Association of calcium and vitamin D supplementation with cancer incidence and cause-specific mortality in Black women: Extended follow-up of the Women's Health Initiative calcium-vitamin D trial.

Low circulating vitamin D levels are more prevalent in Black than White individuals. We analyzed the Women's Health Initiative (WHI) calcium plus vitamin D (CaD) randomized clinical trial extended follow-up data to evaluate associations between calcium plus vitamin D supplementation and incident cancer, cardiovascular disease (CVD), and cause-specific mortality endpoints among Black women. Intent-to-treat analysis was performed. Among 3325 Black women in the CaD trial who were randomized into either daily calcium (1000 mg of calcium carbonate) plus vitamin D (400 IU D3) or placebos for an average of 7 years, there were 813 deaths, 588 incident cancers, and 837 CVD events during an average of 15.7 years of follow up (52 230 total person-years). Using Cox's proportional hazards models, we calculated hazard ratios and their confidence intervals for outcomes ascertained during the trial period, posttrial follow-up period and overall periods combined. We found that total mortality, cause-specific mortality, and total cancer incidence were almost identical between CaD and placebo groups. These results suggest that calcium plus vitamin D supplementation does not reduce risks of cancer, CVD, or other major causes of death in Black women overall and, thus, other medical, behavioral or social interventions should be considered to narrow health disparities related to these outcomes. However, other finer endpoints, such as colorectal cancer, warrants further investigation.

Association between postmenopausal vulvovaginal discomfort, vaginal microbiota, and mucosal inflammation.

BACKGROUND: Half of all postmenopausal women report symptoms of vulvar, vaginal, or urinary discomfort with substantial impact on sexual function and quality of life; underlying mechanisms leading to symptoms are poorly understood. OBJECTIVE: To examine the possibility that the vaginal microbiota and/or mucosal immune response contributes to the severity of bothersome vaginal symptoms, we conducted a substudy of samples from a randomized trial of vaginal treatment for genitourinary syndrome of menopause to compare these features between women whose symptoms improved and women whose symptoms did not improve. STUDY DESIGN: This is a secondary analysis of samples collected in a 12-week randomized trial of treatment with vaginal estradiol or moisturizer vs placebo for moderate-severe postmenopausal symptoms of vaginal discomfort. We randomly selected 20 women in each arm with ≥2-point decrease in most bothersome symptom severity (responders) and 20 matched controls with ≤1-point decrease (nonresponders). At 0, 4, and 12 weeks, we characterized vaginal microbiota (16S ribosomal RNA gene sequencing), vaginal fluid metabolites (broad-based metabolomic profiling), vaginal fluid-soluble immune markers (Meso Scale Discovery), pH, and vaginal maturation index. We compared responders with nonresponders at baseline and across all visits using linear mixed models to evaluate associations with microbiota, metabolites, and immune markers, incorporating visit and participant-specific random effects while controlling for treatment arm. RESULTS: Here, the mean age of women was 61 years (n=120), and most women (92%) were White. At enrollment, no significant differences were observed between responders and nonresponders in age, most bothersome symptom type or severity, microbiota composition or diversity, Lactobacillus dominance, metabolome, or immune markers. There was a significant decrease in diversity of the vaginal microbiota in both responders and nonresponders (P<.001) over 12 weeks. Although this change did not differ by responder status, diversity was associated with treatment arm: more women in the estradiol arm (63%) had Lactobacillus-dominant, lower diversity bacterial communities than women in the moisturizer (35%) or dual placebo (23%) arms (P=.001) at 12 weeks. The metabolome, vaginal maturation index, and measured immune markers were not associated with responder status over the 12 weeks but varied by treatment arm. CONCLUSION: Postmenopausal vaginal symptom severity was not significantly associated with vaginal microbiota or mucosal inflammatory markers in this small study. Women receiving vaginal estradiol experienced greater abundance of lactobacilli and lower vaginal pH at end of treatment.

Patient-centered change in the day-to-day impact of postmenopausal vaginal symptoms: results from a multicenter randomized trial.

BACKGROUND: Vulvovaginal symptoms, which include dryness, irritation, and pain with intercourse, are common among postmenopausal women and are associated with impaired sexual functioning and quality of life. Previous assessment of treatment strategies for these symptoms has been limited by a lack of sensitive patient-centered outcome measures that assess symptom impact on functional and quality-of-life domains. OBJECTIVE: We aimed to (1) examine change in the impact of postmenopausal vulvovaginal symptoms on multiple aspects of well-being and functioning in relation to vaginal estradiol and moisturizer treatment and (2) guide meaningful interpretation of scores on a structured-item questionnaire measure of condition-specific impact. STUDY DESIGN: Data were drawn from postmenopausal women who were enrolled in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health Vaginal Health Trial (a 12-week, double-blind, placebo-controlled randomized trial of treatment for vulvovaginal symptoms) who were assigned to vaginal 10-µg estradiol tablet plus placebo gel (n=98), vaginal moisturizer plus placebo tablet (n=97), or dual placebo (n=94). At baseline and 12-week follow up, participants completed the Day-to-Day Impact of Vaginal Aging questionnaire to assess the impact of vaginal symptoms on 4 domains (activities of daily living, emotional well-being, sexual functioning, and body image), each on a 0-4 point scale. Day-to-Day Impact of Vaginal Aging sensitivity to change was assessed by the examination of the associations between change in Day-to-Day Impact of Vaginal Aging domain scores and vulvovaginal symptom severity from baseline to 12 weeks with analysis of covariance. Within-woman and between-group minimal clinically important improvement was assessed with the use of an anchor-based approach that relates change in Day-to-Day Impact of Vaginal Aging domain scores with self-reported benefit from treatment. RESULTS: Participants in all treatment arms (n=289) demonstrated reduced impact of vulvovaginal symptoms on all domains of well-being and functioning as assessed by Day-to-Day Impact of Vaginal Aging at 12-week follow up, with no significant differences in improvement between women who were assigned to either estradiol tablet or vaginal moisturizer compared with placebo. For all Day-to-Day Impact of Vaginal Aging domains, mean impact scores were reduced when participants reported symptom improvement (-0.3 to -0.8 point change in Day-to-Day Impact of Vaginal Aging scores for <2-point symptom severity change vs -0.4 to -1.6 point change in Day-to-Day Impact of Vaginal Aging scores for 2+ point symptom severity change; all P<.001). Minimal clinically important change in Day-to-Day Impact of Vaginal Aging domain scale scores, which are anchored to self-reported meaningful benefit from treatment at 12 weeks, ranged from -0.4 to -1.3 (within-woman) and -0.2 to -0.7 (between-group). Observed change and minimal clinically important difference were largest for the sexual functioning domain. CONCLUSION: The impact of vulvovaginal symptoms on day-to-day activities, sexual function, emotional well-being, and body image may be improved with low-dose vaginal estradiol, moisturizer, or topical placebo. The Day-to-Day Impact of Vaginal Aging questionnaire demonstrates sensitivity to change with treatment of vulvovaginal symptoms, particularly Day-to-Day Impact of Vaginal Aging scales that focus on symptom impact on sexual functioning and body image. Minimal clinically important improvement in the impact of vulvovaginal symptoms as measured by the Day-to-Day Impact of Vaginal Aging can be defined with the use of these measures.

Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial.

INTRODUCTION: Clinical research and management of postmenopausal vaginal symptoms have been limited by the lack of validated measures for assessing symptom impact. AIM: To evaluate convergent-divergent validity of the Day-to-Day Impact of Vaginal Aging (DIVA) questionnaire among postmenopausal women with moderate-to-severe vulvovaginal symptoms and identify demographic and clinical factors associated with greater symptom impact. METHODS: We examined baseline data from postmenopausal women with moderate-to-severe vulvovaginal itching, pain, irritation, dryness, or pain with intercourse in a randomized trial of vaginal estradiol, moisturizer, or placebo. In addition to completing the DIVA questionnaire, participants rated the severity of their most bothersome vulvovaginal symptom, underwent assessment of vaginal pH and epithelial cytology, and completed other self-report measures including the Female Sexual Function Index (FSFI), Female Sexual Distress Scale (FSDS), and Patient Health Questionnaire-8 for depression (PHQ-8). MAIN OUTCOME MEASURE: The main outcome measures were the unadjusted correlations and multivariable-adjusted associations with 4 DIVA domain scales designed to assess symptom impact on day-to-day activities, sexual functioning, emotional well-being, and body image/self-concept on a scale of 0 to 4. RESULTS: Among 301 women, we detected moderately strong correlations between the DIVA emotional well-being scale and PHQ-8 scores (Pearson correlation coefficient [r] = 0.39) and strong correlations between the DIVA sexual functioning scale and FSFI and FSDS scores (r > 0.50). No significant correlations were detected between any DIVA scales and vaginal pH or epithelial cytology. In adjusted linear-regression analyses, greater vulvovaginal symptom severity was associated with worse DIVA scores for emotional well-being, sexual functioning, and self-concept/body image (average 0.3- to 0.5-point higher DIVA score for each 1-point difference in vulvovaginal symptom severity). Depression symptoms were associated with worse DIVA scores for activities of daily living and emotional well-being (0.2- to 0.4-point higher DIVA score for each 5- point worsening of PHQ-8 score). Women reporting recent sexual activity had lower symptom impact on sexual functioning and self-concept/body image domains (-0.3- to -0.4-point lower DIVA score with weekly sexual activity). CLINICAL IMPLICATIONS: Findings suggest that the impact of postmenopausal vaginal symptoms on functioning and well-being is greater in women with co-morbid depression symptoms and less frequent sexual activity, independent of symptom severity. STRENGTHS & LIMITATIONS: Strengths include the multicenter sample and wide array of measures. Results may not generalize to women with mild symptoms. CONCLUSION: Our results support the construct validity of the DIVA questionnaire for clinical practice and research and indicate that depression and lower frequency of sexual activity are markers of greater impact of postmenopausal vaginal symptoms on multiple dimensions of functioning and quality of life. Hunter MM, Guthrie KA, Larson JC, et al. Convergent-Divergent Validity and Correlates of the Day-to-Day Impact of Vaginal Aging Domain Scales in the MsFLASH Vaginal Health Trial. J Sex Med 2020;17:117-125.

Vitamin D with calcium supplementation and risk of atrial fibrillation in postmenopausal women.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in adults. Although vitamin D deficiency is associated with AF risk factors, retrospective studies of association with AF have shown mixed results. We sought to determine the efficacy of calcium and vitamin D (CaD) supplementation for AF prevention in a randomized trial. METHODS: We performed a secondary analysis of the Women's Health Initiative trial on CaD supplementation versus placebo. We linked participants to their Medicare claims to ascertain incident AF. RESULTS: Among 16,801 included participants, there were 1,453 (8.6%) cases of incident AF over an average of 4.5 years, at an average rate of 19.9 events per 1,000 person-years. We found no significant difference in incident AF rates between the CaD and placebo arms (hazard ratio 1.02 for CaD vs placebo, 95% CI 0.92-1.13). After multivariate adjustment, there was no significant association between baseline 25-hydroxyvitamin D serum levels and incident AF (hazard ratio 0.92 for lowest subgroup vs highest subgroup, 95% CI 0.66-1.28). CONCLUSIONS: We present the first analysis of a large randomized trial of daily vitamin D supplementation for AF prevention. We found that CaD had no effect on incidence of AF in Women's Health Initiative CaD trial participants. We also found that baseline serum 25-hydroxyvitamin D level was not predictive of long-term incident AF risk.

Facebook advertising for recruitment of midlife women with bothersome vaginal symptoms: A pilot study.

BACKGROUND: The MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) Network recruited into five randomized clinical trials (n = 100-350) through mass mailings. The fifth trial tested two interventions for postmenopausal vulvovaginal symptoms (itching, pain, irritation, dryness, or pain with sex) and thus required a high level of sensitivity to privacy concerns. For this trial, in addition to mass mailings we pilot tested a social media recruitment approach. We aimed to evaluate the feasibility of recruiting healthy midlife women with bothersome vulvovaginal symptoms to participate in the Vaginal Health Trial through Facebook advertising. METHODS: As part of a larger advertising campaign that enrolled 302 postmenopausal women for the 12-week randomized, double-blind, placebo-controlled Vaginal Health Trial from April 2016 to February 2017, Facebook advertising was used to recruit 25 participants. The target population for recruitment by mailings and by Facebook ads included women aged 50-70 years and living within 20 miles of study sites in Minneapolis, MN and Seattle, WA. Design of recruitment letters and Facebook advertisements was informed by focus group feedback. Facebook ads were displayed in the "newsfeed" of targeted users and included a link to the study website. Response rates and costs are described for both online ads and mailing. RESULTS: Facebook ads ran in Minneapolis for 28 days and in Seattle for 15 days, with ads posted and removed from the site as needed based on clinic flow and a set budget limit. Our estimated Facebook advertising reach was over 200,000 women; 461 women responded and 25 were enrolled at a cost of US$14,813. The response rate per estimated reach was 0.22%; costs were US$32 per response and US$593 per randomized participant. The social media recruitment results varied by site, showing greater effectiveness in Seattle than in Minneapolis. We mailed 277,000 recruitment letters; 2166 women responded and 277 were randomized at a cost of US$98,682. The response rate per letter sent was 0.78%; costs were US$46 per response and US$356 per randomized participant. Results varied little across sites. CONCLUSION: Recruitment to a clinical trial testing interventions for postmenopausal vaginal symptoms is feasible through social media advertising. Variability in observed effectiveness and costs may reflect the small sample sizes and limited budget of the pilot recruitment study.

Branched-chain amino acid, meat intake and risk of type 2 diabetes in the Women's Health Initiative.

Knowledge regarding association of dietary branched-chain amino acid (BCAA) and type 2 diabetes (T2D), and the contribution of BCAA from meat to the risk of T2D are scarce. We evaluated associations between dietary BCAA intake, meat intake, interaction between BCAA and meat intake and risk of T2D. Data analyses were performed for 74 155 participants aged 50-79 years at baseline from the Women's Health Initiative for up to 15 years of follow-up. We excluded from analysis participants with treated T2D, and factors potentially associated with T2D or missing covariate data. The BCAA and total meat intake was estimated from FFQ. Using Cox proportional hazards models, we assessed the relationship between BCAA intake, meat intake, and T2D, adjusting for confounders. A 20 % increment in total BCAA intake (g/d and %energy) was associated with a 7 % higher risk for T2D (hazard ratio (HR) 1·07; 95 % CI 1·05, 1·09). For total meat intake, a 20 % increment was associated with a 4 % higher risk of T2D (HR 1·04; 95 % CI 1·03, 1·05). The associations between BCAA intake and T2D were attenuated but remained significant after adjustment for total meat intake. These relations did not materially differ with or without adjustment for BMI. Our results suggest that dietary BCAA and meat intake are positively associated with T2D among postmenopausal women. The association of BCAA and diabetes risk was attenuated but remained positive after adjustment for meat intake suggesting that BCAA intake in part but not in full is contributing to the association of meat with T2D risk.

Lean body mass and risk of incident atrial fibrillation in post-menopausal women.

AIMS: High body mass index (BMI) is a risk factor for atrial fibrillation (AF). The aim of this study was to determine whether lean body mass (LBM) predicts AF. METHODS AND RESULTS: The Women's Health Initiative is a study of post-menopausal women aged 50-79 enrolled at 40 US centres from 1994 to 1998. A subset of 11 393 participants at three centres underwent dual-energy X-ray absorptiometry. Baseline demographics and clinical histories were recorded. Incident AF was identified using hospitalization records and diagnostic codes from Medicare claims. A multivariable Cox hazard regression model adjusted for demographic and clinical risk factors was used to evaluate associations between components of body composition and AF risk. After exclusion for prevalent AF or incomplete data, 8832 participants with an average age of 63.3 years remained for analysis. Over the 11.6 years of average follow-up time, 1035 women developed incident AF. After covariate adjustment, all measures of LBM were independently associated with higher rates of AF: total LBM [hazard ratio (HR) 1.24 per 5 kg increase, 95% confidence intervals (CI) 1.14-1.34], central LBM (HR 1.51 per 5 kg increase, 95% CI 1.31-1.74), and peripheral LBM (HR 1.39 per 5 kg increase, 95% CI 1.19-1.63). The association between total LBM and AF remained significant after adjustment for total fat mass (HR 1.22 per 5 kg increase, 95% CI 1.13-1.31). CONCLUSION: Greater LBM is a strong independent risk factor for AF. After adjusting for obesity-related risk factors, the risk of AF conferred by higher BMI is primarily driven by the association between LBM and AF.

Racial and ethnic differences in atrial fibrillation risk factors and predictors in women: Findings from the Women's Health Initiative.

BACKGROUND: The incidence of atrial fibrillation (AF) is higher in non-Hispanic whites (NHWs) compared with other race-ethnic groups, despite more favorable cardiovascular risk profiles. To explore reasons for this paradox, we compared the hazards of AF from traditional and other risk factors between 4 race-ethnic groups in a large cohort of postmenopausal women. METHODS: We included 114,083 NHWs, 11,876 African Americans, 5,174 Hispanics, and 3,803 Asians from the Women's Health Initiative free of AF at baseline. Women, averaging 63 years old, were followed up for incident AF using hospitalization records and diagnostic codes from Medicare claims. RESULTS: Over a mean of 13.7 years, 19,712 incident cases of AF were recorded. Despite a higher burden of hypertension, diabetes, and obesity, annual AF incidence was lower among nonwhites (0.7%, 0.4%, and 0.4% for African American, Hispanic, and Asian participants, respectively, compared with 1.2% for NHWs). The hazards of AF from hypertension, diabetes, obesity, heart failure, and coronary artery disease were similar across race-ethnic groups. Major risk factors, including hypertension, obesity, diabetes, smoking, peripheral arterial disease, coronary artery disease, and heart failure, accounted for an attributable risk of 50.3% in NHWs, 83.1% in African Americans, 65.6% in Hispanics, and 37.4% in Asians. Established AF prediction models performed comparably across race-ethnic groups. CONCLUSIONS: In this large study of postmenopausal women, traditional cardiovascular risk factors conferred a similar degree of individual risk of AF among 4 race-ethnic groups. However, major AF risk factors conferred a higher-attributable risk in African Americans and Hispanics compared with NHWs and Asians.

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.

Placebo improvement in pharmacologic treatment of menopausal hot flashes: time course, duration, and predictors.

OBJECTIVES: To characterize the time course, duration of improvement, and clinical predictors of placebo response in treatment of menopausal hot flashes. METHODS: Data were pooled from two trials conducted in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network, providing a combined placebo group (n = 247) and a combined active treatment group (n = 297). Participants recorded hot flash frequency in diaries twice daily during treatment (Weeks 0-8) and subsequent follow-up (Weeks 9-11). The primary outcome variable was clinically significant improvement, defined as a 50% or greater decrease in hot flash frequency from baseline and calculated for each week in the study. Subgroups were defined a priori using standard clinical definitions for significant improvement and partial improvement. Clinical and demographic characteristics of the participants were evaluated as predictors of improvement. RESULTS: Clinically significant improvement with placebo accrued each treatment week, with 33% significantly improved at Week 8. Of placebo responders who were improved at both Weeks 4 and 8, 77% remained clinically improved at Week 11 after treatment ended. Independent predictors of significant placebo improvement in the final multivariable model were African American race (odds ratio [OR] = 5.61, 95% confidence interval [CI] = 2.41-13.07, p < .001), current smokers (OR = 2.30, 95% CI = 1.05-5.06, p = .038), and hot flash severity in screening (OR = 1.45, 95% CI = 1.00-2.10, p = .047). CONCLUSIONS: Clinically significant improvement with placebo accrued throughout treatment with a time course similar to improvement with active drug. A meaningful number of participants in the placebo group sustained a clinically significant response after stopping placebo pills. The results suggest that nonspecific effects are important components of treatment and warrant further studies to optimize their contributions in clinical care.

Comparison of Medicare claims versus physician adjudication for identifying stroke outcomes in the Women's Health Initiative.

BACKGROUND AND PURPOSE: Many studies use medical record review for ascertaining outcomes. One large, longitudinal study, the Women's Health Initiative (WHI), ascertains strokes using participant self-report and subsequent physician review of medical records. This is resource-intensive. Herein, we assess whether Medicare data can reliably assess stroke events in the WHI. METHODS: Subjects were WHI participants with fee-for-service Medicare. Four stroke definitions were created for Medicare data using discharge diagnoses in hospitalization claims: definition 1, stroke codes in any position; definition 2, primary position stroke codes; and definitions 3 and 4, hemorrhagic and ischemic stroke codes, respectively. WHI data were randomly split into training (50%) and test sets. A concordance matrix was used to examine the agreement between WHI and Medicare stroke diagnosis. A WHI stroke and a Medicare stroke were considered a match if they occurred within ±7 days of each other. Refined analyses excluded Medicare events when medical records were unavailable for comparison. RESULTS: Training data consisted of 24 428 randomly selected participants. There were 577 WHI strokes and 557 Medicare strokes using definition 1. Of these, 478 were a match. With regard to algorithm performance, specificity was 99.7%, negative predictive value was 99.7%, sensitivity was 82.8%, positive predictive value was 85.8%, and κ=0.84. Performance was similar for test data. Whereas specificity and negative predictive value exceeded 99%, sensitivity ranged from 75% to 88% and positive predictive value ranged from 80% to 90% across stroke definitions. CONCLUSIONS: Medicare data seem useful for population-based stroke research; however, performance characteristics depend on the definition selected.

Menopausal quality of life: RCT of yoga, exercise, and omega-3 supplements.

OBJECTIVE: The purpose of this study was to determine the efficacy of 3 nonhormonal therapies for the improvement of menopause-related quality of life in women with vasomotor symptoms. STUDY DESIGN: We conducted a 12-week 3 × 2 randomized, controlled, factorial design trial. Peri- and postmenopausal women, 40-62 years old, were assigned randomly to yoga (n = 107), exercise (n = 106), or usual activity (n = 142) and also assigned randomly to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules. We performed the following interventions: (1) weekly 90-minute yoga classes with daily at-home practice, (2) individualized facility-based aerobic exercise training 3 times/week, and (3) 0.615 g omega-3 supplement, 3 times/day. The outcomes were assessed with the following scores: Menopausal Quality of Life Questionnaire (MENQOL) total and domain (vasomotor symptoms, psychosocial, physical and sexual). RESULTS: Among 355 randomly assigned women who average age was 54.7 years, 338 women (95%) completed 12-week assessments. Mean baseline vasomotor symptoms frequency was 7.6/day, and the mean baseline total MENQOL score was 3.8 (range, 1-8 from better to worse) with no between-group differences. For yoga compared to usual activity, baseline to 12-week improvements were seen for MENQOL total -0.3 (95% confidence interval, -0.6 to 0; P = .02), vasomotor symptom domain (P = .02), and sexuality domain (P = .03) scores. For women who underwent exercise and omega-3 therapy compared with control subjects, improvements in baseline to 12-week total MENQOL scores were not observed. Exercise showed benefit in the MENQOL physical domain score at 12 weeks (P = .02). CONCLUSION: All women become menopausal, and many of them seek medical advice on ways to improve quality of life; little evidence-based information exists. We found that, among healthy sedentary menopausal women, yoga appears to improve menopausal quality of life; the clinical significance of our finding is uncertain because of the modest effect.

Correlations among Core Outcomes in Menopause-recommended vasomotor symptom outcomes in MsFLASH trials.

OBJECTIVE: This study aimed to advance understanding of vasomotor symptom (VMS) outcomes measurement using pooled data from three Menopause Strategies Finding Lasting Answers to Symptoms and Health (MsFLASH) trials. METHODS: Participants self-reported VMS frequency, severity, and bother using daily diaries; completed standardized measures of VMS interference, insomnia severity, and sleep quality/disturbance; and completed four treatment satisfaction items. Analyses included descriptive statistics, Pearson correlations (baseline pooled sample, posttreatment pooled sample, posttreatment placebo only), t tests, and analysis of variance. RESULTS: Participants were mostly postmenopausal (82.9%) and a mean of 54.5 years old. VMS frequency was fairly correlated with severity, bother, and interference for pooled baseline and placebo posttreatment samples ( r values = 0.21-0.39, P values < 0.001) and moderately correlated with severity, bother, and interference for pooled posttreatment ( r values = 0.40-0.44, P values < 0.001). VMS severity, bother, and interference were moderately correlated ( r values = 0.37-0.48, P values < 0.001), with one exception. VMS severity and bother were strongly correlated ( r values = 0.90-0.92, P values < 0.001). VMS interference was moderately correlated with insomnia ( r values = 0.45-0.54, P values < 0.001) and fairly to moderately correlated with sleep quality/disturbance ( r values = 0.31-0.44, P values < 0.001). Other VMS outcomes were weakly to fairly correlated with insomnia ( r values = 0.07-0.33, P values < 0.001 to < 0.05) and sleep quality/disturbance ( r values = 0.06-0.26, P values < 0.001 to > 0.05). Greater improvement in VMS and sleep over time was associated with higher treatment satisfaction ( P values < 0.001). CONCLUSIONS: This pooled analysis advances understanding of VMS outcomes measurement and has implications for selecting measures and creating future research.

African American race but not genome-wide ancestry is negatively associated with atrial fibrillation among postmenopausal women in the Women's Health Initiative.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia in women and is associated with higher rates of stroke and death. Rates of AF are lower in African American subjects compared with European Americans, suggesting European ancestry could contribute to AF risk. METHODS: The Women's Health Initiative (WHI) Observational Study (OS) followed up 93,676 women since the mid 1990s for various cardiovascular outcomes including AF. Multivariate Cox hazard regression analysis was used to measure the association between African American race and incident AF. A total of 8,119 African American women from the WHI randomized clinical trials and OS were genotyped on the Affymetrix Human SNP Array 6.0. Genome-wide ancestry and previously reported single nucleotide polymorphisms associated with AF in European cohorts were tested for association with AF using multivariate logistic regression analyses. RESULTS: Self-reported African American race was associated with lower rates of AF (hazard ratio 0.43, 95% CI 0.32-0.60) in the OS, independent of demographic and clinical risk factors. In the genotyped cohort, there were 558 women with AF. By contrast, genome-wide European ancestry was not associated with AF. None of the single nucleotide polymorphisms previously associated with AF in European populations, including rs2200733, were associated with AF in the WHI African American cohort. CONCLUSION: African American race is significantly and inversely correlated with AF in postmenopausal women. The etiology of this association remains unclear and may be related to unidentified environmental differences. Larger studies are necessary to identify genetic determinants of AF in African Americans.

The complexity of genitourinary syndrome of menopause: number, severity, and frequency of vulvovaginal discomfort symptoms in women enrolled in a randomized trial evaluating treatment for genitourinary syndrome of menopause.

OBJECTIVE: The aim of the study is to describe the location, severity, and frequency of genitourinary symptoms in postmenopausal women enrolled in a randomized trial of treatment for vulvovaginal discomfort. METHODS: This is a post hoc analysis of enrollment responses for participants in the MsFLASH Vaginal Health Trial. Participants were asked about the severity (0-3), frequency (in days per week) and location (vulvar or vaginal) of itch, dryness, pain/soreness, irritation, as well as severity and frequency of pain with penetration, vaginal discharge, urinary incontinence, and urinary urgency. RESULTS: A total of 302 participants were enrolled, with a mean age of 60.9 ± 4.1 years. The mean number of moderate-severe vulvovaginal symptoms experienced by trial participants in the month before enrollment was 3.4 ± 1.5, with a range from 1 to 7. The most commonly reported symptom across all severity categories was vaginal dryness (285/302, 94%), but the one most frequently rated as severe was pain with vaginal penetration (121/302, 40%). Vaginal dryness was the symptom with highest frequency; 53% of participants with that symptom reported experiencing it ≥4 d/wk. For vaginal symptoms, 80% of participants (241/302) reported that at least one of these symptoms occurred during or after sex while only 43% (158/302) reported that at least one vulvar symptom occurred during or after sex. Urinary incontinence (202/302, 67%) and urinary frequency (128/302, 43%) were the two most commonly reported urinary issues. CONCLUSIONS: Our data highlight the complexity of genitourinary syndrome of menopause symptoms in quantity, severity, and frequency, suggesting that measuring distress, bother, or interference may be the most comprehensive measure.

Long-term pelvic fracture and overall mortality risk after pelvic cancer and pelvic radiation.

BACKGROUND: The association of pelvic radiation with pelvic fracture risk has not been examined in prospective cohort settings with comprehensive fracture risk assessment, cancer-free comparison populations, and long-term follow-up. Our objective is to better characterize pelvic fracture and overall mortality risks in postmenopausal women participating in the Women's Health Initiative. METHODS: A total of 135 743 Women's Health Initiative participants aged 50 to 79 years enrolled from 40 US clinical centers from 1993 to 1998 who had entry Fracture Risk Assessment Tool scores were eligible. Outcomes included pelvic cancer diagnosis, pelvic fracture occurrence, and mortality. Cox proportional hazards regression models were used to examine associations of pelvic cancer and pelvic radiation with pelvic fracture and mortality risk. RESULTS: After 17.7 years (median) follow-up, 4451 pelvic cancers, 10 139 pelvic fractures, and 33 040 deaths occurred. In multivariable analyses, women with incident pelvic cancer, compared with women who remained pelvic cancer free, had higher pelvic fracture risk (hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.11 to 1.43) and higher overall mortality risk (HR = 2.91, 95% CI = 2.77 to 3.05). Women with pelvic cancer treated with pelvic radiation, compared with women with pelvic cancer not treated with pelvic radiation, had higher pelvic fracture risk (HR = 1.98, 95% CI = 1.41 to 2.78) and higher overall mortality after pelvic cancer (HR = 1.32, 95% CI = 1.15 to 1.52). CONCLUSIONS: Postmenopausal women with pelvic cancer, especially those receiving pelvic radiation, are at higher pelvic fracture risk and higher overall mortality risk. As therapeutic advances have reduced cancer mortality, attention to and interventions for pelvic fracture prevention may be important in pelvic cancer survivors.

Association Between Insomnia, Stress Events, and Other Psychosocial Factors and Incident Atrial Fibrillation in Postmenopausal Women: Insights From the Women's Health Initiative.

Background The association between psychosocial factors and atrial fibrillation (AF) is poorly understood. Methods and Results Postmenopausal women from the Women's Health Initiative were retrospectively analyzed to identify incident AF in relation to a panel of validated psychosocial exposure variables, as assessed by multivariable Cox proportional hazard regression and hierarchical cluster analysis. Among the 83 736 women included, the average age was 63.9±7.0 years. Over an average of 10.5±6.2 years follow-up, there were 23 954 cases of incident AF. Hierarchical cluster analysis generated 2 clusters of highly correlated psychosocial variables: the Stress Cluster included stressful life events, depressive symptoms, and insomnia, and the Strain Cluster included optimism, social support, social strain, cynical hostility, and emotional expressiveness. Incident AF was associated with higher values in the Stress Cluster (hazard ratio [HR], 1.07 per unit cluster score [95% CI, 1.05-1.09]) and the Strain Cluster (HR, 1.03 per unit cluster score [95% CI, 1.00-1.05]). Of the 8 individual psychosocial predictors that were tested, insomnia (HR, 1.04 [95% CI, 1.03-1.06]) and stressful life events (HR, 1.02 [95% CI, 1.01-1.04]) were most strongly associated with increased incidence of AF in Cox regression analysis after multivariate adjustment. Subgroup analyses showed that the Strain Cluster was more strongly associated with incident AF in those with lower traditional AF risks (P for interaction=0.02) as determined by the cohorts for heart and aging research in genomic epidemiology for atrial fibrillation score. Conclusions Among postmenopausal women, 2 clusters of psychosocial stressors were found to be significantly associated with incident AF. Further research is needed to validate these associations.

Race and Ethnicity and Fracture Prediction Among Younger Postmenopausal Women in the Women's Health Initiative Study.

Importance: The best approach to identify younger postmenopausal women for osteoporosis screening is uncertain. The Fracture Risk Assessment Tool (FRAX), which includes self-identified racial and ethnic information, and the Osteoporosis Self-assessment Tool (OST), which does not, are risk assessment tools recommended by US Preventive Services Task Force guidelines to identify candidates for bone mineral density (BMD) testing in this age group. Objective: To compare the ability of FRAX vs OST to discriminate between younger postmenopausal women who do and do not experience incident fracture during a 10-year follow-up in the 4 racial and ethnic groups specified by FRAX. Design, Setting, and Participants: This cohort study of Women's Health Initiative participants included 67 169 women (baseline age range, 50-64 years) with 10 years of follow-up for major osteoporotic fracture (MOF; including hip, clinical spine, forearm, and shoulder fracture) at 40 US clinical centers. Data were collected from October 1993 to December 2008 and analyzed between May 11, 2022, and February 23, 2023. Main Outcomes and Measures: Incident MOF and BMD (in a subset of 4607 women) were assessed. The area under the receiver operating characteristic curve (AUC) for FRAX (without BMD information) and OST was calculated within each racial and ethnic category. Results: Among the 67 169 participants, mean (SD) age at baseline was 57.8 (4.1) years. A total of 1486 (2.2%) self-identified as Asian, 5927 (8.8%) as Black, 2545 (3.8%) as Hispanic, and 57 211 (85.2%) as White. During follow-up, 5594 women experienced MOF. For discrimination of MOF, AUC values for FRAX were 0.65 (95% CI, 0.58-0.71) for Asian, 0.55 (95% CI, 0.52-0.59) for Black, 0.61 (95% CI, 0.56-0.65) for Hispanic, and 0.59 (95% CI, 0.58-0.59) for White women. The AUC values for OST were 0.62 (95% CI, 0.56-0.69) for Asian, 0.53 (95% CI, 0.50-0.57) for Black, 0.58 (95% CI, 0.54-0.62) for Hispanic, and 0.55 (95% CI, 0.54-0.56) for White women. For discrimination of femoral neck osteoporosis, AUC values were excellent for OST (range, 0.79 [95% CI, 0.65-0.93] to 0.85 [95% CI, 0.74-0.96]), higher for OST than FRAX (range, 0.72 [95% CI, 0.68-0.75] to 0.74 [95% CI, 0.60-0.88]), and similar in each of the 4 racial and ethnic groups. Conclusions and Relevance: These findings suggest that within each racial and ethnic category, the US FRAX and OST have suboptimal performance in discrimination of MOF in younger postmenopausal women. In contrast, for identifying osteoporosis, OST was excellent. The US version of FRAX should not be routinely used to make screening decisions in younger postmenopausal women. Future investigations should improve existing tools or create new approaches to osteoporosis risk assessment for this age group.