Abstract

Are urinary phthalate concentrations associated with altered semen quality parameters among males recruited from the general population? Urinary levels of metabolites of phthalate diesters are associated with lower total sperm counts, larger sperm head sizes, and higher percentages of morphologically abnormal sperm. High dose experiments in rats implicate phthalates as anti-androgens. Studies involving infertile men seeking care suggest that phthalates influence measures of semen quality raising concern about the implications for men in the general population. This prospective cohort study comprised 501 male partners in couples discontinuing contraception to become pregnant, who were recruited from 16 US counties using population-based sampling frameworks from 2005 to 2009. Urine and semen samples were obtained at baseline from 473 (94%) men, of whom 378 (80%) men provided a second sample the following month. Urine was analyzed for 14 monoester metabolites of phthalate diesters by high-performance liquid chromatography coupled to tandem mass spectrometry. Semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure. Urinary mono-[2-(carboxymethyl) hexyl] phthalate (MCMHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), and mono-isononyl phthalate (MNP) were significantly associated with lower total sperm counts and concentrations, larger sperm head sizes, higher proportions of megalo head sperm morphology, and/or other morphological changes. Urinary mono-methyl phthalate (MMP) and mono-cyclohexyl phthalate (MCPP) were significantly associated with lower sperm motility, and urine mono-2-ethylhexyl phthalate (MEHP) was significantly associated with higher sperm motility. While adverse associations were observed, the implications of the findings for couple fecundity and fertility remain to be established. Cautious interpretation is needed in light of reliance on a single measurement of phthalate measure and no correction for multiple comparisons.

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