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Surgical Menopause Before Age 45 Linked To Higher Heart Death Risk

A massive analysis of 2.6 million women finds that having ovaries removed young carries a cardiovascular cost that fades once surgery happens closer to natural menopause age.

By Dr. Axe Editorial Team · October 5, 2026 · 1 source · Understand

A 20% higher risk of cardiovascular death was linked to iatrogenic menopause before age 45, according to a systematic review and meta-analysis published October 2, 2026 in JAMA Network Open.

2.6Mwomen studied

36studies pooled

16-yearfollow-up

Researchers pooled 36 studies covering 2,617,942 women who had surgical removal of the ovaries or chemotherapy/radiation-induced menopause, compared with naturally menopausal or age-matched women. Median follow-up was 16 years, ranging from 4.8 to 36 years. Iatrogenic menopause was linked to a 25% higher risk of combined cardiovascular events, 48% higher coronary heart disease risk, 22% higher stroke risk, and 8% higher all-cause mortality risk. Splitting women by age at surgery changed the picture: cardiovascular death risk was 20% higher and all-cause death risk 15% higher among women whose ovaries were removed before age 45, while women having surgery at or after 45 showed no excess death risk. Each additional 5 years of age at surgery was linked to an 11% lower risk of the combined illness-and-death outcome, based on 37 estimates from 11 independent study populations.

The study authors propose that abruptly removing the ovaries before the body adapts to declining hormones disrupts vascular tone, cholesterol and blood sugar regulation, cellular energy production, and inflammation control, functions normally supported by estrogen and related ovarian hormones. Natural menopause unfolds over several years, giving blood vessels and metabolism time to adjust; surgery near the expected age of natural menopause affects a body already partway through that adjustment, while the same procedure much earlier removes hormonal support all at once.

Cardiovascular Death Risk by Age at Surgical Menopause

JAMA Network Open, 2026, Armeni et al

Every included study was observational, so the findings show a link between early surgical menopause and heart risk, not proof that one causes the other. Hormone therapy use varied widely and was reported inconsistently, and race and ethnicity data came from only 18 of 36 studies, predominantly white or European ancestry populations.

Dr. Axe’s Take

The age-45 cutoff is the detail I want women and surgeons weighing before any oophorectomy, prophylactic or otherwise. Pulling ovarian hormones out overnight, versus the years-long taper of natural menopause, appears to hit blood vessels and inflammation pathways before the body compensates. For a woman under 45 facing this surgery, I'd prioritize cardiovascular monitoring, blood pressure, lipids, inflammatory markers, starting immediately, not years later. I'd also lean on anti-inflammatory nutrition, resistance training, and sun or sauna exposure for vascular support. Keep taking any prescribed hormone therapy exactly as directed; this review can't tell us whether it lowers this risk.

— Dr. Axe

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Study summary

Who: 2,617,942 women across 36 studies; iatrogenic menopause cohort mean age 55.52 years (SD 12.41), comparators mean age 45.58 years (SD 16.02); 18 of 36 studies reported race/ethnicity, predominantly white or European ancestry
Design: Systematic review and meta-analysis of observational cohort, cross-sectional, case-control studies and 2 randomized trials; searched January 2004 to March 2026
Dose: Not applicable; exposure was surgical removal of ovaries or chemotherapy/radiation-induced menopause compared with natural menopause or age-matched controls
Primary result: Iatrogenic menopause vs comparators: all-cause mortality pooled HR 1.08 (95% CI 1.01-1.16), cardiovascular events HR 1.25 (95% CI 1.12-1.39), coronary heart disease HR 1.48 (95% CI 1.07-2.03), stroke HR 1.22 (95% CI 1.15-1.28); median follow-up 16.0 years (range 4.8-36.0)
Secondary: Below age 45 at surgery: cardiovascular mortality HR 1.20 (95% CI 1.04-1.37), all-cause mortality HR 1.15 (95% CI 1.06-1.25); at or after 45: both null (HR 0.95 and 0.99). Each 5-year increase in age at surgery linked to HR 0.89 (95% CI 0.83-0.97) for combined morbidity/mortality outcome
Funding / conflicts: Funding statement in the paper: one author was supported by the National Institute for Health and Care Research, and the University of Birmingham paid the article processing charges; the funders had no role in the study. Conflict statement in the PubMed record: None reported.
Date: Oct 2, 2026