Per- and polyfluoroalkyl substances and incident metabolic syndrome in midlife women: The Study of Women's Health Across the Nation (SWAN)

Per- and polyfluoroalkyl substances (PFAS) contribute to lipid and insulin dysregulation which are central mechanisms of metabolic syndrome (MetS). Here, we prospectively examine associations between PFAS and incident MetS in midlife women. This study included 1307 participants from the Study of Women Health Across the Nation Multi-Pollutant Study with follow-up visits from 1999 to 2000 through 2015-2016. Baseline serum PFAS concentrations were quantified using online solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry. MetS was defined as having three or more of the following: race-specific abdominal obesity, impaired fasting glucose or antidiabetic medication use, high blood pressure or antihypertensive medication use, low HDL cholesterol, and high triglycerides. Accelerated failure time models fit with a Weibull distribution and interval censoring estimated hazard ratios (HR) and 95% confidence intervals for time to MetS. PFAS mixtures were assessed using k-means clustering of exposure z-scores for seven PFAS. At study commencement, there were 312 (23.9%) prevalent cases of MetS. Among the 995 participants at risk, 238 (23.9%) developed MetS during follow-up. The HR (95% CI) comparing the highest to the lowest exposure tertile was 1.30 for perfluorooctanoate (PFOA) (1.05, 1.62) (p-trend = 0.02), 1.23 for perfluorooctane sulfonate (PFOS) (1.0, 1.51) (p-trend = 0.05), and 1.30 for sum of branched PFOS isomers (Sm-PFOS) (1.05, 1.62) (p-trend = 0.01). The HR comparing those in the cluster of high exposure of seven PFAS compared to the cluster of low exposure was 1.10 (0.63, 1.91) (p-trend = 0.25). Together, these findings suggest that greater serum PFOA and PFOS concentrations were associated with earlier incident MetS diagnosis.