Relating Phthalate and BPA Exposure to Metabolism in Peripubescence: The Role of Exposure Timing, Sex, and Puberty

J Clin Endocrinol Metab. 2016 Jan;101(1):79-88. doi: 10.1210/jc.2015-2706. Epub 2015 Nov 3.


Context: Exposure to endocrine-disrupting chemicals during development may play a role in the increasing prevalence of metabolic syndrome and type 2 diabetes among children and adolescents by interfering with metabolic homeostasis.

Objective: To explore associations between in utero and peripubertal urinary phthalate metabolite and bisphenol A (BPA) concentrations and markers of peripubertal metabolic homeostasis.

Design: Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT): a longitudinal cohort study of pregnant women in Mexico City and their offspring.

Setting: Public maternity hospitals in Mexico City.

Patients or other participants: Women recruited during pregnancy; offspring recruited for follow-up at age 8-14 years (n = 250).

Interventions: None.

Main outcome measures: Fasting serum c-peptide, IGF-1, leptin, and glucose concentrations among children at follow-up; calculated measures of insulin secretion and insulin resistance.

Results: Phthalate metabolites and BPA were associated with metabolism biomarkers at age 8-14 years in patterns that varied by sex, pubertal status, and exposure timing. For example, in utero monoethyl phthalate was associated with lower insulin secretion among pubertal boys (P = .02) and higher leptin among girls (P = .04). In utero di-2-ethylhexyl phthlate was associated with higher IGF-1 among pubertal girls; peripubertal di-2-ethylhexyl phthlate was associated with higher IGF-1, insulin secretion, and resistance among prepubertal girls. In contrast, peripubertal dibutyl phthalate, monobenzyl phthalate, and mono-3-carboxypropyl phthalate were associated with lower IGF-1 among pubertal boys. Peripubertal BPA was associated with higher leptin in boys (P = .01).

Conclusions: Considering the long-term health effects related to metabolic syndrome, additional research on exposure and metabolic outcomes across developmental periods and early adulthood is needed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Benzhydryl Compounds / toxicity*
  • Biomarkers / blood
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Cohort Studies
  • Diethylhexyl Phthalate / toxicity*
  • Diethylhexyl Phthalate / urine
  • Endocrine Disruptors / toxicity*
  • Energy Metabolism / drug effects
  • Environmental Exposure / adverse effects
  • Female
  • Homeostasis
  • Humans
  • Infant, Newborn
  • Insulin Resistance
  • Leptin / blood
  • Longitudinal Studies
  • Male
  • Mexico / epidemiology
  • Middle Aged
  • Phenols / toxicity*
  • Pregnancy
  • Puberty / metabolism*
  • Sex Factors
  • Young Adult


  • Benzhydryl Compounds
  • Biomarkers
  • Blood Glucose
  • Endocrine Disruptors
  • Leptin
  • Phenols
  • Diethylhexyl Phthalate
  • bisphenol A