Association of In Utero Exposures with Risk of Early Natural Menopause

Abstract

Abstract Suboptimal pregnancy conditions may impact ovarian function of the fetus and be associated with early natural menopause (EM) for offspring.106,633 premenopausal participants in the Nurses’ Health Study II who provided data on prenatal characteristics including diethylstilbestrol (DES) exposure, cigarette smoke exposure, multiplicity, prematurity, and birth weight were followed from 1989-2017. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of in utero exposures with EM. During 1.6 million person-years of follow-up, 2,579 participants experienced EM. In multivariable models, women with prenatal DES exposure had higher risk of EM versus those without (HR = 1.33, 95% CI: 1.06, 1.67). Increased risk of EM was observed for those with low (<2.5 kg) versus normal (3.2-3.8 kg) birthweight (HR = 1.21, 95% CI: 1.01, 1.45). Decreasing risk was observed per 1-pound (0.45 kg) of higher birth weight (HR = 0.93, 95% CI: 0.90, 0.97). Prenatal smoke exposure, being part of a multiple birth, and prematurity were not associated with EM. In this large cohort study, lower birth weight and prenatal DES exposure were associated with higher risk of EM. Our results support future research to examine in utero exposures that may affect offspring reproductive health.