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

Unintended exposure to oral contraceptives in early pregnancy showed a tendency toward slightly earlier mean age at pubertal timing in boys and girls.

Volume 112, Issue 3, Pages 552–561.e2


Andreas Ernst, M.D., Lea L.B. Lauridsen, M.D., Nis Brix, M.D., Onyebuchi A. Arah, Ph.D., Jørn Olsen, Ph.D.b,, Erik T. Parner, Ph.D., Anne-Marie Nybo Andersen, Ph.D., Lars H. Olsen, D.M.Sc., Cecilia H. Ramlau-Hansen, Ph.D.



To study the associations between exposure to oral contraceptives before conception and early in pregnancy and pubertal timing in boys and girls.


Population-based cohort study.


Not applicable.


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.



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.


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.


This study shows some evidence that intrauterine exposure to oral contraceptives might slightly affect pubertal timing.

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