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

Abstract

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.

The authors' abstract, as published at the source. Menopause The Journal of The North American Menopause Society, 2026 · DOI ↗