Advertisement

Current Hepatology Reports

, Volume 18, Issue 4, pp 417–424 | Cite as

Spectrum of Drug Induced Liver Injury Caused by Anabolic Androgenic Steroids Abuse

  • Varun Takyar
  • Andrew StolzEmail author
Drug-Induced Liver Injury (P Hayashi, Section Editor)
First Online:
Part of the following topical collections:
  1. Topical Collection on Drug-Induced Liver Injury

Abstract

Purpose of Review

Potent anabolic androgenic steroids (AAS) are often illegally present in commercially available body building supplements (BBS) and may cause drug induced liver injury (DILI) with different phenotypes.

Recent Findings

AAS induced DILI typically presents with a prolonged cholestatic liver injury with pruritus and a typical enzyme pattern of elevated transaminases that rapidly fall as alkaline phosphatase slowly increases. Liver biopsy reveals bland cholestasis that usually does not have chronic sequalae. Pathophysiology is unknown and genetic variants in genes associated with cholestatic syndromes were observed in a minority of patients. Chemical analysis of BBS have identified controlled AAS, which were not documented on the label.

Summary

More frequent use of BBS in males to enhance physical performance is predicted to increase the incidence of cholestatic DILI. The typical presentation of AAS induced liver injury in an at risk populations should prompt careful assessment of BBS exposure.

Keywords

Herbal Dietary Supplement Bodybuilding Hepatotoxicity Jaundice 

Abbreviations

AAS

Anabolic Androgenic Steroids

AKP

Alkaline Phosphatase

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

BBS

Body building supplements

DEA

Drug Enforcement Agency

DILI

Drug induced liver injury

DILIN

Drug induced liver injury network

FDA

Food and Drug Administration

GGT

gamma glutamyl transpeptidase

HDS

Herbal and Dietary supplements

NIH

National Institutes of Health

NRH

Nodular regenerative hyperplasia

RUCAM

Roussel Uclaf Causality Assessment Method

T Bili

Total Bilirubin

ULN

Upper limit of normal

This is a preview of subscription content, log in to check access.

Notes

Compliance with Ethical Standards

Conflict of Interest

Varun Takyar and Andrew Stolz each declare no potential conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    • Navarro VJ, Khan I, Bjornsson E, Seeff LB, Serrano J, Hoofnagle JH. Liver injury from herbal and dietary supplements. Hepatology. 2017;65(1):363–73.  https://doi.org/10.1002/hep.28813A comprehensive review of DILI related to herbal and dietary supplements from DILIN. CrossRefPubMedGoogle Scholar
  2. 2.
  3. 3.
    Alison EF, Kendrin RS, Ross DC, Sonja AS, Kamryn TE, Carlos AC, et al. Prospective associations of concerns about physique and the development of obesity, binge drinking, and drug use among adolescent boys and Young adult men. JAMA Pediatr. 2014;168:34–9.  https://doi.org/10.1001/jamapediatrics.2013.2915.CrossRefGoogle Scholar
  4. 4.
    Ruzicka L, Wettstein A. Sex hormones VII. On the artificial manufacture of testicular hormone testosteron (Androstene-3-one-17-ol). Helvetica Chimica Acta. 1935;18:1264–75.  https://doi.org/10.1002/hlca.193501801176.CrossRefGoogle Scholar
  5. 5.
    • Kanayama G, Pope HG Jr. History and epidemiology of anabolic androgens in athletes and non-athletes. Mol Cell Endocrinol. 2018;464:4–13.  https://doi.org/10.1016/j.mce.2017.02.039Important review about the changing epidemiology of androgenic anabolic steriod use since their discovery to current heavy use by non-athletes. CrossRefPubMedGoogle Scholar
  6. 6.
    Basaria S, Wahlstrom JT, Dobs AS. Clinical review 138: Anabolic-androgenic steroid therapy in the treatment of chronic diseases. J Clin Endocrinol Metab. 2001;86(11):5108–17.  https://doi.org/10.1210/jcem.86.11.7983.CrossRefPubMedGoogle Scholar
  7. 7.
    Grunfeld C, Kotler DP, Dobs A, Glesby M, Bhasin S. Oxandrolone in the treatment of HIV-associated weight loss in men: a randomized, double-blind, placebo-controlled study. J Acquir Immune Defic Syndr. 2006;41(3):304–14.  https://doi.org/10.1097/01.qai.0000197546.56131.40.CrossRefPubMedGoogle Scholar
  8. 8.
    Wade N. Anabolic steroids: doctors denounce them, but athletes Aren't listening. Science. 1972;176(4042):1399–403.  https://doi.org/10.1126/science.176.4042.1399.CrossRefPubMedGoogle Scholar
  9. 9.
    Bhasin S, Storer TW, Berman N, Callegari C, Clevenger B, Phillips J, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996;335(1):1–7.  https://doi.org/10.1056/NEJM199607043350101.CrossRefPubMedGoogle Scholar
  10. 10.
    van Amsterdam J, Opperhuizen A, Hartgens F. Adverse health effects of anabolic-androgenic steroids. Regul Toxicol Pharmacol. 2010;57(1):117–23.  https://doi.org/10.1016/j.yrtph.2010.02.001.CrossRefPubMedGoogle Scholar
  11. 11.
    Hall RC, Hall RC. Abuse of supraphysiologic doses of anabolic steroids. South Med J. 2005;98(5):550–5.  https://doi.org/10.1097/01.SMJ.0000157531.04472.B2.CrossRefPubMedGoogle Scholar
  12. 12.
    Hershberger LG, Shipley EG, Meyer RK. Myotrophic activity of 19-nortestosterone and other steroids determined by modified levator ani muscle method. Proc Soc Exp Biol Med. 1953;83(1):175–80.CrossRefGoogle Scholar
  13. 13.
    Kicman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–21.  https://doi.org/10.1038/bjp.2008.165.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Brower KJ, Blow FC, Young JP, Hill EM. Symptoms and correlates of anabolic-androgenic steroid dependence. Br J Addict. 1991;86(6):759–68.  https://doi.org/10.1111/j.1360-0443.1991.tb03101.x.CrossRefGoogle Scholar
  15. 15.
    Pope HG Jr, Katz DL, Champoux R. Anabolic-androgenic steroid use among 1,010 college men. Phys Sportsmed. 1988;16(7):75–81.  https://doi.org/10.1080/00913847.1988.11709554.CrossRefPubMedGoogle Scholar
  16. 16.
    Pope HG Jr, Kanayama G, Athey A, Ryan E, Hudson JI, Baggish A. The lifetime prevalence of anabolic-androgenic steroid use and dependence in Americans: current best estimates. Am J Addict. 2014;23(4):371–7.  https://doi.org/10.1111/j.1521-0391.2014.12118.x.CrossRefPubMedGoogle Scholar
  17. 17.
    McCabe SE, Brower KJ, West BT, Nelson TF, Wechsler H. Trends in non-medical use of anabolic steroids by U.S. college students: results from four national surveys. Drug Alcohol Depend. 2007;90(2–3):243–51.  https://doi.org/10.1016/j.drugalcdep.2007.04.004.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cohen J, Collins R, Darkes J, Gwartney D. A league of their own: demographics, motivations and patterns of use of 1,955 male adult non-medical anabolic steroid users in the United States. J Int Soc Sports Nutr. 2007;4:12.  https://doi.org/10.1186/1550-2783-4-12.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Parssinen M, Kujala U, Vartiainen E, Sarna S, Seppala T. Increased premature mortality of competitive powerlifters suspected to have used anabolic agents. Int J Sports Med. 2000;21(3):225–7.  https://doi.org/10.1055/s-2000-304.CrossRefPubMedGoogle Scholar
  20. 20.
    Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363(2):109–22.  https://doi.org/10.1056/NEJMoa1000485.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Pope HG Jr, Katz DL. Psychiatric and medical effects of anabolic-androgenic steroid use. A controlled study of 160 athletes. Arch Gen Psychiatry. 1994;51(5):375–82.  https://doi.org/10.1001/archpsyc.1994.03950050035004.CrossRefGoogle Scholar
  22. 22.
    Pope HG Jr, Gruber AJ, Mangweth B, Bureau B, deCol C, Jouvent R, et al. Body image perception among men in three countries. Am J Psychiatry. 2000;157(8):1297–301.  https://doi.org/10.1176/appi.ajp.157.8.1297.CrossRefPubMedGoogle Scholar
  23. 23.
    Pope HG Jr, Gruber AJ, Choi P, Olivardia R, Phillips KA. Muscle dysmorphia. An underrecognized form of body dysmorphic disorder. Psychosomatics. 1997;38(6):548–57.  https://doi.org/10.1016/S0033-3182(97)71400-2.CrossRefPubMedGoogle Scholar
  24. 24.
    Kanayama G, Hudson JI, Pope HG Jr. Features of men with anabolic-androgenic steroid dependence: a comparison with nondependent AAS users and with AAS nonusers. Drug Alcohol Depend. 2009;102(1–3):130–7.  https://doi.org/10.1016/j.drugalcdep.2009.02.008.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Bjornsson ES, Bergmann OM, Bjornsson HK, Kvaran RB, Olafsson S. Incidence, presentation, and outcomes in patients with drug-induced liver injury in the general population of Iceland. Gastroenterology. 2013;144(7):1419–25, 25 e1–3; quiz e19–20.  https://doi.org/10.1053/j.gastro.2013.02.006.CrossRefPubMedGoogle Scholar
  26. 26.
    Navarro VJ, Barnhart H, Bonkovsky HL, Davern T, Fontana RJ, Grant L, et al. Liver injury from herbals and dietary supplements in the U.S. drug-induced liver injury network. Hepatology. 2014;60(4):1399–408.  https://doi.org/10.1002/hep.27317.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    • Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017;112(1):18–35.  https://doi.org/10.1038/ajg.2016.517A recent review and guideline statement from American College of Gastroenterology regarding normal values of transaminases and also diagnostic evaluation of abnormal liver function. CrossRefPubMedGoogle Scholar
  28. 28.
    Robles-Diaz M, Gonzalez-Jimenez A, Medina-Caliz I, Stephens C, Garcia-Cortes M, Garcia-Munoz B, et al. Distinct phenotype of hepatotoxicity associated with illicit use of anabolic androgenic steroids. Aliment Pharmacol Ther. 2015;41(1):116–25.  https://doi.org/10.1111/apt.13023.CrossRefPubMedGoogle Scholar
  29. 29.
    • Stolz A, Navarro V, Hayashi PH, Fontana RJ, Barnhart HX, Gu J, et al. Severe and protracted cholestasis in 44 young men taking bodybuilding supplements: assessment of genetic, clinical and chemical risk factors. Aliment Pharmacol Ther. 2019;49(9):1195–204.  https://doi.org/10.1111/apt.15211A comprehensive prospective analysis of BBS related DILI from the DILIN with majority of patients having prolonged pruritic cholestasis. CrossRefPubMedGoogle Scholar
  30. 30.
    Abbate V, Kicman AT, Evans-Brown M, McVeigh J, Cowan DA, Wilson C, et al. Anabolic steroids detected in bodybuilding dietary supplements - a significant risk to public health. Drug Test Anal. 2015;7(7):609–18.  https://doi.org/10.1002/dta.1728.CrossRefPubMedGoogle Scholar
  31. 31.
    Kapuria D, Ben-Yakov G, Ortolano R, Cho MH, Kalchiem-Dekel O, Takyar V, et al. The Spectrum of hepatic involvement in patients with telomere disease. Hepatology. 2019.  https://doi.org/10.1002/hep.30578.
  32. 32.
    Bagheri SA, Boyer JL. Peliosis hepatis associated with androgenic-anabolic steroid therapy. A severe form of hepatic injury. Ann Intern Med. 1974;81(5):610–8.  https://doi.org/10.7326/0003-4819-81-5-610.CrossRefGoogle Scholar
  33. 33.
    Choi SK, Jin JS, Cho SG, Choi SJ, Kim CS, Choe YM, et al. Spontaneous liver rupture in a patient with peliosis hepatis: a case report. World J Gastroenterol. 2009;15(43):5493–7.  https://doi.org/10.3748/wjg.15.5493.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Cabasso A. Peliosis hepatis in a young adult bodybuilder. Med Sci Sports Exerc. 1994;26(1):2–4.CrossRefGoogle Scholar
  35. 35.
    Velazquez I, Alter BP. Androgens and liver tumors: Fanconi's anemia and non-Fanconi's conditions. Am J Hematol. 2004;77(3):257–67.  https://doi.org/10.1002/ajh.20183.CrossRefPubMedGoogle Scholar
  36. 36.
    Bagia S, Hewitt PM, Morris DL. Anabolic steroid-induced hepatic adenomas with spontaneous haemorrhage in a bodybuilder. Aust N Z J Surg. 2000;70(9):686–7.  https://doi.org/10.1046/j.1440-1622.2000.01932.x.CrossRefGoogle Scholar
  37. 37.
    Gorayski P, Thompson CH, Subhash HS, Thomas AC. Hepatocellular carcinoma associated with recreational anabolic steroid use. Br J Sports Med. 2008;42(1):74–5; discussion 5.  https://doi.org/10.1136/bjsm.2007.03932.CrossRefPubMedGoogle Scholar
  38. 38.
    Martin NM, Abu Dayyeh BK, Chung RT. Anabolic steroid abuse causing recurrent hepatic adenomas and hemorrhage. World J Gastroenterol. 2008;14(28):4573–5.  https://doi.org/10.3748/wjg.14.4573.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Montgomery RR, Ducore JM, Githens JH, August CS, Johnson ML. Regression on oxymetholone-induced hepatic tumors after bone marrow transplantation in aplastic anemia. Transplantation. 1980;30(2):90–6.  https://doi.org/10.1097/00007890-198008000-00002.CrossRefGoogle Scholar
  40. 40.
    Westaby D, Portmann B, Williams R. Androgen related primary hepatic tumors in non-Fanconi patients. Cancer. 1983;51(10):1947–52.  https://doi.org/10.1002/1097-0142(19830515)51:10<1947::aid-cncr2820511034>3.0.co;2-5.CrossRefGoogle Scholar
  41. 41.
    Socas L, Zumbado M, Perez-Luzardo O, Ramos A, Perez C, Hernandez JR, et al. Hepatocellular adenomas associated with anabolic androgenic steroid abuse in bodybuilders: a report of two cases and a review of the literature. Br J Sports Med. 2005;39(5):e27.  https://doi.org/10.1136/bjsm.2004.013599.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Stromeyer FW, Ishak KG. Nodular transformation (nodular "regenerative" hyperplasia) of the liver. A clinicopathologic study of 30 cases. Hum Pathol. 1981;12(1):60–71.  https://doi.org/10.1016/s0046-8177(81)80242-0.CrossRefGoogle Scholar
  43. 43.
    Shah NL, Zacharias I, Khettry U, Afdhal N, Gordon FD. Methasteron-associated cholestatic liver injury: clinicopathologic findings in 5 cases. Clin Gastroenterol Hepatol. 2008;6(2):255–8.  https://doi.org/10.1016/j.cgh.2007.11.010.CrossRefPubMedGoogle Scholar
  44. 44.
    • Alkhunaizi AM, ElTigani MA, Rabah RS, Nasr SH. Acute bile nephropathy secondary to anabolic steroids. Clin Nephrol. 2016;85(2):121–6.  https://doi.org/10.5414/CN108696A case report of tubular obstruction by bile casts in a patient with prolonged cholestatic pattern of AAS DILI. CrossRefPubMedGoogle Scholar
  45. 45.
    Luciano RL, Castano E, Moeckel G, Perazella MA. Bile acid nephropathy in a bodybuilder abusing an anabolic androgenic steroid. Am J Kidney Dis. 2014;64(3):473–6.  https://doi.org/10.1053/j.ajkd.2014.05.010.CrossRefPubMedGoogle Scholar
  46. 46.
    Bispo M, Valente A, Maldonado R, Palma R, Gloria H, Nobrega J, et al. Anabolic steroid-induced cardiomyopathy underlying acute liver failure in a young bodybuilder. World J Gastroenterol. 2009;15(23):2920–2.  https://doi.org/10.3748/wjg.15.2920.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Norman AW, Mizwicki MT, Norman DP. Steroid-hormone rapid actions, membrane receptors and a conformational ensemble model. Nat Rev Drug Discov. 2004;3(1):27–41.  https://doi.org/10.1038/nrd1283.CrossRefPubMedGoogle Scholar
  48. 48.
    Jacquemin E. Progressive familial intrahepatic cholestasis. Clin Res Hepatol Gastroenterol. 2012;36(Suppl 1):S26–35.  https://doi.org/10.1016/S2210-7401(12)70018-9.CrossRefPubMedGoogle Scholar
  49. 49.
    Hayashi PH. Causality assessment in drug-induced liver injury. Semin Liver Dis. 2009;29(4):348–56.  https://doi.org/10.1055/s-0029-1240003.CrossRefPubMedGoogle Scholar
  50. 50.
    • Hoofnagle JH. LiverTox. National Library of medicine. https://livertox.nlm.nih.gov/. Accessed 5/18/2019 2019 Comprehensive review of HDS and AAS induced DILI available online via LiverTox website.
  51. 51.
    Capell PT, Paulsen CA. The effect of exogenous testosterone upon serum FSH and LH concentrations in normal males. Contraception. 1972;6(2):135–43.  https://doi.org/10.1016/0010-7824(72)90055-8.CrossRefGoogle Scholar
  52. 52.
    Catlin DH, Hatton CK, Starcevic SH. Issues in detecting abuse of xenobiotic anabolic steroids and testosterone by analysis of athletes' urine. Clin Chem. 1997;43(7):1280–8.PubMedGoogle Scholar
  53. 53.
    Ayotte C, Goudreault D, Charlebois A. Testing for natural and synthetic anabolic agents in human urine. J Chromatogr B Biomed Appl. 1996;687(1):3–25.  https://doi.org/10.1016/s0378-4347(96)00032-1.CrossRefGoogle Scholar
  54. 54.
    Saudan C, Baume N, Robinson N, Avois L, Mangin P, Saugy M. Testosterone and doping control. Br J Sports Med. 2006;40(Suppl 1):i21–4.  https://doi.org/10.1136/bjsm.2006.027482.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Gastrointestinal and Liver DiseasesKeck School of Medicine of the University of Southern CaliforniaLos AngelesUSA
  2. 2.Keck School of Medicine of USCLos AngelesUSA

Personalised recommendations

Cite article

Buy options