Journal Article

Associations of per- and polyfluoroalkyl substances with uterine leiomyomata incidence and growth: a prospective ultrasound study

Coleman, Chad M., Lovett, Sharonda M., Wise, Lauren A., Claus Henn, Birgit, Botelho, Julianne Cook, Geller, Ruth J., Calafat, Antonia M., Baird, Donna D., Wesselink, Amelia K., Schildroth, Samantha, Bethea, Traci N., Marsh, Erica E., Noel, Nyia, Wegienka, Ganesa R., Harmon, Quaker E.

2025

Overview

Background Per- and polyfluoroalkyl substances (PFAS) are endocrine-disrupting chemicals used in commercial and consumer products. Objective We evaluated PFAS exposure in relation to incidence and growth of uterine leiomyomata (UL), hormone-dependent neoplasms that are associated with severe gynecologic morbidity. Methods We studied 1158 participants in the Study of Environment, Lifestyle, and Fibroids, a Detroit-based prospective cohort study of Black females aged 23–35 years at enrollment (2010–2012). At enrollment and four subsequent visits during 10 years of follow-up, participants attended in-person clinic visits, completed questionnaires, provided non-fasting blood samples, and underwent ultrasound for UL detection. We quantified 7 PFAS in baseline plasma samples using mass spectrometry. We used Cox regression and probit Bayesian kernel machine regression to estimate individual and joint effects of PFAS on UL incidence. We fit linear mixed models to estimate effects of individual PFAS on UL growth. We stratified by parity, an important route of PFAS elimination and determinant of UL. Results In individual PFAS analyses, we observed inverse associations for perfluorodecanoate (PFDA; ≥0.3 vs. <0.2 ng/ml: hazard ratio [HR] = 0.74; 95% confidence interval [CI]: 0.54–1.00) and perfluoroundecanoate (detected vs. non-detected: HR = 0.78; 95% CI: 0.61–1.01) and a weak positive association for perfluorohexane sulfonate (≥1 vs. <0.6 ng/ml: HR = 1.17; 95% CI: 0.85–1.61), while perfluorooctane sulfonate, perfluorooctanoate, perfluorononanoate (PFNA), and 2-N-methyl-perfluorooctane sulfonamido acetate (MeFOSAA) showed little association with UL incidence. The PFAS mixture was inversely associated with UL incidence, a finding driven by MeFOSAA and PFDA; however, PFNA was positively associated with UL incidence. The inverse association for PFDA and positive association for PFNA were stronger among nulliparous participants. Most PFAS showed slight inverse associations with UL growth. Impact statement In this prospective ultrasound study of 1158 Black females aged 23–35 years at enrollment, we conducted a mixtures analysis to account for co-pollutant confounding and interaction. MeFOSAA and PFDA concentrations were inversely associated with UL incidence, while PFNA concentrations were positively associated with UL incidence. Concentrations of most PFAS were associated with decreased UL growth. This study contributes data to the sparse literature on PFAS exposure and UL development.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Acetic acid / Adult / Alkanesulfonic Acids - blood / Bayesian analysis / Black or African American / Caprylates - blood / Consumer products / Endocrine disruptors / Endocrine Disruptors - blood / Environmental Exposure - adverse effects / Environmental Pollutants - blood / Epidemiology / Female / Females / Fibroids / Fluorocarbons - adverse effects / Fluorocarbons - blood / Health disparities / Humans / Incidence / Leiomyoma - chemically induced / Leiomyoma - diagnostic imaging / Leiomyoma - epidemiology / Mass spectrometry / Mass spectroscopy / Mathematical models / Medicine / Medicine & Public Health / Michigan - epidemiology / Mixtures / Morbidity / Neoplasms / Perfluoro compounds / Perfluoroalkyl & polyfluoroalkyl substances / Perfluorochemicals / Perfluorohexane / Prospective Studies / Regression analysis / Reproductive health / Statistical analysis / Sulfonates / Ultrasonic imaging / Ultrasonography / Ultrasound / Uterine Neoplasms - chemically induced / Uterine Neoplasms - diagnostic imaging / Uterine Neoplasms - epidemiology / Uterus / Young Adult