Age at Menopause As a Risk Factor for Cardiovascular Mortality

Background: Although an association of occurrence of menopause and subsequent oestrogen deficiency with increased cardiovascular disease has been postulated, studies on this association have not shown convincing results. We investigated whether age at menopause is associated with cardiovascular mortality risk.

Methods: We studied a cohort of 12115 postmenopausal women living in Utrecht, Netherlands, aged 50-65 years at enrolment in a breast cancer screening project. During follow-up of up to 20 years the women attended screening rounds at which we asked questions on menopausal status, age of menopause, medication use, cardiovascular risk factors, and ovarian function. Deaths were ascertained from the patient's family physicians. Life-table analysis and Cox regression analysis were used to investigate the association between aga at menopause and cardiovascular mortality. All analyses were adjusted for biological age.

Findings: 824 women died of cardiovascular causes. 1459 women had left the study area. The risk of cardiovascular mortality was higher for women with early menopauses than for those with late menopauses. The age-adjusted hazard ratio of age at menopause was 0.982 (95% CI 0-968-0-996, p=0.01)_ie, for each year's delay in the menopause the cardiovascular mortality risk decreased by 2%. The extra risk of early menopause seemed to decrease with biological age (p for interaction 0.07); at biological age 60 the reduction of the annual hazard was 3%, but at age 80 there was no reduction. Adjustment for known cardiovascular risk factors and indicators of ovarian function did not significantly alter the risk estimate.

Interpretation: These results support the hypothesis that longer exposure to endogenous oestrogens protects against cardiovascular diseases. The effect of an early menopause may be more important at younger biological ages.