Phthalate exposure and human semen parameters

Background. There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. Methods. We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (20 million/ml) and motility (50% motile), as well as Tygerberg Strict criteria for morphology (4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. Results. There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile 1.0, 1.8, 3.0; P-value for trend 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend 0.07). In addition, there was a dose-response relation between tertiles of monobenzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend 0.02). Conclusions. There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates. (EPIDEMIOLOGY 2003;14:269 –277)