| Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males Richard W. Stahlhut,1 Edwin van Wijngaarden,1 Timothy D. Dye,1,2 Stephen Cook,3 and Shanna H. Swan4 1Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA; 2Department of Research and Evaluation, Axios International, Paris, France; 3Department of Pediatrics, and 4Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA Abstract
Background: Phthalates impair rodent testicular function and have been associated with antiandrogenic 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. Objectives: Our objective in this study was to investigate phthalate exposure and its associations with abdominal obesity and insulin resistance. Methods: 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) . Results: 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. Conclusions: 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. Key words: androgens, homeostatic model assessment, insulin resistance, obesity, phthalates. Environ Health Perspect 115:876–882 (2007) . doi:10.1289/ehp.9882 available via http://dx.doi.org/ [Online 14 March 2007]
Address correspondence to R.W. Stahlhut, Department of Community and Preventive Medicine, 601 Elmwood Ave., Box 644, Rochester, New York 14642 USA. E-mail: richard_stahlhut@urmc.rochester.edu We thank D. Fernandez, P. Winters, and P. Auinger for their study-design advice ; J. DeWester for alerting R.W.S. to links between testosterone, obesity, and diabetes in the mid-1990s ; and our anonymous reviewers for their thoughtful comments. The authors declare they have no competing financial interests. Received 3 November 2006 ; accepted 1 March 2007. An erratum was published in Environ HealthPerspect 115:A443 (2007) .
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