Female-specific risk factors for cardiovascular morbidity and mortality in postmenopauseal women: a systematic review and meta-analysis

The objective was to systematically evaluate the association between selected female reproductive factors (age at menopause, type of menopause, menstrual cycle, number of children, age at first birth, history of pregnancy loss, and use of hormonal contraceptives) and cardiovascular outcomes in postmenopausal women without prior cardiovascular disease.

We conducted a systematic review and meta-analysis following PRISMA guidelines. PubMed, EMBASE, and Scopus were searched from inception to 6 February 2026. Observational studies assessing associations between reproductive factors and cardiovascular outcomes were included. Pooled effect estimates (PEEs) were calculated by combining odds ratios, risk ratios, and hazard ratios through their regression coefficients on the log scale. Heterogeneity was assessed using the I² statistic. Publication bias and sensitivity analyses were performed. We used the Joanna Briggs Institute critical appraisal tools to assess risk of bias, and applied the GRADE approach to assess evidence certainty. Thirty-four studies were included, of which 18 contributed to the meta-analysis. A later age at menopause was associated with a lower risk of cardiovascular events (per 5-year increase: PEE 0.94, 95% CI 0.90–0.98), although no clear association was observed for cardiovascular mortality. The number of children (PEE 0.99, 95% CI 0.96–1.01) and age at first childbirth (PEE 0.99, 95% CI 0.97–1.00) showed little to no association with cardiovascular outcomes. A history of pregnancy loss showed no significant association in the overall analysis (PEE 1.22, 95% CI 0.93–1.61), although results were sensitive to individual studies. Substantial heterogeneity was observed across analyses. Evidence on type of menopause and contraceptive use was limited and heterogeneous, precluding quantitative synthesis. Overall, the certainty of the evidence ranged from low to very low.

In postmenopausal women without prior CVD, later age at menopause may be associated with a lower risk of cardiovascular events. No clear associations were observed for number of children, age at first childbirth or pregnancy loss. Further high-quality prospective studies with longer follow-up are needed, and evidence remains insufficient for some reproductive factors.