Objective In this conceptual review, we propose a novel mechanistic candidate in the etiology of depression with onset in the menopause transition (a.k.a. perimenopausal depression) involving alterations in stress-responsive pathways, induced by ovarian hormone fluctuation. Methods The relevant literature in perimenopausal depression was reviewed, including its prevalence, predictors, and treatment with estrogen therapy. Subsequently, the growing evidence from animal models and clinical research in other reproductive mood disorders was synthesized to describe a heuristic model of perimenopausal depression development. Results The rate of major depressive disorder and of clinically meaningful elevations in depressive symptoms increases two- to threefold during the menopause transition. While the mechanisms by which ovarian hormone fluctuation might impact mood are poorly understood, growing evidence from basic and clinical research suggests that fluctuations in ovarian hormones and their derived neurosteroids result in altered GABAergic regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Our heuristic model suggests that for some women, failure of the GABAA receptor to regulate overall GABAergic tone in the face of shifting levels of these neurosteroids may induce HPA axis dysfunction, thereby increasing sensitivity to stress, and generating a period of greater vulnerability to depression. Conclusions The proposed model provides a basis for understanding the mechanisms by which the changing hormonal environment of the menopause transition may interact with the psychosocial environment of mid-life to contribute to perimenopausal depression risk. Future research investigating this model may inform the development of novel pharmacological treatments for perimenopausal depression and related disorders such as postpartum depression and premenstrual dysphoric disorder.

Background: Women report many nonvasomotor symptoms across the menopausal transition, including sleep disturbances, depressed mood, and sexual problems. The co-occurrence of these three symptoms may represent a specific menopausal symptom triad. We sought to evaluate the interrelatedness of disturbed sleep, depressed mood, and sexual problems in the Study of Women's Health Across the Nation (SWAN) and determine the characteristics of women exhibiting this symptom triad. Methods: SWAN is a multisite, multiethnic observational cohort study of the menopausal transition in the United States. Sleep disturbance, sexual problems, and depressed mood were determined based on self-report. Women who reported all three symptoms simultaneously were compared to those who did not. Logistic regression models estimated the association of demographic, psychosocial, and clinical characteristics with the symptom triad. Results: Study participants (n = 1716) were 49.8 years old on average and primarily in very good or excellent health. Sixteen and a half percent had depressed mood, 36.6% had a sleep problem, and 42.2% had any sexual problem. Five percent of women (n = 90) experienced all three symptoms. Women with the symptom triad compared with those without had lower household incomes, less education, were surgically postmenopausal or late perimenopausal, rated their general health as fair or poor, and had more stressful life events and lower social support. Conclusions: The symptom triad of sleep disturbance, depressed mood, and sexual problems occurred in only 5% of women, and occurred most often among women with lower socioeconomic status, greater psychosocial distress, and who were surgically menopausal or in the late perimenopause.

Objective: The etiology of preterm birth (PTB) is likely caused by multiple factors, which may include disturbed sleep. We evaluated whether sleep disturbance was associated with PTB and whether the association was affected by other psychosocial risk factors. Methods: Pregnant women (n = 217) for whom we had depression and sleep data at 20 or 30 weeks gestation and delivery information were evaluated. Logistic models were used to test the hypotheses that disturbed sleep was associated with PTB. Results: Time in bed at 20 weeks was significantly associated with risk for preterm delivery (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.08-1.88). However, after controlling for depression/selective serotonin reuptake inhibitors (SSRI) status, history of PTB, age, employment, and marital status, this relationship was no longer significant (OR 1.26, 95% CI .92-1.71). No other relationships were significant. Conclusions: We report preliminary evidence suggesting that poor sleep may contribute to risk for PTB. Although it is speculative and additional work is needed to confirm or refute whether sleep is an independent or mediating risk factor for PTB, disturbed sleep does appear to play a role in adverse pregnancy outcomes.

Gestational choriocarcinoma incidence rates have declined and survivals have improved, but blacks continue to have higher incidence and lower survival rates.