Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites

Epidemiology. 2006 Nov;17(6):682-91. doi: 10.1097/01.ede.0000235996.89953.d7.


Background: Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites.

Methods: Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid-phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry.

Results: There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters.

Conclusion: The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites.

Publication types

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

MeSH terms

  • Adult
  • Chromatography, High Pressure Liquid
  • Confidence Intervals
  • Diethylhexyl Phthalate / adverse effects
  • Diethylhexyl Phthalate / metabolism*
  • Diethylhexyl Phthalate / urine
  • Humans
  • Infertility, Male / chemically induced*
  • Infertility, Male / urine
  • Male
  • Middle Aged
  • Phthalic Acids / adverse effects
  • Phthalic Acids / metabolism*
  • Phthalic Acids / urine*
  • Reference Values
  • Semen / drug effects*
  • Sperm Count
  • Sperm Motility / drug effects


  • Phthalic Acids
  • Diethylhexyl Phthalate
  • butylbenzyl phthalate
  • monobutyl phthalate