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Objective: The Menopause Strategies: Finding Lasting Answers for Symptoms and Health clinical trials network was funded by the National Institutes of Health to find new ways to alleviate the most common, bothersome menopausal symptoms by designing and conducting multiple concurrent clinical intervention studies, accommodating a wide scope of populations and intervention strategies., Methods: Trials were conducted in Boston, Indianapolis, Minneapolis, Oakland, Philadelphia, and Seattle, with the Data Coordinating Center in Seattle, and were designed with standardized eligibility criteria and endpoints. Primary outcomes focused on vasomotor symptoms, sleep quality and insomnia symptoms, and vaginal symptoms. Secondary outcomes included quality of life, sexual function, and mood., Results: We completed five randomized clinical trials and three ancillary studies, testing nine interventions in over 1,300 women and collecting nearly 16,000 bio-specimens. Escitalopram, venlafaxine hydrochloride extended release, and low-dose estradiol diminished hot flashes by approximately 50% as compared with a 30% decrease by placebo. No benefits on vasomotor symptoms were observed with yoga or exercise compared with usual activity, nor with omega-3 supplementation compared with placebo. Cognitive behavioral therapy for insomnia reduced self-reported insomnia symptoms and improved overall sleep quality compared with menopause education control. We did not find significant benefit from a vaginal estradiol tablet or a vaginal moisturizer compared with placebo tablet and gel in diminishing the severity of vaginal symptoms., Conclusions: The MsFLASH trials contributed substantially to our understanding of bothersome menopausal symptom treatment. It is important that clinicians counseling women about available treatment options consider all therapies-both nonhormonal and hormonal.

Background: In a preliminary trial, we assessed the efficacy of vortioxetine for major depressive disorder (MDD) during the menopausal transition. Secondary outcomes included hot flashes (HFs), anxiety, and cognitive complaints., Methods: Perimenopausal and early postmenopausal women with MDD (N = 27) received 8 weeks of open-label, flexible-dose treatment with vortioxetine. The Montgomery-Åsberg Depression Rating Scale (MADRS) was the primary outcome measure. Secondary measures included: HF frequency, the Greene Climacteric Scale (GCS), Menopause-Specific Quality of Life Questionnaire (MEN-QOL), Beck Anxiety Inventory (BAI), Cognitive and Physical Functioning Questionnaire (CPFQ), Digit Symbol Substitution Test (DSST), and Cogstate testing., Results: Of the 27 women, 24 (88.8%) were evaluated (≥1 follow-up), and 21 (77.8%) completed the study; 1 discontinued because of adverse effects. The mean MADRS score decreased significantly (P = .0001) from 31.3 (standard deviation [SD] = 5.5) at pretreatment to 8.1 (SD = 7.8) at posttreatment. The depression response rate (≥50% reduction in MADRS) and remission rate (final MADRS ≤10) were 75% and 70.8%, respectively. GCS, MEN-QOL, BAI, CPFQ, and DSST scores improved significantly (P = .0030, P = .0001, P = .0001, P = .0001, and P = .0133, respectively); Cogstate test scores did not. Frequency and severity of HFs improved significantly (P = .0291 and P = .0299, respectively)., Conclusions: These data support further study of vortioxetine for treating menopausal depression and associated symptoms.

Objective: To examine associations between the composition of the vaginal microbiota and genitourinary menopausal symptoms, serum estrogen, and vaginal glycogen., Methods: For 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., Results: Of 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., Conclusions: Presence 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.

Objective: Our objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health clinical trial at baseline, including hot flash interference, and sleep, depressive, anxiety, and pain symptoms., Methods: Data from all women randomized to interventions and controls from Menopausal Strategies: Finding Lasting Answers to Symptoms and Health studies 1, 2, and 3 (N = 899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included the following: Hot Flash-Related Daily Interference Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9 measure of depressed mood, Generalized Anxiety Disorder, and Brief Pain Inventory PEG scores (pain intensity [P], interference with enjoyment of life [E], and interference with daily activity [G]). Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points., Results: We identified five classes using the Bayesian Information Criterion and the Akaike Information Criterion. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%), women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all the five symptoms (low severity symptoms)., Conclusions: Women meeting hot flash frequency criteria for inclusion in clinical trials exhibited multiple co-occurring symptoms that clustered into identifiable groups according to symptom interference and severity. Variability of symptom profiles between the classes was evident, indicating that the classes were composed of differing symptom types and not simply differing severity levels. These symptom clusters may be useful phenotypes for differentiating treatment effects or evaluating associations with biomarkers or genes.

Objective: This study aims to obtain preliminary data on the efficacy of armodafinil for improving menopause-related fatigue and quality of life., Methods: Women (aged 40-65 y) experiencing menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/d) for 4 weeks. Changes from baseline in Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL) physical domain score were examined using the Wilcoxon signed rank test. Exploratory analyses examined the effects of armodafinil on hot flashes, overall quality of life, insomnia, depression, anxiety, and perceived cognitive performance. After open-label treatment, participants were randomized to double-blind continuation of armodafinil versus placebo for 2 weeks to examine whether treatment discontinuation would precipitate symptom recurrence., Results: Of 29 eligible participants, 20 women (69.0%) completed the trial. During treatment with armodafinil (mean dose, 120 mg/d), median Brief Fatigue Inventory scores decreased by 57.7% from 5.2 (interquartile range [IQR], 4.6-6.2) to 2.2 (IQR, 1.1-4.4; P = 0.0002), and median MENQOL physical domain scores decreased by 51.3% from 3.9 (IQR, 2.3-4.8) to 1.9 (IQR, 1.3-2.7; P = 0.0001). Median hot flashes for 24 hours decreased by 48.3% from 2.9 (IQR, 1.1-4.6) to 1.5 (IQR, 0.4-2.4; P = 0.0005). Improvements in MENQOL total score (49%; P = 0.0001), cognitive function (59.2%; P = 0.0002), depressive symptoms (64.7%; P = 0.0006), insomnia (72.7%; P = 0.0012), and excessive sleepiness (57.1%; P = 0.0006) were noted. Randomized continuation (n = 10) or discontinuation (n = 10) did not indicate group differences. Armodafinil was well-tolerated; three women (12%) were withdrawn for adverse events., Conclusions: These preliminary results suggest a therapeutic effect of armodafinil on fatigue affecting quality of life during menopause, and a potential benefit for other menopause-related symptoms.

Objective: This study aims to determine the efficacy of yoga in alleviating vasomotor symptoms (VMS) frequency and bother., Methods: This 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., Results: Among 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)., Conclusions: Among 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.

Objective: This 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., Methods: This 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)., Results: The 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)., Conclusions: Among 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.

Objective: This study aims to determine the efficacy of exercise training for alleviating vasomotor and other menopausal symptoms., Methods: Late 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)., Results: At 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., Conclusions: These 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.

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., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: This report describes the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health network and methodological issues addressed in designing and implementing vasomotor symptom trials., Methods: Established 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., Conclusions: The 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.

Background: We sought to obtain preliminary data regarding the efficacy of duloxetine for major depressive disorder (MDD) during the menopausal transition. The secondary outcomes were vasomotor symptoms (VMS, or hot flashes), specifically assessed as daytime or nighttime, and anxiety., Methods: After a single-blind placebo lead-in, peri- and postmenopausal women with MDD (n=19) received eight weeks of open-label treatment with duloxetine (60 mg/day). The Hamilton Rating Scale for Depression (17-item) (HAM-D) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries, the Greene Climacteric Scale (GCS), and the Hot Flash-Related Daily Interference Scale (HFRDIS). Anxiety was measured with the Generalized Anxiety Disorder scale (GAD-7)., Results: Of 19 participants treated with duloxetine, 16 (84.2%) were evaluable (returned for ≥ 1 follow up), and 13 (68.4%) completed the study. Three discontinued due to side effects. The pre-treatment and final median HAM-D scores were 15 (interquartile range [IQR] 14-18), and 6.5 (IQR 4-11.5), respectively, reflecting a significant decrease (p=.0006). The response and remission rates were 56.3% (all responders were also remitters, having ≥ 50% decrease in HAM-D scores and final scores ≤ 7). Anxiety improved with treatment (p=.012). GCS and HFRDIS scores decreased significantly. Among those who reported hot flashes at baseline, number and severity of hot flashes improved significantly overall (p=.009 and p=.008, respectively). Daytime but not nighttime hot flashes improved significantly., Conclusions: These data support further study of duloxetine for the treatment of a spectrum of symptoms associated with the menopausal transition., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

This study took place in eastern Massachusetts and included respondents from the Harvard Study of Moods and Cycles Cohort 1, enrolled between 1995 and 1997, and the Harvard Study of Moods and Cycles Cohort 2, enrolled between 2005 and 2009. In prospectively assessing rates of new-onset depression in 2 populations of late-reproductive-aged women with no Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) lifetime history of depression, we were surprised to find far lower rates of depression in the population with greater racial diversity and lower socioeconomic status, contrary to what had been reported in the scientific literature. To better understand why these disparate results occurred, we assessed confounding and outcome misclassification as potential explanations for the discrepancy. After determining that these were unlikely explanations for the findings, we explored 2 potential sources of selection bias: one induced by self-referral of healthy participants into the study and the other induced by the design of the study itself. We concluded that both types of selection bias were likely to have occurred in this study and could account for the observed difference in rates.

Objective: Vasomotor symptoms (VMS) recur after discontinuation of hormonal therapy. Selective serotonin reuptake inhibitors (SSRIs) are used increasingly to treat VMS, but whether VMS recur after cessation of SSRI is unknown. We hypothesized that relapse of VMS to baseline levels after SSRI cessation would be common and predicted by menopausal and psychological characteristics., Methods: Recurrence of VMS (frequency, severity, and bother) was measured with daily diaries for 3 weeks after cessation of escitalopram, which was administered to perimenopausal/postmenopausal women with hot flashes and night sweats in an 8-week randomized, placebo-controlled trial. Blinding of staff and participants was maintained throughout. Relapse was defined as mean daily VMS frequency, severity, or bother 20% or less lower than pretreatment levels., Results: Of 76, 57, and 51 women included in the analysis for VMS frequency, severity, and bother, 34.2%, 38.6%, and 37.3%, respectively, had relapse of VMS frequency, severity, and bother. In adjusted models, VMS frequency relapse was predicted by higher levels of pretreatment insomnia symptoms (P = 0.02) and a weaker response to escitalopram (P = 0.03)., Conclusions: Among women whose VMS improved with escitalopram, approximately one third relapsed swiftly after discontinuation of the medication. Those with pretreatment insomnia and those with a weaker response to escitalopram may be at greatest risk for VMS relapse after treatment discontinuation. Women should be educated about the likelihood of VMS symptom relapse when they discontinue SSRIs after receiving benefits from short-term treatment.

Objective: To 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 Design: A 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 Measures: The 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)., Results: Outcome 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<0.001), as well as Vasomotor, Psychosocial, and Physical domain scores with the largest difference seen in the Vasomotor domain (mean difference -0.75; 95% CI -1.28 to -0.22; p=0.02). There was no significant treatment group difference for the Sexual Function domain. Escitalopram treatment resulted in statistically significant improvements in PEG scores compared to placebo (mean treatment group difference at 8 weeks of -0.33; 95% CI -0.81 to 0.15; p=0.045)., Conclusions: Treatment with escitalopram 10-20mg/day in healthy women with vasomotor symptoms significantly improved menopause-related quality of life and pain., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objectives: We sought to obtain preliminary data regarding the efficacy of omega-3 fatty acids for major depressive disorder associated with the menopausal transition. Secondary outcomes were assessed for vasomotor symptoms (or hot flashes)., Methods: After a single-blind placebo lead-in, participants received 8 weeks of treatment with open-label omega-3 fatty acid capsules (eicosapentaenoic acid and docosahexaenoic acid, 2 g/d). The Montgomery-Asberg Depression Rating Scale (MADRS) was the primary outcome measure. Hot flashes were monitored prospectively using daily diaries and the Hot Flash Related Daily Interference Scale. Blood samples for plasma pretreatment and posttreatment essential fatty acid assays were obtained. Because of the small sample size, data were analyzed using nonparametric techniques., Results: Of 20 participants treated with omega-3 fatty acids, 19 (95%) completed the study. None discontinued because of adverse effects. The pretreatment and final mean MADRS scores were 24.2 and 10.7, respectively, reflecting a significant decrease in MADRS scores (P < 0.0001). The response rate was 70% (MADRS score decrease of ≥50%), and the remission rate was 45% (final MADRS score of ≤). Responders had significantly lower pretreatment docosahexaenoic acid levels than nonresponders did (P = 0.03). Hot flashes were present in 15 (75%) participants. Among those with hot flashes at baseline, the number of hot flashes per day improved significantly from baseline (P = 0.02) and Hot Flash Related Daily Interference Scale scores decreased significantly (P = 0.006)., Conclusions: These data support further study of omega-3 fatty acids for major depressive disorder and hot flashes in women during the menopausal transition.

Context: Concerns 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., Objective: To 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 Patients: A 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., Intervention: Women received 10 to 20 mg/d of escitalopram or a matching placebo for 8 weeks., Main Outcome Measures: Primary 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)., Results: Mean (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., Conclusion: Among 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 Registration: clinicaltrials.gov Identifier: NCT00894543.

Objective: Depression occurs more commonly during the menopausal transition in women with vasomotor symptoms (VMS) than in those without, but most women with VMS do not develop depression. It has been hypothesized that VMS are associated with depression because VMS lead to repeated awakenings, which impair daytime well-being. We aimed to determine if objectively measured sleep and perceived sleep quality are worse in depressed women with VMS than in nondepressed women with VMS., Methods: Objectively and subjectively measured sleep parameters were compared between 52 depressed women with VMS and 51 nondepressed controls with VMS. Actigraphic measures of objective sleep conducted in the home environment and subjective measures of sleep quality (Pittsburgh Sleep Questionnaire Index) were compared using linear regression models., Results: On objective assessments, depressed women with VMS spent less time in bed (by 64.8 min; P < 0.001) and had shorter total sleep time (by 47.7 min; P = 0.008), longer sleep-onset latency (by 13.8 min; P = 0.03), and lower sleep efficiency (by 3.2 percentage points; P = 0.09), but did not awaken more or spend more time awake after sleep onset than nondepressed controls with VMS. Depressed women also reported worse sleep quality (mean Pittsburgh Sleep Questionnaire Index 12.0 vs 8.3; P < 0.001). Adjustment for VMS frequency and important demographic characteristics did not alter these associations., Conclusions: Sleep quality and selected parameters of objectively measured sleep, but not sleep interruption, are worse in depressed than in nondepressed women with VMS. The type of sleep disturbance seen in depressed participants was not consistent with the etiology of depression secondary to VMS-associated awakenings.

Recent census data indicate that, in the United States, an increasing number of women--almost 1.5 million each year--are reaching menopause. The menopausal transition is marked by intense hormonal fluctuations, and may be accompanied by vasomotor complaints, sleep disturbances, changes in sexual function, and increased risk for osteoporosis and cardiovascular disease. In addition, there is evidence of increased risk for developing depression, even among women who never experienced depressive symptoms before. Thus depression during the perimenopause may have a substantial impact on personal, family, and professional spheres of life. A challenge to clinicians and health professionals lies in the identification of the most tolerable treatments to manage depression and improve quality of life in an aging population. Any treatment strategy should take into account not only the spectrum of side effects that may complicate treatment but also other menopause-related factors (e.g., vasomotor symptoms, psychosocial stressors) that may modulate risk for the development of mood disturbance. This article reviews the current literature on the prevalence and risk factors associated with depression during the menopausal transition. The benefits and risks of using hormonal and nonhormonal strategies for the management of depression and other menopause-related somatic symptoms are critically reviewed.

More than 1 million women are expected to reach menopause each year, many of whom will experience hot flushes and other neuropsychological symptoms that may diminish their quality of life. Hot flushes are the core symptoms that reflect the brain's response to the changing hormonal milieu of the menopause transition, particularly to the rapidly fluctuating and falling levels of estradiol. The physical symptoms of hot flushes and the associated changes in sleep, mood, and cognition will lead many women to seek medical care. It is critical to understand the interrelationship of hot flushes and other neuropsychological symptoms of the menopause transition so that treatment priorities can be established. For example, if sleep disruption explains most daytime neuropsychological problems in women with hot flushes, treating insomnia should be considered a priority. Alternatively, mood, cognition, and quality of life may be disturbed independent of sleep problems. In such a situation, each symptom should be evaluated separately from any assessment of sleep. As recent data from the WHI establish the risks of long-term HRT use, concern about using HRT, even as a short-term intervention, has increased substantially. Although HRT remains the first-line treatment for hot flushes, the WHI findings have drawn attention to nonhormonal treatments of hot flushes and other menopausal symptoms. Growing evidence to support the efficacy of serotonergic antidepressants and other psychoactive medications in the treatment for hot flushes suggests that nonhormonal interventions will prove important alternatives to HRT. As further evidence of the benefits of psychoactive medications for menopausal symptoms is established, the choice between using hormonal and nonhormonal therapies for management of menopausal symptoms will continue to evolve.

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.

ObjectiveOur objective was to identify symptom clusters using standardized measures completed by participants in the Menopausal Strategies: Finding Lasting Answers to Symptoms and Health clinical trial at baseline, including hot flash interference, and sleep, depressive, anxiety, and pain symptoms.MethodsData from all women randomized to interventions and controls from Menopausal Strategies: Finding Lasting Answers to Symptoms and Health studies 1, 2, and 3 (N = 899) were included; 797 with complete data were used in the analyses. Scores from standardized measures obtained at baseline included the following: Hot Flash-Related Daily Interference Scale, Insomnia Severity Index, Pittsburgh Sleep Quality Index, Patient Health Questionnaire-9 measure of depressed mood, Generalized Anxiety Disorder, and Brief Pain Inventory PEG scores (pain intensity [P], interference with enjoyment of life [E], and interference with daily activity [G]). Latent class analysis was used to identify symptom clusters using standardized scale scores and their established cut points.ResultsWe identified five classes using the Bayesian Information Criterion and the Akaike Information Criterion. Women in classes 1 and 2 had high hot flash interference levels relative to the others, and class 1 (10.5% of total) included severe hot flash interference, severe sleep symptoms, and moderately severe pain symptoms (hot flash, sleep, pain). In class 2 (14.1%), severe hot flash interference was paired with the severe sleep symptoms, and moderate to severe depressed and anxious mood symptoms and pain (hot flash, sleep, mood, pain). In class 3 (39.6%), women reported moderately severe sleep symptoms with moderate hot flash interference, and low severity mood and pain symptoms (hot flash, sleep). Those in class 4 (7.0%) reported moderate hot flash interference with severe levels of anxiety and depressed mood symptoms, but low levels of other symptoms (hot flash, mood). Women in class 5 (28.7%) reported the lowest levels of all the five symptoms (low severity symptoms).ConclusionsWomen meeting hot flash frequency criteria for inclusion in clinical trials exhibited multiple co-occurring symptoms that clustered into identifiable groups according to symptom interference and severity. Variability of symptom profiles between the classes was evident, indicating that the classes were composed of differing symptom types and not simply differing severity levels. These symptom clusters may be useful phenotypes for differentiating treatment effects or evaluating associations with biomarkers or genes.

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

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 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.

ObjectiveVasomotor symptoms (VMS) recur after discontinuation of hormonal therapy. Selective serotonin reuptake inhibitors (SSRIs) are used increasingly to treat VMS, but whether VMS recur after cessation of SSRI is unknown. We hypothesized that relapse of VMS to baseline levels after SSRI cessation would be common and predicted by menopausal and psychological characteristics.MethodsRecurrence of VMS (frequency, severity, and bother) was measured with daily diaries for 3 weeks after cessation of escitalopram, which was administered to perimenopausal/postmenopausal women with hot flashes and night sweats in an 8-week randomized, placebo-controlled trial. Blinding of staff and participants was maintained throughout. Relapse was defined as mean daily VMS frequency, severity, or bother 20% or less lower than pretreatment levels.ResultsOf 76, 57, and 51 women included in the analysis for VMS frequency, severity, and bother, 34.2%, 38.6%, and 37.3%, respectively, had relapse of VMS frequency, severity, and bother. In adjusted models, VMS frequency relapse was predicted by higher levels of pretreatment insomnia symptoms (P = 0.02) and a weaker response to escitalopram (P = 0.03).ConclusionsAmong women whose VMS improved with escitalopram, approximately one third relapsed swiftly after discontinuation of the medication. Those with pretreatment insomnia and those with a weaker response to escitalopram may be at greatest risk for VMS relapse after treatment discontinuation. Women should be educated about the likelihood of VMS symptom relapse when they discontinue SSRIs after receiving benefits from short-term treatment.

There is a new appreciation of the perimenopause—defined as the early and late menopause transition stages as well as the early postmenopause—as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: (1) epidemiology; (2) clinical presentation; (3) therapeutic effects of antidepressants; (4) effects of hormone therapy; and (5) efficacy of other therapies (e.g., psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (i.e., antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive. [ABSTRACT FROM AUTHOR]

The article discusses the association between the menopausal transition and onset of first lifetime episode of depression among women having no previous experience of mood disturbance. The Harvard Study of Moods and Cycles conducted an evaluation of premenopausal women with and without a lifetime history of major depression. It led to results signifying that women who enter the menopausal transition earlier have a significant risk for first onset of depression.

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

Objective: Menopause-associated insomnia is commonly associated with other symptoms (hot flashes, depression, anxiety). Given frequent symptom cooccurrence, therapies targeting sleep may provide an important approach to treatment during midlife. Study Design: Peri/postmenopausal women (40-65 years old) with sleep-onset and/or sleep-maintenance insomnia cooccurring with hot flashes and depressive and/or anxiety symptoms were randomized to eszopiclone 3 mg orally or placebo in a double-blinded, crossover 11 week trial. Changes in the Insomnia Severity Index (ISI) scale and secondary outcomes (diary-based sleep parameters, depression/anxiety, hot flashes, quality of life) were analyzed using repeated-measure linear models. Results: Of 59 women, 46 (78%) completed the study. Eszopiclone reduced ISI scores by 8.7 ± 1.4 more points than placebo (P < .0001). Eszopiclone improved (P < .05) all sleep parameters, depressive symptoms, anxiety symptoms, quality of life, and nighttime but not daytime hot flashes. Conclusion: Eszopiclone treats insomnia and cooccurring menopause-related symptoms. Our results provide evidence that hypnotic therapies may improve multiple domains of well-being during midlife. [Copyright &y& Elsevier]

OBJECTIVE: To 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. METHODS: An 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. RESULTS: The 8-week reduction in vasomotor symptom frequency from baseline relative to placebo was similar for escitalopram at 21.4 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. CONCLUSION: These 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. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Concerns about hormone therapy have led many menopausal women to discontinue hormone treatment. This study examines the efficacy of paroxetine controlled-release versus placebo for the treatment of women with vasomotor symptoms after discontinuing hormone therapy. Methods: Sixty-four perimenopausal and postmenopausal women without depression or anxiety but reporting vasomotor symptoms after hormone discontinuation entered a 1-week, single-blind, placebo lead-in phase, followed by a 6-week, flexible-dose, double-blind phase with paroxetine controlled-release (12.5-25 mg/d) or placebo. The primary outcome measure was a change in vasomotor symptoms. Other measures included changes in depressive symptoms and overall functioning. Results: Fifty subjects (paroxetine controlled-release, n=27; placebo, n=23) completed the study. At study entry, subjects had an average of 17 hot flushes per week, had used hormones for more than 5 years (median=66 months, interquartile range=18-120 months), and had discontinued treatment for less than 1 year (median=5 months, interquartile range=2-10 months) before study enrollment. Paroxetine controlled-release was more efficacious than placebo for the alleviation of vasomotor symptoms (mean reduction of 6.1 vs 2.8 hot flashes per week, respectively; P =.03). Depressive symptoms also improved with paroxetine (mean reduction of 3.6 points vs 0.4 points in Montgomery-Asberg Depression Rating Scale total scores; P =.01). Conclusion: Treatment with paroxetine controlled-release may constitute an efficacious alternative for symptomatic perimenopausal and postmenopausal women after menopausal hormone discontinuation. [Copyright &y& Elsevier]

The article discusses a study that evaluated eszopiclone treatment of insomnia in perimenopausal and early postmenopausal women, as well as the impact of the treatment on mood, menopause-related symptoms, and quality of life. Four hundred ten women were involved in the double-blind, placebo-controlled study.