Foetal exposure to phthalate esters and anogenital distance in male newborns

Int J Androl. 2012 Jun;35(3):236-44. doi: 10.1111/j.1365-2605.2011.01190.x. Epub 2011 Jun 22.


Phthalate esters, commonly used as plasticizers, show anti-androgenic activity and cause male reproductive malformation in experimental animals. However, the effects of prenatal exposure to phthalate esters in humans have not been extensively studied. The purpose of this study was to examine the relationship between prenatal exposure to phthalate esters and the anogenital distance (AGD) as a reproductive endpoint in human male newborns. Spot urine samples were collected from 111 Japanese pregnant women after obtaining their informed consent. Seven urinary phthalate ester metabolites were determined by high performance liquid chromatography-tandem mass spectrometry. Urinary isoflavones concentrations were measured as possible covariates because their oestrogenicities and high exposure levels among Japanese have the potential to affect male genital development. Birth outcomes and AGD, the distance from the centre of the anus to external genitalia, were measured for their male newborns. In a multiple regression model, the log-transformed mono-2-ethylhexyl phthalate concentration (specific gravity-corrected) was negatively significant, and maternal smoking status was positively significant, in explaining anogenital index (AGI) when potential covariates were controlled for. Urinary isoflavones did not significantly contribute to AGI in any models. Our results suggest that prenatal exposure to di(2-ethylhexyl) phthalate affects reproductive development in human males.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Diethylhexyl Phthalate / analogs & derivatives
  • Environmental Pollutants / pharmacology
  • Equol / urine
  • Esters / pharmacology
  • Female
  • Genitalia, Male / drug effects
  • Genitalia, Male / embryology
  • Humans
  • Infant, Newborn
  • Isoflavones / urine
  • Male
  • Phthalic Acids / pharmacology
  • Phthalic Acids / urine*
  • Plasticizers / pharmacology
  • Pregnancy / urine
  • Prenatal Exposure Delayed Effects
  • Regression Analysis
  • Smoking / epidemiology


  • Environmental Pollutants
  • Esters
  • Isoflavones
  • Phthalic Acids
  • Plasticizers
  • Equol
  • daidzein
  • Diethylhexyl Phthalate
  • mono-(2-ethylhexyl)phthalate