Impact of In Utero and Adolescent Phthalate Exposure on Sexual Maturation Progression

Abstract

Phthalates are endocrine disrupting compounds commonly found in consumer products, exposure to which may influence reproductive maturation in adolescence. Differential effects from exposure in utero versus later in life are understudied. We examined sex-stratified longitudinal associations between the geometric mean of 3 trimester-specific spot urine phthalate measurements and sexual maturation at two points in adolescence (8-14, 9-18 years), as well as cross-sectional associations at 9-18 years. Sexual maturation was assessed using Tanner stages and menarche onset for girls (N=246) and Tanner stages and testicular volume for boys (N=226). 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. Cross-sectional analyses employed GA models (female N=281; male N=264). Among girls, MEP in utero exposure was associated with increased odds of being at a higher Tanner stage for breast development at 8-14 years, but with slower progression of breast development over the follow-up period (OR=0.74 per year; 95% CI: 0.57, 0.96) after adjustment for child age, BMI z-score and time between study visits. Similar results were found for breast development with in utero exposure to MEOHP, MBzP, and MCPP. There were no significant associations of in utero exposures with pubertal stage among boys, but concurrent MEP exposure was associated with lower odds of progression of genital development (OR=0.87; 95% CI: 0.76, 0.99). These results suggest in utero exposure to phthalates may disrupt estrogenic pathways to impact breast development during puberty, and that exposure results in earlier onset but slower progression of sexual development. In addition, MEP exposure during late adolescence may impede genital development among boys.