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

Joanna M Marroquin; Jenna R Krall; Karen C Schliep; Leslie V Farland; Vimalkumar Krishnamoorthi; Kurunthachalam Kannan; Anna Z Pollack

doi:10.1289/EHP15852

Lifestyle and Environment · Environmental Exposures

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

Marroquin JM, Krall JR, Schliep KC, Farland LV, Krishnamoorthi V, Kannan K, Pollack AZ

Published June 2025 Environmental health perspectives, 133(6), 67001

DOI 10.1289/EHP15852 PMID 40257857 PMC PMC12129303

RRM Academy Synopsis

Uterine lining PFAS were not associated with endometriosis diagnosis

Researchers in Utah and California measured PFAS directly in uterine lining samples collected during pelvic surgery from 434 women. The five chemicals appeared at comparable amounts in women who had endometriosis and in women who did not. Among the 181 women with the condition, three of the five chemicals ran higher in those with more advanced disease.

Key Findings

The study included 434 women aged 18 to 44 who had laparoscopy or laparotomy for any indication in 2007 to 2009. Of these, 181 were diagnosed with endometriosis and 253 were not.
PFOS was detected above the detection limit in 100% of uterine lining samples, PFOA in 99.5%, PFHxS in 98.6%, PFNA in 94.2% and PFOSA in 80.4%.
No PFAS was associated with an endometriosis diagnosis after adjustment: PFOA had a relative risk of 1.01 (95% CI: 0.90, 1.15) and PFOS 0.98 (95% CI: 0.85, 1.13).
Among women with endometriosis, PFHxS (RR=1.37; 95% CI: 1.12, 1.68) and PFOS (RR=1.36; 95% CI: 1.02, 1.81) were associated with greater risk of stage 3 or 4 than stage 1 or 2.
No clear association appeared between any PFAS and endometriosis subtype. For PFOS, deep versus superficial endometriosis had a relative risk of 0.91 (95% CI: 0.69, 1.19).

Interpretation

This cohort study followed 434 women having pelvic surgery and measured PFAS in uterine lining tissue taken at the time of surgery. Among women with endometriosis, PFOSA was also linked with higher disease stage, and a combined analysis of all five PFAS together pointed to a positive link with stage. The authors note they could not measure tissue PFAS levels from before the disease began. The findings support larger studies of PFAS exposure and endometriosis stage.

RRM Context

Restorative reproductive medicine treats endometriosis as a disease with a cause. It asks why disease starts and why it gets worse. Research on exposures like PFAS feeds those root-cause questions. NaProTechnology surgeons favor excision over ablation, since excision removes the disease tissue directly.

Our editorial summary of this paper, not the article's abstract.

Abstract

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 high-performance liquid chromatography-tandem mass spectrometry [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 (stages 3 and 4) compared to minimal and mild (stages 1 and 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 >10 ng/mL), study site (Utah, California), and body mass index (continuous) to obtain relative risks (RR) of endometriosis diagnosis and 95% confidence intervals (CIs) 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 or 2, while 27% had stage 3 or 4. Median [interquartile range (IQR)] eutopic endometrium tissue levels, in nanograms per gram, 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, and 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.

Topics

Lifestyle and Environment Environmental Exposures Persistent Organic Pollutants

Lifestyle and Environment › Environmental Exposures › Persistent Organic Pollutants

Joanna M Marroquin, Jenna R Krall, Karen C Schliep, Leslie V Farland, Vimalkumar Krishnamoorthi, Kurunthachalam Kannan, Anna Z Pollack

J Marroquin, J Krall, K Schliep, L Farland, V Krishnamoorthi, K Kannan, A Pollack

PMID 40257857 40257857 DOI 10.1289/EHP15852 10.1289/EHP15852 Marroquin et al. 2025, Marroquin 2025

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

Uterine lining PFAS were not associated with endometriosis diagnosis

Key Findings

Interpretation

RRM Context

Abstract

Topics

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