Pubertal development after unintended intrauterine exposure to oral contraceptives: a nationwide cohort study

Objective: To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls. Design: Population-based cohort study. Setting: Not applicable. Patient(s): Overall, 15,800 children (70%) born during 2000-2003 into the Danish National Birth Cohort were categorized according to maternal use of combined oral contraceptive pills or progestin-only pills reported around gestational week 17: no exposure (reference), exposure 4 months before conception, and exposure in early pregnancy. Children self-assessed pubertal status using Web-based questionnaires from 11 years and biannually throughout puberty. Intervention(s): None. Main Outcome Measure(s): Adjusted mean age differences (months) for attaining individual pubertal milestones and overall pubertal timing. Proportion mediated by prepubertal body mass index. Result(s): In boys, intrauterine exposure to oral contraceptives showed a tendency toward slightly earlier mean age for voice break (months, -3.8; 95% confidence interval [CI] -6.5, -1.0) and first ejaculation (months, -2.9; 95% CI -5.9, 0.1) and a mean difference of -1.4 months (95% CI -3.3, 0.4) for overall pubertal timing. Girls with intrauterine exposure tended to have slightly earlier age at menarche (months, -1.9; 95% CI -4.0, 0.3) and Tanner breast stages and had a mean difference of -0.9 months (95% CI -2.7, 1.0) for overall pubertal timing. Exposure before conception was not associated with pubertal timing. Prepubertal body mass index did not play a mediating role. Conclusion(s): This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing. ((C) 2019 by American Society for Reproductive Medicine.)