Iatrogenic Menopause Linked to Higher Cardiovascular Risk and Excess Mortality Before Age 45

Iatrogenic menopause was associated with a higher risk of cardiovascular morbidity, according to a systematic review and meta-analysis published in JAMA Network Open. Excess cardiovascular and all-cause mortality was confined to women who had iatrogenic menopause before age 45 years.

The investigators analyzed 36 studies with 2,617,942 women. The studies compared women who had iatrogenic menopause before natural menopause age with naturally menopausal women or age-matched controls. Most studies evaluated bilateral salpingo-oophorectomy with or without hysterectomy. Median follow-up was 16.0 years.

Iatrogenic menopause was associated with a higher risk of composite cardiovascular events (pooled hazard ratio [PHR], 1.25; 95% CI, 1.12-1.39), coronary heart disease (PHR, 1.48; 95% CI, 1.07-2.03), stroke (PHR, 1.22; 95% CI, 1.15-1.28), and all-cause mortality (PHR, 1.08; 95% CI, 1.01-1.16). The analysis found no overall excess in cardiovascular mortality. Among women who had iatrogenic menopause before age 45 years, risk was elevated for cardiovascular mortality (PHR, 1.20) and all-cause mortality (PHR, 1.15). Estimates at or after age 45 years were null.

In a post hoc meta-regression, each 5-year increase in age at iatrogenic menopause was associated with a lower risk of the composite of cardiovascular morbidity and mortality (HR, 0.89; 95% CI, 0.83-0.97). Certainty of evidence was moderate for stroke, low for composite cardiovascular events, and very low for coronary heart disease and both mortality outcomes. The authors noted that data on menopausal hormone therapy were heterogeneous and sparsely reported.

The authors cited limitations including residual confounding, heterogeneity in definitions and comparator groups, reliance on study-level data, and evidence drawn mainly from high-income cohorts. They said the findings could inform counseling and long-term follow-up rather than set an age criterion for surgery.

Source: Armeni E, Ozcivit Erkan IB, Kempegowda P. Age at iatrogenic menopause and cardiovascular morbidity and mortality: a systematic review and meta-analysis. JAMA Netw Open. 2026;9(10):e2637545. doi:10.1001/jamanetworkopen.2026.37545