Phthalate excretion pattern and testicular function: a study of 881 healthy Danish men.

In animals, some phthalates impair male reproductive development and function. Epidemiological studies have reported inconsistent evidence of associations between phthalates and markers of human testicular function. We aimed to provide estimates of the effects of phthalate exposure on reproductive hormone levels and semen quality in healthy men. A total of 881 men gave urine, serum, and semen samples. Serum levels of testosterone, estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and inhibin-B; semen quality; and urinary concentrations of 14 phthalate metabolites, including metabolites of di(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DiNP), were assessed. The proportions of DEHP and DiNP excreted as their respective primary metabolites [mono(2-ethylhexyl) phthalate (MEHP) and mono-isononyl phthalate (MiNP)] were calculated and expressed as percentages (%MEHP and %MiNP, respectively). The free androgen index was 15% lower [95% confidence interval (CI): -23, -8%] for men in the highest %MiNP quartile compared to the lowest quartile (p < 0.001) after adjusting for confounders, and 9% lower (95% CI: -16, -1%) in the highest %MEHP quartile (p = 0.02). %MEHP and %MiNP were negatively associated with the ratio of testosterone/LH and testosterone/FSH. %MEHP was negatively associated with total testosterone, free testosterone, and ratio of testosterone/E(2). %MiNP was positively associated with SHBG. There was little evidence of associations between urinary phthalate metabolites or sums of phthalates with reproductive hormones or semen quality. Our data suggest that both testosterone production and pituitary-hypothalamic feedback may be compromised in individuals excreting a high proportion of primary metabolites of long-chained phthalates relative to the proportion of secondary metabolites.