Environmental Exposure to Emerging Alternatives of Per- and Polyfluoroalkyl Substances and Polycystic Ovarian Syndrome in Women Diagnosed with Infertility: A Mixture Analysis

By Wenqiang Zhan, Wei Qiu, Yan Ao, Wei Zhou, Yun Sun, Han Zhao, and Jun Zhang
Environ Health Perspect
May 3, 2023
DOI: 10.1289/EHP11814


Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined.


This study aimed to explore this association with a variety of PFAS, including legacy, branched-chain isomers, and emerging alternatives, as well as a PFAS mixture.


From 2014 to 2016, we conducted a multicenter, hospital-based case-control study on environmental endocrine disruptors and infertility in China. Three hundred sixty-six women with PCOS-related infertility and 577 control participants without PCOS were included in the current analysis. Twenty-three PFAS, including 3 emerging PFAS alternatives, 6 linear and branched PFAS isomers, 6 short-chain PFAS, and 8 legacy PFAS, were quantified in the plasma. Logistic regression and two multipollutant models [quantile-based g-computation (QGC) and Bayesian kernel machine regression (BKMR) methods] were used to assess the association of individual PFAS and PFAS mixture with PCOS, as well as the potential interactions among the congeners.


After adjusting for potential confounders, Each 1-standard deviation higher difference in ln-transformed 6:2 chlorinated perfluoroalkyl ether sulfonic acid (6:2 Cl-PFESA) and hexafluoropropylene oxide dimer acid (HFPO-DA) level was significantly associated with a 29% (95% CI: 1.11, 1.52) and 39% (95% CI:1.16, 1.68) higher odds of PCOS, respectively. Meanwhile, branched isomers of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) (i.e., br-PFHxS, n-PFOS, , ), short-chain PFAS (i.e., PFPeS and PFHxA) and other legacy PFAS [i.e., total concentrations of PFOS (T-PFOS), and perfluorododecanoic acid (PFDoA)] were significantly associated with increased odds of PCOS. The PFAS mixture was positively related to PCOS in the BKMR model. A similar trend was observed in QGC model, a ln-unit increase in the PFAS mixture was associated with a 20% increased risk of PCOS [ (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, , and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women.


In this group of women, environmental exposure to a PFAS mixture was associated with an elevated odds of PCOS, with 6:2 Cl-PFESA, HFPO-DA, , and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

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