Exploring the relationship between history of infertility and the experience of menopausal symptoms.

OBJECTIVE: The aim of the study is to examine longitudinal associations of history of infertility with menopausal symptoms in midlife. METHODS: Six hundred ninety-five midlife women (≥45 y old or reporting ≥12 mo of amenorrhea at the midlife visit) in Project Viva, a prospective cohort enrolled 1999-2002 during pregnancy and followed for 18 years after enrollment ("midlife visit"). Exposure was history of infertility defined as time to pregnancy ≥12 months (≥6 mo if ≥35 y), use of medical treatment to conceive, or infertility consultation or treatment in the 6-month preceding enrollment. The primary outcome was score below or above the median on the Menopause Rating Scale (MRS). Secondary outcomes included individual symptom score on the MRS and self-reported age of menopause. RESULTS: A total of 36.6% had a history of infertility in their lifetime. At the time of MRS completion, the women with prior infertility were older (53.4 [SD, 3.8] vs 51.2 [SD, 3.7] y) than those without infertility and a larger proportion had reached menopause (62% vs 40%). Women with prior infertility were more likely to score above the median on the MRS (Adjusted Odds Ratio [aOR], 1.45; 95% confidence interval [CI], 1.04-2.01) and had higher odds for reporting any depressive mood (aOR, 1.56; 95% CI, 1.12-2.16) and irritability (aOR, 1.57; 95% CI, 1.13-2.19). There was a trend toward greater severity of sleep problems among women with prior infertility. There was no association of prior infertility with report of other menopausal symptoms or age of menopause. CONCLUSIONS: Our findings suggest that women with prior infertility are more likely to have an MRS score above the median and experience depressive mood, irritability, and sleep problems during midlife than women without infertility. These findings have implications for mental health screening among midlife women.

Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.

Menstrual cycle characteristics and incident cancer: a prospective cohort study.

STUDY QUESTION: Are menstrual cycle characteristics throughout the reproductive lifespan associated with cancer risk? SUMMARY ANSWER: Irregular and long menstrual cycles throughout the reproductive lifespan were associated with increased risk of total invasive cancer, especially obesity-related cancers. WHAT IS KNOWN ALREADY: Long 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, DURATION: Prospective cohort study. Prospective follow-up of 78 943 women participating in the Nurses' Health Study II between 1989 and 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: We 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 CHANCE: We 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 CAUTION: Our 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 FINDINGS: Women 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 INTEREST: This 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 NUMBER: N/A.

Improving the identification of genitourinary syndrome of menopause through the utilization of the Day-to-Day Impact of Vaginal Aging questionnaire.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Sexual frequency and pain in a randomized clinical trial of vaginal estradiol tablets, moisturizer, and placebo in postmenopausal women.

OBJECTIVE: To evaluate the efficacy of two common interventions for bothersome postmenopausal vaginal symptoms on improving sexual frequency and pain. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: Clinical trials.gov: NCT02516202.

Women's experience of vulvovaginal symptoms associated with menopause.

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.

Vaginal estrogen use and chronic disease risk in the Nurses' Health Study.

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 nonusers 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.

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.

Androgens in postmenopausal women: a review.

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.

Female Sexual Function Index Short Version: A MsFLASH Item Response Analysis.

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 postmenopausal women. We used baseline data from 898 peri- and postmenopausal 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 postmenopausal 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 postmenopausal women.

Testosterone for midlife women: the hormone of desire?

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.

Use of compounded hormone therapy in the United States: report of The North American Menopause Society Survey.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Using an FSDS-R Item to Screen for Sexually Related Distress: A MsFLASH Analysis.

INTRODUCTION: The Female Sexual Distress Scale-Revised (FSDS-R) was created and validated to assess distress associated with impaired sexual function, but it is lengthy for use in clinical practice and research when assessing sexual function is not a primary objective. AIM: The study aims to evaluate whether a single item from the FSDS-R could be identified to use to screen midlife women for bothersome diminution in sexual function based on three criteria: (i) highly correlated with total scores; (ii) correlated with commonly assessed domains of female sexual functioning; and (iii) able to differentiate between women reporting high and low sexual concerns during the prior month. METHODS: Data from 93 midlife women were collected by the Menopause Strategies Finding Lasting Answers to Symptoms and Health (MsFLASH) research network. MAIN OUTCOME MEASURES: Women completed the FSDS-R, Female Sexual Function Index (FSFI), and Menopausal Quality of Life Scale (MENQOL). Those who reported a change in the past month on the MENQOL sexual were categorized into a high sexual concerns group, while all others were categorized into a low sexual concerns group. RESULTS: Women were an average of 54.6 years old (SD 3.1) and mostly Caucasian (77.4%), college educated (60.2%), married/living as married (64.5%), and postmenopausal (79.6%). The FSDS-R item number 1 "Distressed about sex life" was: (i) highly correlated with FSDS-R total scores (r = 0.90); (ii) moderately correlated with FSFI total scores (r = -0.38) and FSFI desire (r = -0.37) and satisfaction domains (r = -0.40); and (iii) showed one of the largest mean differences between high and low sexual concerns groups (P < 0.001). Other FSDS-R items met one or two, but not all three of the prespecified criteria (i, ii, iii). CONCLUSIONS: A single FSDS-R item may be a useful screening tool to quickly identify midlife women with sexually related distress when it is not feasible to administer the entire scale, though further validation is warranted. Carpenter JS, Reed SD, Guthrie KA, Larson JC, Newton KM, Lau RJ, Learman LA, and Shifren JL. Using an FSDS-R item to screen for sexually related distress: A MsFLASH analysis. Sex Med 2015;3:7-13.