Lifetime endogenous reproductive factors and severe depressive symptoms in postmenopausal women: findings from the E3N cohort

Objective: This study aims to identify reproductive factors associated with severe depressive symptoms (SDS) in postmenopausal women and to determine whether a past psychological disorder (PPD) and the timing of first-onset PPD in relation to menopause modify associations. Methods: Lifetime reproductive characteristics and PPD were obtained from 51,088 postmenopausal women of the E3N cohort study. The Center for Epidemiologic Studies-Depression Scale (CES-D) was used to assess SDS. Multivariate logistic regression models were performed to estimate the risk of SDS overall and according to the presence and timing of first-onset PPD (before the final menstrual period, in early postmenopause, or in late postmenopause). Results: Women with irregular cycles were at increased risk for SDS (odds ratio [OR], 1.35; 95% CI, 1.19-1.53), except when PPD occurred in early postmenopause (OR, 1.08; 95% CI, 0.74-1.57). Parity was inversely associated with the risk of SDS (P < 0.001), whereas decreasing age at first full-term pregnancy increased the risk of SDS with PPD (P < 0.001) and increasing age at last full-term pregnancy increased the risk of SDS without PPD (P = 0.012). Age at final menstrual period (per 2-y increment) was associated with a decreased risk of SDS with postmenopausal (especially late postmenopausal) PPD (OR, 0.82; 95% CI, 0.80-0.85) but with an increased risk of SDS when PPD occurred before the final menstrual period (OR, 1.15; 95% CI, 1.12-1.19). Artificial menopause increased the risk of SDS with PPD before the final menstrual period (OR, 1.40; 95% CI, 1.18-1.66), whereas menopausal symptoms were associated with SDS across all categories. Conclusions: Associations between endogenous reproductive factors and SDS may vary according to the presence of PPD and the timing of first-onset PPD. Further studies are warranted.