Association of emerging alternatives to per- and polyfluoroalkyl substances with polycystic ovary syndrome among Chinese women: a case-control study.

Per- and polyfluoroalkyl substances (PFAS) have been previously associated with polycystic ovary syndrome (PCOS). However, the health effects of emerging PFAS alternatives on PCOS remain unclear. This study aims to examine the associations between exposure to emerging PFAS alternatives and the odds of PCOS, while also exploring the combined effects of PFAS mixture exposure. From 2019 to 2024, we conducted a case-control study in Jiangsu Province, China, including 94 women diagnosed with PCOS and 81 healthy controls. Serum concentrations of 25 PFAS were quantified using liquid chromatography-tandem mass spectrometry. Firth penalized maximum likelihood estimation and Bayesian kernel machine regression (BKMR) were used to assess associations between individual PFAS, PFAS mixture, and PCOS, as well as potential interactions among PFAS. After adjusting for potential confounders, 14 PFAS were identified as being associated with PCOS. Specifically, 2 emerging alternatives (FTSA (6/2) and HFPO-DA (GenX)), one precursor (FBSA), one long-chain legacy (PFNA), and 2 short-chain (PFHpA and PFPeS) were positively associated with increased odds of PCOS. HFPO-DA (GenX) exhibited the highest odds ratio (OR: 9.26; 95% CI: 4.16, 20.59). In contrast, the alternative F-53B(8/2) was negatively associated with PCOS (OR: 0.40; 95% CI: 0.25, 0.63). The BKMR model suggested that the PFAS mixture had a significant positive overall effect on PCOS. No significant interactions were observed. This study suggests that environmental exposure to PFAS mixtures was associated with an increased odds of PCOS, particularly with emerging PFAS alternatives. These findings highlight the need for further research on the health effects of PFAS and their regulatory implications.