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Epidemiology and Population Health

Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women’s health across the nation 1999–2018

International Journal of Obesity volume 45, pages 1937–1948 (2021)Cite this article

Subjects

Abstract

Background/Objectives

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass, and proportion fat in midlife women.

Subjects/Methods

This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women’s Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0–18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition.

Results

After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P < 0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P < 0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P < 0.0001). PFOS was also significantly related to higher increase rates in WC (difference = 0.12% per year, P = 0.002) and fat mass (difference = 0.25% per year, P = 0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P < 0.0001), WC (P = 0.003), fat mass (P < 0.0001), and proportion fat (P = 0.0009). No significant results were found for PFNA.

Conclusions

Certain PFAS were positively associated with greater body size and body fat, and higher rates of change over time. PFAS may be an underappreciated contributing factor to obesity risk.

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References

  1. ATSDR. Toxicological Profile for Perfluoroalkyls, Draft for Public Comment. 2018 www.regulations.gov. (Accessed 8 May 2020).

  2. Andrews DQ, Naidenko OV. Population-Wide Exposure to Per- And Polyfluoroalkyl Substances from Drinking Water in the United States. Environ Sci Technol Lett. 2020;7:931–6.

    Article  CAS  Google Scholar 

  3. CDC. Fourth National Report on Human Exposure to Environmental Chemicals. Fourth Natl Rep Hum Expo to Environ Chem. 2009 ;1–529.

  4. Ding N, Harlow SD, Batterman S, Mukherjee B, Park SK. Longitudinal trends in perfluoroalkyl and polyfluoroalkyl substances among multiethnic midlife women from 1999 to 2011: The Study of Women’s Health Across the Nation. Environ Int. 2020;135:105381.

    Article  CAS  Google Scholar 

  5. Olsen GW, Burris JM, Ehresman DJ, Froehlich JW, Seacat AM, Butenhoff JL, et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115:1298–305.

    Article  CAS  Google Scholar 

  6. Jensen AA, Leffers H. Emerging endocrine disrupters: perfluoroalkylated substances. Int J Androl. 2008;31:161–9.

    Article  CAS  Google Scholar 

  7. Ding N, Harlow SD, Randolph JF, Loch-Caruso R, Park SK. Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and their effects on the ovary. Hum Reprod Update. 2020;26:724–52.

    Article  CAS  Google Scholar 

  8. Bjork JA, Butenhoff JL, Wallace KB. Multiplicity of nuclear receptor activation by PFOA and PFOS in primary human and rodent hepatocytes. Toxicology. 2011;288:8–17.

    Article  CAS  Google Scholar 

  9. Hines EP, White SS, Stanko JP, Gibbs-Flournoy EA, Lau C, Fenton SE. Phenotypic dichotomy following developmental exposure to perfluorooctanoic acid (PFOA) in female CD-1 mice: Low doses induce elevated serum leptin and insulin, and overweight in mid-life. Mol Cell Endocrinol. 2009;304:97–105.

    Article  CAS  Google Scholar 

  10. Schoonjans K, Staels B, Auwerx J. The peroxisome proliferator activated receptors (PPARs) and their effects on lipid metabolism and adipocyte differentiation. Biochim. Biophys. Acta—Lipids Lipid Metab. 1996;1302:93–109.

    Article  CAS  Google Scholar 

  11. Nelson JW, Hatch EE, Webster TF. Exposure to polyfluoroalkyl chemicals and cholesterol, body weight, and insulin resistance in the general U.S. population. Environ Health Perspect. 2010;118:197–202.

    Article  CAS  Google Scholar 

  12. Tian YP, Zeng XW, Bloom MS, Lin S, Wang SQ, Yim SHL, et al. Isomers of perfluoroalkyl substances and overweight status among Chinese by sex status: Isomers of C8 Health Project in China. Environ Int. 2019;124:130–8.

    Article  CAS  Google Scholar 

  13. Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Fleisch AF, et al. Association of Perfluoroalkyl and Polyfluoroalkyl Substances With Adiposity. JAMA Netw open. 2018;1:e181493.

    Article  Google Scholar 

  14. Liu G, Dhana K, Furtado JD, Rood J, Zong G, Liang L, et al. Perfluoroalkyl substances and changes in body weight and resting metabolic rate in response to weight-loss diets: a prospective study. PLoS Med. 2018.15; https://doi.org/10.1371/journal.pmed.1002502.

  15. Barry V, Darrow LA, Klein M, Winquist A, Steenland K. Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure. Environ Res. 2014;132:62–9.

    Article  CAS  Google Scholar 

  16. Blake BE, Pinney SM, Hines EP, Fenton SE, Ferguson KK. Associations between longitudinal serum perfluoroalkyl substance (PFAS) levels and measures of thyroid hormone, kidney function, and body mass index in the Fernald Community Cohort. Environ Pollut. 2018;242:894–904.

    Article  CAS  Google Scholar 

  17. Davis SR, Castelo-Branco C, Chedraui P, Lumsden MA, Nappi RE, Shah D, et al. Understanding weight gain at menopause. Climacteric. 2012;15:419–29.

    Article  CAS  Google Scholar 

  18. Greendale GA, Sternfeld B, Huang MH, Han W, Karvonen-Gutierrez C, Ruppert K, et al. Changes in body composition and weight during the menopause transition. JCI Insight. 2019.4; https://doi.org/10.1172/jci.insight.124865.

  19. Park SK, Peng Q, Ding N, Mukherjee B, Harlow SD. Determinants of per- and polyfluoroalkyl substances (PFAS) in midlife women: Evidence of racial/ethnic and geographic differences in PFAS exposure. Environ Res. 2019;175:186–99.

    Article  CAS  Google Scholar 

  20. Santoro N, Taylor ES, Sutton-Tyrrell K. The SWAN song: study of women’s health across the nation’s recurring themes. Obstet Gynecol Clin North Am. 2011;38:417–23.

    Article  Google Scholar 

  21. Wang X, Mukherjee B, Batterman S, Harlow SD, Park SK. Urinary metals and metal mixtures in midlife women: The Study of Women’s Health Across the Nation (SWAN). Int J Hyg Environ Health. 2019;222:778–89.

    Article  Google Scholar 

  22. Wang X, Karvonen-Gutierrez CA, Herman WH, Mukherjee B, Harlow SD, Park SK. Urinary metals and incident diabetes in midlife women: Study of Women’s Health Across the Nation (SWAN). BMJ Open Diabetes Res Care. 2020;8:e001233.

    Article  Google Scholar 

  23. Wang X, Karvonen-Gutierrez CA, Mukherjee B, Herman WH, Park SK. Urinary metals and adipokines in midlife women: The Study of Women’s Health Across the nation (SWAN). Environ Res. 2020. https://doi.org/10.1016/j.envres.2020.110426.

  24. Kato K, Basden BJ, Needham LL, Calafat AM. Improved selectivity for the analysis of maternal serum and cord serum for polyfluoroalkyl chemicals. J Chromatogr A. 2011;1218:2133–7.

    Article  CAS  Google Scholar 

  25. Hornung RW, Reed LD. Estimation of average concentration in the presence of nondetectable values. Appl Occup Environ Hyg. 1990;5:46–51.

    Article  CAS  Google Scholar 

  26. Ferris BG. Epidemiology Standardization Project (American Thoracic Society). Am Rev Respir Dis. 1978;118:1–120.

    CAS  PubMed  Google Scholar 

  27. Coghlin J, Hammond SK, Gann PH. Development of epidemiologic tools for measuring environmental tobacco smoke exposure. Am J Epidemiol. 1989;130:696–704.

    Article  CAS  Google Scholar 

  28. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L. A data-based approach to diet questionnaire design and testing. Am J Epidemiol. 1986;124:453–69.

    Article  CAS  Google Scholar 

  29. Sternfeld B, Ainsworth BE, Quesenberry CP. Physical activity patterns in a diverse population of women. Prev Med (Baltim). 1999;28:313–23.

    Article  CAS  Google Scholar 

  30. Harlow SD, Gass M, Hall JE, Lobo R, Maki P, Rebar RW, et al. Executive summary of the stages of reproductive aging workshop + 10: addressing the unfinished agenda of staging reproductive aging. In: Journal of Clinical Endocrinology and Metabolism. The Endocrine Society, 2012, 1159–68.

  31. Ding N, Harlow SD, Randolph JF, Calafat AM, Mukherjee B, Batterman S, et al. Associations of Perfluoroalkyl Substances with Incident Natural Menopause: The Study of Women’s Health across the Nation. J Clin Endocrinol Metab. 2020;105:E3169–82.

    Article  Google Scholar 

  32. Schisterman EF, Cole SR, Platf RW. Overadjustment bias and unnecessary adjustment in epidemiologic studies. Epidemiology. 2009;20:488–95.

    Article  Google Scholar 

  33. Wolf CJ, Takacs ML, Schmid JE, Lau C, Abbott BD. Activation of mouse and human peroxisome proliferator-activated receptor alpha by perfluoroalkyl acids of different functional groups and chain lengths. Toxicol Sci. 2008;106:162–71.

    Article  CAS  Google Scholar 

  34. Takacs ML, Abbott BD. Activation of mouse and human peroxisome proliferator-activated receptors (α, β/δ, γ) by perfluorooctanoic acid and perfluorooctane sulfonate. Toxicol Sci. 2007;95:108–17.

    Article  CAS  Google Scholar 

  35. Watkins AM, Wood CR, Lin MT, Abbott BD. The effects of perfluorinated chemicals on adipocyte differentiation in vitro. Mol Cell Endocrinol. 2015;400:90–101.

    Article  CAS  Google Scholar 

  36. Ballesteros V, Costa O, Iñiguez C, Fletcher T, Ballester F, Lopez-Espinosa MJ. Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: A systematic review of epidemiologic studies. Environ. Int. 2017;99:15–28.

    Article  CAS  Google Scholar 

  37. Kim MJ, Moon S, Oh BC, Jung D, Ji K, Choi K, et al. Association between perfluoroalkyl substances exposure and thyroid function in adults: a meta-analysis. PLoS One. 2018;13:e0197244.

    Article  Google Scholar 

  38. Liu P, Ji Y, Yuen T, Rendina-Ruedy E, Demambro VE, Dhawan S, et al. Blocking FSH induces thermogenic adipose tissue and reduces body fat. Nature. 2017;546:107–12.

    Article  CAS  Google Scholar 

  39. Sowers MF, Zheng H, Tomey K, Karvonen-Gutierrez C, Jannausch M, Li X, et al. Changes in body composition in women over six years at midlife: ovarian and chronological aging. J Clin Endocrinol Metab. 2007;92:895–901.

    Article  CAS  Google Scholar 

  40. Fletcher T, Galloway TS, Melzer D, Holcroft P, Cipelli R, Pilling LC, et al. Associations between PFOA, PFOS and changes in the expression of genes involved in cholesterol metabolism in humans. Environ Int. 2013;57–58:2–10.

    Article  Google Scholar 

  41. Watkins DJ, Wellenius GA, Butler RA, Bartell SM, Fletcher T, Kelsey KT. Associations between serum perfluoroalkyl acids and LINE-1 DNA methylation. Environ Int. 2014;63:71–6.

    Article  CAS  Google Scholar 

  42. Sheehan TJ, DuBrava S, DeChello LM, Fang Z. Rates of weight change for black and white Americans over a twenty year period. Int J Obes. 2003;27:498–504.

    Article  CAS  Google Scholar 

  43. Baumgartner RN, Stauber PM, McHugh D, Koehler KM, Garry PJ. Cross-sectional age differences in body composition in persons 60 + years of age. J Gerontol Ser A Biol Sci Med Sci. 1995;50A:M307–16.

    Article  Google Scholar 

  44. Villareal DT, Apovian CM, Kushner RF, Klein S. Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am. J. Clin. Nutr. 2005;82:923–34.

    Article  CAS  Google Scholar 

  45. Xu J, Shimpi P, Armstrong L, Salter D, Slitt AL. PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway. Toxicol Appl Pharmacol. 2016;290:21–30.

    Article  CAS  Google Scholar 

  46. Wang X, Mukherjee B, Karvonen-Gutierrez CA, Herman WH, Batterman S, Harlow SD, et al. Urinary metal mixtures and longitudinal changes in glucose homeostasis: the Study of Women’s Health Across the Nation (SWAN). Environ Int. 2020;145:106109.

    Article  CAS  Google Scholar 

  47. USEPA. Health effects support document for perfluorooctane sulfonate (PFOS). 2016 http://www.epa.gov/ Accessed 11 Mar 2019.

  48. USEPA. Health Effects Support Document for Perfluorooctanoic Acid (PFOA). 2016 https://www.epa.gov/sites/production/files/2016-05/documents/pfoa_hesd_final-plain.pdf Accessed 11 Mar 2019.

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Acknowledgements

The Study of Women’s Health Across the Nation (SWAN) has grant support from the National Institutes of Health (NIH), DHHS, through the National Institute on Aging (NIA), the National Institute of Nursing Research (NINR) and the NIH Office of Research on Women’s Health (ORWH) (Grants U01NR004061; U01AG012505, U01AG012535, U01AG012531, U01AG012539, U01AG012546, U01AG012553, U01AG012554, U01AG012495). The study was supported by the SWAN Repository (U01AG017719). This study was also supported by grants from the National Institute of Environmental Health Sciences (NIEHS) R01-ES026578, R01-ES026964 and P30-ES017885, and by the Center for Disease Control and Prevention (CDC)/National Institute for Occupational Safety and Health (NIOSH) grant T42-OH008455. The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the NIA, NINR, ORWH or the NIH. The findings and conclusions of this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention (CDC). Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the U.S. Department of Health and Human Services. Clinical Centers: University of Michigan, Ann Arbor—Siobán Harlow, PI 2011—present, MaryFran Sowers, PI 1994–2011; Massachusetts General Hospital, Boston, MA—Joel Finkelstein, PI 1999—present; Robert Neer, PI 1994–1999; Rush University, Rush University Medical Center, Chicago, IL—Howard Kravitz, PI 2009—present; Lynda Powell, PI 1994–2009; University of California, Davis/Kaiser—Ellen Gold, PI; University of California, Los Angeles—Gail Greendale, PI; Albert Einstein College of Medicine, Bronx, NY—Carol Derby, PI 2011—present, Rachel Wildman, PI 2010–2011; Nanette Santoro, PI 2004–2010; University of Medicine and Dentistry—New Jersey Medical School, Newark—Gerson Weiss, PI 1994–2004; and the University of Pittsburgh, Pittsburgh, PA—Karen Matthews, PI. NIH Program Office: National Institute on Aging, Bethesda, MD—Chhanda Dutta 2016- present; Winifred Rossi 2012–2016; Sherry Sherman 1994–2012; Marcia Ory 1994–2001; National Institute of Nursing Research, Bethesda, MD—Program Officers. Central Laboratory: University of Michigan, Ann Arbor—Daniel McConnell (Central Ligand Assay Satellite Services). CDC Laboratory: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA. SWAN Repository: University of Michigan, Ann Arbor—Siobán Harlow 2013—Present; Dan McConnell 2011–2013; MaryFran Sowers 2000–2011. Coordinating Center: University of Pittsburgh, Pittsburgh, PA—Maria Mori Brooks, PI 2012—present; Kim Sutton-Tyrrell, PI 2001–2012; New England Research Institutes, Watertown, MA—Sonja McKinlay, PI 1995–2001. Steering Committee:Susan Johnson, Current Chair Chris Gallagher, Former Chair. We thank the study staff at each site and all the women who participated in SWAN.

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Authors and Affiliations

  1. Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Ning Ding, Carrie A. Karvonen-Gutierrez, William H. Herman & Sung Kyun Park

  2. Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

    William H. Herman

  3. Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA

    Antonia M. Calafat

  4. Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Bhramar Mukherjee

  5. Department of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Sung Kyun Park

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Correspondence to Sung Kyun Park.

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Ding, N., Karvonen-Gutierrez, C.A., Herman, W.H. et al. Perfluoroalkyl and polyfluoroalkyl substances and body size and composition trajectories in midlife women: the study of women’s health across the nation 1999–2018. Int J Obes 45, 1937–1948 (2021). https://doi.org/10.1038/s41366-021-00848-9

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