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

In a population-based study of postmenopausal women, late age at first andlastbirthwereprotective for mortality, whereas longer maternal lifespan, postmaternal fertile lifespan, and estrogen exposure were harmful.

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Volume 107, Issue 2, Pages 448–456


Loes Jaspers, M.D., Maryam Kavousi, M.D., Ph.D., Nicole S. Erler, Dipl.-Stat., Albert Hofman, M.D., Ph.D., Joop S.E. Laven, M.D., Ph.D., Oscar H. Franco, M.D., Ph.D.



To characterize the relation between established and previously unexplored characteristics of the fertile life with all-cause and cause-specific mortality.


Prospective cohort study.


Not applicable.


A total of 4,076 postmenopausal women.


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.


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.


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.

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Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders.