Onset and tempo of sexual maturation is differentially associated with gestational phthalate exposure between boys and girls in a Mexico City birth cohort

Phthalates are endocrine disrupting compounds commonly found in consumer products, exposure to which may influence reproductive maturation. Effects from exposure in utero on the onset and progression of sexual development are understudied. We examined longitudinal associations between gestational phthalate exposure and sexual maturation at two points in adolescence (8-14, 9-18 years). Gestational exposure was quantified using the geometric mean of 3 trimester-specific urinary phthalate metabolite measurements. Sexual maturation was assessed using Tanner stages and menarche onset for girls and Tanner stages and testicular volume for boys. Generalized estimating equations for correlated ordinal multinomial responses were used to model relationships between phthalates and odds of transitioning to the next Tanner stage, while generalized additive (GA) mixed models were used to assess the odds of menarche. All models were adjusted for child age (centered around the mean), BMI z-score, change in BMI between visits, time (years) between visits (Delta T), and interactions between Delta T and mean-centered child age and the natural log of exposure metabolite concentration. Among girls, a doubling of gestational MBzP concentrations was associated with increased odds of being at a higher Tanner stage for breast development at 8-14 years (OR = 4.62; 95% CI: 1.38, 15.5), but with slower progression of breast development over the follow-up period (OR = 0.65 per year; 95% CI: 0.46, 0.92) after adjustment for child age and BMI z-score. Similar results were found for Sigma DEHP levels and breast development. In boys, a doubling of gestational MBP concentrations was associated with lower odds of being at a higher Tanner stage for pubic hair growth at 8-14 years (OR = 0.37; 95% CI: 0.14, 0.95) but with faster progression (OR: 1.28; 95% CI: 0.97, 1.69). These results indicate that gestational phthalate exposures may impact the onset and progression of sexual development, and that these relationships differ between boys and girls.