In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation

Deborah J Watkins, Martha Maria Téllez-Rojo, Kelly K Ferguson, Joyce M Lee, Maritsa Solano-Gonzalez, Clara Blank-Goldenberg, Karen E Peterson, John D Meeker
Environmental Research 2014, 134: 233-41
The age of pubertal onset for girls has declined over past decades. Research suggests that endocrine disrupting chemicals (EDCs) may play a role but exposure at multiple stages of development has not been considered. We examined in utero and peripubertal exposure to bisphenol-A (BPA) and phthalates in relation to serum hormones and sexual maturation among females in a Mexico City birth cohort. We measured phthalate metabolite and BPA concentrations in urine collected from mothers during their third trimester (n=116) and from their female children at ages 8-13 years (n=129). Among girls, we measured concurrent serum hormone concentrations, Tanner stages for breast and pubic hair development, and collected information on menarche onset. We used linear and logistic regression to model associations between in utero and peripubertal measures of exposure with hormones and sexual maturation, respectively, controlling for covariates. An interquartile range (IQR) increase in in utero urinary mono-2-ethylhexyl phthalate (MEHP) was positively associated with 29% (95% CI: 9.2-52.6%) higher dehydroepiandrosterone sulfate (DHEA-S), an early indicator of adrenarche, and 5.3 (95% CI: 1.13-24.9) times higher odds of a Tanner stage >1 for pubic hair development. Similar relationships were observed with other in utero but not peripubertal di-2-ethylhexyl phthalate (DEHP) metabolites. IQR increases in in utero monobenzyl phthalate (MBzP) and monoethyl phthalate (MEP) were associated with 29% and 25% higher serum testosterone concentrations (95% CI: 4.3-59.3; 2.1-54.1), respectively. In addition, we observed suggestive associations between in utero and peripubertal MEP concentrations and increased odds of having undergone menarche, and between peripubertal MnBP concentrations and increased odds of having a Tanner stage >1 for both breast and pubic hair development. BPA was not associated with in utero or peripubertal serum hormones or sexual maturation. Our findings suggest in utero phthalate exposure may impact hormone concentrations during peripubescence and timing of sexual maturation. Efforts to control phthalate exposure during pregnancy should be of high priority.

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