Associations of per- and polyfluoroalkyl substances (PFAS) with muscle mass and function in women in midlife

Background: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous chemicals that disrupt hormonal and inflammatory pathways and may thereby influence body composition. Reduced muscle mass increases risk of frailty, a condition disproportionately affecting women. Methods: In the Project Viva cohort (N = 551), we assessed outcomes in midlife (2017–2024, mean age 50.7 years) including appendicular lean mass index (ALMI), a marker of muscle mass measured via dual X-ray absorptiometry, and plasma concentrations of PFAS at enrollment in pregnancy (1999–2002) and in midlife. We used covariate-adjusted linear regression of individual PFAS and the PFAS burden score and quantile g-computation (qgcomp) mixture models to examine PFAS-ALMI associations, and we explored effect modification by menopausal status, diet, and physical activity at midlife. In secondary analyses, we evaluated associations of midlife PFAS with midlife muscle function measures, and pregnancy PFAS with midlife ALMI. Results: Mean (standard deviation) ALMI was 6.93 (1.11) kg/m 2 , and PFAS concentrations compared well with those from contemporaneous National Health and Nutrition Examination Survey cycles. Women with higher concentrations of perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), and the qgcomp PFAS mixture in midlife had lower ALMI (e.g., −0.04 [95% confidence interval = −0.09, −0.0001]; kg/m 2 per 0.2 ng/mL increment in PFNA). There was no consistent evidence of effect modification by menopausal status, diet, or physical activity. Associations of midlife PFAS with muscle function (grip strength, physical performance), and pregnancy PFAS with midlife ALMI, were null or positive. Conclusion: Women with higher plasma concentrations of select PFAS had small decrements in ALMI, but muscle function measures were unchanged or slightly better.