The Influence of Persistent Organic Pollutants on Thyroidal, Reproductive and Adrenal Hormones After Bariatric Surgery

  • Aina JansenEmail author
  • Jens Petter Berg
  • Ole Klungsøyr
  • Mette Helen Bjørge Müller
  • Jan Ludvig Lyche
  • Jan Olav Aaseth
Original Contributions



Persistent organic pollutants (POPs) including organochlorine pesticides, polychlorinated biphenyls (PCBs), and per- and polyfluoroalkylated substances (PFASs) are suspected endocrine disruptors.


To evaluate the associations between POPs and thyroidal, reproductive, and adrenal hormones in a study population treated with bariatric surgery.


Blood samples from a cohort of 63 participants before and 1 year after bariatric surgery were analyzed for 16 lipophilic POPs, 17 PFASs, and thyroidal, reproductive, and adrenal hormones. Participants reporting relevant medical conditions or interfering medication were excluded, and plausible confounders were corrected for in multiple regression analyses.


Free thyroxine (fT4) showed a significant decrease from preoperative to postoperative follow-up, and regression analyses demonstrated that p,p'-dichlorodiphenyldichloroethylene (p,p-DDE) was inversely associated with the ratio free triiodothyronine/free thyroxine (fT3/fT4). Testosterone concentrations in male participants increased significantly in the study period, and sex hormone-binding globulin (SHBG) increased in both gender. Regression analyses showed positive associations between increased levels of lipophilic POPs and the raised postoperative testosterone and SHBG concentrations in males. For females, an inverse association between the sum perfluoroalkyl carboxylic acids (ΣPFCA) and SHBG was seen. Regression analyses of postoperative serum cortisol concentrations on changes in hexachlorobenzene (HCB) showed a non-significant inverse association.


The results suggest that POPs may have an influence on the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-gonadal (HPG) axes after bariatric surgery. Because of small sample sizes and discrepancy in the sampling time points pre- and postoperatively, the observed hormonal impacts of POPs must be interpreted as associative and not causative. Further studies are needed to confirm the findings.


Bariatric surgery Obesity Thyroid hormones Reproductive hormones Cortisol Endocrine disrupting chemicals 



We sincerely thank the study participants and surgical staff and colleagues at the surgical department, Innlandet Hospital Trust. The staff at all three laboratories are acknowledged for their contribution and service. Prof. Eystein Skjerve at NMBU is acknowledged for his scientific contribution.

Funding Information

This study was financially supported by the Innlandet Hospital Trust (grant number 150260).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

The study was approved by the Regional Committee for Medical and Health Research Ethics South East Norway, reference 2012/1394, and conducted in accordance with the Declaration of Helsinki.

Informed Consent

Written informed consent was obtained from all individual participants before inclusion in the study.


  1. 1.
    IPCS. International Programme on Chemical Safety. Global Assessment of the State-of-the-Science of Endocrine Disruptors. World Health Organization: Geneva; 2002.Google Scholar
  2. 2.
    SC. Stockholm Convention. 2019. Listing of POPs in the Stockholm Convention Web-page Available: [Accessed on 5 Nov 2019].
  3. 3.
    Gore AC et al. EDC-2: The Endocrine Society’s Second Scientific Statement on Endocrine-Disrupting Chemicals. Endocr Rev. 2015;36(6):E1–e150.PubMedPubMedCentralCrossRefGoogle Scholar
  4. 4.
    Lindstrom AB, Strynar MJ, Libelo EL. Polyfluorinated compounds: past, present, and future. Environ Sci Technol. 2011;45(19):7954–61.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Olsen GW, Burris JM, Ehresman DJ, et al. Half-life of serum elimination of perfluorooctanesulfonate,perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115(9):1298–305.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Calafat AM et al. Polyfluoroalkyl chemicals in the U.S. population: data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000. Environ Health Perspect. 2007;115(11):1596–602.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Kissa E. Fluorinated surfactants and repellents, 2nd edition. In: Hubbard AT, editor. Surfactant science series, Vol. 97. 2nd ed. New York: Marcel Dekker Inc.; 2001. p. 615.Google Scholar
  8. 8.
    Schafer KS, Kegley SE. Persistent toxic chemicals in the US food supply. J Epidemiol Community Health. 2002;56(11):813–7.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Vestergren R, Cousins IT. Tracking the pathways of human exposure to perfluorocarboxylates. Environ Sci Technol. 2009;43(15):5565–75.PubMedCrossRefGoogle Scholar
  10. 10.
    AMAP, AMAP Assessment 2015: Human Health in the Arctic. Arctic Monitoring and Assessment Programme (AMAP), Oslo, Norway. vii + 165 pp., in Assessment 2015: Human Health in the Arctic. S. Donaldson, et al., Editors. 2015, Arctic Monitoring and Assessment Programme:
  11. 11.
    Deribe E, Rosseland BO, Borgstrøm R, et al. Bioaccumulation of persistent organic pollutants (POPs) in fish species from Lake Koka, Ethiopia: The influence of lipid content and trophic position. Sci Total Environ. 2011;410-411:136–45.PubMedCrossRefGoogle Scholar
  12. 12.
    EFSA. Update of the monitoring of levels of dioxins and PCBs in food and feed. 2012. EFSA J. 2012;10(7):2832. [82 pp.]Google Scholar
  13. 13.
    Harrad S, Goosey E, Desborough J, et al. Dust from U.K. primary school classrooms and daycare centers: the significance of dust as a pathway of exposure of young U.K. children to brominated flame retardants and polychlorinated biphenyls. Environ Sci Technol. 2010;44(11):4198–202.PubMedCrossRefGoogle Scholar
  14. 14.
    Trudel D, Scheringer M, von Goetz N, et al. Total consumer exposure to polybrominated diphenyl ethers in North America and Europe. Environ Sci Technol. 2011;45(6):2391–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Muller MH et al. Organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in human breast milk and associated health risks to nursing infants in Northern Tanzania. Environ Res. 2017;154:425–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Muller MH et al. Brominated flame retardants (BFRs) in breast milk and associated health risks to nursing infants in Northern Tanzania. Environ Int. 2016;89-90:38–47 Scholar
  17. 17.
    Bloom MS, Jansing RL, Kannan K, et al. Thyroid hormones are associated with exposure to persistent organic pollutants in aging residents of upper Hudson River communities. Int J Hyg Environ Health. 2014;217(4-5):473–82.PubMedCrossRefGoogle Scholar
  18. 18.
    Dallaire R, Dewailly E, Pereg D, et al. Thyroid function and plasma concentrations of polyhalogenated compounds in Inuit adults. Environ Health Perspect. 2009;117(9):1380–6.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Schell LM, Gallo MV, Ravenscroft J, et al. Persistent organic pollutants and anti-thyroid peroxidase levels in Akwesasne Mohawk young adults. Environ Res. 2009;109(1):86–92.PubMedCrossRefGoogle Scholar
  20. 20.
    Pelletier C, Doucet E, Imbeault P, et al. Associations between weight loss-induced changes in plasma organochlorine concentrations, serum T(3) concentration, and resting metabolic rate. Toxicol Sci. 2002;67(1):46–51.PubMedCrossRefGoogle Scholar
  21. 21.
    Giwercman AH, Rignell-Hydbom A, Toft G, et al. Reproductive hormone levels in men exposed to persistent organohalogen pollutants: a study of inuit and three European cohorts. Environ Health Perspect. 2006;114(9):1348–53.PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Haugen TB, Tefre T, Malm G, et al. Differences in serum levels of CB-153 and p,p’-DDE, and reproductive parameters between men living south and north in Norway. Reprod Toxicol. 2011;32(3):261–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Grandjean P, Grønlund C, Kjær IM, et al. Reproductive hormone profile and pubertal development in 14-year-old boys prenatally exposed to polychlorinated biphenyls. Reprod Toxicol. 2012;34(4):498–503.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Joensen UN, Veyrand B, Antignac JP, et al. PFOS (perfluorooctanesulfonate) in serum is negatively associated with testosterone levels, but not with semen quality, in healthy men. Hum Reprod. 2013;28(3):599–608.PubMedCrossRefGoogle Scholar
  25. 25.
    Vested A, Giwercman A, Bonde JP, et al. Persistent organic pollutants and male reproductive health. Asian J Androl. 2014;16(1):71–80.PubMedCrossRefGoogle Scholar
  26. 26.
    Goudarzi H, Araki A, Itoh S, et al. The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study. Environ Health Perspect. 2017;125(1):111–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Johansson M, Nilsson S, Lund BO. Interactions between methylsulfonyl PCBs and the glucocorticoid receptor. Environ Health Perspect. 1998;106(12):769–72.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Li LA, Wang PW. PCB126 induces differential changes in androgen, cortisol, and aldosterone biosynthesis in human adrenocortical H295R cells. Toxicol Sci. 2005;85(1):530–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Wilson J, Berntsen HF, Zimmer KE, et al. Do persistent organic pollutants interact with the stress response? Individual compounds, and their mixtures, interaction with the glucocorticoid receptor. Toxicol Lett. 2016;241:121–32.PubMedCrossRefGoogle Scholar
  30. 30.
    Verboven N, Verreault J, Letcher RJ, et al. Adrenocortical function of Arctic-breeding glaucous gulls in relation to persistent organic pollutants. Gen Comp Endocrinol. 2010;166(1):25–32.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Zimmer KE, Gutleb AC, Lyche JL, et al. Altered stress-induced cortisol levels in goats exposed to polychlorinated biphenyls (PCB 126 and PCB 153) during fetal and postnatal development. J Toxicol Environ Health A. 2009;72(3-4):164–72.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Dirinck EL et al. Endocrine-disrupting polychlorinated biphenyls in metabolically healthy and unhealthy obese subjects before and after weight loss: difference at the start but not at the finish. Am J Clin Nutr. 2016;103(4):989–98.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Dirtu AC, Dirinck E, Malarvannan G, et al. Dynamics of organohalogenated contaminants in human serum from obese individuals during one year of weight loss treatment. Environ Sci Technol. 2013;47(21):12441–9.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Jansen A et al. Increased levels of persistent organic pollutants in serum one year after a great weight loss in humans: are the levels exceeding health based guideline values? Sci Total Environ. 2018;622–623:1317–26.PubMedCrossRefGoogle Scholar
  35. 35.
    Kim MJ, Marchand P, Henegar C, et al. Fate and complex pathogenic effects of dioxins and polychlorinated biphenyls in obese subjects before and after drastic weight loss. Environ Health Perspect. 2011;119(3):377–83.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Bischel HN, Macmanus-Spencer LA, Zhang C, et al. Strong associations of short-chain perfluoroalkyl acids with serum albumin and investigation of binding mechanisms. Environ Toxicol Chem. 2011;30(11):2423–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Jones PD, Hu W, de Coen W, et al. Binding of perfluorinated fatty acids to serum proteins. Environ Toxicol Chem. 2003;22(11):2639–49.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Rantakokko P et al. Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly obese patients: a cohort study. Environ Health. 2015;14:79.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Jansen A et al. Decreased plasma levels of perfluoroalkylated substances one year after bariatric surgery. Sci Total Environ, Pages. 2019;657:863–70.Google Scholar
  40. 40.
    Fried M, Yumuk V, Oppert JM, et al. Interdisciplinary European guidelines on metabolic and bariatric surgery. Obes Surg. 2014;24(1):42–55.PubMedCrossRefGoogle Scholar
  41. 41.
    Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab. 1999;84(10):3666–72.PubMedCrossRefGoogle Scholar
  42. 42.
    Guan B, Chen Y, Yang J, et al. Effect of bariatric surgery on thyroid function in obese patients: a Systematic review and meta-analysis. Obes Surg. 2017;27(12):3292–305.PubMedCrossRefGoogle Scholar
  43. 43.
    Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol. 2010;316(2):165–71.PubMedCrossRefGoogle Scholar
  44. 44.
    Santini F, Marzullo P, Rotondi M, et al. Mechanisms in endocrinology: the crosstalk between thyroid gland and adipose tissue: signal integration in health and disease. Eur J Endocrinol. 2014;171(4):R137–52.PubMedCrossRefGoogle Scholar
  45. 45.
    Abdelouahab N, Langlois MF, Lavoie L, et al. Maternal and cord-blood thyroid hormone levels and exposure to polybrominated diphenyl ethers and polychlorinated biphenyls during early pregnancy. Am J Epidemiol. 2013;178(5):701–13.PubMedCrossRefGoogle Scholar
  46. 46.
    Soechitram SD et al. Polychlorinated biphenyl exposure and deiodinase activity in young infants. Sci Total Environ. 2017;574:1117–24.PubMedCrossRefGoogle Scholar
  47. 47.
    Kampf-Lassin A, Prendergast BJ. Acute downregulation of type II and type III iodothyronine deiodinases by photoperiod in peripubertal male and female Siberian hamsters. Gen Comp Endocrinol. 2013;193:72–8.PubMedCrossRefGoogle Scholar
  48. 48.
    Calderon B et al. Effects of bariatric surgery on male obesity-associated secondary hypogonadism: comparison of laparoscopic gastric bypass with restrictive procedures. Obes Surg. 2014;24(10):1686–92.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Pham NH, Bena J, Bhatt DL, et al. Increased free testosterone levels in men with uncontrolled type 2 diabetes five years after randomization to bariatric surgery. Obes Surg. 2018;28(1):277–80.PubMedCrossRefGoogle Scholar
  50. 50.
    Chiofalo F, Ciuoli C, Formichi C, et al. Bariatric surgery reduces serum anti-mullerian hormone levels in obese women with and without polycystic ovarian syndrome. Obes Surg. 2017;27(7):1750–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Escobar-Morreale HF, Santacruz E, Luque-Ramírez M, et al. Prevalence of ‘obesity-associated gonadal dysfunction’ in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum Reprod Update. 2017;23(4):390–408.PubMedCrossRefGoogle Scholar
  52. 52.
    Kjaer MM et al. The impact of gastric bypass surgery on sex hormones and menstrual cycles in premenopausal women. Gynecol Endocrinol. 2017;33(2):160–3.PubMedCrossRefGoogle Scholar
  53. 53.
    Saboor Aftab SA, Kumar S, Barber TM. The role of obesity and type 2 diabetes mellitus in the development of male obesity-associated secondary hypogonadism. Clin Endocrinol. 2013;78(3):330–7.CrossRefGoogle Scholar
  54. 54.
    Taylor SR, Meadowcraft LM, Williamson B. Prevalence, pathophysiology, and management of androgen deficiency in men with metabolic syndrome, type 2 diabetes mellitus, or both. Pharmacotherapy. 2015;35(8):780–92.PubMedCrossRefGoogle Scholar
  55. 55.
    Dhindsa S, Ghanim H, Batra M, et al. Hypogonadotropic hypogonadism in men with diabesity. Diabetes Care. 2018;41(7):1516–25.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Brambilla DJ, Matsumoto AM, Araujo AB, et al. The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab. 2009;94(3):907–13.PubMedCrossRefGoogle Scholar
  57. 57.
    Crawford ED et al. The association of time of day and serum testosterone concentration in a large screening population. BJU Int. 2007;100(3):509–13.PubMedCrossRefGoogle Scholar
  58. 58.
    Glass AR, Swerdloff RS, Bray GA, et al. Low serum testosterone and sex-hormone-binding-globulin in massively obese men. J Clin Endocrinol Metab. 1977;45(6):1211–9.PubMedCrossRefGoogle Scholar
  59. 59.
    Simo R et al. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol Metab. 2015;26(7):376–83.PubMedCrossRefGoogle Scholar
  60. 60.
    Petersen MS, et al. Reproductive function in a population of young Faroese men with elevated exposure to polychlorinated biphenyls (PCBs) and perfluorinated alkylate substances (PFAS). Int J Environ Res Public Health, 2018. 15(9).Google Scholar
  61. 61.
    Warembourg C, Debost-Legrand A, Bonvallot N, et al. Exposure of pregnant women to persistent organic pollutants and cord sex hormone levels. Hum Reprod. 2016;31(1):190–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Vested A, Ramlau-Hansen CH, Olsen SF, et al. In utero exposure to persistent organochlorine pollutants and reproductive health in the human male. Reproduction. 2014;148(6):635–46.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Borlak J, Dangers M, Thum T. Aroclor 1254 modulates gene expression of nuclear transcription factors: implications for albumin gene transcription and protein synthesis in rat hepatocyte cultures. Toxicol Appl Pharmacol. 2002;181(2):79–88.PubMedCrossRefGoogle Scholar
  64. 64.
    Hammond GL. Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod. 2011;85(3):431–41.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Tsai MS et al. Association between perfluoroalkyl substances and reproductive hormones in adolescents and young adults. Int J Hyg Environ Health. 2015;218(5):437–43.PubMedCrossRefGoogle Scholar
  66. 66.
    Cambras T et al. Seasonal variations of changes in lipid and glucidic variables after bariatric surgery. Chronobiol Int. 2018:1–8.Google Scholar
  67. 67.
    Pardina E, Baena-Fustegueras JA, Fort JM, et al. Hepatic and visceral adipose tissue 11betaHSD1 expressions are markers of body weight loss after bariatric surgery. Obesity (Silver Spring). 2015;23(9):1856–63.CrossRefGoogle Scholar
  68. 68.
    Horrocks PM, Jones AF, Ratcliffe WA, et al. Patterns of ACTH and cortisol pulsatility over twenty-four hours in normal males and females. Clin Endocrinol. 1990;32(1):127–34.CrossRefGoogle Scholar
  69. 69.
    Weitzman ED, Fukushima D, Nogeire C, et al. Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab. 1971;33(1):14–22.PubMedCrossRefGoogle Scholar
  70. 70.
    Fommei E, Turci R, Ripoli A, et al. Evidence for persistent organochlorine pollutants in the human adrenal cortex. J Appl Toxicol. 2017;37(9):1091–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Iwanowicz LR, Blazer VS, McCormick S, et al. Aroclor 1248 exposure leads to immunomodulation, decreased disease resistance and endocrine disruption in the brown bullhead, Ameiurus nebulosus. Aquat Toxicol. 2009;93(1):70–82.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Asp V et al. Biphasic hormonal responses to the adrenocorticolytic DDT metabolite 3-methylsulfonyl-DDE in human cells. Toxicol Appl Pharmacol. 2010;242(3):281–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Kato N, Kawai K, Yoshida A. Effect of dietary level of ascorbic acid on the growth, hepatic lipid peroxidation, and serum lipids in guinea pigs fed polychlorinated biphenyls. J Nutr. 1981;111(10):1727–33.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Kraugerud M et al. Three structurally different polychlorinated biphenyl congeners (Pcb 118, 153, and 126) affect hormone production and gene expression in the human H295R in vitro model. J Toxicol Environ Health A. 2010;73(16):1122–32.PubMedCrossRefGoogle Scholar
  75. 75.
    Emeville E, Giton F, Giusti A, et al. Persistent organochlorine pollutants with endocrine activity and blood steroid hormone levels in middle-aged men. PLoS One. 2013;8(6):e66460.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Antunes-Fernandes EC, Bovee TF, Daamen FE, et al. Some OH-PCBs are more potent inhibitors of aromatase activity and (anti-) glucocorticoids than non-dioxin like (NDL)-PCBs and MeSO(2)-PCBs. Toxicol Lett. 2011;206(2):158–65.PubMedCrossRefGoogle Scholar
  77. 77.
    Kortenkamp A. Low dose mixture effects of endocrine disrupters and their implications for regulatory thresholds in chemical risk assessment. Curr Opin Pharmacol. 2014;19:105–11.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of SurgeryInnlandet Hospital TrustGjøvikNorway
  2. 2.Department of Food Safety and Infection BiologyNorwegian University of Life Sciences (NMBU)OsloNorway
  3. 3.Department of Medical BiochemistryOslo University HospitalOsloNorway
  4. 4.Institute of Clinical MedicineOslo University HospitalOsloNorway
  5. 5.Centre for Biostatistics and Epidemiology, Section for Treatment Research, Department for Research and Education, Division of Mental Health and AddictionOslo University HospitalOsloNorway
  6. 6.Research DepartmentInnlandet Hospital TrustBrumunddalNorway
  7. 7.Faculty of Health and Social SciencesInland Norway University of Applied SciencesElverumNorway

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