Developmental effect modification of DEHP exposure and serum testosterone levels in a Taiwanese population-based...

Di-(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer and pervasive endocrine-disrupting chemical. Whether endocrine responses to DEHP vary across developmental stages remains incompletely understood. We conducted a cross-sectional analysis of 771 individuals (239 adolescents and 532 young adults; age 12-30 years) from a Taiwanese cohort (2006-2008) to examine associations between urinary DEHP metabolites and serum testosterone levels, and to assess developmental effect modification. Urinary mono-2-ethylhexyl phthalate (MEHP) and the molar sum of DEHP metabolites (∑DEHP) were measured using HPLC-MS/MS and adjusted for creatinine. Serum total testosterone and free testosterone concentrations were measured using an immunoluminometric assay with an Architect random access assay system (Abbott Diagnostics, Abbott Park, IL). Multivariable linear regression models were used to evaluate associations between urinary phthalate metabolite concentrations and serum testosterone levels. Higher MEHP concentrations were inversely associated with total testosterone (P for trend = 0.002) and free testosterone (P for trend = 0.007), with stronger associations in adolescents. Adolescent males in the highest exposure category (≥90th percentile) had approximately 30% lower total testosterone than those in the lowest category (<50th percentile). Associations were attenuated in adults, and estradiol showed no consistent trends. These findings suggest that environmental DEHP exposure is associated with reduced androgen concentrations, with greater effects during adolescence, indicating heightened endocrine susceptibility during this developmental stage.