Association between novel per- and poly-fluoroalkyl substances and premature ovarian insufficiency: a case-control study.
Level 4 - case-series / case-control
Retrospective case-control study
PubMed 40740667 · doi:10.1093/hropen/hoaf044
What was done
A retrospective case-control study in China evaluated the relationship between 13 novel per- and poly-fluoroalkyl substances (PFAS) and premature ovarian insufficiency (POI) in 371 women (151 cases and 220 controls) recruited between June 2023 and May 2024. Novel PFAS concentrations and basal reproductive hormones (FSH, LH, estradiol, AMH) were quantified from plasma samples collected during days 2–5 of a natural menstrual cycle. Multivariable logistic regression and Bayesian kernel machine regression (BKMR) were used to analyze individual PFAS and mixture associations with POI risk.
What was found
Concentrations of HFPO-DA, PFBA, PFPeA, and PFPeS were significantly higher in women with POI compared to controls. Per 2.7-fold increase in novel PFAS concentrations, adjusted odds ratios for POI were: - HFPO-DA: aOR = 2.89 (95% CI: 1.84–4.53) - PFBA: aOR = 1.54 (95% CI: 1.17–2.02) - PFPeA: aOR = 3.12 (95% CI: 2.20–4.43) - PFPeS: aOR = 2.07 (95% CI: 1.31–3.27) High novel PFAS concentrations correlated negatively with AMH and antral follicle count, and positively with FSH. In BKMR mixture models, HFPO-DA, PFBA, PFBS, PFPeA, and PFPeS were the major contributors to elevated POI risk.
Why it matters
As legacy PFAS are phased out globally, newer short-chain and ether-based substitutes are increasingly detected in humans. This study provides early clinical evidence linking novel PFAS exposure, individually and in mixtures, to reduced ovarian reserve and higher POI risk.
Limits
The retrospective case-control design cannot establish temporality or exclude reverse causality. The study included a single-center sample (n = 371), relied on single-timepoint plasma measurements, and could not fully exclude false-positive associations or residual confounding from unmeasured environmental chemicals.
Cited by
- supports Endocrine-disrupting chemicals (EDCs) are associated with an increased risk of premature ovarian insufficiency.