Associations between urinary phthalate metabolite mixtures, semen quality, and serum reproductive hormone levels in Japanese men seeking fertility treatment.

Phthalate mixtures may adversely affect men's reproductive functioning. This study aimed to analyze the association between exposure to phthalate mixtures, semen quality, and reproductive hormone concentrations in Japanese men seeking fertility treatment. This cross-sectional study analyzed data from 197 Japanese adult males who visited clinics for infertility consultations in 2020 and 2021. Semen samples were collected to measure volume, sperm count, sperm concentration, and motility. Spot urine samples were collected to quantify phthalate monoesters, specifically phthalate diester metabolites, using liquid chromatography-tandem mass spectrometry. Serum concentrations of testosterone, estradiol, luteinizing hormone, follicle-stimulating hormone, and prolactin were obtained from clinical records. Three statistical methods-weighted quantile sum regression, quantile g-computation, and Bayesian kernel machine regression-were applied. Urinary concentrations of phthalate metabolite mixtures were positively associated with sperm motility, with monoethyl phthalate being the most important contributor to the observed association. No significant associations were found between phthalate mixtures and semen volume, sperm count, or concentration. These associations were consistent across all three statistical methods. Higher urinary concentrations of phthalate metabolite mixtures were associated with lower testosterone and higher prolactin concentrations in serum; however, there were no significant associations between phthalate mixtures or individual phthalate metabolites and estradiol, follicle-stimulating hormone, or luteinizing hormone concentrations. Higher exposure to phthalate mixtures may be associated with increased sperm motility and serum prolactin and reduced serum testosterone concentrations. Overall, these findings suggest that even at a relatively low level, exposure to phthalate mixtures may affect male reproductive health.