Associations between urinary phthalate metabolites and reproductive, adrenal, and gonadotropic hormones in peripubertal children: the Hokkaido study

Phthalates have raised concerns regarding the disruption of hormone synthesis and signaling. The purpose of this study was to investigate the associations between urinary phthalate metabolites and 18 hormones, including reproductive, adrenal, and gonadotropic hormones, in peripubertal children. The study comprised a cross-sectional analysis of participants in the Hokkaido Birth Cohort Study. We collected data from 429 school children aged 9-12 living in Sapporo, Japan. Ten phthalate metabolites and 14 steroid hormones were analyzed using LC-MS/MS, whereas four peptide hormones were detected using immunoassays. Multivariable linear regression, quantile-based g-computation (qg-computation), and Bayesian kernel machine regression (BKMR) were used to investigate the associations between the individual phthalate metabolites and the phthalate mixtures with hormone levels, as well as with puberty based on hormone levels. In girls, we found that higher phthalate metabolite levels, as well as phthalate mixtures, were significantly associated with lower dehydroepiandrostenedione-sulfate (DHEA-S) and higher (androstenedione + testosterone)/DHEA-S. The higher phthalate mixture showed lower levels of LH, FSH, and cortisol levels among girls, whereas higher 11-deoxycortisol levels. In boys, a higher phthalates mixture was significantly associated with a higher estradiol/testosterone ratio, whereas lower levels of insulin-like factor-3 (INSL3), testosterone, (androstenedione + testosterone)/DHEA-S, testosterone/androstenedione, and cortisol/cortisone. Higher phthalate mixtures were associated with lower prevalence of puberty in girls. These findings indicate that phthalate exposure may disrupt the hormones in children during puberty.