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

Abstract

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.

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-PFOS, Σ3,4,5m-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 [adjusted odds ratio (aOR)=1.20 (95% CI: 1.06, 1.37)]. After controlling for other PFAS homologs, 6:2 Cl-PFESA, HFPO-DA, Σ3,4,5m-PFOS, 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-PFOS, and PFDoA being the major contributors, especially in overweight/obese women. https://doi.org/10.1289/EHP11814.

• Authors: Wenqiang Zhan, Wei Qiu, Yan Ao, Wei Zhou, Yun Sun, Han Zhao, Jun Zhang
• Journal: Environmental health perspectives (Environ Health Perspect) Vol. 131 Issue 5 Pg. 57001 (05 2023) ISSN: 1552-9924 [Electronic] United States
• PMID: 37134253 (Publication Type: Multicenter Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate
• perfluorooctane sulfonic acid
• Fluorocarbons
• perfluorododecanoic acid
• perflexane
• Alkanesulfonic Acids
• Alkanesulfonates
• Environmental Pollutants

Topics

• Humans
• Female
• Polycystic Ovary Syndrome (epidemiology)
• Case-Control Studies
• Bayes Theorem
• Overweight
• Fluorocarbons
• Environmental Exposure
• Alkanesulfonic Acids (analysis)
• Infertility
• Alkanesulfonates (analysis)
• Obesity
• Environmental Pollutants