV-infected women experienced a disproportionately high level of affective symptom burden over a 12-month observation period. Given the potential for these factors to influence adherence to HIV clinical care and quality of life, careful assessment and referral for treatment of these symptoms is essential.

ObjectiveThis study aims to evaluate the effects of low-dose estradiol (E2) or venlafaxine on menopause-related quality of life and associated symptoms in healthy perimenopausal and postmenopausal women with hot flashes.MethodsA double-blind, placebo-controlled, randomized trial of low-dose oral 17β-E2 0.5 mg/day and venlafaxine XR 75 mg/day, versus identical placebo, was conducted among 339 women (aged 40-62 y) experiencing two or more vasomotor symptoms (VMS) per day (mean [SD], 8.07 [5.29]) who were recruited at three clinical sites from November 2011 to October 2012. The primary trial outcome, as reported previously, was frequency of VMS at 8 weeks. Here, we report on secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and from measures of pain (Pain, Enjoyment in life, and General activity scale), depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder Questionnaire-7), and perceived stress (Perceived Stress Scale).ResultsTreatment with both E2 and venlafaxine resulted in significantly greater improvement in quality of life, as measured by total MENQOL scores, compared with placebo (E2: mean difference at 8 wk, -0.4; 95% CI, -0.7 to -0.2; P < 0.001; venlafaxine: mean difference at 8 wk, -0.2; 95% CI, -0.5 to 0.0; P = 0.04). Quality-of-life domain analyses revealed that E2 had beneficial treatment effects on all domains of the MENQOL except for the psychosocial domain, whereas venlafaxine benefits were observed only in the psychosocial domain. Neither E2 nor venlafaxine improved pain, anxiety, or depressive symptoms, although baseline symptom levels were low. Modest benefits were observed for perceived stress with venlafaxine.ConclusionsBoth low-dose E2 and venlafaxine are effective pharmacologic agents for improving menopause-related quality of life in healthy women with VMS.

To determine the association between use of vaginal estrogen and risk of a global index event (GIE), defined as time to first occurrence of coronary heart disease (CHD), invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, or death from any cause.For this prospective observational cohort study, we used data from participants of the Women's Health Initiative Observational Study, who were recruited at 40 US clinical centers, aged 50 to 79 years at baseline and did not use systemic estrogen therapy during follow-up (n = 45,663, median follow-up 7.2 years). We collected data regarding incident CHD, invasive breast cancer, stroke, pulmonary embolism, hip fracture, colorectal cancer, endometrial cancer, death, and self-reported use of vaginal estrogen (cream, tablet). We used Cox proportional-hazards regression models to adjust for covariates.Among women with an intact uterus, the risks of stroke, invasive breast cancer, colorectal cancer, endometrial cancer, and pulmonary embolism/deep vein thrombosis were not significantly different between vaginal estrogen users and nonusers, whereas the risks of CHD, fracture, all-cause mortality, and GIE were lower in users than in nonusers (GIE adjusted hazard ratio 0.68, 95% confidence interval 0.55-0.86). Among hysterectomized women, the risks of each of the individual GIE components and of the overall GIE were not significantly different in users versus nonusers of vaginal estrogen (GIE adjusted hazard ratio 0.94, 95% confidence interval 0.70-1.26).The risks of cardiovascular disease and cancer were not elevated among postmenopausal women using vaginal estrogens, providing reassurance about the safety of treatment.

Author(s): Reed, Susan D; Mitchell, Caroline M; Joffe, Hadine; Cohen, Lee; Shifren, Jan L; Newton, Katherine M; Freeman, Ellen W; Larson, Joseph C; Manson, JoAnn E; LaCroix, Andrea Z; Guthrie, Katherine A | Abstract: ObjectiveTo evaluate sexual function in midlife women taking low-dose oral estradiol or venlafaxine for hot flushes.MethodsIn an 8-week randomized controlled trial among women aged 40-62 years, sexual function was compared between 0.5 mg oral estradiol per day or 75 mg venlafaxine per day (both compared with a placebo). Measures included composite and six domain scores from the Female Sexual Function Index and sexually related personal distress.ResultsParticipants were aged 54.6 years (standard deviation [SD] 3.8) years, 59% white, with 8.1 (SD 5.3) daily hot flushes. Median composite baseline Female Sexual Function Index score was 16.3 (SD 11.9, n=256) for all women and 21.7 (SD 9.3, n=198) among sexually active women. Composite mean Female Sexual Function Index change from baseline to week 8 was 1.4 (95% confidence interval [CI] -0.4 to 3.2) for estradiol, 1.1 (95% CI -0.5 to 2.7) for venlafaxine, and -0.3 (95% CI -1.6 to 1.0) for placebo. Composite Female Sexual Function Index and sexually related distress change from baseline did not differ between estradiol and placebo (P=.38, P=.30) or venlafaxine and placebo (P=.79, P=.48). Among sexually active women, Female Sexual Function Index domain score change from baseline differences (active compared with placebo) in desire was 0.3 (95% CI 0.0-0.6) for estradiol, -0.6 (95% CI -1.2 to 0.0) in orgasm for venlafaxine, and 0.9 (95% CI 0.2-1.6) in penetration pain for venlafaxine. No women reported adverse events related to sexual dysfunction.ConclusionOverall sexual function among nondepressed midlife women experiencing hot flushes did not change over 8 weeks with low-dose oral estradiol or venlafaxine (compared with placebo), although a subtle increase in desire (estradiol) and decreases in orgasm and pain (venlafaxine) may exist.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT01418209.Level of evidenceI.

Objective As women with HIV are living longer, more are entering the perimenopause. Prior studies suggest that HIV-infected women are more likely to have hot flashes than non-HIV-infected women. However, little is known regarding the severity and degree of interference that hot flashes have on daily function, mood, and quality of life in this population.

Testosterone declines with aging, so most midlife women have "low" testosterone levels. Because libido also declines with aging, and distressing sexual problems peak at midlife, should midlife women with low libido and associated distress be treated with testosterone? This Practice Pearl reports clinical trial evidence, reviews the risks, and explains how testosterone might be used in a clinical setting. For women who may be considering a trial of testosterone therapy, limitations and adverse effects should be disclosed and appropriate monitoring instituted once treatment has begun.

To investigate treatment seeking and utilization of women diagnosed with hypoactive sexual desire disorder (HSDD) in the clinical setting.We used interim baseline data from the ongoing HSDD Registry for Women (n = 724, enrolled at 27 clinical sites across the United States in 2008-2009). The recent diagnosis of generalized, acquired HSDD was confirmed by clinician's administration of the validated diagnostic Decreased Sexual Desire Screener. Treatment-seeking behavior was categorized as formal (discussion with a healthcare provider or use of off-label prescription treatment for HSDD) or informal/none (over-the-counter products, anonymous media, or no help seeking).Over half (n = 386, 53%) of these women with clinically diagnosed HSDD had not sought formal healthcare for their decreased sexual desire problem. Among formal healthcare seekers, 36% remained untreated, whereas 64% received some form of treatment. The most common treatments reported were nonprescription lubricants or arousal creams (36%) and off-label prescription medications (20%). Women were more likely to have sought formal help if they were married/cohabiting, were postmenopausal, had private health insurance, had5 current prescription medications, had depression symptoms, had a longer duration of sexual desire problems, or reported that the partner relationship or sense of femininity/sexual self was threatened by HSDD.In these women with HSDD, less than half had sought healthcare, but of those who had sought healthcare, almost two thirds received some form of treatment. Regardless of treatment-seeking behavior, most women had a strong desire to "feel like a normal person again" regarding sexuality, which was the most common motivating factor for treatment seeking.

Introduction. Endocrine changes during aging as well as endocrine disorders may either directly or indirectly modulate female sexual function by altering sex hormones, or by impacting on vascular, neurogenic, or psychologic factors. Aim. To review information on the impact of the hormonal changes associated with aging or those caused by endocrine disorders on female sexual function and current information on the risks and benefits of hormonal treatments. Methods. Committee members outlined topics and reviewed the published literature on endocrine aspects of female sexual function over a 2-year period. Presentation of the recommendations were presented at the International Consultation on Sexual Medicine Paris, France 2009 and revised accordingly. Main Outcome Measures. Quality of data published in the literature and recommendations were based on the GRADES system. Results. Recommendations and guidelines concerning the role of sex hormones and endocrine disorders in female sexual function were derived. Conclusions. Hormones are only one component of the many factors that contribute to normal sexual function in women. Further research is needed as to the impact of hormones and endocrine disorders on female sexual dysfunction and the benefits and risks of hormonal therapies. Wierman ME, Nappi RE, Avis N, Davis SR, Labrie F, Rosner W, and Shifren JL. Endocrine aspects of women's sexual function. J Sex Med 2010;7:561-585.

Objective With data from the population-based Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking (PRESIDE) study, which has previously estimated the prevalence of sexual problems and sexually related personal distress in United States women, the prevalence of sexual disorders of desire, arousal, and orgasm was re-estimated, taking concurrent depression into consideration. Method Current depression was defined in 3 ways as (1) self-reported symptoms alone, (2) antidepressant medication use alone, or (3) symptoms and/or antidepressant use. The unadjusted population prevalence for each distressing sexual problem in the 31,581 respondents was calculated first irrespective of concurrent depression and then in women without concurrent depression, thus determining the size of the population with both conditions present. Results The unadjusted population-based prevalence of desire disorder was 10.0% and was reduced to 6.3% for those without concurrent depression, leading to an estimate of 3.7% for those with both conditions present. The same pattern was observed for arousal and orgasm disorders, although overall prevalence estimates were lower. Conclusions Our findings indicate that about 40% of those with a sexual disorder of desire, arousal, or orgasm have concurrent depression, As this study was cross-sectional, causality versus comorbidity cannot be determined. However, our findings stress the importance of evaluating depression along with sexual problems in routine clinical practice and epidemiology research.

Introduction Sexual distress is an important component of diagnostic criteria for sexual dysfunctions, but little is known about the factors associated with sexual distress in women with low sexual desire. Aim To investigate the correlates of sexual distress in women with self-reported low sexual desire. Methods The Prevalence of Female Sexual Problems Associated with Distress and Determinants of Treatment Seeking study was a cross-sectional, nationally representative, mailed survey of U.S. adult women. There were 31,581 respondents (response rate 63.2%) to the 42-item questionnaire that measured sexual function, sexual distress, demographic, and health-related factors. Multivariable logistic regression was used to explore the correlates of distress. Main Outcome Measures Low sexual desire was defined as a response of “never” or “rarely” to the question, “How often do you desire to engage in sexual activity?” Sexual distress was measured with the Female Sexual Distress Scale (range 0–48), with a score of 15 or higher indicating presence of distress. Results Of 10,429 women with low desire, 2,868 (27.5%) had sexual distress (mean age 48.6 years, 81% with a current partner). Women without distress were 10 years older on average, and 44% had a current partner. Having a partner was strongly related to distress (odds ratio 4.6, 95% confidence interval 4.1–5.2). Other correlates were age, race, current depression, anxiety, lower social functioning, hormonal medication use, urinary incontinence, and concurrent sexual problems (arousal or orgasm). Dissatisfaction with sex life was more common in women with low desire and distress (65%) than in those without distress (20%). Conclusions Age has a curvilinear relationship with distress, and the strongest correlate of sexual distress was having a current partner. Sexual distress and dissatisfaction with sex life are strongly correlated. Distress is higher in women with low sexual desire in a partner relationship; further research on this factor is needed. Rosen RC, Shifren JL, Monz BU, Odom DM, Russo PA, and Johannes CB. Correlates of sexually related personal distress in women with low sexual desire. J Sex Med 2009;6:1549–1560.

The objective was to describe the healthcare and information-seeking behavior of women with self-reported sexual problems and accompanying sexually related personal distress identified from a large, population-based U.S. survey.Women (n = 3,239) agedor =18 years with self-reported sexual problems of desire, arousal, and/or orgasm accompanied by sexually related personal distress were identified from a cross-sectional mailed survey of 50,002 U.S. households sampled from a national research panel. Healthcare and information-seeking behavior was examined as four ordered categories: sought formal medical advice, sought informal advice, sought information from anonymous sources, and did not seek help or information. Correlates of help seeking for each type of distressing sexual problem were modeled with multivariable proportional odds regression.Just over a third of women with any distressing sexual problems had sought formal care, most often from a gynecologist or primary care physician; about 80% of the time, the woman, rather than the physician, initiated the conversation. Only 6% of women who sought medical advice scheduled a visit specifically for a sexual problem. Factors related to help seeking were having a current partner and interacting with the healthcare system. Barriers were poor self-perceived health and embarrassment about discussing sexual topics with a physician.Our results suggest inadequacies in the U.S. medical care system in addressing sexual problems in women. Gynecologists and primary care physicians, by including discussions about sexual health during routine visits, can increase the likelihood that adequate care can be offered.

To investigate the feasibility of conducting a randomized trial of the effect of acupuncture in decreasing hot flashes in peri- and postmenopausal women.Fifty-six women ages 44 to 55 with no menses in the past 3 months and at least four hot flashes per day were recruited from two clinical centers and randomized to one of three treatment groups: usual care (n = 19), sham acupuncture (n = 18), or Traditional Chinese Medicine acupuncture (n = 19). Acupuncture treatments were scheduled twice weekly for 8 consecutive weeks. The sham acupuncture group received shallow needling in nontherapeutic sites. The Traditional Chinese Medicine acupuncture group received one of four treatments based on a Traditional Chinese Medicine diagnosis. Usual care participants were instructed to not initiate any new treatments for hot flashes during the study. Daily diaries were used to track frequency and severity of hot flashes. The mean daily index score was based on the number of mild, moderate, and severe hot flashes. Follow-up analyses were adjusted for baseline values, clinical center, age, and body mass index.There was a significant decrease in mean frequency of hot flashes between weeks 1 and 8 across all groups (P = 0.01), although the differences between the three study groups were not significant. However, the two acupuncture groups showed a significantly greater decrease than the usual care group (P0.05), but did not differ from each other. Results followed a similar pattern for the hot flash index score. There were no significant effects for changes in hot flash interference, sleep, mood, health-related quality of life, or psychological well-being.These results suggest either that there is a strong placebo effect or that both traditional and sham acupuncture significantly reduce hot flash frequency.

Objective Women anticipating surgical menopause often have significant concerns regarding the effects of surgery on psychological well-being and sexuality. Results The impact of hysterectomy, often with concurrent oophorectomy, on well-being and sexuality will vary depending on many factors. These include a woman's preoperative mental health and sexual function, the indications for surgery, and the specific procedure being performed. Whether or not estrogen therapy is an option also will affect a woman's postoperative symptoms and experience of surgical menopause. Conclusions The majority of research on the effects of surgical menopause shows improved psychological well-being and sexual function after hysterectomy for benign disease. Women with depression or sexual problems preoperatively are at increased risk for experiencing a worsening of mood and libido postoperatively.

To update and expand The North American Menopause Society's evidence-based position on nonhormonal management of menopause-associated vasomotor symptoms (VMS), previously a portion of the position statement on the management of VMS.NAMS enlisted clinical and research experts in the field and a reference librarian to identify and review available evidence. Five different electronic search engines were used to cull relevant literature. Using the literature, experts created a document for final approval by the NAMS Board of Trustees.Nonhormonal management of VMS is an important consideration when hormone therapy is not an option, either because of medical contraindications or a woman's personal choice. Nonhormonal therapies include lifestyle changes, mind-body techniques, dietary management and supplements, prescription therapies, and others. The costs, time, and effort involved as well as adverse effects, lack of long-term studies, and potential interactions with medications all need to be carefully weighed against potential effectiveness during decision making.Clinicians need to be well informed about the level of evidence available for the wide array of nonhormonal management options currently available to midlife women to help prevent underuse of effective therapies or use of inappropriate or ineffective therapies. Recommended: Cognitive-behavioral therapy and, to a lesser extent, clinical hypnosis have been shown to be effective in reducing VMS. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS, although other selective serotonin reuptake/norepinephrine reuptake inhibitors, gabapentinoids, and clonidine show evidence of efficacy. Recommend with caution: Some therapies that may be beneficial for alleviating VMS are weight loss, mindfulness-based stress reduction, the S-equol derivatives of soy isoflavones, and stellate ganglion block, but additional studies of these therapies are warranted. Do not recommend at this time: There are negative, insufficient, or inconclusive data suggesting the following should not be recommended as proven therapies for managing VMS: cooling techniques, avoidance of triggers, exercise, yoga, paced respiration, relaxation, over-the-counter supplements and herbal therapies, acupuncture, calibration of neural oscillations, and chiropractic interventions. Incorporating the available evidence into clinical practice will help ensure that women receive evidence-based recommendations along with appropriate cautions for appropriate and timely management of VMS.

The Female Sexual Function Index (FSFI) is a psychometrically sound and popular 19-item self-report measure, but its length may preclude its use in studies with multiple outcome measures, especially when sexual function is not a primary endpoint. Only one attempt has been made to create a shorter scale, resulting in the Italian FSFI-6, later translated into Spanish and Korean without further psychometric analysis. Our study evaluated whether a subset of items on the 19-item English-language FSFI would perform as well as the full-length FSFI in peri- and post-menopausal women. We used baseline data from 898 peri- and post-menopausal women recruited from multiple communities, ages 42–62 years, and enrolled in randomized controlled trials for vasomotor symptom management. Goals were to (1) create a psychometrically sound, shorter version of the FSFI for use in peri- and post-menopausal women as a continuous measure and (2) compare it to the Italian FSFI-6. Results indicated that a 9-item scale provided more information than the FSFI-6 across a spectrum of sexual functioning, was able to capture sample variability, and showed sufficient range without floor or ceiling effects. All but one of the items from the Italian 6-item version were included in the 9-item version. Most omitted FSFI items focused on frequency of events or experiences. When assessment of sexual function is a secondary endpoint and subject burden related to questionnaire length is a priority, the 9-item FSFI may provide important information about sexual function in English-speaking peri- and post-menopausal women.

OBJECTIVE To evaluate the efficacy and safety of a testosterone patch for the treatment of women with hypoactive sexual desire disorder after natural menopause. DESIGN A multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted in naturally menopausal women with hypoactive sexual desire disorder receiving a stable dose of oral estrogen with or without progestin (N = 549). Women were randomized to receive testosterone 300 microg/day or placebo patches twice weekly for 24 weeks. The primary efficacy measure was change from baseline in frequency of total satisfying sexual activity over a 4-week period (weeks 21-24). RESULTS A total of 483 women (88%) were included in the primary analysis population (those with baseline sex hormone binding globulin levels < or = 160 nmol/L). The change from baseline in number of total satisfying sexual episodes was significantly greater for testosterone compared with placebo (participants with baseline sex hormone binding globulin levels < or = 160 nmol/L, mean change of 2.1 +/- 0.28 versus 0.5 +/- 0.23 episodes/4 weeks; P < 0.0001; intent-to-treat population, mean change from baseline of 1.9 +/- 0.26 versus 0.5 +/- 0.21 episodes/4 weeks, P < 0.0001). Testosterone also produced statistically significant improvements compared with placebo in all secondary efficacy measures, including sexual desire and personal distress. The testosterone patch was well tolerated. CONCLUSIONS Testosterone patch treatment increased the frequency of satisfying sexual activity and sexual desire, decreased personal distress, and was well tolerated in naturally menopausal women with hypoactive sexual desire disorder.

Evaluation of the use of testosterone therapy for hypoactive sexual desire disorder (HSDD) after oophorectomy has mostly involved women treated with oral estrogen preparations. We investigated the efficacy and safety of a testosterone patch in surgically menopausal women receiving concurrent transdermal estrogen. Women with HSDD after oophorectomy, for whom this was a concern, who were using transdermal estrogen, were recruited to a 24-week, randomized, double-blind, placebo-controlled trial in Europe and Australia. Patients were randomly allocated to placebo (n = 40) or testosterone 300 microg/day (n = 37) treatment. Primary endpoints were changes in sexual desire measured by the sexual desire domain of the Profile of Female Sexual Function and the frequency of satisfying sexual activity at 24 weeks. Sixty-one women (79%) completed the trial. All subjects who received at least one application of study medication were included in analysis. The testosterone-treated group experienced a significantly greater change from baseline in the domain sexual desire score compared with placebo (change from baseline, 16.43 versus 5.98; P = 0.02). The domain scores for arousal, orgasm, decreased sexual concerns, responsiveness, and self-image as well as decreased distress were also significantly greater with testosterone therapy than placebo. The frequency of satisfactory sexual events increased but was not statistically different between treatment groups (P = 0.06) Adverse events occurred with similar frequency in both groups, and no serious risks of therapy were observed In this study, transdermal testosterone therapy via a skin patch improved sexual desire and other sexual function domains. It was well tolerated in these oophorectomized women with HSDD receiving concomitant transdermal estrogen

HIV-infected women increasingly demonstrate insulin resistance and fat redistribution characterized by relative truncal adiposity. It is unknown whether insulin resistance and truncal adiposity are associated with features of the polycystic ovary syndrome in this population.The objective of the study was to characterize ovarian morphology and reproductive indices in a large cohort of HIV-infected women in comparison with healthy age- and body mass index-matched control subjects.The study was conducted at an academic medical center.Eighty-eight HIV-infected women were compared with 94 age- and body mass index-matched healthy control subjects.Androgen, SHBG, and gonadotropin levels and ovarian morphology were measured.HIV-infected subjects demonstrated increased visceral adipose tissue (VAT) (101 +/- 6 vs. 71 +/- 5 cm2; P0.0001), increased VAT to s.c. adipose tissue ratio, and a trend toward decreased abdominal s.c. adipose tissue. Fasting insulin (12 +/- 1 vs. 6 +/- 1 microIU/ml; P0.001) and 2-h glucose (124 +/- 4 vs. 106 +/- 4 mg/dl; P = 0.001) were also significantly increased in the HIV-infected women, compared with control subjects, respectively. Despite significant hyperinsulinemia and visceral adiposity, HIV-infected women did not demonstrate irregular menses or an increased number of small ovarian follicles (8.0 +/- 0.9 vs. 8.5 +/- 0.7 follicles; P = 0.65, HIV-infected vs. controls). Rather, SHBG (124 +/- 10 vs. 84 +/- 4 nmol/liter; P0.001) was increased significantly in HIV-infected women, and free testosterone by equilibrium dialysis was significantly reduced (2.2 +/- 0.2 vs. 2.7 +/- 0.2 pg/ml; P = 0.04), as was LH to FSH ratio (0.62 +/- 0.05 vs. 0.83 +/- 0.07; P = 0.03). Menstrual function, androgen levels, and ovarian morphology by ultrasonography were not different between HIV-infected women and healthy controls.These data demonstrate that among HIV-infected subjects with severe abdominal fat accumulation and hyperinsulinemia, common features of polycystic ovary syndrome are not seen.

Introduction Various endogenous hormones, including estrogen, testosterone, progesterone and prolactin, may influence female sexual function. Aim To provide recommendations for the diagnosis and treatment of women with endocrinologic sexual difficulties. Methods The Endocrine Aspects of Female Sexual Dysfunction Committee was part of a multidisciplinary International Consultation. It included four experts from two countries and several peer reviewers. Main Outcome Measure Expert opinion was based on committee discussion, a comprehensive literature review and evidence-based grading of available publications. Results The impact of hormones on female sexual function and their etiological roles in dysfunction is complex. Research data are limited as studies have been hampered by lack of precise hormonal assays and validated measures of sexual function in women. Sex steroid insufficiency is associated with urogenital atrophy and may also adversely affect central sexual thought processes. Systemic estrogen/estrogen progestin therapy alleviates climacteric symptoms but there is no evidence that this therapy specifically improves hypoactive sexual desire disorder (HSDD) in premenopausal or postmenopausal women. Exogenous testosterone has been shown in small randomized controlled trials (RCT) to improve sexual desire, arousal and sexual satisfaction in both premenopausal and postmenopausal women. However, as there is no biochemical measure that clearly identifies who to treat, use of exogenous testosterone should be considered only after other causes of HSDD have been excluded, such as depression, relationship problems and ill health. The clinical assessment of HSDD should include detailed medical, gynecologic, sexual and psychosocial history and physical examination including the external/internal genitalia. Hormonal therapy should be individualized and risks/benefits fully discussed, and all treated women should be carefully followed up and monitored for therapeutic side effects. Conclusions There is a need for prospective, multi-institutional clinical trials to define safe and effective endocrine treatments for female sexual dysfunction.

There are many treatment options for female sexual dysfunction (FSD), with the optimal therapy depending on the etiology of the problem. The cause of sexual dysfunction is multifactorial and may include psychological problems such as depression or anxiety disorders, conflict within the relationship, partner performance and technique, issues relating to prior abuse, medical illness, medications, fatigue, stress, or gynecological problems that make sexual activity uncomfortable. The role of low androgen concentrations in FSD is gaining increasing attention. Available therapeutic options include adjusting medications, counseling, treating depression or anxiety, reducing stress and fatigue, sex therapy, devices, estrogen therapy for genitourinary atrophy, and possibly vasoactive substances. Although no androgen therapies are currently approved by the Food and Drug Administration for FSD, they are being used in clinical practice, and early clinical trial results suggest that they may be both effective and safe in the treatment of FSD, specifically low libido. Androgen therapy should be considered primarily in women who have a physiological reason for reduced androgen concentrations, including aging, hypopituitarism, oophorectomy, or adrenal insufficiency. Products in use include oral methyltestosterone and dehydroepiandrosterone, topical testosterone ointment, and testosterone implants and injections. Products available for men, including skin patches and gels, are currently being studied at doses appropriate for women. Possible risks include hirsutism, acne, liver dysfunction, lowering of the voice, adverse lipid changes, virilization of a female fetus, and, as androgens are aromatized to estrogens, potentially the risks of estrogen therapy.

The authors examined the effect of a 4-week course of estrogen therapy on depression in perimenopausal and postmenopausal women.Twenty-two depressed women who were either perimenopausal (N=10) or postmenopausal (N=12) received open-label treatment with transdermal 17beta-estradiol (100 micro g/day) for 4 weeks. The Montgomery-Asberg Depression Rating Scale and the Beck Depression Inventory were used to assess depressive symptoms, the Greene Climacteric Scale was used to assess menopause-related symptoms, and the Clinical Global Impression (CGI) was used to assess global clinical improvement in these women at baseline and after treatment. Remission of depression was defined as a score10 on the Montgomery-Asberg Depression Rating Scale and a score/=2 on the CGI at week 4.Remission of depression was noted in eight of the 20 women who completed the study; two of these women were postmenopausal, and six were perimenopausal. Antidepressant response was not associated with severity or subtypes of depression at study entry or with concomitant improvement in menopause-related symptoms.Some perimenopausal women with depression may benefit from short-term use of estrogen therapy, and its role for postmenopausal depressed women warrants further investigation. Antidepressant benefit associated with estrogen therapy may be independent of improvement in physical symptoms.

Sexual dysfunction is an extremely common problem in the gynecologic patient population, affecting over 40% of women. There is little consensus, however, as to the appropriate treatment of women with sexual dysfunction. This review will evaluate the epidemiology and etiology of sexual dysfunction including menopause, aging, hormone deficiency, and vascular insufficiency. It will then evaluate some potential medical therapies for female sexual dysfunction in terms of their risks and benefits. It will specifically address the use of estrogen and androgen supplementation, dehydroepiandrosterone, tibolone, and sildenafil. All of these therapies have shown some benefit in select patient populations. However, large-scale, randomized placebo-controlled double-blind trials remain to be done to establish the true long-term efficacy and side effects of these interventions.

Author(s): Ensrud, Kristine E; Guthrie, Katherine A; Hohensee, Chancellor; Caan, Bette; Carpenter, Janet S; Freeman, Ellen W; LaCroix, Andrea Z; Landis, Carol A; Manson, JoAnn; Newton, Katherine M; Otte, Julie; Reed, Susan D; Shifren, Jan L; Sternfeld, Barbara; Woods, Nancy F; Joffe, Hadine | Abstract: Study objectivesDetermine effects of low-dose estradiol and low-dose venlafaxine on self-reported sleep measures in menopausal women with hot flashes.Design3-arm double-blind randomized trial. Participants assigned in a 2:2:3 ratio to 17β estradiol 0.5 mg/day (n = 97), venlafaxine XR 75 mg/day (n = 96), or placebo (n = 146) for 8 weeks.SettingAcademic research centers.Participants339 community-dwelling perimenopausal and postmenopausal women with ≥2 bothersome hot flashes per day.Measurements and resultsInsomnia symptoms (Insomnia Severity Index [ISI]) and sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at baseline, week 4 and 8; 325 women (96%) provided ISI data and 312 women (92%) provided PSQI data at baseline and follow-up. At baseline, mean (SD) hot flash frequency was 8.1/day (5.3), mean ISI was 11.1 (6.0), and mean PSQI was 7.5 (3.4). Mean (95% CI) change from baseline in ISI at week 8 was -4.1 points (-5.3 to -3.0) with estradiol, -5.0 points (-6.1 to -3.9) with venlafaxine, and -3.0 points (-3.8 to -2.3) with placebo (P overall treatment effect vs. placebo 0.09 for estradiol and 0.007 for venlafaxine). Mean (95% CI) change from baseline in PSQI at week 8 was -2.2 points (-2.8 to -1.6) with estradiol, -2.3 points (-2.9 to -1.6) with venlafaxine, and -1.2 points (-1.7 to -0.8) with placebo (P overall treatment effect vs. placebo 0.04 for estradiol and 0.06 for venlafaxine).ConclusionsAmong perimenopausal and postmenopausal women with hot flashes, both low dose oral estradiol and low-dose venlafaxine compared with placebo modestly reduced insomnia symptoms and improved subjective sleep quality.Clinical trial registrationNCT01418209 at www.clinicaltrials.gov.

Purpose: The purpose of this study is to determine if baseline antral follicle assessment may serve as additional information in predicting in vitro fertilization outcome. Methods: Prospective, descriptive preliminary study of in vitro fertilization outcome. From July 1998 to July 1999, 224 patients underwent antral follicle assessment (follicle 2–6 mm in diameter) on baseline of the planned, stimulated in vitro fertilization cycle. The outcomes were analyzed with respect to antral follicle assessment (≤6 or >6), basal cycle day 3 follicle stimulated harmone (≤10 or >10 IU/L) and maternal age (≤35 or >35 years). Results: The clinical pregnancy rate was significantly higher in the group with baseline antral follicle >6 compared to that in the group with antral follicle ≥6 (51% vs. 19%, respectively). Controlling for patient age, and basal follicle stimulated harmone, the pregnancy rate was significantly higher in the group with antral follicle >6 compared to that in the group with antral follicle ≤6. The cancellation rate was significantly increased with advancing maternal age, elevated basal follicle stimulated harmone levels, and baseline antral follicle ≤6. The cancellation rate was significantly higher in the group with antral follicle ≤6 compared to that in the group with antral follicle ≥6 (33% vs. 1%, respectively). Conclusions: In vitro fertilization outcome is strongly correlated with both maternal ages, basal cycle, day 3 follicle, stimulated harmone, and antral follicle assessment. Antral follicle assessment was a better predictor of in vitro fertilization outcome than were age or follicle stimulated harmone. Antral follicle assessment may provide a marker for ovarian age that is distinct from chronological age or hormonal markers.