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

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

Fourth consensus of the International Society for Premenstrual Disorders (ISPMD): auditable standards for diagnosis and management of premenstrual disorder.

Whilst professional bodies such as the Royal College and the American College of Obstetricians and Gynecologists have well-established standards for audit of management for most gynaecology disorders, such standards for premenstrual disorders (PMDs) have yet to be developed. The International Society of Premenstrual Disorders (ISPMD) has already published three consensus papers on PMDs covering areas that include definition, classification/quantification, clinical trial design and management (American College Obstetricians and Gynecologists 2011; Brown et al. in Cochrane Database Syst Rev 2:CD001396, 2009; Dickerson et al. in Am Fam Physician 67(8):1743-1752, 2003). In this fourth consensus of ISPMD, we aim to create a set of auditable standards for the clinical management of PMDs. All members of the original ISPMD consensus group were invited to submit one or more auditable standards to be eligible in the inclusion of the consensus. Ninety-five percent of members (18/19) responded with at least one auditable standard. A total of 66 auditable standards were received, which were returned to all group members who then ranked the standards in order of priority, before the results were collated. Proposed standards related to the diagnosis of PMDs identified the importance of obtaining an accurate history, that a symptom diary should be kept for 2 months prior to diagnosis and that symptom reporting demonstrates symptoms in the premenstrual phase of the menstrual cycle and relieved by menstruation. Regarding treatment, the most important standards were the use of selective serotonin reuptake inhibitors (SSRIs) as a first line treatment, an evidence-based approach to treatment and that SSRI side effects are properly explained to patients. A set of comprehensive standards to be used in the diagnosis and treatment of PMD has been established, for which PMD management can be audited against for standardised and improved care.

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

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

Bayesian estimation of associations between identified longitudinal hormone subgroups and age at final menstrual period.

BACKGROUND: Although follicle stimulating hormone (FSH) is known to be predictive of age at final menstrual period (FMP), previous methods use FSH levels measured at time points that are defined relative to the age at FMP, and hence are not useful for prospective prediction purposes in clinical settings where age at FMP is an unknown outcome. This study is aimed at assessing whether FSH trajectory feature subgroups identified relative to chronological age can be used to improve the prediction of age at FMP. METHODS: We develop a Bayesian model to identify latent subgroups in longitudinal FSH trajectories, and study the relationship between subgroup membership and age at FMP. Data for our study is taken from the Penn Ovarian Aging study, 1996-2010. The proposed model utilizes mixture modeling and nonparametric smoothing methods to capture hypothesized latent subgroup features of the FSH longitudinal trajectory; and simultaneously studies the prognostic value of these latent subgroup features to predict age at FMP. RESULTS: The analysis identified two FSH trajectory subgroups that were significantly associated with FMP age: 1) early FSH class (15%), which displayed initial increases in FSH shortly after age 40; and 2) late FSH class (85%), which did not have a rise in FSH until after age 45. The use of FSH subgroup memberships, along with class-specific characteristics, i.e., level and rate of FSH change at class-specific pre-specified ages, improved prediction of FMP age by 20-22% in comparison to the prediction based on previously identified risk factors (BMI, smoking and pre-menopausal levels of anti-mullerian hormone (AMH)). CONCLUSIONS: To the best of our knowledge, this work is the first in the area to demonstrate the existence of subgroups in FSH trajectory patterns relative to chronological age and the fact that such a subgroup membership possesses prediction power for age at FMP. Earlier ages at FMP were found in a subgroup of women with rise in FSH levels commencing shortly after age 40, in comparison to women who did not exhibit an increase in FSH until after 45 years of age. Periodic evaluations of FSH in these age ranges are potentially useful for predicting age at FMP.

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

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

Depressed, stressed, and inflamed: C-reactive protein linked with depression symptoms in midlife women with both childhood and current life stress.

To determine whether the relationship between inflammatory factors and clinically significant depression symptoms is moderated by high exposure to adverse childhood experiences and current life stressors in a longitudinal community cohort of midlife women. Methods: Participants from the Penn Ovarian Ageing Study community cohort (age at baseline: M = 45.3 [SD = 3.8]) were included in analyses if they had a blood sample measuring basal inflammatory markers during at least one visit where depression symptom severity and current stressful life events were also assessed (N = 142, average number of visits per participant = 1.75 [SD = 0.92]). Approximately annually over the course of 16 years, participants self-reported depression symptom severity using the Centre for Epidemiologic Studies Depression (CESD) Scale, provided menstrual diaries to determine menopause stage, and contributed blood samples. Residual blood samples were assayed for interleukin (IL)-6, IL 1-beta (IL-1ß), tumour necrosis factor alpha (TNF-α), and high sensitivity C-reactive protein (hsCRP). Early life stress was quantified using the Adverse Childhood Experiences questionnaire (low [0-1 experience(s)] versus high [≥ 2 experiences]). Current stressful life events were assessed using a structured interview (low [0-1 events] vs. high [≥ 2 events]). Generalised estimating equation models were used to model associations with the outcome of interest-clinically significant depression symptoms (CESD ≥16)-and risk factors: inflammatory marker levels (log transformed), adverse childhood experiences group, and current life stressors group. Covariates included menopause stage, age at study baseline, body mass index, race, and smoking status. We found a significant three-way interaction between log hsCRP levels, adverse childhood experiences group, and current life stressors group on likelihood of experiencing clinically significant depression symptoms (OR: 4.33; 95% CI: 1.22, 15.46; p = 0.024) after adjusting for covariates. Solely for women with high adverse childhood experiences and with high current life stressors, higher hsCRP was associated with higher odds of having clinically significant depression symptoms (OR: 1.46; 95% CI 1.07, 1.98; p = 0.016). This three-way interaction was not significant for IL-6, IL-1ß, or TNF-α. For women in midlife with exposure to high adverse childhood experiences and multiple current life stressors, elevated levels of CRP were uniquely associated with clinically significant depression symptoms. Early life adversity and current life stressors represent identifiable individual risk factors whose negative impact may be curtailed with inventions to target inflammation in midlife women.

Clinical subtypes of core premenstrual disorders: a Delphi survey.

The purpose of this study was to classify the clinical subtypes of core premenstrual disorders during the International Society for Premenstrual Disorders' second consensus meeting. Multiple iterations were used to achieve consensus between a group of experts; these iterations included a two-generational Delphi technique that was preceded and followed by open group discussions. The first round was to generate a list of all potential clinical subtypes, which were subsequently prioritized using a Delphi methodology and then finalised in a final round of open discussion. On a six-point scale, 4 of the 12 potential clinical subtypes had a mean score of ≥5.0 following the second iteration and only 3 of the 4 still had a mean score of ≥5.0 after the third iteration. The final list consisted of these three subtypes and an additional subtype, which was introduced and agreed upon, in the final iteration. There is consensus amongst experts that core premenstrual disorder is divided into three symptom-based subtypes: predominantly physical, predominantly psychological and mixed. A proportion of psychological and mixed subtypes may meet the DSM-IV diagnostic criteria for premenstrual dysphoric disorder.

ISPMD consensus on the management of premenstrual disorders.

The second consensus meeting of the International Society for Premenstrual Disorders (ISPMD) took place in London during March 2011. The primary goal was to evaluate the published evidence and consider the expert opinions of the ISPMD members to reach a consensus on advice for the management of premenstrual disorders. Gynaecologists, psychiatrists, psychologists and pharmacologists each formally presented the evidence within their area of expertise; this was followed by an in-depth discussion leading to consensus recommendations. This article provides a comprehensive review of the outcomes from the meeting. The group discussed and agreed that careful diagnosis based on the recommendations and classification derived from the first ISPMD consensus conference is essential and should underlie the appropriate management strategy. Options for the management of premenstrual disorders fall under two broad categories, (a) those influencing central nervous activity, particularly the modulation of the neurotransmitter serotonin and (b) those that suppress ovulation. Psychotropic medication, such as selective serotonin reuptake inhibitors, probably acts by dampening the influence of sex steroids on the brain. Oral contraceptives, gonadotropin-releasing hormone agonists, danazol and estradiol all most likely function by ovulation suppression. The role of oophorectomy was also considered in this respect. Alternative therapies are also addressed, with, e.g. cognitive behavioural therapy, calcium supplements and Vitex agnus castus warranting further exploration.

Adverse childhood experiences interact with inflammation and menopause transition stage to predict verbal memory in women.

OBJECTIVE: Women with more adverse childhood experiences (ACEs) may face a triple threat of risk factors for cognitive concerns during the menopause transition: reduced estradiol, increased inflammation, and early life stress sequelae. Our objective was to determine the extent to which ACEs and peripheral basal inflammatory markers associate with verbal memory across the menopause transition. METHODS: Penn Ovarian Aging cohort participants (n â€‹= â€‹167) were assessed for ACEs (low (0-1) or high (≥2)) and had remaining stored blood samples at study end assayed for interleukin (IL)-6, IL-1-beta (IL-1ß), C-reactive protein (CRP), and tumor necrosis factor alpha (TNF-α). Annual assessment included a verbal memory test (the Buschke Selective Reminding Test) and menopause stage determination. To estimate the effects of menopause stage, ACEs, and cytokines on verbal memory, repeated cognitive outcome measures were modeled in generalized estimating equations. Covariates included body mass index, smoking, race, education, age at baseline, and baseline verbal memory performance. Cytokine levels were log-transformed. RESULTS: Advancing menopause stage was associated with worse performance on immediate verbal recall and delayed verbal recall (ps â€‹< â€‹0.001). During perimenopause, higher ACE exposure was associated with worse immediate verbal recall at higher levels of TNF-α (slope difference p â€‹= â€‹0.041). CONCLUSIONS: Inflammation may mechanistically link ACEs and verbal memory for high ACE women during perimenopause. Reducing inflammation for these individuals may have positive impact on verbal memory across the menopause transition.

A dose-response study of a novel, oral tranexamic formulation for heavy menstrual bleeding.

OBJECTIVE: We sought to assess the efficacy and safety of 2 dosing regimens of a novel, oral tranexamic acid formulation (Lysteda; Ferring Pharmaceuticals Inc, Parsippany, NJ) in women with cyclic heavy menstrual bleeding. STUDY DESIGN: This was a multicenter, double-blind, placebo-controlled, randomized, parallel-group trial for 3 menstrual cycles (n = 304). Women with mean menstrual blood loss (MBL) of ≥ 80 mL/cycle were randomized to receive either 1.95 g/d or 3.9 g/d of tranexamic acid or placebo for up to 5 days of menstrual bleeding. Primary efficacy endpoints were mean MBL reduction from baseline, mean MBL reductions that were considered "meaningful" by subjects, and mean MBL reductions from baseline > 50 mL/cycle. Adverse events (AEs) were also assessed. RESULTS: Only the 3.9 g/d group met all 3 primary efficacy endpoints. AEs did not significantly differ among the 3 groups. There were no serious study-related AEs. CONCLUSION: The 3.9-g/d dose met all 3 primary efficacy endpoints, whereas the 1.95 g/d dose met 2 primary efficacy endpoints. Both doses were well tolerated.

Higher DHEA-S (dehydroepiandrosterone sulfate) levels are associated with depressive symptoms during the menopausal transition: results from the PENN Ovarian Aging Study.

The influence of sex hormones on mood during the menopausal transition has been the subject of ongoing investigation. Because dehydroepiandrosterone sulfate (DHEA-S) has been associated with several indicators of healthy aging, we conducted a population-based study of midlife women to determine the relationship between DHEA-S levels and depressive symptoms and major depression during the transition through menopause. Unexpectedly, the original report revealed a positive correlation between DHEA-S levels and depressive symptoms at baseline. The cohort was studied over 11 years to determine whether the positive association between DHEA-S levels and depression persists through the menopausal transition. We conducted a longitudinal cohort study with 11 assessments during an 11-year interval in Philadelphia, Pennsylvania, using a randomly identified, population-based sample of 436 African American and Caucasian premenopausal women aged 35 to 47 years at enrollment. For outcome measures, we used the Center for Epidemiologic Studies Depression Scale and standardized diagnosis of major depression. In a multivariable model, DHEA-S levels were positively associated with depressive symptoms when adjusted for age, menopausal stage, race, smoking status, and body mass index. There was no association between DHEA-S levels and a diagnosis of major depression. DHEA-S levels were positively associated with depressive symptoms through the menopausal transition. No association with major depression was apparent during the menopausal transition, but results may have limited power due to low prevalence of major depression in this cohort. These findings suggest that taking DHEA supplements may increase depressive symptoms for some women, and women and their physicians should be cautious about instituting DHEA replacement therapy during the menopausal transition.

The Premenstrual Symptoms Screening Tool revised for adolescents (PSST-A): prevalence of severe PMS and premenstrual dysphoric disorder in adolescents.

The Premenstrual Symptoms Screening Tool was modified for use in adolescents and piloted in 578 girls at three international sites. Nearly one third (29.6%) reported experiencing severe PMS or PMDD, with irritability being the most commonly reported symptom. Rates of menstrual-related pain were high, particularly in those with severe PMS or PMDD. Severe PMS and PMDD present with similar rates and symptoms in adolescents as in adults, and the Premenstrual Symptoms Screening Tool modified for adolescents is a fast, reliable tool to screen for these syndromes in adolescents.

Efficacy of escitalopram for hot flashes in healthy menopausal women: a randomized controlled trial.

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.

Influences of the menopause transition and adverse childhood experiences on peripheral basal inflammatory markers.

OBJECTIVE: To characterize the influence of early life stress on peripheral basal inflammatory markers across the menopause transition. METHODS: Participants from the longitudinal Penn Ovarian Aging study were assessed for childhood adversity at study end (14 years) using the Adverse Childhood Experiences (ACE) questionnaire. Responses were categorized as low (0-1) or high (≥2) ACE exposure. The stored blood sample catalogue was reviewed to exclude those samples collected during use of medications that could impact immune status or medications suggestive of infection or allergies. Remaining blood samples (n â€‹= â€‹640) from 167 participants were assayed for interleukin-6 (IL-6), interleukin 1-beta (IL-1ß), high sensitivity C-reactive protein (hsCRP), and tumor necrosis factor alpha (TNF-α). Menopause staging (premenopause, early transition, late transition, and postmenopause) was determined by questionnaire and menstrual diaries at yearly assessments. Generalized linear models for repeated measures were used to quantify the association between outcomes of interest (i.e., IL-6, IL-1ß, hsCRP, and TNF-α) and exposures (i.e., menopause stage, ACE status, their interaction) while controlling for relevant covariates (i.e., BMI, smoking, age at first blood sample, and race). Inflammatory marker levels were log-transformed for modeling. RESULTS: Log IL-6 levels were higher in the late perimenopause versus premenopause (p â€‹= â€‹0.035). Menopause stage â€‹× â€‹ACE interaction was observed for log IL-6, IL-1ß, and TNF-α (p â€‹= â€‹0.042, p â€‹= â€‹0.054, p â€‹= â€‹0.053, respectively); for individuals with high (≥2) ACE exposure, IL-6 was higher in the late perimenopause (p â€‹= â€‹0.015) while IL-1ß and TNF-α were lower in the postmenopause versus premenopause (p â€‹= â€‹0.019 and p â€‹= â€‹0.020). CONCLUSIONS: Results from this investigation indicate that the late perimenopause stage may be a window of risk for inflammation, particularly for individuals with greater childhood adversity. Prospective studies designed to address childhood stress and inflammation across the menopause transition are needed to confirm these findings. Heightened inflammation, even if transitory, may have negative impact on healthy aging.

Weight gain is associated with increased risk of hot flashes in breast cancer survivors on aromatase inhibitors.

Hot flashes in breast cancer survivors (BCS) receiving adjuvant aromatase inhibitor (AI) therapy are common, but risk factors for these symptoms are ill-defined. This study tested if body size is associated with hot flashes in BCS on AI therapy. A cross-sectional study of postmenopausal BCS receiving adjuvant AI therapy was performed. The primary outcome was occurrence of patient-reported hot flashes. The primary exposures of interest were current body size and weight change since breast cancer diagnosis. Three hundred participants were enrolled at a mean age of 61 years (range 33-86) after an average AI exposure of 23 months (range 1 month-9 years). Fifty-nine percent reported hot flashes, 32% reported moderate to severe hot flashes, and 25% reported significant worsening of hot flashes since starting AI therapy. Sixty-one percent experienced weight maintenance (±10 lb), while 27% had weight gain (gained 10 lb or more), and 11% had weight loss (lost 10 lb or more). In multivariable analysis, weight gain was independently associated with hot flash occurrence (OR 2.1, 95% CI 1.1-4.4) and hot flash severity (OR 2.6, 95% CI 1.3-5.0) after adjusting for confounding. Current body size was not associated with hot flash occurrence, severity or change with AI therapy. In an outpatient BCS population on AI therapy, weight gain is a risk factor for hot flash occurrence. Women who gained at least 10 lb since breast cancer diagnosis were two times more likely to have hot flashes than women who maintained or lost weight. These results support the thermoregulatory model of hot flashes and argue against a protective effect of body fat in this population.

Lights on MsFLASH: a review of contributions.

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.

Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations.

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.

Hot flashes and panic attacks: a comparison of symptomatology, neurobiology, treatment, and a role for cognition.

Despite decades of research, the causal mechanisms of hot flashes are not adequately understood, and a biopsychosocial perspective on hot flashes remains underdeveloped. This article explores overlooked parallels between hot flashes and panic attacks within 5 areas: course and symptomatology, physiological indicators, neurocircuitry and biochemical mechanisms, pharmacotherapy, and psychological treatment, noting both similarities and important differences between the 2 events. An integrative conceptual model is presented that identifies key ways in which psychological factors may influence the experience of hot flashes, with clinical implications and areas of future research. This model yields readily testable hypotheses and may provide a template for exploring the role of cognition in the frequency and severity of hot flashes and, in turn, a basis for the development of nonpharmacological treatments.

Investigating the associations between nocturia and sleep disorders in perimenopausal women.

PURPOSE: We determined the associations between nocturia and sleep disorders in perimenopausal women. MATERIALS AND METHODS: A total of 100 women with nocturia were compared to 200 without nocturia. Obstructive sleep apnea, insomnia, anxiety and menopausal stage were assessed using validated questionnaires. Comorbidities associated with nocturia were determined by bivariate analysis and multivariate logistic regression. RESULTS: Independent associations for nocturia were anxiety (OR 2.11, 95% CI 1.08-4.13), black American race (OR 2.00, 95% CI 1.06-3.85), obstructive sleep apnea symptoms (OR 1.73, 95% CI 1.18-2.53) and insomnia (OR 1.11, 95% CI 1.05-1.12). CONCLUSIONS: Nocturia is associated with sleep disorders in perimenopausal women.

Predictors of sleep quality in women in the menopausal transition.

STUDY OBJECTIVES: To determine associations between menopausal status, reproductive hormone levels, menopausal symptoms, and poor sleep quality. DESIGN: The present study examines subjective sleep quality over an 8-year period in participants in an ongoing longitudinal study of ovarian aging in a randomly identified cohort of African American and Caucasian women. PARTICIPANTS: The Penn Ovarian Aging Study, a population-based cohort of 436 women from Philadelphia County who were 35 to 47 years of age and had regular menstrual cycles at enrollment. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: The primary outcome measure was the Sleep Quality factor score, derived from the St. Mary's Hospital Sleep Questionnaire, which was adapted for this population and collected at each assessment period over the 8-year follow-up. Associations between menopausal status, reproductive hormone levels, menopausal symptoms, sleep quality, age, and race were examined in multivariable linear mixed regression models for repeated measures. Menopausal status was not significantly associated with sleep quality (P = 0.12). In the adjusted model, independent predictors of sleep quality were hot flashes (P < 0.0001), Center for Epidemiological Studies Depression Scale scores (P < 0.0001) and levels of the reproductive hormone inhibin B (P = 0.05). CONCLUSIONS: Sleep quality was predicted by hormone levels and symptoms that occur in the menopausal transition but did not worsen with advancing menopausal status alone. Lower inhibin B levels, hot flashes, and symptoms of depression were all strong and independent predictors of difficulty sleeping. Race was not a significant contributor to sleep quality. Together, the findings demonstrate that women who experience other perimenopausal symptoms are likely to experience sleep problems during the menopausal transition.