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Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease

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Abstract

OBJECTIVE

The evaluation of serum sex steroids and sex hormone-binding globulin (SHBG) levels in postmenopausal women with nonalcoholic fatty liver disease (NAFLD) and their association to the disease severity.

DESIGN

Twenty-two postmenopausal women with biopsy-proven NAFLD and 18 matched controls were recruited. Blood samples for serum SHBG, total testosterone, estradiol levels and standard biochemical tests were obtained after overnight fasting. Free androgen index (FAI), calculated free (cFT) and bioavailable testosterone were estimated by standard formulas.

RESULTS

The NAFLD group had lower serum SHBG levels and higher values of cFT, bioavailable testosterone and FAI, despite exhibiting similar to controls levels of serum total testosterone and estradiol. Serum SHBG levels (adjusted odds ratio [aOR] =0.912; 95% CI 0.854–0.973), bioavailable testosterone (aOr=1.254; 95% CI 1.0101.556) and FAI (aOr=2.567; 95% CI 1.153–5.716), but not cFT, were associated with NAFLD independently of age, body mass index (BMI) and waist circumference. Serum estradiol levels were associated with the presence of nonalcoholic steatohepatitis (NASH) independently of age, BMI and waist circumference (aOR=0.727; 95% CI 0.537–0.985).

CONCLUSIONS

Low SHBG levels and high metabolically active testosterone fractions were independently associated with NAFLD. Among NAFLD patients, serum estradiol levels were independently associated with NASH. However, these results need further validation from large-scale studies.

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References

  1. Polyzos SA, Kountouras J, Zavos C, 2009 Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines. Curr Mol Med 72: 299–314.

    Article  Google Scholar 

  2. Vernon G, Baranova A, Younossi ZM, 2011 Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther 34: 274–285.

    Article  CAS  PubMed  Google Scholar 

  3. Polyzos SA, Kountouras J, Zavos C, Deretzi G, 2012 Nonalcoholic fatty liver disease: Multimodal treatment options for a pathogenetically multiple-hit disease. J Clin Gastroenterol 46: 272–284.

    Article  PubMed  Google Scholar 

  4. Baranova A, Tran TP, Birerdinc A, Younossi ZM, 2011 Systematic review: association of polycystic ovary syndrome with metabolic syndrome and non-alcoholic fatty liver disease. Aliment Pharmacol Ther 33: 801–814.

    Article  CAS  PubMed  Google Scholar 

  5. Vassilatou E, Lafoyianni S, Vryonidou A, et al, 2010 Increased androgen bioavailability is associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome. Hum Reprod 25: 212–220.

    Article  CAS  PubMed  Google Scholar 

  6. Shin JY, Kim SK, Lee MY, et al, 2011 Serum sex hormone-binding globulin levels are independently associated with nonalcoholic fatty liver disease in people with type 2 diabetes. Diabetes Res Clin Pract 94: 156–162.

    Article  CAS  PubMed  Google Scholar 

  7. Mojiminiyi OA, Safar FH, Al RH, Diejomaoh M, 2010 Variations in alanine aminotransferase levels within the normal range predict metabolic and androgenic phenotypes in women of reproductive age. Scand J Clin Lab Invest 70: 554–560.

    Article  CAS  PubMed  Google Scholar 

  8. Kauffman RP, Baker TE, Baker V, Kauffman MM, Castracane VD, 2010 Endocrine factors associated with non-alcoholic fatty liver disease in women with polycystic ovary syndrome: do androgens play a role? Gynecol Endocrinol 26: 39–46.

    Article  CAS  PubMed  Google Scholar 

  9. Tian GX, Sun Y, Pang CJ, et al, 2012 Oestradiol is a protective factor for non-alcoholic fatty liver disease in healthy men. Obes Rev 13: 381–387.

    Article  CAS  PubMed  Google Scholar 

  10. Gutierrez-Grobe Y, Ponciano-Rodriguez G, Ramos MH, Uribe M, Mendez-Sanchez N, 2010 Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens. Ann Hepatol 9: 402–409.

    PubMed  Google Scholar 

  11. Tan S, Bechmann LP, Benson S, et al, 2010 Apoptotic markers indicate nonalcoholic steatohepatitis in polycystic ovary syndrome. J Clin Endocrinol Metab 95: 343–348.

    Article  CAS  PubMed  Google Scholar 

  12. Kim S, Kwon H, Park JH, et al, 2012 A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol 12: 69. doi: https://doi.org/10.1186/1471-230X-12-69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC, 1985 Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28: 412–419.

    Article  CAS  PubMed  Google Scholar 

  14. Vermeulen A, Verdonck L, Kaufman JM, 1999 A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84: 3666–3672.

    Article  CAS  PubMed  Google Scholar 

  15. Kleiner DE, Brunt EM, Van NM, et al, 2005 Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41: 1313–1321.

    Article  PubMed  Google Scholar 

  16. Brand JS, van dT, I, Grobbee DE, Emmelot-Vonk MH, van der Schouw YT, 2011 Testosterone, sex hormone-binding globulin and the metabolic syndrome: a systematic review and meta-analysis of observational studies. Int J Epidemiol 40: 189–207.

    Article  PubMed  Google Scholar 

  17. Selva DM, Hogeveen KN, Innis SM, Hammond GL, 2007 Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. J Clin Invest 117: 3979–3987.

    PubMed  PubMed Central  CAS  Google Scholar 

  18. Yasui T, Tomita J, Miyatani Y, et al, 2007 Associations of adiponectin with sex hormone-binding globulin levels in aging male and female populations. Clin Chim Acta 386: 69–75.

    Article  CAS  PubMed  Google Scholar 

  19. Laaksonen DE, Niskanen L, Punnonen K, et al, 2003 Sex hormones, inflammation and the metabolic syndrome: a population-based study. Eur J Endocrinol 149: 601–608.

    Article  CAS  PubMed  Google Scholar 

  20. McKenzie J, Fisher BM, Jaap AJ, Stanley A, Paterson K, Sattar N, 2006 Effects of HRT on liver enzyme levels in women with type 2 diabetes: a randomized placebo-controlled trial. Clin Endocrinol (Oxf) 65: 40–44.

    Article  CAS  Google Scholar 

  21. Kim MH, Kang KS, Lee YS, 2010 The inhibitory effect of genistein on hepatic steatosis is linked to visceral adipocyte metabolism in mice with diet-induced nonalcoholic fatty liver disease. Br J Nutr 104: 1333–1342.

    Article  CAS  PubMed  Google Scholar 

  22. Kamada Y, Kiso S, Yoshida Y, et al, 2011 Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high-cholesterol diet. Am J Physiol Gastrointest Liver Physiol 301: G1031–G1043.

    Article  CAS  PubMed  Google Scholar 

  23. Fukui M, Senmaru T, Hasegawa G, et al, 2011 17beta-Estradiol attenuates saturated fatty acid diet-induced liver injury in ovariectomized mice by up-regulating hepatic senescence marker protein-30. Biochem Biophys Res Commun 415: 252–257.

    Article  CAS  PubMed  Google Scholar 

  24. Chow JD, Jones ME, Prelle K, Simpson ER, Boon WC, 2011 A selective estrogen receptor alpha agonist ameliorates hepatic steatosis in the male aromatase knockout mouse. J Endocrinol 210: 323–334.

    Article  CAS  PubMed  Google Scholar 

  25. Giannitrapani L, Soresi M, La SE, Cervello M, D’Alessandro N, Montalto G, 2006 Sex hormones and risk of liver tumor. Ann N Y Acad Sci 1089: 228–236.

    Article  CAS  PubMed  Google Scholar 

  26. Kountouras J, Boura P, Karolides A, Zaharioudaki E, Tsapas G, 1995 Recombinant a2 interferon (a-IFN) with chemo-hormonal therapy in patients with hepatocellular carcinoma (HCC). Hepatogastroenterology 42: 31–36.

    PubMed  CAS  Google Scholar 

  27. Yin PH, Lee HC, Chau GY, et al, 2004 Polymorphisms of estrogen-metabolizing genes and risk of hepatocellular carcinoma in Taiwan females. Cancer Lett 212: 195–201.

    Article  CAS  PubMed  Google Scholar 

  28. Koehler E, Swain J, Sanderson S, Krishnan A, Watt K, Charlton M, 2012 Growth hormone, dehydroepiandrosterone and adiponectin levels in non-alcoholic steatohepatitis: an endocrine signature for advanced fibrosis in obese patients. Liver Int 32: 279–286.

    Article  CAS  PubMed  Google Scholar 

  29. Sumida Y, Yonei Y, Kanemasa K, et al, 2010 Lower circulating levels of dehydroepiandrosterone, independent of insulin resistance, is an important determinant of severity of non-alcoholic steatohepatitis in Japanese patients. Hepatol Res 40: 901–910.

    Article  CAS  PubMed  Google Scholar 

  30. Charlton M, Angulo P, Chalasani N, et al, 2008 Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology 47: 484–492.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ahmed A, Rabbitt E, Brady T, et al, 2012 A switch in hepatic cortisol metabolism across the spectrum of non alcoholic fatty liver disease. PLos One 7: e29531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Konopelska S, Kienitz T, Hughes B, et al, 2009 Hepatic 11beta-HSD1 mRNA expression in fatty liver and nonalcoholic steatohepatitis. Clin Endocrinol (Oxf) 70: 554–560.

    Article  CAS  Google Scholar 

  33. Bedogni G, Bellentani S, Miglioli L, et al, 2006 The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population. BMC Gastroenterol 6: 33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Vongsuvanh R, George J, McLeod D, van der PD, 2012 Visceral adiposity index is not a predictor of liver histology in patients with non-alcoholic fatty liver disease. J Hepatol 57: 392–398.

    Article  PubMed  Google Scholar 

  35. Ly LP, Sartorius G, Hull L, et al, 2010 Accuracy of calculated free testosterone formulae in men. Clin Endocrinol (Oxf) 73: 382–388.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Second Medical Clinic, Aristotle University of Thessaloniki, Ippokration Hospital, Thessaloniki, Greece

    Stergios A. Polyzos MD, MSc, PhD (Endocrinologist), Jannis Kountouras & Christos Zavos

  2. Department of Endocrinology, University of Ioannina, Ioannina, Greece

    Agathocles Tsatsoulis

  3. Department of Radiology, Ippokration Hospital, Thessaloniki, Greece

    Efthimia Zafeiriadou

  4. Department of Pathology, Ippokration Hospital, Thessaloniki, Greece

    Evangelia Katsiki & Kalliopi Patsiaoura

  5. Department of Gynecology and Obstetrics, Maternity Hospital “Mitera”, Athens, Greece

    Vasiliki V. Anastasiadou

  6. Department of Biochemistry, Ippokration Hospital, Thessaloniki, Greece

    Aristidis Slavakis

Authors
  1. Stergios A. Polyzos MD, MSc, PhD
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  2. Jannis Kountouras
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  3. Agathocles Tsatsoulis
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  4. Efthimia Zafeiriadou
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  7. Christos Zavos
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Correspondence to Stergios A. Polyzos MD, MSc, PhD.

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Polyzos, S.A., Kountouras, J., Tsatsoulis, A. et al. Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones 12, 405–416 (2013). https://doi.org/10.1007/BF03401306

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  • DOI: https://doi.org/10.1007/BF03401306

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