Prenatal and infant exposures and age at menarche.

Early menarche is related to increased risk of breast cancer. The number of established factors that contribute to early menarche is limited. We studied prenatal and infant exposures in relation to age at menarche in a nationwide cohort of women who have a family history of breast cancer. The study comprised 33,501 women in the Sister Study who were 35-59 years of age at baseline (2003-2009). We used polytomous logistic regression to estimate separate relative risk ratios (rRRs) and 95% confidence intervals (CIs) for associations of self-reported exposures with menarche at ≤10, 11, 14, and ≥15 years relative to menarche at 12-13 years. Early menarche (≤10 or 11 years) was associated with having low birth weight, having had a teenage mother, being firstborn, and specific prenatal exposures: mother's smoking, diethylstilbestrol (DES), prepregnancy diabetes, and pregnancy-related hypertensive disorder. Prenatal exposures most strongly associated with very early menarche (≤10 years) were DES (rRR = 1.56 [95% CI = 1.24-1.96]), maternal prepregnancy diabetes (2.24 [1.37-3.68]), and pregnancy-related hypertensive disorder (1.45 [1.18-1.79]). Soy formula was associated with both very early menarche (1.21 [0.94-1.54]) and late menarche (14 years: 1.17 [0.98-1.40] or ≥15 years: 1.28 [1.06-1.56]). Although menarche is only one marker of pubertal development, it is a commonly used surrogate. The observed associations of prenatal DES and soy formula exposure with age at menarche are consistent with animal data on exogenous estrogens and pubertal timing. Early-life exposures may confound associations between age at menarche and hormonally dependent outcomes in adults.