Early iatrogenic menopause is linked to cardiovascular risk, mainly before age 45

Design

Systematic review and random-effects meta-analysis of observational studies and trials

Population

2,617,942 women across 36 studies; median follow-up 16.0 years

Primary outcome

Cardiovascular morbidity, cardiovascular mortality and all-cause mortality

Effect

Cardiovascular events pooled HR 1.25 (95% CI 1.12 to 1.39); cardiovascular mortality before age 45 HR 1.20 (95% CI 1.04 to 1.37)

This meta-analysis pooled 36 studies covering 2,617,942 women, with a median follow-up of 16 years. Iatrogenic menopause (for example after surgery or cancer treatment) 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).

The mortality excess was confined to menopause before age 45. In that group cardiovascular mortality was 1.20 (1.04 to 1.37) and all-cause mortality 1.15 (1.06 to 1.25). At or after 45 the estimates were null (cardiovascular mortality 0.95, 0.81 to 1.11). A post hoc meta-regression found each 5 years later was associated with lower risk (HR 0.89, 0.83 to 0.97).

These are observational data, and women who have iatrogenic menopause differ from comparators in age and underlying disease. The association should prompt attention to cardiovascular risk factors in this group rather than a change in treatment on its own.

• Record the age and cause of menopause in cardiovascular risk assessment.
• Review blood pressure, lipids, glucose and smoking in women after menopause before age 45.
• Pay attention to stroke symptoms and risk factors in this group.
• Discuss menopausal hormone therapy with the gynaecologist case by case; this study does not address it.

Why it matters

It suggests the risk is a period of vulnerability before 45 rather than a single cut-off, which affects who is flagged for prevention.

Don't overread it

The studies were observational, so the association is not proof that menopause itself caused the excess risk, and the age pattern was a post hoc finding.

The statistics, in plain English

A pooled hazard ratio of 1.25 means about 25% more cardiovascular events than comparators over follow-up. The age finding comes from a post hoc meta-regression across 11 populations, which is weaker than a pre-specified analysis. Intervals for the 45-and-over mortality estimates cross 1.0, meaning no excess was detected there, not that none exists.

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