Concentrations of Urinary Phthalate Metabolites Are Associated with Increased Waist Circumference and Insulin Resistance in Adult U.S. Males
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Background: 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. 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.
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Epidemiological studies in the US reported that women with higher urinary concentrations of MBP, MiBP, MBzP, and MCPP and those of DEHP metabolites showed increased risk of diagnosis for diabetes compared with those who had lower concentrations.
“Epidemiological studies in the US [192,193] reported that women with higher urinary concentrations of MBP, MiBP, MBzP, and MCPP and those of DEHP metabolites showed increased risk of diagnosis for diabetes in comparison with those who had lower concentrations of phthalates.”
From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [193]
The Results report associations between some urinary phthalate metabolites and increased insulin resistance, including MBP and MBzP. But Methods > Study population limits the analysis to adult men, and the Discussion says women were excluded and their results were dissimilar (not shown). The paper measured waist circumference and insulin resistance, not women's risk of a diabetes diagnosis; it also does not report the claimed MCPP association. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMBzP, MEHHP, MEOHP, and MEP were associated with increased waist circumference and BMI.
“MBzP, MEHHP, MEOHP, and MEP were associated with increased waist circumference and BMI [193]”
From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [193]
The Results report that MBzP, MEHHP, MEOHP, and MEP were associated with increased waist circumference in adult U.S. males. The Methods identify waist circumference and HOMA as the outcomes; BMI is mentioned as a comparison measure, but no association between these metabolites and BMI is reported. Page numbers are not available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSeveral studies have shown a significant association between obesity and phthalate exposure.
“Several studies have shown a significant association between obesity and phthalate exposure [193,196,198].”
From A Review of Biomonitoring of Phthalate Exposures (2019) · cites this paper as [193]
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- Authors
- Stahlhut, R. W., van Wijngaarden, E., Dye, T. D., Cook, S., & Swan, S. H.
- Affiliations
- University of Rochester Medicine (US)
- Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
- Department of Pediatrics and
- Corresponding author
- Stahlhut, Richard W.
- Venue
- Environmental Health Perspectives
- Publisher
- American Chemical Society (ACS)
- Published
- 2007-03-14
- Volume
- 115
- Issue
- 6
- Pages
- 876-882
- ISSN
- 0091-6765 (ISSN-L)
- 1552-9924
- PMC
- PMC1892109
- OpenAlex
- W2155797089
- Cited by
- 646
- References
- 10
- Citations by year
- 2026: 10 · 2025: 26 · 2024: 27 · 2023: 23 · 2022: 38 · 2021: 43 · 2020: 41 · 2019: 35 · 2018: 34 · 2017: 47 · 2016: 40 · 2015: 40 · 2014: 48 · 2013: 36 · 2012: 47
- FWCI
- 18.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- public-domain
- creativecommons.org/licenses/by/4.0/ (vor, 3943 d)
- Locations
- Environmental Health Perspectives (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Keywords
- phthalate metabolites, urinary biomarkers, abdominal obesity, waist circumference, insulin resistance, antiandrogenic effects, mono-n-butyl phthalate, monoethyl phthalate, monobenzyl phthalate, MEHHP, MEOHP, endocrine disruptors, adult male, HOMA
- MeSH terms
- Adult, Age Factors, Body Weights and Measures, Cotinine, Creatinine, Diet, Environmental Exposure, Humans, Insulin Resistance, Male, Obesity, Phthalic Acids, United States, Biomarkers, Linear Models
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