title: In utero and peripubertal exposure to phthalates and BPA in relation to female sexual maturation.
abstract: 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.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1835 SPH I, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Watkins
authors.affiliation: National Institute of Public Health, Ministry of Health, Mexico.
authors.forename: Martha Maria
authors.initials: MM
authors.lastname: Téllez-Rojo
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1835 SPH I, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Ferguson
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1835 SPH I, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Pediatric Endocrinology, Child Health Evaluation and Research Unit (CHEAR), University of Michigan, Ann Arbor, MI,USA.
authors.forename: Joyce M
authors.initials: JM
authors.lastname: Lee
authors.affiliation: National Institute of Public Health, Ministry of Health, Mexico.
authors.forename: Maritsa
authors.initials: M
authors.lastname: Solano-Gonzalez
authors.affiliation: National Institute of Public Health, Ministry of Health, Mexico.
authors.forename: Clara
authors.initials: C
authors.lastname: Blank-Goldenberg
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1835 SPH I, 1415 Washington Heights, Ann Arbor, MI 48109, USA; Center for Human Growth and Development, University of Michigan, Ann Arbor, MI, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Peterson
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan, 1835 SPH I, 1415 Washington Heights, Ann Arbor, MI 48109, USA. Electronic address: meekerj@umich.edu.
authors.forename: John D
authors.initials: JD
authors.lastname: Meeker
mesh_terms: D000293:Adolescent; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002648:Child; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D010636:Phenols / Q000633:toxicity*; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012741:Sexual Maturation; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D012739:Gonadal Steroid Hormones; D010636:Phenols; D010795:Phthalic Acids; C032279:phthalic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Adrenarche; Bisphenol A; In utero exposure; Phthalates; Sexual maturation