Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males

Abstract

Phthalates impair rodent testicular function and have been associated with anti-androgenic effects in humans, including decreased testosterone levels. Low testosterone in adult human males has been associated with increased prevalence of obesity, insulin resistance, and diabetes. Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance. Subjects were adult U.S. male participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2002. We modeled six phthalate metabolites with prevalent exposure and known or suspected antiandrogenic activity as predictors of waist circumference and log-transformed homeostatic model assessment (HOMA; a measure of insulin resistance) using multiple linear regression, adjusted for age, race/ethnicity, fat and total calorie consumption, physical activity level, serum cotinine, and urine creatinine (model 1); and adjusted for model 1 covariates plus measures of renal and hepatic function (model 2). Metabolites were mono-butyl phthalates (MBP), mono-ethyl phthalate (MEP), mono-(2-ethyl)-hexyl phthalate (MEHP), mono-benzyl phthalate (MBzP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP). In model 1, four metabolites were associated with increased waist circumference (MBzP, MEHHP, MEOHP, and MEP; p-values </= 0.013) and three with increased HOMA (MBP, MBzP, and MEP; p-values </= 0.011). When we also adjusted for renal and hepatic function, parameter estimates declined but all significant results remained so except HOMA-MBP. In this national cross-section of U.S. men, concentrations of several prevalent phthalate metabolites showed statistically significant correlations with abdominal obesity and insulin resistance. If confirmed by longitudinal studies, our findings would suggest that exposure to these phthalates may contribute to the population burden of obesity, insulin resistance, and related clinical disorders.