Temporal associations of hot flashes and depression in the transition to menopause

Objective: The aim of this study was to evaluate associations between hot flashes and depressed mood in the menopausal transition and associations of these symptoms with reproductive hormone changes. Methods: A 10-year follow-up in a population-based cohort of women who had no experience of hot flashes or depressed mood at baseline was conducted. Results: The incidence of hot flashes significantly increased compared with the incidence of depressed mood in the 10-year follow-up (P < 0.001). Sixty-seven percent of the women reported hot flashes, 50% reported depressed mood, and 41% reported both symptoms during the study interval. Reporting of both hot flashes and depressed mood was greater than expected if the processes operated independently (P < 0.001). Of the women who experienced both symptoms, depressed mood was more likely to precede hot flashes (relative risk = 2.1; 95% Cl, 1.5-2.9). Within-woman increases in follicle-stimulating hormone levels were associated with the onset of depressed mood in unadjusted analysis (P = 0.05). Increased follicle-stimulating hormone levels, decreased inhibin B levels, and the variability of estradiol were significantly associated with hot flashes. Follicle-stimulating hormone and inhibin B remained significantly associated with hot flashes in the final multivariable models (P < 0.001). Conclusions: Both hot flashes and depressive symptoms occur early in the menopausal transition in women with no previous experience of these symptoms. Depressive symptoms are more likely to precede hot flashes in women who report both symptoms. The findings support the concept that the changing hormonal milieu of the menopausal transition is one of multiple factors associated with the onset of symptoms.