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IntroductionClinical research and management of postmenopausal vaginal symptoms have been limited by the lack of validated measures for assessing symptom impact.AimTo 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.MethodsWe 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 measureThe 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.ResultsAmong 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 implicationsFindings 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 & limitationsStrengths include the multicenter sample and wide array of measures. Results may not generalize to women with mild symptoms.ConclusionOur 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.

ObjectiveCompare the effects of a vaginal estradiol tablet and a vaginal moisturizer, each to placebo, on menopause-related quality of life and mood in postmenopausal women with moderate-severe vulvovaginal symptoms.MethodsA total of 302 postmenopausal women enrolled in a 12-week, double-blind, placebo-controlled randomized trial were assigned to vaginal 10 μg estradiol tablet plus placebo gel (n = 102), vaginal moisturizer plus placebo tablet (n = 100), or dual placebo (n = 100). We measured change from randomization to 12 weeks in total score of the Menopause-Specific Quality of Life (MENQOL) questionnaire. We also evaluated the four MENQOL domains, depressive symptoms as measured by the Patient Health Questionnaire 8, and anxiety symptoms as measured by the Generalized Anxiety Disorder (GAD-7) questionnaire.ResultsTreatment with vaginal estradiol resulted in significantly greater improvement in total MENQOL scores compared to dual placebo (mean difference between arms -0.3 at 12 weeks (95% confidence interval [CI] -0.5, 0.0; P = 0.01). A statistically significant group mean difference favoring vaginal estradiol was observed for the MENQOL sexual function domain (-0.4 at 12 weeks; 95% CI -1.0, 0.1; P = 0.005), but not for any of the other domains. Treatment with vaginal moisturizer did not provide greater improvement compared to placebo in total MENQOL scores (mean difference 0.2 at 12 weeks; 95% CI -0.1, 0.4; P = 0.38) or in any of the MENQOL domains. Neither treatment group showed improvement compared with placebo in the Patient Health Questionnaire 8 or Generalized Anxiety Disorder Questionnaire .ConclusionsTreatment with low-dose vaginal estradiol, but not vaginal moisturizer, modestly improved menopause-related quality of life and sexual function domain scores in postmenopausal women with moderate-severe vulvovaginal symptoms.

ObjectiveCompare the effects of a vaginal estradiol tablet and a vaginal moisturizer, each to placebo, on menopause-related quality of life and mood in postmenopausal women with moderate-severe vulvovaginal symptoms.MethodsA total of 302 postmenopausal women enrolled in a 12-week, double-blind, placebo-controlled randomized trial were assigned to vaginal 10 μg estradiol tablet plus placebo gel (n = 102), vaginal moisturizer plus placebo tablet (n = 100), or dual placebo (n = 100). We measured change from randomization to 12 weeks in total score of the Menopause-Specific Quality of Life (MENQOL) questionnaire. We also evaluated the four MENQOL domains, depressive symptoms as measured by the Patient Health Questionnaire 8, and anxiety symptoms as measured by the Generalized Anxiety Disorder (GAD-7) questionnaire.ResultsTreatment with vaginal estradiol resulted in significantly greater improvement in total MENQOL scores compared to dual placebo (mean difference between arms -0.3 at 12 weeks (95% confidence interval [CI] -0.5, 0.0; P = 0.01). A statistically significant group mean difference favoring vaginal estradiol was observed for the MENQOL sexual function domain (-0.4 at 12 weeks; 95% CI -1.0, 0.1; P = 0.005), but not for any of the other domains. Treatment with vaginal moisturizer did not provide greater improvement compared to placebo in total MENQOL scores (mean difference 0.2 at 12 weeks; 95% CI -0.1, 0.4; P = 0.38) or in any of the MENQOL domains. Neither treatment group showed improvement compared with placebo in the Patient Health Questionnaire 8 or Generalized Anxiety Disorder Questionnaire .ConclusionsTreatment with low-dose vaginal estradiol, but not vaginal moisturizer, modestly improved menopause-related quality of life and sexual function domain scores in postmenopausal women with moderate-severe vulvovaginal symptoms.

OBJECTIVE:The aim of the study was to identify associations between improvement in genitourinary symptoms of menopause (GSM) and vaginal microbiota, vaginal glycogen, and serum estrogen. METHODS:Thirty postmenopausal women enrolled in a hot flash treatment trial (oral estradiol vs venlafaxine vs placebo) who reported GSM and provided vaginal swabs at 0, 4, and 8 weeks were studied. Bacterial communities were characterized using deep sequencing targeting the 16S rRNA gene V3-V4 region. Participants selected a most bothersome genitourinary symptom (dryness, discharge, pain, itch/burn, or inability to have sex) and rated severity on a 10-point scale at baseline and 8 weeks. Vaginal glycogen and serum estradiol and estrone were measured at enrollment and 8 weeks. Comparisons according to improvement in most bothersome symptom (MBS) were made using χ, Wilcoxon signed-rank test, or Hotelling's t test. RESULTS:Of 30 participants, 21 (70%) had improvement in MBS over the 8-week study and 9 (30%) had no improvement or worsening of MBS. A higher proportion of women receiving estradiol or venlafaxine reported improvement in MBS (88%, 78%) compared with placebo (54%; P = 0.28). MBS improvement was associated with Lactobacillus-dominant vaginal microbiota at enrollment (57% vs 22%, P = 0.08). Vaginal glycogen, serum estradiol, and estrone significantly increased in women whose MBS improved. CONCLUSIONS:A larger proportion of women whose MBS improved had a Lactobacillus dominant microbiota at enrollment than those who had no improvement during the trial, though this difference was not statistically significant. Larger trials are needed to determine whether vaginal microbiota modify or mediate treatment responses in women with GSM.

IMPORTANCE:Nearly half of postmenopausal women report bothersome vulvovaginal symptoms, but few data support the efficacy of 2 commonly recommended treatments.OBJECTIVE:To compare the efficacy of a low-dose vaginal estradiol tablet and a vaginal moisturizer, each vs placebo, for treatment of moderate-to-severe postmenopausal vulvovaginal symptoms.DESIGN, SETTING, AND PARTICIPANTS:This 12-week multicenter randomized clinical trial enrolled postmenopausal women with moderate to severe symptoms of vulvovaginal itching, pain, dryness, irritation, or pain with penetration.INTERVENTIONS:Vaginal 10-μg estradiol tablet (daily for 2 weeks, then twice weekly) plus placebo gel (3 times a week) (n = 102) vs placebo tablet plus vaginal moisturizer (n = 100) vs dual placebo (n = 100).MAIN OUTCOMES AND MEASURES:The main outcome was decrease in severity (0-3) of most bothersome symptom (MBS) between enrollment and 12 weeks. Additional measures included a composite vaginal symptom score, Female Sexual Function Index (FSFI) score (2-36), modified Female Sexual Distress Score-Revised item 1, treatment satisfaction and meaningful benefit, Vaginal Maturation Index, and vaginal pH.RESULTS:The 302 women had a mean (SD) age of 61 (4) years and were primarily white (267 [88%]), college educated (200 [66%]), and sexually active (245 [81%]). Most women (294 [97%]) provided data for the primary analysis. The most commonly reported MBS was pain with vaginal penetration (182 [60%]), followed by vulvovaginal dryness (63 [21%]). Mean baseline MBS severity was similar between treatment groups: estradiol, 2.4 (95% CI, 2.3 to 2.6); moisturizer, 2.5 (95% CI, 2.3 to 2.6); placebo, 2.5 (95% CI, 2.4 to 2.6). All treatment groups had similar mean reductions in MBS severity over 12 weeks: estradiol, -1.4 (95% CI, -1.6 to -1.2); moisturizer, -1.2 (95% CI, -1.4 to -1.0); and placebo, -1.3 (95% CI, -1.5 to -1.1). No significant differences were seen between estradiol (P = .25) or moisturizer (P = .31) compared with placebo. Mean total FSFI improvement was similar between estradiol (5.4; 95% CI, 4.0 to 6.9) and placebo (4.5; 95% CI, 2.8 to 6.1) (P = .64), and between moisturizer (3.1; 95% CI, 1.7 to 4.5) and placebo (P = .17).CONCLUSIONS AND RELEVANCE:Our results suggest that neither prescribed vaginal estradiol tablet nor over-the-counter vaginal moisturizer provides additional benefit over placebo vaginal tablet and gel in reducing postmenopausal vulvovaginal symptoms.

Study objectivesThe Menopause Strategies: Finding Lasting Answers for Symptoms and Health network conducted three randomized clinical trials (RCTs) testing six interventions treating vasomotor symptoms (VMS), and also collected self-reported sleep outcomes. A fourth RCT assessed an intervention for insomnia symptoms among women with VMS. We describe these seven interventions' effects relative to control in women with comparably severe insomnia symptoms and VMS.MethodsWe analyzed pooled individual-level data from 546 peri- and postmenopausal women with Insomnia Severity Index (ISI) ≥ 12, and ≥14 bothersome VMS/week across the four RCTs. Interventions included the following: escitalopram 10-20 mg/day; yoga; aerobic exercise; 1.8 g/day omega-3 fatty acids; oral 17-beta-estradiol 0.5-mg/day; venlafaxine XR 75-mg/day; and cognitive behavioral therapy for insomnia (CBT-I). Outcome measures were ISI and Pittsburgh Sleep Quality Index (PSQI) over 8-12 weeks of treatment.ResultsCBT-I produced the greatest reduction in ISI from baseline relative to control at -5.2 points (95% CI -7.0 to -3.4). Effects on ISI were similar for exercise at -2.1 and venlafaxine at -2.3 points. Comparably small decreases in ISI were observed with escitalopram, yoga, and estradiol. The largest reduction in PSQI from baseline was with CBT-I at -2.7 points (-3.9 to -1.5), although PSQI decreases of 1.2 to 1.6 points were significantly better than control with escitalopram, exercise, yoga, estradiol, and venlafaxine. Omega-3 supplements did not improve insomnia symptoms.ConclusionsThis study's findings support current recommendations for CBT-I as a first line treatment in healthy midlife women with insomnia symptoms and moderately bothersome VMS.

ObjectiveTo examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.MethodsFor this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.ResultsOf the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.ConclusionsPresence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.

ObjectiveTo examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen.MethodsFor this cross-sectional study, 88 women aged 40 to 62 years, enrolled in a hot flash treatment trial, provided vaginal swabs and a blood sample at enrollment. Bacterial communities were characterized using 16S rRNA PCR and deep sequencing targeting the V3-V4 region. Quantities of Lactobacillus crispatus and Lactobacillus iners were measured using qPCR. Self-reported genitourinary symptoms included: presence and severity of individual symptoms and identification of most bothersome symptom. Glycogen was measured fluorometrically in swab eluate. Serum estradiol (E2) and estrone (E1) were measured by liquid chromatography/mass spectrometry. Associations between bacteria, symptoms, glycogen, and serum estrogens were tested by linear regression or Wilcoxon signed-rank test, adjusted for multiple comparisons. Comparisons between groups used Kruskall-Wallis or Fisher's exact test.ResultsOf the 88 women, 33 (38%) had a majority of Lactobacillus species, whereas 58 (66%) had any Lactobacillus detected. Over half (53%) reported at least one vulvovaginal symptom (most commonly dryness), but symptoms were not associated with the presence of Lactobacillus species. Women with Lactobacillus-dominant communities had higher unconjugated serum estrone, but no difference in vaginal glycogen levels, compared with those with non-Lactobacillus-dominant communities. Higher serum E2 and E1 were not associated with either higher vaginal glycogen or detection of individual genera.ConclusionsPresence of Lactobacillus-dominant vaginal microbiota was not associated with fewer vulvovaginal symptoms. Serum estrone was higher in women with Lactobacillus dominance, but vaginal-free glycogen was not associated with composition of the vaginal microbiota.

Study objectivesTo determine effects of yoga and aerobic exercise compared with usual activity on objective assessments of sleep in midlife women.MethodsSecondary analyses of a randomized controlled trial in the Menopause Strategies: Finding Lasting Answers for Symptoms and Health (MsFLASH) network conducted among 186 late transition and postmenopausal women aged 40-62 y with hot flashes. Women were randomized to 12 w of yoga, supervised aerobic exercise, or usual activity. The mean and coefficient of variation (CV) of change in actigraph sleep measures from each intervention group were compared to the usual activity group using linear regression models.ResultsBaseline values of the primary sleep measures for the entire sample were mean total sleep time (TST) = 407.5 ± 56.7 min; mean wake after sleep onset (WASO) = 54.6 ± 21.8 min; mean CV for WASO = 37.7 ± 18.7 and mean CV for number of long awakenings > 5 min = 81.5 ± 46.9. Changes in the actigraphic sleep outcomes from baseline to weeks 11-12 were small, and none differed between groups. In an exploratory analysis, women with baseline Pittsburgh Sleep Quality Index higher than 8 had significantly reduced TST-CV following yoga compared with usual activity.ConclusionsThis study adds to the currently scant literature on objective sleep outcomes from yoga and aerobic exercise interventions for this population. Although small effects on self-reported sleep quality were previously reported, the interventions had no statistically significant effects on actigraph measures, except for potentially improved sleep stability with yoga in women with poor self-reported sleep quality.

ImportanceEffective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women's specialty care settings.ObjectiveTo evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC).Design, setting, and participantsA single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted.InterventionsSix CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women's health.Main outcomes and measuresPrimary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference.ResultsAt 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, -6.1 to -3.3; P

ObjectivesHeart rate variability (HRV) reflects the integration of the parasympathetic nervous system with the rest of the body. Studies on the effects of yoga and exercise on HRV have been mixed but suggest that exercise increases HRV. We conducted a secondary analysis of the effect of yoga and exercise on HRV based on a randomized clinical trial of treatments for vasomotor symptoms in peri/post-menopausal women.DesignRandomized clinical trial of behavioral interventions in women with vasomotor symptoms (n=335), 40-62 years old from three clinical study sites.Interventions12-weeks of a yoga program, designed specifically for mid-life women, or a supervised aerobic exercise-training program with specific intensity and energy expenditure goals, compared to a usual activity group.Main outcome measuresTime and frequency domain HRV measured at baseline and at 12 weeks for 15min using Holter monitors.ResultsWomen had a median of 7.6 vasomotor symptoms per 24h. Time and frequency domain HRV measures did not change significantly in either of the intervention groups compared to the change in the usual activity group. HRV results did not differ when the analyses were restricted to post-menopausal women.ConclusionsAlthough yoga and exercise have been shown to increase parasympathetic-mediated HRV in other populations, neither intervention increased HRV in middle-aged women with vasomotor symptoms. Mixed results in previous research may be due to sample differences. Yoga and exercise likely improve short-term health in middle-aged women through mechanisms other than HRV.

ObjectiveResearch has suggested that the autonomic nervous system (ANS) is involved in the experience of vasomotor symptoms (VMS) during menopause. We examined the relationship of VMS intensity and heart rate variability (HRV), a measure of ANS function.MethodsWomen (n = 282) were recruited from three American states for a clinical trial of yoga, exercise, and omega-3 fatty acid supplements for VMS. To be eligible, women had to report at least 14 VMS per week, with some being moderate to severe. Sitting electrocardiograms were recorded for 15 min using Holter monitors at both baseline and 12-week follow-up. Time and frequency domain HRV measures were calculated. Women completed daily diary measures of VMS frequency and intensity for 2 weeks at baseline and for 1 week at the follow-up assessment 12 weeks later. Multivariable linear regression was used to assess the relationship between VMS and baseline HRV measures and to compare change in HRV with change in VMS over the 12 weeks.ResultsBaseline HRV was not associated with either VMS frequency or intensity at baseline. Change in HRV was not associated with change in VMS frequency or intensity across the follow-up.InterpretationHeart rate variability (HRV) was not associated with basal VMS frequency or intensity in perimenopausal and postmenopausal women experiencing high levels of VMS. Autonomic function may be associated with the onset or presence of VMS, but not with the number or intensity of these symptoms.

ObjectiveTo describe self-reported menopausal symptom priorities and their association with demographics and other symptoms among participants in an intervention trial for vasomotor symptoms (VMS).MethodsCross-sectional study embedded in the MsFLASH 02 trial, a three by two factorial design of yoga vs. exercise vs. usual activity and omega-3-fatty acid vs. placebo. At baseline, women (n=354) completed hot flash diaries, a card sort task to prioritize symptoms they would most like to alleviate, and standardized questionnaires.ResultsThe most common symptom priorities were: VMS (n=322), sleep (n=191), concentration (n=140), and fatigue (n=116). In multivariate models, (1) women who chose VMS as their top priority symptom (n=210) reported significantly greater VMS severity (p=0.004) and never smoking (p=0.012) and (2) women who chose sleep as their top priority symptom (n=100), were more educated (p≤0.001) and had worse sleep quality (p

ObjectiveTo describe the effects of six interventions for menopausal vasomotor symptoms relative to control in a pooled analysis, facilitating translation of the results for clinicians and symptomatic women. The Menopause Strategies: Finding Lasting Answers for Symptoms and Health network tested these interventions in three randomized clinical trials.MethodsAn analysis of pooled individual-level data from three randomized clinical trials is presented. Participants were 899 perimenopausal and postmenopausal women with at least 14 bothersome vasomotor symptoms per week. Interventions included 10-20 mg escitalopram per day, nonaerobic yoga, aerobic exercise, 1.8 g per day omega-3 fatty acid supplementation, 0.5 mg low-dose oral 17-beta-estradiol (E2) per day, and 75 mg low-dose venlafaxine XR per day. The main outcome measures were changes from baseline in mean daily vasomotor symptom frequency and bother during 8-12 weeks of treatment. Linear regression models estimated differences in outcomes between each intervention and corresponding control group adjusted for baseline characteristics. Models included trial-specific intercepts, effects of the baseline outcome measure, and time.ResultsThe 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at -1.4 per day (95% confidence interval [CI] -2.7 to -0.2), low-dose E2 at -2.4 (95% CI -3.4 to -1.3), and venlafaxine at -1.8 (95% CI -2.8 to -0.8); vasomotor symptom bother reduction was minimal and did not vary across these three pharmacologic interventions (mean -0.2 to -0.3 relative to placebo). No effects on vasomotor symptom frequency or bother were seen with aerobic exercise, yoga, or omega-3 supplements.ConclusionThese analyses suggest that escitalopram, low-dose E2, and venlafaxine provide comparable, modest reductions in vasomotor symptom frequency and bother among women with moderate hot flushes.Clinical trial registrationClinicalTrials.gov, www.clinicaltrials.gov, NCT00894543 (MsFLASH 01), NCT01178892 (MsFLASH 02), and NCT01418209 (MsFLASH 03).

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.

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.

ImportanceEstrogen therapy is the gold standard treatment for hot flashes and night sweats, but some women are unable or unwilling to use it because of associated risks. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride is used widely as a nonhormonal treatment. While the clinical impression is that serotonin-norepinephrine reuptake inhibitors are less effective than estrogen, these medications have not been simultaneously evaluated in one clinical trial to date.ObjectiveTo determine the efficacy and tolerability of low-dose oral 17β-estradiol and low-dose venlafaxine extended release in alleviating vasomotor symptoms (VMS).Design, setting, and participantsIn total, 339 perimenopausal and postmenopausal women with at least 2 bothersome VMS per day (mean, 8.1 per day) were recruited from the community to MsFLASH (Menopause Strategies: Finding Lasting Answers for Symptoms and Health) clinical network sites between December 5, 2011, and October 15, 2012.InterventionsParticipants were randomized to double-blind treatment with low-dose oral 17β-estradiol (0.5 mg/d) (n = 97), low-dose venlafaxine hydrochloride extended release (75 mg/d) (n = 96), or placebo (n = 146) for 8 weeks.Main outcomes and measuresThe primary outcome was the mean daily frequency of VMS after 8 weeks of treatment. Secondary outcomes were VMS severity, bother, and interference with daily life. Intent-to-treat analyses compared the change in VMS frequency between each active intervention and placebo and between the 2 active treatments.ResultsCompared with baseline, the mean VMS frequency at week 8 decreased to 3.9 (95% CI, 2.9-4.9) VMS per day (52.9% reduction) in the estradiol group, to 4.4 (95% CI, 3.5-5.3) VMS per day (47.6% reduction) in the venlafaxine group, and to 5.5 (95% CI, 4.7-6.3) VMS per day (28.6% reduction) in the placebo group. Estradiol reduced the frequency of symptoms by 2.3 more per day than placebo (P

BackgroundCareful management of symptoms, particularly sleep and mood disturbances, may assist women in discontinuing hormone therapy (HT). We sought to describe characteristics associated with successful HT cessation in women who attempted to discontinue estrogen pills/patches with or without progestin.MethodsWe invited 2,328 women, aged 45-70, enrolled January 1, 2005, to May 31, 2006, at Group Health in Washington State and Harvard Vanguard Medical Associates in Massachusetts, to participate in a telephone survey about HT practices. For the sample, we selected 2,090 women with estrogen dispensings (pharmacy data) during the study period, 200 women without HT dispensing after January 2005, and 240 women with no estrogen dispensings; 1,358 (58.3%) completed the survey. These analyses are based on survey responses.ResultsAmong 802 women who attempted HT discontinuation, the mean age was 50 years, 93% were postmenopausal, 90% were white, 30% had had a hysterectomy, and 75% experienced hot flashes after discontinuation. Those who did not succeed had greater trouble sleeping (74% vs. 57%) and mood disturbances (51% vs. 34%) than those who succeeded. In multivariable analyses, factors associated with successful discontinuation included doctor advice (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.68-4.08), lack of symptom improvement (OR 4.21, CI 1.50-12.17), vaginal bleeding (OR 5.96, CI 1.44-24.6), and learning to cope with symptoms (OR 3.36, CI 2.21-5.11). Factors associated with unsuccessful HT discontinuation included trouble sleeping (OR 0.40, CI 0.26-0.61) and mood swings or depression (OR 0.63, CI 0.42-0.92).ConclusionsDoctor advice is strongly associated with successful HT discontinuation. Symptom management, particularly sleep and mood disturbances, may help women discontinue HT.

ObjectiveThis study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women.MethodsThis study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules, and simultaneously to yoga (n = 107), aerobic exercise (n = 106), or their usual physical activity (n = 142). Participants received 1.8 g of omega-3 daily for 12 weeks. Each capsule contained ethyl eicosapentaenoic acid (425 mg), docosahexaenoic acid (100 mg), and other omega-3s (90 mg). Primary outcomes were VMS frequency and bother. Secondary outcomes included sleep quality (Pittsburgh Sleep Quality Index), insomnia symptoms (Insomnia Severity Index), depressive symptoms (Physician's Health Questionnaire-8), and anxiety (Generalized Anxiety Disorder-7).ResultsThe mean baseline frequency of VMS per day was 7.6 (95% CI, 7.0 to 8.2). After 12 weeks, the reduction in VMS frequency with omega-3 (-2.5; 95% CI, -3.0 to -1.9) did not differ significantly from that with placebo (-2.7; 95% CI, -3.3 to -2.2), with a relative difference of 0.3 fewer hot flashes per day (95% CI, -0.5 to 1.0; P = 0.28). Changes in VMS bother at 12 weeks were also similar between groups, with no relative difference on a four-point scale (95% CI, -0.1 to 0.2; P = 0.36). Omega-3s compared with placebo showed no improvement in self-reported sleep or mood (P > 0.09 for all comparisons).ConclusionsAmong healthy, sedentary perimenopausal and postmenopausal women, a 12-week treatment with omega-3 does not improve VMS frequency, VMS bother, sleep, or mood compared with placebo.

ObjectiveThis study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms.MethodsLate perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usual activity. The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12. Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index and Pittsburgh Sleep Quality Index), and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire).ResultsAt the end of week 12, changes in VMS frequency in the exercise group (mean change, -2.4 VMS/d; 95% CI, -3.0 to -1.7) and VMS bother (mean change on a four-point scale, -0.5; 95% CI, -0.6 to -0.4) were not significantly different from those in the control group (-2.6 VMS/d; 95% CI, -3.2 to -2.0; P = 0.43; -0.5 points; 95% CI, -0.6 to -0.4; P = 0.75). The exercise group reported greater improvement in insomnia symptoms (P = 0.03), subjective sleep quality (P = 0.01), and depressive symptoms (P = 0.04), but differences were small and not statistically significant when P values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only.ConclusionsThese findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality, insomnia, and depression in midlife sedentary women.

ObjectiveThis study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother.MethodsThis study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of ω-3 fatty acid (n = 177) or placebo (n = 178) capsules. Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6 weeks, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks.ResultsAmong 249 randomized women, 237 (95%) completed 12-week assessments. The mean baseline VMS frequency was 7.4 per day (95% CI, 6.6 to 8.1) in the yoga group and 8.0 per day (95% CI, 7.3 to 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n = 237). There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks (mean difference [yoga--usual activity] from baseline at 6 wk, -0.3 [95% CI, -1.1 to 0.5]; mean difference [yoga--usual activity] from baseline at 12 wk, -0.3 [95% CI, -1.2 to 0.6]; P = 0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga - usual activity] in the change in Insomnia Severity Index, 1.3 [95% CI, -2.5 to -0.1]; P = 0.007).ConclusionsAmong healthy women, 12 weeks of yoga class plus home practice, compared with usual activity, do not improve VMS frequency or bother but reduce insomnia symptoms.

ObjectiveThis study aims to determine the efficacy and tolerability of omega-3 fatty acids in reducing vasomotor symptoms (VMS) frequency and bother in perimenopausal and postmenopausal women.MethodsThis study was a 12-week, three-by-two factorial, randomized controlled trial. Eligible women were randomized to a double-blind comparison of omega-3 (n = 177) or placebo (n = 178) capsules, and simultaneously to yoga (n = 107), aerobic exercise (n = 106), or their usual physical activity (n = 142). Participants received 1.8 g of omega-3 daily for 12 weeks. Each capsule contained ethyl eicosapentaenoic acid (425 mg), docosahexaenoic acid (100 mg), and other omega-3s (90 mg). Primary outcomes were VMS frequency and bother. Secondary outcomes included sleep quality (Pittsburgh Sleep Quality Index), insomnia symptoms (Insomnia Severity Index), depressive symptoms (Physician's Health Questionnaire-8), and anxiety (Generalized Anxiety Disorder-7).ResultsThe mean baseline frequency of VMS per day was 7.6 (95% CI, 7.0 to 8.2). After 12 weeks, the reduction in VMS frequency with omega-3 (-2.5; 95% CI, -3.0 to -1.9) did not differ significantly from that with placebo (-2.7; 95% CI, -3.3 to -2.2), with a relative difference of 0.3 fewer hot flashes per day (95% CI, -0.5 to 1.0; P = 0.28). Changes in VMS bother at 12 weeks were also similar between groups, with no relative difference on a four-point scale (95% CI, -0.1 to 0.2; P = 0.36). Omega-3s compared with placebo showed no improvement in self-reported sleep or mood (P > 0.09 for all comparisons).ConclusionsAmong healthy, sedentary perimenopausal and postmenopausal women, a 12-week treatment with omega-3 does not improve VMS frequency, VMS bother, sleep, or mood compared with placebo.

ObjectiveThis study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms.MethodsLate perimenopausal and postmenopausal sedentary women with frequent vasomotor symptoms (VMS) participated in a randomized controlled trial conducted in three sites: 106 women randomized to exercise and 142 women randomized to usual activity. The exercise intervention consisted of individual facility-based aerobic exercise training three times per week for 12 weeks. VMS frequency and bother were recorded on daily diaries at baseline and on weeks 6 and 12. Intent-to-treat analyses compared between-group differences in changes in VMS frequency and bother, sleep symptoms (Insomnia Severity Index and Pittsburgh Sleep Quality Index), and mood (Patient Health Questionnaire-8 and Generalized Anxiety Disorder-7 questionnaire).ResultsAt the end of week 12, changes in VMS frequency in the exercise group (mean change, -2.4 VMS/d; 95% CI, -3.0 to -1.7) and VMS bother (mean change on a four-point scale, -0.5; 95% CI, -0.6 to -0.4) were not significantly different from those in the control group (-2.6 VMS/d; 95% CI, -3.2 to -2.0; P = 0.43; -0.5 points; 95% CI, -0.6 to -0.4; P = 0.75). The exercise group reported greater improvement in insomnia symptoms (P = 0.03), subjective sleep quality (P = 0.01), and depressive symptoms (P = 0.04), but differences were small and not statistically significant when P values were adjusted for multiple comparisons. Results were similar when considering treatment-adherent women only.ConclusionsThese findings provide strong evidence that 12 weeks of moderate-intensity aerobic exercise do not alleviate VMS but may result in small improvements in sleep quality, insomnia, and depression in midlife sedentary women.

ObjectiveThis study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother.MethodsThis study was a three-by-two factorial, randomized controlled trial. Eligible women were randomized to yoga (n = 107), exercise (n = 106), or usual activity (n = 142), and were simultaneously randomized to a double-blind comparison of ω-3 fatty acid (n = 177) or placebo (n = 178) capsules. Yoga intervention consisted of 12 weekly 90-minute yoga classes with daily home practice. Primary outcomes were VMS frequency and bother assessed by daily diaries at baseline, 6 weeks, and 12 weeks. Secondary outcomes included insomnia symptoms (Insomnia Severity Index) at baseline and 12 weeks.ResultsAmong 249 randomized women, 237 (95%) completed 12-week assessments. The mean baseline VMS frequency was 7.4 per day (95% CI, 6.6 to 8.1) in the yoga group and 8.0 per day (95% CI, 7.3 to 8.7) in the usual activity group. Intent-to-treat analyses included all participants with response data (n = 237). There was no difference between intervention groups in the change in VMS frequency from baseline to 6 and 12 weeks (mean difference [yoga--usual activity] from baseline at 6 wk, -0.3 [95% CI, -1.1 to 0.5]; mean difference [yoga--usual activity] from baseline at 12 wk, -0.3 [95% CI, -1.2 to 0.6]; P = 0.119 across both time points). Results were similar for VMS bother. At week 12, yoga was associated with an improvement in insomnia symptoms (mean difference [yoga - usual activity] in the change in Insomnia Severity Index, 1.3 [95% CI, -2.5 to -0.1]; P = 0.007).ConclusionsAmong healthy women, 12 weeks of yoga class plus home practice, compared with usual activity, do not improve VMS frequency or bother but reduce insomnia symptoms.

ObjectiveThe 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 designWe 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).ResultsAmong 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).ConclusionAll 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.

ObjectiveThis report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials.MethodsEstablished in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed.ConclusionsThe methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

ObjectiveThis report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials.MethodsEstablished in response to a National Institutes of Health request for applications, the network was charged with conducting rapid throughput randomized trials of novel and understudied available interventions postulated to alleviate vasomotor and other menopausal symptoms. Included are descriptions of and rationale for criteria used for interventions and study selection, common eligibility and exclusion criteria, common primary and secondary outcome measures, consideration of placebo response, establishment of a biorepository, trial duration, screening and recruitment, statistical methods, and quality control. All trial designs are presented, including the following: (1) a randomized, double-blind, placebo-controlled clinical trial designed to evaluate the effectiveness of the selective serotonin reuptake inhibitor escitalopram in reducing vasomotor symptom frequency and severity; (2) a two-by-three factorial design trial to test three different interventions (yoga, exercise, and ω-3 supplementation) for the improvement of vasomotor symptom frequency and bother; and (3) a three-arm comparative efficacy trial of the serotonin-norepinephrine reuptake inhibitor venlafaxine and low-dose oral estradiol versus placebo for reducing vasomotor symptom frequency. The network's structure and governance are also discussed.ConclusionsThe methods used in and the lessons learned from the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health trials are shared to encourage and support the conduct of similar trials and to encourage collaborations with other researchers.

This review summarizes our current understanding of associations of the postmenopausal vaginal microbiome with genitourinary syndrome of menopause. We review the normal postmenopausal microbiota, examine the association of the microbiome with vulvovaginal symptoms, describe microbial communities associated with physical and laboratory findings, and report the impact of different treatments for genitourinary syndrome of menopause on microbiota and symptom improvement. Postmenopausal vaginal symptoms have an underlying pathophysiology that has not been fully elucidated. Estrogen treatment may not be sufficient to relieve symptoms of vaginal discomfort in all postmenopausal individuals. In addition, other interventions targeted at changing the microbiota or pH do not consistently improve symptom severity. [ABSTRACT FROM AUTHOR]

BackgroundBehavioral strategies are recommended for menopausal symptoms, but little evidence exists regarding efficacy.PurposeDescribe design and methodology of a randomized controlled 3 by 2 factorial trial of yoga, exercise and omega-3 fatty acids.MethodsWomen from three geographic areas with a weekly average of ≥14 hot flashes/night sweats, who met exclusion/inclusion criteria, were randomized to 12weeks of: 1) yoga classes and daily home practice; 2) supervised, facility-based aerobic exercise training; or 3) usual activity. Women in each arm were further randomized to either omega-3 supplement or placebo. Standardized training, on-going monitoring, and site visits were adopted to ensure consistency across sites and fidelity to the intervention. Participant adherence to the intervention protocol was monitored continuously, and retention was actively encouraged by staff. Information on adverse events was systematically collected.ResultsOf 7377 women who responded to mass mailings, 355 (4.8%) were randomized; mean age was 54.7 (sd=3.7), 26.2% were African American, 81.7% were post-menopausal, and mean baseline frequency of daily hot flashes/night sweats was 7.6 (sd=3.8). Adherence of ≥80% was 59% for yoga, 77% for exercise training, and 80% for study pills. Final week 12 data were collected from 95.2%ConclusionsConducting a multi-site, multi-behavioral randomized trial for menopausal symptoms is challenging but feasible. Benefits included cost-effective study design, centralized recruitment, and methodologic standardization.

ObjectiveTo evaluate the effects of escitalopram 10-20 mg/day on menopause-related quality of life and pain in healthy menopausal women with hot flashes.Study designA double-blind, placebo-controlled randomized trial of escitalopram 10-20mg/day vs. identical placebo was conducted among 205 women ages 40-62 years with an average of ≥4 daily hot flashes recruited at 4 clinical sites from July 2009 to June 2010.Main outcome measuresThe primary trial outcomes, reported previously, were the frequency and severity of vasomotor symptoms at 8 weeks. Here, we report on the pre-specified secondary endpoints of total and domain scores from the Menopause-Specific Quality of Life Questionnaire (MENQOL) and the pain intensity and interference scale (PEG).ResultsOutcome data were collected on 97% of randomized women and 87% of women took at least 70% of their study medication. Treatment with escitalopram resulted in significantly greater improvement in total MENQOL scores (mean difference at 8 weeks of -0.41; 95% confidence interval (CI) -0.71 to -0.11; p

ObjectiveThe aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes.MethodsA randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between July 2009 and June 2010. The participants received escitalopram (10-20 mg/d) or placebo. Insomnia symptoms (Insomnia Severity Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at weeks 4 and 8 were the prespecified secondary outcomes. A total of 199 women (97%) provided ISI data, and 194 (95%) women provided PSQI data at follow-up.ResultsAt baseline, mean hot flash frequency was 9.78 per day (SD, 5.60), mean ISI was 11.4 (SD, 6.3), and mean PSQI was 8.0 (SD, 3.7). Treatment with escitalopram reduced ISI at week 8 (mean difference, -2.00; 95% CI, -3.43 to -0.57; P < 0.001 overall treatment effect), with mean differences of -4.73 (95% CI, -5.72 to -3.75) in the escitalopram group and -2.73 (95% CI, -3.78 to -1.69) in the placebo group. The reduction in PSQI was greater in the escitalopram than in the placebo group at week 8 (mean difference, -1.31; 95% CI, -2.14 to -0.49; P < 0.001 overall treatment effect). Clinical improvement in insomnia symptoms and subjective sleep quality (≥50% decreases in ISI and PSQI from baseline) was observed more frequently in the escitalopram group than in the placebo group (ISI, 50.0% vs 35.4%, P = 0.04; PSQI, 29.6% vs 19.2%, P = 0.09).ConclusionsAmong healthy perimenopausal and postmenopausal women with hot flashes, escitalopram at 10 to 20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 8 weeks of follow-up.

ObjectiveThe aim of this study was to determine the effect of escitalopram on insomnia symptoms and subjective sleep quality in healthy perimenopausal and postmenopausal women with hot flashes.MethodsA randomized, blinded, multicenter, placebo-controlled parallel-group 8-week trial with 205 women (95 African American, 102 white, 8 other) was conducted between July 2009 and June 2010. The participants received escitalopram (10-20 mg/d) or placebo. Insomnia symptoms (Insomnia Severity Index [ISI]) and subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]) at weeks 4 and 8 were the prespecified secondary outcomes. A total of 199 women (97%) provided ISI data, and 194 (95%) women provided PSQI data at follow-up.ResultsAt baseline, mean hot flash frequency was 9.78 per day (SD, 5.60), mean ISI was 11.4 (SD, 6.3), and mean PSQI was 8.0 (SD, 3.7). Treatment with escitalopram reduced ISI at week 8 (mean difference, -2.00; 95% CI, -3.43 to -0.57; P < 0.001 overall treatment effect), with mean differences of -4.73 (95% CI, -5.72 to -3.75) in the escitalopram group and -2.73 (95% CI, -3.78 to -1.69) in the placebo group. The reduction in PSQI was greater in the escitalopram than in the placebo group at week 8 (mean difference, -1.31; 95% CI, -2.14 to -0.49; P < 0.001 overall treatment effect). Clinical improvement in insomnia symptoms and subjective sleep quality (≥50% decreases in ISI and PSQI from baseline) was observed more frequently in the escitalopram group than in the placebo group (ISI, 50.0% vs 35.4%, P = 0.04; PSQI, 29.6% vs 19.2%, P = 0.09).ConclusionsAmong healthy perimenopausal and postmenopausal women with hot flashes, escitalopram at 10 to 20 mg/day compared with placebo reduced insomnia symptoms and improved subjective sleep quality at 8 weeks of follow-up.

ObjectiveTo estimate the effect of escitalopram (10-20 mg/d) versus placebo for reducing hot flash interference in daily life and understand correlates and predictors of reductions in hot flash interference, a key measure of quality of life.DesignMultisite, randomized, double-blind, placebo-controlled clinical trial.SettingMsFLASH clinical sites in Boston, Indianapolis, Oakland, and Philadelphia.Patient(s)A total of 205 midlife women (46% African-American) who met criteria participated.Intervention(s)After baseline, women were randomized to one pill of escitalopram 10 mg/d (n = 104) or placebo (n = 101) with follow-up at 4 and 8 weeks. At week 4, those not achieving 50% fewer hot flashes were increased to two pills daily (20 mg/d or 2 placebo pills).Main outcome measure(s)The Hot Flash Related Daily Interference Scale; correlates were variables from hot flash diaries; predictors were baseline demographics, clinical variables, depression, anxiety, sleep quality, and hot flashes.Result(s)Compared to placebo, escitalopram significantly reduced hot flash interference by 6.0 points at week 4 and 3.4 points at week 8 more than placebo. Reductions in hot flash interference correlated with changes in hot flash diary variables. However, baseline variables did not significantly predict reductions in hot flash interference.Conclusion(s)Escitalopram (10-20 mg/d) for 8 weeks improves women's quality of life and this benefit did not vary by demographic, clinical, mood, sleep, or hot flash variables.Clinical trial registration numberNCT00894543.

ContextConcerns regarding the risks associated with estrogen and progesterone to manage menopausal symptoms have resulted in its declining use and increased interest in nonhormonal treatments with demonstrated efficacy for hot flashes.ObjectiveTo determine the efficacy and tolerability of 10 to 20 mg/d escitalopram, a selective serotonin reuptake inhibitor, in alleviating the frequency, severity, and bother of menopausal hot flashes.Design, setting, and patientsA multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel group trial that enrolled 205 women (95 African American; 102 white; 8 other) between July 2009 and June 2010.InterventionWomen received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks.Main outcome measuresPrimary outcomes were the frequency and severity of hot flashes assessed by prospective daily diaries at weeks 4 and 8. Secondary outcomes were hot flash bother, recorded on daily diaries, and clinical improvement (defined as hot flash frequency ≥50% decrease from baseline).ResultsMean (SD) daily hot flash frequency was 9.78 (5.60) at baseline. In a modified intent-to-treat analysis that included all randomized participants who provided hot flash diary data, the mean difference in hot flash frequency reduction was 1.41 (95% CI, 0.13-2.69) fewer hot flashes per day at week 8 among women taking escitalopram (P < .001), with mean reductions of 4.60 (95% CI, 3.74-5.47) and 3.20 (95% CI, 2.24-4.15) hot flashes per day in the escitalopram and placebo groups, respectively. Fifty-five percent of women in the escitalopram group vs 36% in the placebo group reported a decrease of at least 50% in hot flash frequency (P = .009) at the 8-week follow-up. Reductions in hot flash severity scores were significantly greater in the escitalopram group (-0.52; 95% CI, -0.64 to -0.40 vs -0.30; 95% CI, -0.42 to -0.17 for placebo; P < .001). Race did not significantly modify the treatment effect (P = .62). Overall discontinuation due to adverse events was 4% (7 in the active group, 2 in the placebo group). Three weeks after treatment ended, women in the escitalopram group reported a mean 1.59 (95% CI, 0.55-2.63; P = .02) more hot flashes per day than women in the placebo group.ConclusionAmong healthy women, the use of escitalopram (10-20 mg/d) compared with placebo resulted in fewer and less severe menopausal hot flashes at 8 weeks of follow-up.Trial registrationclinicaltrials.gov Identifier: NCT00894543.

BackgroundPrescribing and counseling practices in hormone therapy (HT) since publication of the Women's Health Initiative (WHI) trials have changed. Our objective was to compare changes by practice field and region.MethodsBetween December 2005 and May 2006, we mailed surveys to 938 practitioners from two large integrated health systems in the Northeastern and Northwestern United States. We received 736 responses and excluded 144 who do not prescribe/counsel about HT, leaving 592. Data included prescriber characteristics, knowledge about HT trials, and self-reported HT counseling and prescribing changes. We compared provider characteristics and HT counseling and prescribing by region and practice field (obstetrician/gynecology [OB/GYN] or primary care).ResultsRespondents included 79 OB/GYNs and 513 primary care providers. OB/GYNs were more likely, than primary care providers to consider themselves experts regarding the Heart and Estrogen/progestin Replacement Study (HERS) and WHI trials (30.4% vs. 8.2%, p