Background
Per- and polyfluoroalkyl substances (PFAS) have been previously linked to polycystic ovarian syndrome (PCOS), but only a few legacy PFAS were examined. Objectives: 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.
Conclusions
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, Σ3,4,5m-PFOSΣ3,4,5m-PFOS<math><mrow><mo>Σ</mo><mn>3,4,5</mn><mi>m</mi><mtext>-PFOS</mtext></mrow></math>, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.
Methods
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.
Results
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, 1m-PFOS1m-PFOS<math><mrow><mn>1</mn><mi>m</mi><mtext>-PFOS</mtext></mrow></math>, Σ3,4,5m-PFOSΣ3,4,5m-PFOS<math><mrow><mo>Σ</mo><mn>3,4,5</mn><mi>m</mi><mtext>-PFOS</mtext></mrow></math>), 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 [adjusted odds ratio(aOR)=1.20adjusted odds ratio(aOR)=1.20<math><mrow><mtext>adjusted odds ratio </mtext><mo>(</mo><mtext>aOR</mtext><mo>)</mo><mo>=</mo><mn>1.20</mn></mrow></math> (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOSΣ3,4,5m-PFOS<math><mrow><mo>Σ</mo><mn>3,4,5</mn><mi>m</mi><mtext>-PFOS</mtext></mrow></math>, and PFDoA were the major contributors based on the QGC and BKMR models. The associations were more pronounced in overweight/obese women. Conclusions: 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, Σ3,4,5m-PFOSΣ3,4,5m-PFOS<math><mrow><mo>Σ</mo><mn>3,4,5</mn><mi>m</mi><mtext>-PFOS</mtext></mrow></math>, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.