Associations between depressed mood and hormonal changes during transition to menopause are controversial. To our knowledge, there has been no prospective study of these associations in women commencing when they are premenopausal.To longitudinally study the associations among reproductive hormones, menopausal status, and other predictors of depressed mood in midlife women.Cohort study with 6 assessment periods during a 4-year interval. Blood samples were collected 12 times during the follicular phase (days 2-6).Philadelphia County, Pennsylvania.A randomly identified, population-based, stratified sample of African American (n = 218) and white (n = 218) women aged 35 to 47 years with regular menstrual cycles, no hormonal or psychotropic medication use, and no serious physical or mental health problems at enrollment.Center for Epidemiologic Studies Depression Scale score and history of depression via the Primary Care Evaluation of Mental Disorders.There was an increased likelihood of depressive symptoms during transition to menopause and a decreased likelihood after menopause after adjustment for other predictors of depression, including history of depression, severe premenstrual syndrome, poor sleep, age, race, and employment status (P =.03). The likelihood of depressive symptoms decreased for individuals with a rapidly increasing follicle-stimulating hormone profile (P< or =.001) and also decreased with age compared with premenopausal women (P =.02). Participant aggregate profiles with increasing estradiol levels were significantly associated with depressive symptoms in bivariate analysis (P =.053).Depressive symptoms as assessed herein increased during transition to menopause and decreased in postmenopausal women. Hormone associations provided corroborating evidence that the changing hormonal milieu contributes to dysphoric mood during transition to menopause.