Associations Between PFAS Exposure and HPG Axis Hormones in U.S. Women

Purpose: This study aimed to investigate the associations between serum per- and polyfluoroalkyl substances (PFAS) and reproductive hormones, including follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol, and progesterone, in U.S. women. Approach and Results: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. The study included 612 women aged ≥18 years with available PFAS and sex hormone measurements. Serum concentrations of four major PFASs (linear perfluorooctanoic acid [n-PFOA], perfluorooctane sulfonic acid [PFOS], perfluorononanoic acid [PFNA], and perfluorohexane sulfonic acid [PFHxS]) were analyzed, along with serum levels of FSH, AMH, estradiol, and progesterone measured by isotope dilution liquid chromatography-tandem mass spectrometry. Higher serum PFAS concentrations were associated with increased FSH and decreased AMH, estradiol, and progesterone. For example, each interquartile range (IQR) increase in ln-PFNA was associated with a 42.0% increase in ln-FSH (p = 0.01) and 32.2% lower ln-AMH (p < 0.001), 33.0% lower ln-estradiol (p = 0.004), and 40.9% lower ln-progesterone (p = 0.02). A PFAS exposure index was related to higher FSH and lower AMH, estradiol, and progesterone, with stronger effects in premenopausal women. Conclusions: PFAS exposure was linked to broad endocrine disruption in women, with consistent alterations across gonadotropins and sex steroids. These findings suggest that PFAS exposure was associated with hormonal patterns consistent with diminished ovarian reserve and potential changes in reproductive function, underscoring the need for longitudinal studies and regulatory actions to mitigate exposure.