Prediction of endometrial tissue PFAS concentrations using serum levels, demographic, and reproductive factors: Findings from the Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) study

Background: Per- and polyfluoroalkyl substances (PFAS) accumulate in reproductive tissues, yet most studies rely on serum measurements. It remains unclear whether serum concentrations adequately reflect levels in target tissues. We evaluated whether serum PFAS predicts endometrial tissue concentrations and examined associations with endometriosis. Methods: The Investigating Mixtures of Pollutants and Endometriosis in Tissue study included 433 reproductive-aged women undergoing laparoscopy or laparotomy in Salt Lake City, Utah, and San Francisco, California. Nine PFAS—perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluoroheptanoic acid (PFHpA), and perfluorooctane sulfonamide (PFOSA)—were quantified in matched serum (ng/mL) and endometrial tissue (ng/g) using high-performance liquid chromatography with tandem mass spectrometry. Values below the limit of detection were multiply imputed. Linear regression estimated log-transformed tissue concentrations from serum PFAS and covariates. Logistic regression estimated odds ratios (ORs) for endometriosis. Composite variables were created by summing log-transformed concentrations of short-chain PFAS (<8 carbons: PFHpA, PFHxS, PFOA, and PFOS) and long-chain PFAS (≥8 carbons: PFNA, PFDA, PFUnDA, PFDoDA, and PFOSA). Results: Serum PFAS was moderately associated with tissue levels, with the strongest performance for PFOS (R 2 = 0.46) and PFHxS (R 2 = 0.37). Model fit was low for longer-chain compounds (e.g., PFUnDA R 2 = 0.09, PFDoDA R 2 = 0.07). Serum PFOA (OR = 3.38, 95% CI = 1.08, 10.59) and PFNA (OR = 3.12, 95% CI = 1.15, 8.45) were significantly associated with endometriosis, whereas corresponding tissue-based estimates were attenuated. The serum long-chain composite was associated with increased odds of endometriosis (OR = 2.74, 95% CI = 1.15, 6.59), while the short-chain composite showed no association. Conclusions: Serum PFAS minimally reflect endometrial tissue burden, with variability by chain length. While serum remains practical for large studies, tissue-based measures may provide more accurate estimates of exposure in tissue. These findings inform PFAS–endometriosis research and may extend to other gynecologic conditions.