Early Prenatal Phthalate Exposure, Sex Steroid Hormones, and Birth Outcomes

J Clin Endocrinol Metab. 2017 Jun 1;102(6):1870-1878. doi: 10.1210/jc.2016-3837.

Abstract

Context: Adequate sex steroid hormone concentrations are essential for normal fetal genital development in early pregnancy. Our previous study demonstrated an inverse relationship between third-trimester di-2-ethyl hexyl phthalate exposure and total testosterone (TT) concentrations. Here, we examine early-pregnancy phthalates, sex steroid hormone concentrations, and newborn reproductive outcomes.

Design: We examined associations between urinary phthalate metabolite concentrations in early pregnancy and serum free testosterone (FT), TT, estrone (E1), and estradiol (E2) in 591 woman/infant dyads in The Infant Development and Environment Study; we also examined relationships between hormones and newborn genital outcomes using multiple regression models with covariate adjustment.

Results: E1 and E2 concentrations were 15% to 30% higher in relation to 1-unit increases in log monoisobutyl phthalate (MiBP), mono-2-ethyl hexyl phthalate, and mono-2-ethyl-5-oxy-hexyl phthalate concentrations, and E2 was 15% higher in relation to increased log monobenzyl phthalate (MBzP). FT concentrations were 12% lower in relation to 1-unit increases in log mono(carboxynonyl) phthalate (MCNP) and mono-2-ethyl-5-carboxypentyl phthalate concentrations. Higher maternal FT was associated with a 25% lower prevalence of having a male genital abnormality at birth.

Conclusions: The positive relationships between MiBP, MBzP, and DEHP metabolites and E1/E2 are unique and suggest a positive estrogenic effect in early pregnancy. The inverse relationship between MCNP and DEHP metabolites and serum FT supports previous work examining phthalate/testosterone relationships later in pregnancy. Higher FT in relation to a 25% lower prevalence of male genital abnormalities confirms the importance of testosterone in early fetal development.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Chromatography, Liquid
  • Cryptorchidism / epidemiology
  • Disorders of Sex Development / epidemiology
  • Estradiol / blood*
  • Estrone / blood*
  • Female
  • Humans
  • Hypospadias / epidemiology
  • Infant, Newborn
  • Linear Models
  • Male
  • Phthalic Acids / urine*
  • Pregnancy
  • Pregnancy Trimester, First
  • Prenatal Exposure Delayed Effects / blood
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Tandem Mass Spectrometry
  • Testicular Hydrocele / epidemiology
  • Testosterone / blood*
  • United States / epidemiology
  • Urogenital Abnormalities / epidemiology*
  • Young Adult

Substances

  • Phthalic Acids
  • Estrone
  • Testosterone
  • Estradiol