- Design
- Systematic review and meta-analysis of observational studies and trials
- Population
- 36 studies, 2,617,942 women; median follow-up 16 years
- Primary outcome
- Cardiovascular morbidity, cardiovascular and all-cause mortality
- Effect
- Cardiovascular events HR 1.25 (95% CI 1.12 to 1.39); stroke HR 1.22 (1.15 to 1.28); mortality excess only before age 45
A meta-analysis of 36 studies, with 2,617,942 women and median follow-up of 16 years, compared iatrogenic menopause with natural menopause or age-matched controls.
Iatrogenic menopause was associated with higher all-cause mortality (pooled HR 1.08, 95% CI 1.01 to 1.16), cardiovascular events (1.25, 1.12 to 1.39), coronary heart disease (1.48, 1.07 to 2.03) and stroke (1.22, 1.15 to 1.28).
Mortality excess was confined to menopause before age 45: cardiovascular mortality HR 1.20 (1.04 to 1.37) and all-cause HR 1.15 (1.06 to 1.25). At or after 45 the estimates were null. A post hoc meta-regression found each additional five years of age at menopause linked to lower risk (HR 0.89, 0.83 to 0.97).
These are observational associations. Even so, they argue for treating younger women who undergo oophorectomy or other causes of early menopause as a group needing deliberate cardiovascular follow-up, and for weighing ovarian conservation and hormone therapy individually.
- Flag women with iatrogenic menopause before 45 for cardiovascular risk review.
- Check blood pressure, lipids, glucose and smoking status, and act on what is found.
- Discuss ovarian conservation at the time of hysterectomy, weighing the indication.
- Discuss hormone therapy individually; this analysis did not test it.
Why it matters
It points to a defined window, before 45, when early menopause has the clearest link to deaths, and shifts attention from a single cut-off.
Don't overread it
These are observational pooled associations, and the age-trend meta-regression was post hoc.
The statistics, in plain English
A pooled hazard ratio of 1.25 means about a quarter higher rate of events over follow-up, not a 25% absolute chance. Confidence intervals that include 1.0, as for mortality at or after 45, mean no difference could be shown. The age-trend analysis was post hoc, so it is weaker than the headline pooled results.
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