Howard M. Kravitz

Sleep difficulty in women at midlife: a community survey of sleep and the menopausal transition.

Objective To compare age-adjusted and ethnic differences in prevalences of sleep difficulty at various stages of the menopausal transition and to determine the relative contribution of other factors, including vasomotor symptoms, sociodemographics, and psychological and physical health factors, to self-reported sleep difficulty in middle-aged women. Design A community-based survey of womens health and menopausal symptoms was conducted between November 1995 and October 1997 at each of the seven US sites participating in the Study of Womens Health Across the Nation. A multiethnic sample of 12,603 Caucasian, African American, Chinese, Japanese, and Hispanic women aged 40 to 55 years was categorized into six groups: premenopausal, early perimenopausal, late perimenopausal, naturally postmenopausal, surgically postmenopausal, and postmenopausal receiving hormone replacement therapy. The women were asked whether they had experienced difficulty sleeping in the past 2 weeks. Results Difficulty sleeping was reported by 38%. Age-adjusted rates were highest in the late perimenopausal (45.4%) and surgically postmenopausal (47.6%) groups. Among ethnic groups, rates ranged from 28% in Japanese women to 40% in Caucasian women. In the multivariate analysis, menopausal status was significantly associated with difficulty sleeping. Ethnicity, vasomotor and psychological symptoms, self-perceived health and health behaviors, arthritis, and education also were significantly associated with difficulty sleeping. Conclusions These results suggest that stage of the menopausal transition, independent of other potential explanatory factors, is associated with self-reported sleep difficulty. Older age per se was not significantly associated with difficulty sleeping.

Psychologic Distress and Natural Menopause: A Multiethnic Community Study

OBJECTIVES This study examined the association between psychologic distress and natural menopause in a community sample of African American, White, Chinese, Hispanic, and Japanese women participating in a national womens health study. METHODS A cohort of 16,065 women aged 40 to 55 years provided information on menstrual regularity in the previous year, psychosocial factors, health, and somatic-psychologic symptoms. Psychologic distress was defined as feeling tense, depressed, and irritable in the previous 2 weeks. RESULTS Rates of psychologic distress were highest in early perimenopause (28.9%) and lowest in premenopause (20.9%) and postmenopause (22%). In comparison with premenopausal women, early perimenopausal women were at a greater risk of distress, with and without adjustment for vasomotor and sleep symptoms and covariates. Odds of distress were significantly higher for Whites than for the other racial/ethnic groups. CONCLUSIONS Psychologic distress is associated with irregular menses in midlife. It is important to determine whether distress is linked to alterations in hormone levels and to what extent a mood-hormone relationship may be influenced by socioeconomic and cultural factors.

Racial/Ethnic Differences in the Prevalence of Depressive Symptoms Among Middle-Aged Women: The Study of Women’s Health Across the Nation (SWAN)

OBJECTIVES We examined racial/ethnic differences in significant depressive symptoms among middle-aged women before and after adjustment for socioeconomic, health-related, and psychosocial characteristics. METHODS Racial/ethnic differences in unadjusted and adjusted prevalence of significant depressive symptoms (score >/= 16 on the Center for Epidemiologic Studies Depression [CES-D] Scale) were assessed with univariate and multiple logistic regressions. RESULTS Twenty-four percent of the sample had a CES-D score of 16 or higher. Unadjusted prevalence varied by race/ethnicity (P <.0001). After adjustment for covariates, racial/ethnic differences overall were no longer significant. CONCLUSIONS Hispanic and African American women had the highest odds, and Chinese and Japanese women had the lowest odds, for a CES-D score of 16 or higher. This variation is in part because of health-related and psychosocial factors that are linked to socioeconomic status.

Longitudinal Change in Reproductive Hormones and Depressive Symptoms Across the Menopausal Transition: Results From the Study of Women’s Health Across the Nation (SWAN)

CONTEXT The contribution of reproductive hormones to mood has been the focus of considerable research. Results from clinical and epidemiological studies have been inconsistent. It remains unclear whether alterations in serum hormone levels across the menopausal transition are linked to depressive symptoms. OBJECTIVES To evaluate the relationship between serum hormone levels and high depressive symptoms and whether hormone levels or their change might explain the association of menopausal status with depressive symptoms previously reported in a national sample of midlife women. DESIGN A longitudinal, community-based, multisite study of menopause. Data were collected at baseline and annually from December 1995 to January 2008 on a range of factors. Early follicular phase serum samples were assayed for levels of estradiol, follicle-stimulating hormone, testosterone, and dehydroepiandrosterone sulfate. SETTING Seven communities nationwide. PARTICIPANTS A community-based sample of 3302 multiethnic women, aged 42 to 52 years, still menstruating and not using exogenous reproductive hormones. Main Outcome Measure Depressive symptoms assessed with the Center for Epidemiological Studies Depression Scale (CES-D). The primary outcome was a CES-D score of 16 or higher. RESULTS In multivariable random-effects logistic regression models, log-transformed testosterone level was significantly positively associated with higher odds of a CES-D score of 16 or higher (odds ratio = 1.15; 95% confidence interval, 1.01-1.31) across 8 years, and a larger increase in log-transformed testosterone from baseline to each annual visit was significantly associated with increased odds of a CES-D score of 16 or higher (odds ratio = 1.23; 95% confidence interval, 1.04-1.45). Less education, being Hispanic, and vasomotor symptoms, stressful life events, and low social support at each visit were each independently associated with a CES-D score of 16 or higher. No other hormones were associated with a CES-D score of 16 or higher. Being perimenopausal or postmenopausal compared with being premenopausal remained significantly associated with a CES-D score of 16 or higher in all analyses. CONCLUSIONS Higher testosterone levels may contribute to higher depressive symptoms during the menopausal transition. This association is independent of menopausal status, which remains an independent predictor of higher depressive symptoms.

Duration of Menopausal Vasomotor Symptoms Over the Menopause Transition

IMPORTANCE The expected duration of menopausal vasomotor symptoms (VMS) is important to women making decisions about possible treatments. OBJECTIVES To determine total duration of frequent VMS (≥ 6 days in the previous 2 weeks) (hereafter total VMS duration) during the menopausal transition, to quantify how long frequent VMS persist after the final menstrual period (FMP) (hereafter post-FMP persistence), and to identify risk factors for longer total VMS duration and longer post-FMP persistence. DESIGN, SETTING, AND PARTICIPANTS The Study of Womens Health Across the Nation (SWAN) is a multiracial/multiethnic observational study of the menopausal transition among 3302 women enrolled at 7 US sites. From February 1996 through April 2013, women completed a median of 13 visits. Analyses included 1449 women with frequent VMS. MAIN OUTCOMES AND MEASURES Total VMS duration (in years) (hot flashes or night sweats) and post-FMP persistence (in years) into postmenopause. RESULTS The median total VMS duration was 7.4 years. Among 881 women who experienced an observable FMP, the median post-FMP persistence was 4.5 years. Women who were premenopausal or early perimenopausal when they first reported frequent VMS had the longest total VMS duration (median, >11.8 years) and post-FMP persistence (median, 9.4 years). Women who were postmenopausal at the onset of VMS had the shortest total VMS duration (median, 3.4 years). Compared with women of other racial/ethnic groups, African American women reported the longest total VMS duration (median, 10.1 years). Additional factors related to longer duration of VMS (total VMS duration or post-FMP persistence) were younger age, lower educational level, greater perceived stress and symptom sensitivity, and higher depressive symptoms and anxiety at first report of VMS. CONCLUSIONS AND RELEVANCE Frequent VMS lasted more than 7 years during the menopausal transition for more than half of the women and persisted for 4.5 years after the FMP. Individual characteristics (eg, being premenopausal and having greater negative affective factors when first experiencing VMS) were related to longer-lasting VMS. Health care professionals should counsel women to expect that frequent VMS could last more than 7 years, and they may last longer for African American women.

Quality of life in diverse groups of midlife women: Assessing the influence of menopause, health status and psychosocial and demographic factors

This paper examines whether menopausal status is associated with global quality of life (QOL) among women aged 40–55 and whether this association varies by race/ethnicity. We further examine the contributions of other health-related and psychosocial factors to QOL and whether these associations vary by racial/ethnic group. Analyses are based on 13,874 women who participated in the multi-ethnic, multi-race study of mid-aged women called the Study of Womens Health Across the Nation (SWAN). Study participants completed a 15-min telephone or in-person interview that contained questions on a variety of health-related topics. Items of interest for these analyses include global QOL, menstrual history (to assess menopausal status), sociodemographics, health status, lifestyle, and psychosocial variables. Results showed that in unadjusted analyses, early perimenopausal women reported lower QOL compared with premenopausal women, but menopausal status was no longer associated with QOL when analyses were adjusted for other variables. In multivariable models, being married and having low levels of perceived stress were associated with better QOL across all racial/ethnic groups. While there were many consistencies across racial/ethnic groups, we also found that the nature of the associations between QOL and education, marital status, perceived stress and social support varied across racial/ethnic groups.

Major depression during and after the menopausal transition: Study of Women's Health Across the Nation (SWAN)

BACKGROUND It is unclear whether risk for major depression during the menopausal transition or immediately thereafter is increased relative to pre-menopause. We aimed to examine whether the odds of experiencing major depression were greater when women were peri- or post-menopausal compared to when they were pre-menopausal, independent of a history of major depression at study entry and annual measures of vasomotor symptoms (VMS), serum levels of, or changes in, estradiol (E2), follicular stimulating hormone (FSH) or testosterone (T) and relevant confounders. METHOD Participants included the 221 African American and Caucasian women, aged 42-52 years, who were pre-menopausal at entry into the Pittsburgh site of a community-based study of menopause, the Study of Womens Health Across the Nation (SWAN). We conducted the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) to assess diagnoses of lifetime, annual and current major depression at baseline and at annual follow-ups. Psychosocial and health factors, and blood samples for assay of reproductive hormones, were obtained annually. RESULTS Women were two to four times more likely to experience a major depressive episode (MDE) when they were peri-menopausal or early post-menopausal. Repeated-measures logistic regression analyses showed that the effect of menopausal status was independent of history of major depression and annually measured upsetting life events, psychotropic medication use, VMS and serum levels of or changes in reproductive hormones. History of major depression was a strong predictor of major depression throughout the study. CONCLUSIONS The risk of major depression is greater for women during and immediately after the menopausal transition than when they are pre-menopausal.

CNS STIMULANT POTENTIATION OF MONOAMINE OXIDASE INHIBITORS IN TREATMENT-REFRACTORY DEPRESSION

We report on our clinical experience with a combination of a CNS stimulant (either pemoline or dextroamphetamine) and a monoamine oxidase inhibitor (MAOI) for treating 32 depressed patients (mainly outpatients) refractory to standard antidepressant pharmacotherapy. This combination, though not approved by the FDA, appears to be safe and effective. Twenty-five (78%) of these patients experienced at least 6 months of symptom remission with a stimulant + MAOI combination. Many patients required adjunctive antidepressant treatment, including tricyclics and lithium. Side effects were not excessive, though 6 patients (3 unipolar and 3 bipolar) cycled to mania (N = 1) or hypomania (N = 5). None developed hypertensive crises. With properly motivated and complaint patients and careful clinical monitoring by the prescribing psychiatrist, stimulant potentiation of MAOIs may be a viable option for treatment-resistant depressed patients.

Suicide: A Four-pathway Clinical-Biochemical Model

Abstract This chapter, based on a review of recent research as well as data presented in this report, proposes four hypothetical pathways leading to suicide in clinical depression: (1) an acute pathway involving severe anxiety/agitation associated with high brain corticotrophin‐releasing factor (CRF or CRH) levels, (2) trait baseline and reactivity hopelessness, (3) severe anhedonia, and (4) trait impulsiveness associated with low brain serotonin turnover and low total cholesterol as a possible peripheral correlate.

A population-based longitudinal study of cognitive functioning in the menopausal transition

Background: No longitudinal studies have tracked cognitive performance through the menopausal transition and thus the impact of the transition on cognition, independent of aging, is not known. The authors hypothesized that a decline in cognitive functioning occurs as women progress through the menopausal transition, independent of age, educational level, family income, ethnicity, and baseline self-perceived health. Method: The authors began a population-based, longitudinal study in January 1996 with yearly follow-up interviews. This report includes follow-up through November 2001. The authors randomly selected African American and white women from a census of two contiguous Chicago communities. After screening for eligibility (age 42 to 52 years, premenopausal or early perimenopausal, no exogenous hormone use in the past 3 months, and no hysterectomy), 868 agreed to participate. Women who became pregnant, had a hysterectomy, or began using hormones were censored from that time onward. This study reports on 803 women for whom cognitive assessments were available. The authors assessed working memory (Digit Span Backward) and perceptual speed (Symbol Digit Modalities Test). Results: Contrary to the hypothesis, the authors found small but significant increases over time during the premenopausal and perimenopausal phases. This trend was not accounted for by chronological age, education, family income, ethnicity, or baseline self-perceived health. Conclusions: Transition through menopause is not accompanied by a decline in working memory and perceptual speed.