Joint impact of premature age at menopause and depression on mortality in older females: an NHANES analysis

Objectives: Premature ovarian failure and depression are independently associated with adverse health outcomes, but their combined association with long-term mortality remains unclear. We examined these associations using National Health and Nutrition Examination Survey data 2005-2018 linked to mortality records through 2019. Methods: Postmenopausal women aged older than or equal to 40 years with available information on age at final menstrual period, depression status, and mortality follow-up were included. Premature ovarian failure was defined as a last menstrual period before age 40. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9), with scores ≥10 indicating clinically significant depression. Participants were classified into four groups according to premature ovarian failure and depression status. Cox proportional hazards models estimated adjusted hazard ratios (aHRs) for all-cause mortality; cardiovascular disease (CVD) mortality was evaluated as an exploratory secondary outcome. Results: A total of 4,754 women were included, representing 27.2 million US women. Premature ovarian failure alone (aHR: 2.50; 95% CI: 1.72-3.64) and depression alone (aHR: 1.64; 95% CI: 1.14-2.38) were associated with higher all-cause mortality compared with neither condition. Women with both conditions had the highest observed risk (aHR: 5.04; 95% CI: 2.18-11.62). Exploratory analyses showed a similar direction of association for CVD mortality. Conclusions: Premature ovarian failure and depression were independently associated with higher all-cause mortality, and women with both conditions had the highest observed risk. Findings for CVD mortality were exploratory and require confirmation in larger studies with sufficient numbers of cardiovascular deaths.