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Ellen W. Freeman, PhD; Mary D. Sammel, ScD; Hui Lin, MS; Deborah B. Nelson, PhD

Arch Gen Psychiatry. 2006;63:375-382.

Context  Whether depressed mood reported in the transition to menopause by women with no history of depression is associated with menopausal status and changes in reproductive hormones is controversial and lacks scientific information.

Objectives  To identify new onset of depressive symptoms and diagnosed depressive disorders in the menopausal transition and to determine the associations of menopausal status, reproductive hormones, and other risk factors with these cases.

Design  A within-woman, longitudinal (8-year) study to identify risk factors of depressed mood.

Setting  A subset of a randomly identified, population-based cohort.

Participants  Premenopausal women with no history of depression at cohort enrollment.

Main Outcome Measures  The Center for Epidemiological Studies of Depression scale (CES-D) was used to assess depressive symptoms, and the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify clinical diagnoses of depressive disorders.

Results  High CES-D scores (16) were more than 4 times more likely to occur during a woman's menopausal transition compared with when she was premenopausal (odds ratio, 4.29; 95% confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal status, increased levels of follicle-stimulating hormone and luteinizing hormone, and increased variability of estradiol, follicle-stimulating hormone, and luteinizing hormone around the woman's own mean levels were each significantly associated with high CES-D scores after adjusting for smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status. A diagnosis of depressive disorder was 2 times more likely to occur in the menopausal transition compared with when the woman was premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the hormone measures were also significantly associated with this outcome.

Conclusion  Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression.

Author Affiliations: Departments of Obstetrics/Gynecology and Psychiatry (Dr Freeman), Center for Clinical Epidemiology and Biostatistics (Dr Sammel), and Center for Research in Reproduction and Women's Health (Ms Lin), University of Pennsylvania School of Medicine, Philadelphia; Temple University College of Health Professions, Philadelphia (Dr Nelson).

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