Association of Di(2-ethylhexyl) Phthalate Exposure with Reproductive Hormones in the General Population and the Susceptible Population: A Systematic Review and Meta-Analysis

Di(2-ethylhexyl) phthalate (DEHP), an environmental endocrine disruptor, has hormone-like activity and endocrine-disrupting effects. However, the types of reproductive hormones associated with DEHP vary across the studies. Thus, we conducted a systematic review and meta-analysis to pool existing epidemiological evidence. We searched three databases up to January 31, 2024, for eligible original studies to ultimately include 37 studies from eight countries with a total of 28 911 participants. DEHP exposure was evaluated with urinary metabolites. Since the main types, production sites, blood concentrations, and functions of reproductive hormones differ between men and women, we reported the combined effect values by gender. Subgroup analyses were conducted by age, subfertility status, and the national sociodemographic index (SDI) level. Furthermore, the effect of maternal exposure during pregnancy on children's reproductive hormone levels was analyzed separately. Overall, in general, in men, DEHP was positively correlated with sex hormone binding-globulin (SHBG) and adversely correlated with total testosterone (TT), free androgen index (FAI), and follicle-stimulating hormone (FSH). Results indicated that among men of reproductive age, DEHP exposure was associated with more significant hormonal suppression in infertile men compared with fertile men. Notably, age subgroup analysis among women revealed that postmenopausal women were more vulnerable to DEHP, which was related to lower TT and estradiol (E2). However, this study did not observe a significant association between prenatal DEHP metabolites and reproductive hormone levels in children. Our research identifies the most susceptible hormones (androgen suppression) after DEHP exposure and suggests that infertile men and postmenopausal women are in great need of more attention as sensitive populations.