Environmental exposure to legacy and emerging per- and polyfluoroalkyl substances and endometriosis in women of childbearing age

Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals known for their adverse effects on humans. Growing concern has risen regarding the reproductive toxicity of PFAS, but whether PFAS affect endometriosis remains to be explored. This hospital-based case-control study included 240 laparoscopic-confirmed endometriosis cases and 334 normal controls in China from 2014 to 2018. Concentrations of thirty-three legacy and emerging PFAS were measured in the plasma samples. Associations between single PFAS and endometriosis were estimated by binary logistic regression. The elastic net regression (ENR) model was used to identify dominant PFAS related to endometriosis. The joint effect of the PFAS mixture on endometriosis was assessed by principal component analysis (PCA), Bayesian kernel machine regression (BKMR), and quantile-based g-computation (qgcomp). In the single-PFAS model, significant positive associations of PFOA [adjusted odds ratio (95 % CI): 1.22 (1.00, 1.51)], total PFOS [1.19 (1.05, 1.34)] and two branched PFOS isomers [1.16 (1.09, 1.22) for 1m-PFOS; 1.18 (1.04, 1.34) for 6m-PFOS] with increased endometriosis odds were observed. Mixture models showed that the joint effect of PFAS mixture on endometriosis was significant [1.24 (1.05, 1.48)], mainly driven by 1m PFOS. The PFOS isomers profile suggested a PFOS precursor biotransformation source of 1m-PFOS in our pop-ulation. Our study suggests that branched isomers of PFOS may be associated with endometriosis.