Fertile lifespan characteristics and all-cause and cause-specific mortality among postmenopausal women: the Rotterdam Study

Objective To characterize the relation between established and previously unexplored characteristics of the fertile life with all-cause and cause-specific mortality. Design Prospective cohort study. Setting Not applicable. Patient(s) A total of 4,076 postmenopausal women. Intervention(s) Women's fertile lifespan (age at menarche to menopause), number of children, maternal age at first and last child, maternal lifespan (interval between maternal age at first and last child), postmaternal fertile lifespan (interval between age at last child and menopause), lifetime cumulative number of menstrual cycles, and unopposed cumulative endogenous estrogen (E) exposure. Main Outcome Measure(s) Registry-based all-cause and cause-specific mortality. Result(s) A total of 2,754 women died during 14.8 years of follow-up. Compared with women with 2–3 children, a 12% higher hazard of dying was found for women having 1 child (hazard ratio [HR], 1.12; 95% confidence interval [CI] 1.01–1.24), which became nonsignificant in models adjusted for confounders (HR, 1.08; 95% CI 0.96–1.21). Late age at first and last birth were associated with a 1% lower hazard of dying (HR, 0.99; 95% CI 0.98–1.00). Longer maternal and postmaternal fertile lifespan (HR 1.01; 95% CI 1.00–1.02), longer fertile lifespan (HR 1.02; 95% CI 1.00–1.05), and unopposed cumulative E exposure (HR, 1.02; 95% CI 1.00–1.04) were significantly harmful for all-cause mortality. Findings differed with regard to direction, size, and statistical significance when stratifying for cardiovascular disease, cancer, and other mortality. Conclusion(s) Overall, we found that late first and last reproduction were protective for all-cause mortality, whereas a longer maternal lifespan, postmaternal fertile lifespan, and E exposure were harmful for all-cause mortality. More research is needed in contemporary cohorts with larger sample sizes and more extreme ages of birth.