The mixture of non-persistent endocrine-disrupting chemicals in relation to endometriosis

Non-persistent endocrine-disrupting chemicals (EDCs) are of significant concern due to their reproductive toxicity. Previous research reported a relationship between a single type of EDCs and endometriosis. Yet, evidence regarding mixed exposure of multiple categories of EDCs is scarce. Between 2014 and 2018, our hospital-based case-control study recruited 238 endometriosis cases diagnosed by laparoscopy and 296 normal controls in China. Seventeen non-persistent EDCs (phthalates and bisphenols) were measured in urine. The association of single EDC with endometriosis was estimated using logistic regression, while the association between EDC mixture and endometriosis was modeled by Bayesian kernel machine regression (BKMR), quantile-based g-computation (q-gcomp), and principal component analysis (PCA). Consistent results were observed in both single and mixture models where phthalates and bisphenols were associated with increased risk of endometriosis (mixture effect: adjusted odds ratio (aOR)=1.44, 1.22-1.70) and the major contributors were bisphenol A (BPA) and the metabolites of di(2-ethylhexyl) phthalate (DEHP). Interaction analysis showed that bisphenols exhibited significant synergistic interactions with phthalates. Our results suggest that non-persistent EDCs are associated with endometriosis but the underlying mechanisms remain to be elucidated. Our finding may have important public health implications in preventing endometriosis.