Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women

International Journal of Obesity volume 38, pages 1532–1537 (2014)Cite this article

Subjects

Abstract

Objective:

Both bisphenol A (BPA) and phthalates are known endocrine-disrupting chemicals for which there is widespread general population exposure. Human exposure occurs through dietary and non-dietary routes. Although animal studies have suggested a potential role of these chemicals in obesity, evidence from human studies is sparse and inconsistent, and prospective evidence is lacking. This study evaluated urinary concentrations of BPA and major phthalate metabolites in relation to prospective weight change.

Methods:

The study population was from the controls in a prospective case-control study of type 2 diabetes in the Nurses’ Health Study (NHS) and NHSII. A total of 977 participants provided first-morning-void urine samples in 1996–2002. Urinary concentrations of BPA and nine phthalate metabolites were measured using liquid chromatography–mass spectrometry. Body weights were self-reported at baseline and updated biennially thereafter for 10 years.

Results:

On average, the women gained 2.09 kg (95% confidence interval (CI), −2.27 to 6.80 kg) during the 10-year follow-up. In multivariate analysis with adjustment of lifestyle and dietary factors, in comparison with women in the lowest quartile of BPA concentration, those in the highest quartile had 0.23 kg per year (95% CI, 0.07–0.38 kg per year) greater weight gain during the 10-year follow-up (P-trend=0.02). Several phthalate metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also associated with faster prospective weight gain in a dose-response fashion (P-trend<0.01), whereas other phthalates metabolites, including MEP and monoethylhexyl phthalate, were not monotonically associated with body weight change.

Conclusions:

These data suggest urinary concentrations of BPA and certain individual phthalate metabolites that were associated with modestly greater weight gain in a dose-response fashion. These data are consistent with a potential role of BPA and phthalates in obesity, although more prospective data are needed to corroborate these observations.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP . The continuing epidemic of obesity in the United States. JAMA 2000; 284: 1650–1651.

    Article  CAS  PubMed  Google Scholar 

  2. Hoyt CL, Burnette JL, Auster-Gussman L . "Obesity is a disease": examining the self-regulatory impact of this public-health message. Psychol Sci 2014; 25: 997–1002.

    Article  PubMed  Google Scholar 

  3. De Coster S, van Larebeke N . Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J Environ Public Health 2012; 2012: 713696.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Alonso-Magdalena P, Quesada I, Nadal A . Endocrine disruptors in the etiology of type 2 diabetes mellitus. Nat Rev Endocrinol 2011; 7: 346–353.

    Article  CAS  PubMed  Google Scholar 

  5. Crews D, McLachlan JA . Epigenetics, evolution, endocrine disruption, health, and disease. Endocrinology 2006; 147: S4–10.

    Article  CAS  PubMed  Google Scholar 

  6. Hauser R, Calafat AM . Phthalates and human health. Occup Environ Med 2005; 62: 806–818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Geens T, Aerts D, Berthot C, Bourguignon JP, Goeyens L, Lecomte P et al. A review of dietary and non-dietary exposure to bisphenol-A. Food Chem Toxicol 2012; 50: 3725–3740.

    Article  CAS  PubMed  Google Scholar 

  8. Newbold RR, Padilla-Banks E, Jefferson WN . Environmental estrogens and obesity. Mol Cell Endocrinol 2009; 304: 84–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Grun F, Blumberg B . Perturbed nuclear receptor signaling by environmental obesogens as emerging factors in the obesity crisis. Rev Endocr Metab Disord 2007; 8: 161–171.

    Article  PubMed  Google Scholar 

  10. Bhandari R, Xiao J, Shankar A . Urinary bisphenol A and obesity in U.S. children. Am J Epidemiol 2013; 177: 1263–1270.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Li DK, Miao M, Zhou Z, Wu C, Shi H, Liu X et al. Urine bisphenol-a level in relation to obesity and overweight in school-age children. PLoS One 2013; 8: e65399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Harley KG, Aguilar Schall R, Chevrier J, Tyler K, Aguirre H, Bradman A et al. Prenatal and postnatal bisphenol A exposure and body mass index in childhood in the CHAMACOS cohort. Environ Health Perspect 2013; 121: 514–520.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wells EM, Jackson LW, Koontz MB . Association between bisphenol A and waist-to-height ratio among children: National Health and Nutrition Examination Survey, 2003-2010. Ann Epidemiol 2013; 24: 165–167.

    Article  PubMed  Google Scholar 

  14. Wang HX, Zhou Y, Tang CX, Wu JG, Chen Y, Jiang QW . Association between bisphenol A exposure and body mass index in Chinese school children: a cross-sectional study. Environ Health 2012; 11: 79.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Trasande L, Attina TM, Blustein J . Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA 2012; 308: 1113–1121.

    Article  CAS  PubMed  Google Scholar 

  16. Shankar A, Teppala S, Sabanayagam C . Urinary bisphenol a levels and measures of obesity: results from the national health and nutrition examination survey 2003-2008. ISRN Endocrinol 2012; 2012: 965243.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Wang T, Li M, Chen B, Xu M, Xu Y, Huang Y et al. Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. J Clin Endocrinol Metab 2012; 97: E223–E227.

    Article  CAS  PubMed  Google Scholar 

  18. Carwile JL, Michels KB . Urinary bisphenol A and obesity: NHANES 2003-2006. Environ Res 2011; 111: 825–830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang H, Zhou Y, Tang C, He Y, Wu J, Chen Y et al. Urinary phthalate metabolites are associated with body mass index and waist circumference in Chinese school children. PLoS One 2013; 8: e56800.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lind PM, Roos V, Ronn M, Johansson L, Ahlstrom H, Kullberg J et al. Serum concentrations of phthalate metabolites are related to abdominal fat distribution two years later in elderly women. Environ Health 2012; 11: 21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M et al. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999-2002. Environ Health 2008; 7: 27.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH . Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect 2007; 115: 876–882.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Trasande L, Attina TM, Sathyanarayana S, Spanier AJ, Blustein J . Race/ethnicity-specific associations of urinary phthalates with childhood body mass in a nationally representative sample. Environ Health Perspect 2013; 121: 501–506.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sun Q, Cornelis M, Townsend M, Tobias D, Eliassen A, Franke A et al. Association of urinary concentrations of bisphenol A and phthalate metabolites with risk of type 2 diabetes: a prospective investigation in the Nurses' Health Study (NHS) and NHSII cohorts. Environ Health Perspect 2014; e-pub ahead of print 14 March 2014; doi:10.1289/ehp.1307201.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Willett W, Stampfer MJ, Bain C, Lipnick R, Speizer FE, Rosner B et al. Cigarette smoking, relative weight, and menopause. Am J Epidemiol 1983; 117: 651–658.

    Article  CAS  PubMed  Google Scholar 

  26. Chiuve SE, Fung TT, Rimm EB, Hu FB, McCullough ML, Wang M et al. Alternative dietary indices both strongly predict risk of chronic disease. J Nutr 2012; 142: 1009–1018.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Fox SD, Falk RT, Veenstra TD, Issaq HJ . Quantitation of free and total bisphenol A in human urine using liquid chromatography-tandem mass spectrometry. J Sep Sci 2011; 34: 1268–1274.

    Article  CAS  PubMed  Google Scholar 

  28. Kato K, Silva MJ, Needham LL, Calafat AM . Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Anal Chem 2005; 77: 2985–2991.

    Article  CAS  PubMed  Google Scholar 

  29. Blount BC, Milgram KE, Silva MJ, Malek NA, Reidy JA, Needham LL et al. Quantitative detection of eight phthalate metabolites in human urine using HPLC-APCI-MS/MS. Anal Chem 2000; 72: 4127–4134.

    Article  CAS  PubMed  Google Scholar 

  30. Melzer D, Osborne NJ, Henley WE, Cipelli R, Young A, Money C et al. Urinary bisphenol A concentration and risk of future coronary artery disease in apparently healthy men and women. Circulation 2012; 125: 1482–1490.

    Article  CAS  PubMed  Google Scholar 

  31. Braun JM, Kalkbrenner AE, Calafat AM, Bernert JT, Ye X, Silva MJ et al. Variability and predictors of urinary bisphenol A concentrations during pregnancy. Environ Health Perspect 2011; 119: 131–137.

    Article  CAS  PubMed  Google Scholar 

  32. Buckley JP, Palmieri RT, Matuszewski JM, Herring AH, Baird DD, Hartmann KE et al. Consumer product exposures associated with urinary phthalate levels in pregnant women. J Expo Sci Environ Epidemiol 2012; 22: 468–475.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Grun F, Blumberg B . Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 2006; 147: S50–S55.

    Article  CAS  PubMed  Google Scholar 

  34. Masuno H, Kidani T, Sekiya K, Sakayama K, Shiosaka T, Yamamoto H et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J Lipid Res 2002; 43: 676–684.

    CAS  PubMed  Google Scholar 

  35. Wada K, Sakamoto H, Nishikawa K, Sakuma S, Nakajima A, Fujimoto Y et al. Life style-related diseases of the digestive system: endocrine disruptors stimulate lipid accumulation in target cells related to metabolic syndrome. J Pharmacol Sci 2007; 105: 133–137.

    Article  CAS  PubMed  Google Scholar 

  36. Soriano S, Alonso-Magdalena P, Garcia-Arevalo M, Novials A, Muhammed SJ, Salehi A et al. Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: role of estrogen receptor beta. PLoS One 2012; 7: e31109.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Heudorf U, Mersch-Sundermann V, Angerer J . Phthalates: toxicology and exposure. Int J Hyg Environ Health 2007; 210: 623–634.

    Article  CAS  PubMed  Google Scholar 

  38. Desvergne B, Feige JN, Casals-Casas C . PPAR-mediated activity of phthalates: a link to the obesity epidemic? Mol Cell Endocrinol 2009; 304: 43–48.

    Article  CAS  PubMed  Google Scholar 

  39. Feige JN, Gelman L, Rossi D, Zoete V, Metivier R, Tudor C et al. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem 2007; 282: 19152–19166.

    Article  CAS  PubMed  Google Scholar 

  40. Hurst CH, Waxman DJ . Activation of PPARalpha and PPARgamma by environmental phthalate monoesters. Toxicol Sci 2003; 74: 297–308.

    Article  CAS  PubMed  Google Scholar 

  41. Lee DH, Steffes MW, Sjodin A, Jones RS, Needham LL, Jacobs DR Jr . Low dose organochlorine pesticides and polychlorinated biphenyls predict obesity, dyslipidemia, and insulin resistance among people free of diabetes. PLoS One 2011; 6: e15977.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Lee DH, Steffes MW, Sjodin A, Jones RS, Needham LL, Jacobs DR Jr . Low dose of some persistent organic pollutants predicts type 2 diabetes: a nested case-control study. Environ Health Perspect 2010; 118: 1235–1242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Townsend MK, Franke AA, Li X, Hu FB, Eliassen AH . Within-person reproducibility of urinary bisphenol A and phthalate metabolites over a 1 to 3 year period among women in the Nurses' Health Studies: a prospective cohort study. Environ Health 2013; 12: 80.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Mahalingaiah S, Meeker JD, Pearson KR, Calafat AM, Ye X, Petrozza J et al. Temporal variability and predictors of urinary bisphenol A concentrations in men and women. Environ Health Perspect 2008; 116: 173–178.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Dr Xingnan Li for her skillful performance of the liquid chromatography–mass spectrometry assays. This work is supported by grants U54CA155626, P30 DK46200, CA87969, CA49449, DK58845, DK58785, DK082486, CA50385, CA67262 and CA71789 from the National Institutes of Health (NIH). QS is supported by a career development award R00HL098459 from the National Heart, Lung, and Blood Institute. YS is a recipient of Burroughs Wellcome Fund Inter-school Training Program in Metabolic Diseases at UCLA.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles, CA, USA

    Y Song

  2. Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA

    Y Song & S Liu

  3. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

    R Hauser & F B Hu

  4. Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA

    R Hauser

  5. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA

    F B Hu & Q Sun

  6. Channing Division of Network Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    F B Hu & Q Sun

  7. Natural Products and Experimental Therapeutics Program, University of Hawaii Cancer Center, Honolulu, Hawaii

    A A Franke

  8. Department of Medicine, Alpert School of Medicine, Brown University, Providence, RI, USA

    S Liu

  9. Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

    S Liu

Authors
  1. Y Song
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F B Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A A Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Q Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Q Sun.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Supplementary Information accompanies this paper on International Journal of Obesity website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, Y., Hauser, R., Hu, F. et al. Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women. Int J Obes 38, 1532–1537 (2014). https://doi.org/10.1038/ijo.2014.63

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2014.63

Keywords

This article is cited by

Search

Advanced search

Quick links