Per- and polyfluoroalkyl substances in eutopic endometrium tissue and risk of endometriosis: findings from the Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) Study.

BACKGROUND Per- and polyfluoroalkyl substances (PFAS) exposure is widespread and has been linked with gynecologic disease. To our knowledge, no study has measured PFAS in endometrial tissue. METHODS Eutopic endometrial tissue specimens (n=434) were collected from Investigating Mixtures of Pollutants and Endometriosis in Tissue (IMPLANT) Study participants undergoing laparoscopy or laparotomy for any indication (2007-2009). Nine PFAS were measured by HPLC-tandem MS (perfluorodecanoic acid [PFDA], perfluorohexane sulfonic acid [PFHxS], perfluorononanoic acid [PFNA], perfluorooctanoic acid [PFOA], perfluorooctane sulfonic acid [PFOS], perfluorododecanoic acid [PFDoDA], perfluoroheptanoic acid [PFHpA], perfluorooctanesulfonamide [PFOSA], and perfluoroundecanoic acid [PFUnDA]. Surgeons diagnosed endometriosis by gold-standard visualization and evaluated the endometriosis staging as moderate and severe (stage 3-4) compared to minimal and mild (stage 1-2), using American Society of Reproductive Medicine (ASRM) classification. We used modified Poisson regression models adjusted for age (continuous), race (white, all other race/ethnicities), smoking status (serum cotinine > ng/mL), study site (Utah, California), and body mass index (continuous) to obtain relative risks (RR) of endometriosis diagnosis and 95% confidence intervals (CI) for each PFAS. PFAS mixtures were evaluated using Bayesian Kernel Machine Regression. RESULTS Participants were, on average, 33 ± 7 years old, and 75% of participants were non-Hispanic white. Of the 181 participants with an incident endometriosis diagnosis, 73% had ASRM stage 1-2, while 27% had stage 3-4. Median (IQR) eutopic endometrium tissue levels, in ng/g, were 6.58 (6.44) for PFOS, 1.93 (1.71) for PFOA, 0.65 (0.75) for PFHxS, 0.58 (0.52) for PFNA, 0.12 (0.18) for PFOSA. PFAS in the endometrial tissue was not associated with endometriosis. However, select PFAS in the eutopic tissue were associated with a risk of more advanced (stage 3 or 4 vs. 1 or 2) endometriosis [(PFOSA RR=1.25 (95% CI: 1.10-1.43), PFHxS RR=1.37 (95% CI: 1.12, 1.68), PFOS RR=1.36 (95% CI: 1.02, 1.81)]. CONCLUSION PFAS were widely detected in eutopic endometrial tissue. There was no evidence that PFAS in endometrial tissue were associated with a higher risk of endometriosis diagnosis. However, PFOS, PFOSA and PFHxS in the endometrial tissue were associated with risk of more severe stage of endometriosis. https://doi.org/10.1289/EHP15852.