Abstract

Abstract Study question What is the association between serum per- and poly-fluoroalkyl substances (PFAS) concentrations and polycystic ovary syndrome (PCOS) risk in populations with low-level PFAS exposure. Summary answer Higher serum concentrations of perfluorooctane sulfonate (PFOS) and perfluorohexane sulfonate (PFHxS) were associated with elevated risk of PCOS among women attending a U.S. fertility clinic. What is known already Previous studies reported that exposure to high-levels of PFAS exposure was associated with elevated risk of PCOS. However, studies evaluating PCOS risk in populations with exposure to lower levels of PFAS are limited. Study design, size, duration A cohort study of 502 females who sought fertility evaluation for medically assisted reproduction in a U.S. fertility clinic and had similar PFAS exposure level as the general U.S. population. Participants/materials, setting, methods Nine PFAS were quantified in non-fasting serum samples collected at study entry. Diagnosis of PCOS was based on the Rotterdam criteria after study entry before treatment. We used logistic regression to examine the odds ratio (OR) of PCOS in relation to PFAS concentrations (continuous and by tertiles). We applied quantile g-computation (QGC) and Bayesian Kernel Machine Regression (BKMR) to examine the joint associations of PFAS mixture with PCOS. Main results and the role of chance A total of 38 (7.6%) females were diagnosed with PCOS. Doubling of serum PFOS and PFHxS concentrations were associated with higher odds of PCOS [OR (95%CI): 1.70 (1.06, 2.81) and 1.45 (1.02, 2.08), respectively]. There was a dose-response relationship of PFOS with PCOS risk (p of trend by tertiles = 0.07). Both QGC and BKMR identified PFOS as the most important contributor among the PFAS mixture to PCOS risk. No clear joint effect was found for other examined PFAS nor for PFAS as a total mixture on PCOS risk. Limitations, reasons for caution Findings in this subfertile population may not be directly generalizable to reproductive aged women in the general population. Wider implications of the findings Our findings are consistent with existing evidence from populations with higher concentrations of some of the evaluated PFAS and supports the potential adverse effects of PFAS on female reproductive function. Larger prospective studies are needed to validate the findings. Trial registration number NA

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