Premature menopause and depression jointly associated with higher mortality in NHANES analysis

An observational study published in Menopause examined the joint association of premature menopause and depression with mortality using NHANES data from 2005–2018 linked to mortality records through 2019. The analysis included 4,754 postmenopausal women aged 40 years or older, representing 27.2 million US women. Researchers defined premature ovarian failure as a final menstrual period before age 40 and clinically significant depression as a Patient Health Questionnaire-9 score of at least 10. All-cause mortality was the primary outcome; cardiovascular mortality was exploratory.

Compared with women with neither condition, those with premature ovarian failure alone had an adjusted mortality hazard ratio of 2.50 (95% CI, 1.72–3.64), and those with depression alone had a hazard ratio of 1.64 (95% CI, 1.14–2.38). Women with both conditions had the highest observed hazard ratio, 5.04 (95% CI, 2.18–11.62). Exploratory cardiovascular mortality analyses showed associations in the same direction.

The findings identify women with both conditions as a potentially higher-risk group, but the observational design does not establish causation or demonstrate that treatment reduces mortality. The wide confidence interval for the combined group indicates substantial uncertainty. Cardiovascular findings require confirmation in larger studies with sufficient cardiovascular deaths.