Testosterone in men with advanced liver disease: Abnormalities and implications

Journal of Gastroenterology and Hepatology (Australia)

Volumn 30, Issue 2, 2015, Pages 244-251

  Sinclair, Marie ^a,b   Grossmann, Mathis ^a,b   Gow, Paul J ^a,b   Angus, Peter W ^a,b  

^a AUSTIN HOSPITAL   (Australia)

^b UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Advanced liver disease; Cirrhosis; Sarcopenia; Testosterone

Indexed keywords

ANABOLIC AGENT; ANDROGEN; HEMOGLOBIN; TESTOSTERONE;

ANDROGEN DEFICIENCY; ANDROGEN THERAPY; BONE; BONE DENSITY; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; DRUG SAFETY; FAT MASS; GLUCOSE METABOLISM; GYNECOMASTIA; HEMATOPOIESIS; HUMAN; HYPOGONADISM; HYPOPHYSIS TESTIS SYSTEM; IMMUNITY; INSULIN RESISTANCE; LIBIDO DISORDER; LIVER CELL CARCINOMA; LIVER CIRRHOSIS; LIVER DISEASE; MALE; MODEL FOR END STAGE LIVER DISEASE SCORE; MORTALITY; MUSCLE; MUSCLE MASS; NONHUMAN; OSTEOPOROSIS; PRIORITY JOURNAL; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; SARCOPENIA; TESTOSTERONE BLOOD LEVEL; BLOOD; DEFICIENCY; HORMONE SUBSTITUTION; METABOLISM; PHYSIOLOGY; SEVERITY OF ILLNESS INDEX;

HORMONE REPLACEMENT THERAPY; HUMANS; LIVER CIRRHOSIS; MALE; PROGNOSIS; SEVERITY OF ILLNESS INDEX; TESTOSTERONE;

EID: 84921459799     PISSN: 08159319     EISSN: 14401746     Source Type: Journal    
DOI: 10.1111/jgh.12695     Document Type: Review

References (66)

1. Handelsman DJ, Strasser S, McDonald JA, Conway AJ, McCaughan GW. Hypothalamic-pituitary-testicular function in end-stage non-alcoholic liver disease before and after liver transplantation. Clin. Endocrinol. (Oxf). 1995; 43: 331-337.
2. Grossmann M, Hoermann R, Gani L etal. Low testosterone levels as an independent predictor of mortality in men with chronic liver disease. Clin. Endocrinol. (Oxf). 2012; 77: 323-328.
3. Kovacs WJ, Ojeda SR. Textbook of Endocrine Physiology, 6th edn. New York, NY: Oxford University Press, 2011.
4. 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: 3666-3672.
5. van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J. Clin. Endocrinol. Metab. 2000; 85: 3276-3282.
6. Bhasin S, Woodhouse L, Casaburi R etal. Testosterone dose-response relationships in healthy young men. Am. J. Physiol. Endocrinol. Metab. 2001; 281: E1172-1181.
7. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S. Testosterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab. 2003; 285: E197-205.
8. Vanderschueren D, Bouillon R. Androgens and bone. Calcif. Tissue Int. 1995; 56: 341-346.
9. Abu EO, Horner A, Kusec V, Triffitt JT, Compston JE. The localization of androgen receptors in human bone. J. Clin. Endocrinol. Metab. 1997; 82: 3493-3497.
10. Amory JK, Watts NB, Easley KA etal. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J. Clin. Endocrinol. Metab. 2004; 89: 503-510.
11. Snyder PJ, Peachey H, Hannoush P etal. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J. Clin. Endocrinol. Metab. 1999; 84: 1966-1972.
12. Singh R, Artaza JN, Taylor WE etal. Testosterone inhibits adipogenic differentiation in 3T3-L1 cells: nuclear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic transcription factors. Endocrinology 2006; 147: 141-154.
13. Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Aging Male. 2003; 6: 1-7.
14. Grossmann M. Testosterone and glucose metabolism in men: current concepts and controversies. J. Endocrinol. 2014; 220: R37-55.
15. Haider A, Gooren LJ, Padungtod P, Saad F. Improvement of the metabolic syndrome and of non-alcoholic liver steatosis upon treatment of hypogonadal elderly men with parenteral testosterone undecanoate. Exp. Clin. Endocrinol. Diabetes 2010; 118: 167-171.
16. Fernandez-Balsells MM, Murad MH, Lane M etal. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2010; 95: 2560-2575.
17. Coviello AD, Kaplan B, Lakshman KM, Chen T, Singh AB, Bhasin S. Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. J. Clin. Endocrinol. Metab. 2008; 93: 914-919.
18. Bachman E, Feng R, Travison T etal. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J. Clin. Endocrinol. Metab. 2010; 95: 4743-4747.
19. Muehlenbein MP, Bribiescas RG. Testosterone-mediated immune functions and male life histories. Am. J. Hum. Biol. 2005; 17: 527-558.
20. Gold SM, Chalifoux S, Giesser BS, Voskuhl RR. Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone. J. Neuroinflammation 2008; 5: 32.
21. Sinclair M, Angus P, Gow P, Hoermann R, Mogilevski T, Grossmann M. Low serum testosterone levels pre-liver transplantation are associated with reduced rates of early acute allograft rejection in men. Transplantation 2014; 98: 788-792.
22. Sikaris K, McLachlan RI, Kazlauskas R, de Kretser D, Holden CA, Handelsman DJ. Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. J. Clin. Endocrinol. Metab. 2005; 90: 5928-5936.
23. Bhasin S, Pencina M, Jasuja GK etal. Reference ranges for testosterone in men generated using liquid chromatography tandem mass spectrometry in a community-based sample of healthy nonobese young men in the Framingham Heart Study and applied to three geographically distinct cohorts. J. Clin. Endocrinol. Metab. 2011; 96: 2430-2439.
24. Meier C, Nguyen TV, Handelsman DJ etal. Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Arch. Intern. Med. 2008; 168: 47-54.
25. Grossmann M, Thomas MC, Panagiotopoulos S etal. Low testosterone levels are common and associated with insulin resistance in men with diabetes. J. Clin. Endocrinol. Metab. 2008; 93: 1834-1840.
26. Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2011; 96: 3007-3019.
27. Monegal A, Navasa M, Guanabens N etal. Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics. Osteoporos. Int. 2001; 12: 484-492.
28. Zietz B, Lock G, Plach B etal. Dysfunction of the hypothalamic-pituitary-glandular axes and relation to Child-Pugh classification in male patients with alcoholic and virus-related cirrhosis. Eur. J. Gastroenterol. Hepatol. 2003; 15: 495-501.
29. Zifroni A, Schiavi RC, Schaffner F. Sexual function and testosterone levels in men with nonalcoholic liver disease. Hepatology 1991; 14: 479-482.
30. Mowat NA, Edwards CR, Fisher R, McNeilly AS, Green JR, Dawson AM. Hypothalamic-pituitary-gonadal function in men with cirrhosis of the liver. Gut 1976; 17: 345-350.
31. Jones TH, Kennedy RL. Cytokines and hypothalamic-pituitary function. Cytokine 1993; 5: 531-538.
32. MacAdams MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann. Intern. Med. 1986; 104: 648-651.
33. Burke CW, Anderson DC. Sex-hormone-binding globulin is an oestrogen amplifier. Nature 1972; 240: 38-40.
34. Maruyama Y, Adachi Y, Aoki N, Suzuki Y, Shinohara H, Yamamoto T. Mechanism of feminization in male patients with non-alcoholic liver cirrhosis: role of sex hormone-binding globulin. Gastroenterol. Jpn. 1991; 26: 435-439.
35. Bandyopadhyay SK, Moulick A, Saha M, Dutta A, Bandyopadhyay R, Basu AK. A study on endocrine dysfunction in adult males with liver cirrhosis. J. Indian Med. Assoc. 2009; 107: 866, 8-8669.
36. Gordon GG, Olivo J, Rafil F, Southren AL. Conversion of androgens to estrogens in cirrhosis of the liver. J. Clin. Endocrinol. Metab. 1975; 40: 1018-1026.
37. Green JR, Mowat NA, Fisher RA, Anderson DC. Plasma oestrogens in men with chronic liver disease. Gut 1976; 17: 426-430.
38. Braunstein GD. Gynecomastia. N. Engl. J. Med. 1993; 328: 490-495.
39. Iturriaga H, Lioi X, Valladares L. Sex hormone-binding globulin in non-cirrhotic alcoholic patients during early withdrawal and after longer abstinence. Alcohol. Alcohol. 1999; 34: 903-909.
40. Rose LI, Underwood RH, Newmark SR, Kisch ES, Williams GH. Pathophysiology of spironolactone-induced gynecomastia. Ann. Intern. Med. 1977; 87: 398-403.
41. Durand F, Buyse S, Francoz C etal. Prognostic value of muscle atrophy in cirrhosis using psoas muscle thickness on computed tomography. J. Hepatol. 2014; 60: 1151-1157.
42. Montano-Loza AJ, Meza-Junco J, Prado CM etal. Muscle wasting is associated with mortality in patients with cirrhosis. Clin. Gastroenterol. Hepatol. 2012; 10: 166-173.
43. Alcalde Vargas A, Pascasio Acevedo JM, Gutierrez Domingo I etal. Prevalence and characteristics of bone disease in cirrhotic patients under evaluation for liver transplantation. Transplant Proc. 2012; 44: 1496-1498.
44. Rouillard S, Lane NE. Hepatic osteodystrophy. Hepatology 2001; 33: 301-307.
45. Kawaguchi T, Taniguchi E, Itou M, Sakata M, Sumie S, Sata M. Insulin resistance and chronic liver disease. World J. Hepatol. 2011; 3: 99-107.
46. D'Souza R, Sabin CA, Foster GR. Insulin resistance plays a significant role in liver fibrosis in chronic hepatitis C and in the response to antiviral therapy. Am. J. Gastroenterol. 2005; 100: 1509-1515.
47. Hung CH, Wang JH, Hu TH etal. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection. World J. Gastroenterol. 2010; 16: 2265-2271.
48. Gluud C, Hardt F, Juhl E. Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The Copenhagen Study Group for Liver Diseases. Hepatology 1986; 6: 807-813.
49. Wells R. Prednisolone and testosterone propionate in cirrhosis of the liver. A controlled trial. Lancet 1960; 2: 1416-1419.
50. Puliyel MM, Vyas GP, Mehta GS. Testosterone in the management of cirrhosis of the liver-a controlled study. Aust. N. Z. J. Med. 1977; 7: 17-30.
51. Rambaldi A, Gluud C. Anabolic-androgenic steroids for alcoholic liver disease. Cochrane Database Syst. Rev. 2006; 4: CD003045.
52. Fenster F. The nonefficacy of short-term anabolic steroid therapy in alcoholic liver disease. Ann. Intern. Med. 1966; 65: 738-744.
53. Yurci A, Yucesoy M, Unluhizarci K etal. Effects of testosterone gel treatment in hypogonadal men with liver cirrhosis. Clin. Res. Hepatol. Gastroenterol. 2011; 35: 845-854.
54. Buch SC, Kondragunta V, Branch RA, Carr BI. Gender-based outcomes differences in unresectable hepatocellular carcinoma. Hepatol. Int. 2008; 2: 95-101.
55. Yu MW, Chen CJ. Elevated serum testosterone levels and risk of hepatocellular carcinoma. Cancer Res. 1993; 53: 790-794.
56. Tanaka K, Sakai H, Hashizume M, Hirohata T. Serum testosterone:estradiol ratio and the development of hepatocellular carcinoma among male cirrhotic patients. Cancer Res. 2000; 60: 5106-5110.
57. Montalto G, Miceli M, Soresi M etal. Sex hormones in patients with liver cirrhosis and hepatocellular carcinoma. Oncol. Rep. 1997; 4: 173-176.
58. Lukanova A, Becker S, Husing A etal. Pre-diagnostic plasma testosterone, sex hormone binding globulin, IGF-I and hepatocellular carcinoma: etiological factors or risk markers? Int. J. Cancer 134: 164-173.
59. Chen PJ, Yeh SH, Liu WH etal. Androgen pathway stimulates microRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology 2012; 56: 632-643.
60. Boix L, Castells A, Bruix J etal. Androgen receptors in hepatocellular carcinoma and surrounding liver: relationship with tumor size and recurrence rate after surgical resection. J. Hepatol. 1995; 22: 616-622.
61. Granata OM, Carruba G, Montalto G etal. Altered androgen metabolism eventually leads hepatocellular carcinoma to an impaired hormone responsiveness. Mol. Cell Endocrinol. 2002; 193: 51-58.
62. Naugler WE, Sakurai T, Kim S etal. Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science 2007; 317: 121-124.
63. Johnson FL, Lerner KG, Siegel M etal. Association of androgenic-anabolic steroid therapy with development of hepatocellular carcinoma. Lancet 1972; 2: 1273-1276.
64. Farrell GC, Joshua DE, Uren RF, Baird PJ, Perkins KW, Kronenberg H. Androgen-induced hepatoma. Lancet 1975; 1: 430-432.
65. Bhasin S, Cunningham GR, Hayes FJ etal. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 2006; 91: 1995-2010.
66. Grimaldi C, Bleiberg H, Gay F etal. Evaluation of antiandrogen therapy in unresectable hepatocellular carcinoma: results of a European Organization for Research and Treatment of Cancer multicentric double-blind trial. J. Clin. Oncol. 1998; 16: 411-417.