Early iatrogenic menopause raises cardiovascular risk

Iatrogenic menopause before age 45 was linked to higher cardiovascular and mortality risk.
*Systematic review/meta-analysis of cohort studies; Level 2a.

Citation

Armeni E, Ozcivit Erkan IB, Kempegowda P. Age at Iatrogenic Menopause and Cardiovascular Morbidity and Mortality: A Systematic Review and Meta-Analysis. JAMA Network Open. 2026;9(10):e2637545. doi:10.1001/jamanetworkopen.2026.37545

Background

Removal or medical loss of ovarian function before natural menopause causes abrupt hormone loss. Its long-term heart and stroke risks have been uncertain, especially by age at menopause.

Patients

Thirty-six studies including 2,617,942 women with iatrogenic menopause before the usual age of natural menopause. Excluded studies lacked cardiovascular or mortality outcomes, an appropriate comparator, peer review, or English language publication.

Intervention

Iatrogenic menopause, mainly ovary removal with or without hysterectomy; some treatment-induced menopause.

Control

Naturally menopausal women, age-matched women, hysterectomy-only groups, or women without surgery.

Outcome

Cardiovascular events, coronary heart disease, stroke, cardiovascular death, and all-cause death.

Follow-up Period

Median 16 years; range 4.8 to 36 years.

Results

OutcomeEffect estimate
Cardiovascular eventsHazard ratio 1.25 (95% CI 1.12 to 1.39)
Coronary heart diseaseHazard ratio 1.48 (95% CI 1.07 to 2.03)
StrokeHazard ratio 1.22 (95% CI 1.15 to 1.28)
All-cause deathHazard ratio 1.08 (95% CI 1.01 to 1.16)
Cardiovascular death before age 45Hazard ratio 1.20 (95% CI 1.04 to 1.37)
All-cause death before age 45Hazard ratio 1.15 (95% CI 1.06 to 1.25)

CI = confidence interval.

Overall cardiovascular death was not increased. At age 45 or older, cardiovascular and all-cause death estimates were null. Each 5-year later iatrogenic menopause age was linked to lower combined cardiovascular and mortality risk: hazard ratio 0.89 (95% CI 0.83 to 0.97). Stroke was the most consistent individual morbidity finding.

Limitations

Evidence was mostly observational, with varied comparators, incomplete hormone therapy data, possible residual confounding, limited subgroup precision, and predominantly high-income, White or European populations.

Funding

United Kingdom public research funding; no conflicts reported.

Clinical Application

Counsel women before early ovary removal about long-term cardiovascular risk and intensify risk-factor surveillance, especially when menopause occurs before age 45.