Advertisement

Sports Medicine

, Volume 47, Issue 9, pp 1869–1883 | Cite as

Effects of Anabolic Androgenic Steroids on the Reproductive System of Athletes and Recreational Users: A Systematic Review and Meta-Analysis

  • Maria A. Christou
  • Panagiota A. Christou
  • Georgios Markozannes
  • Agathocles Tsatsoulis
  • George Mastorakos
  • Stelios TigasEmail author
Systematic Review

Abstract

Background

Anabolic androgenic steroids (AAS) are testosterone derivatives used by athletes and recreational users to improve athletic performance and/or enhance appearance. Anabolic androgenic steroids use may have serious and potentially irreversible adverse effects on different organs and systems, including the reproductive system.

Objective

This systematic review and meta-analysis aimed to critically assess the impact of AAS use on the reproductive system of athletes and recreational users.

Methods

An electronic literature search was conducted using the databases MEDLINE, CENTRAL, and Google Scholar. Studies were included when the following criteria were fulfilled: participants were athletes or recreational users of any age, sex, level or type of sport; AAS use of any type, dose, form or duration; AAS effects on the reproductive system were assessed as stated by medical history, clinical examination, hormone and/or semen analysis. Random-effects meta-analysis was performed to assess the weighted mean difference (WMD) of serum gonadotropin (luteinizing hormone, follicle-stimulating hormone) and testosterone levels compared with baseline, during the period of AAS use, as well as following AAS discontinuation.

Results

Thirty-three studies (three randomized clinical trials, 11 cohort, 18 cross-sectional, and one non-randomized parallel clinical trial) were included in the systematic review (3879 participants; 1766 AAS users and 2113 non-AAS users). The majority of the participants were men; only six studies provided data for female athletes. A meta-analysis (11 studies) was conducted of studies evaluating serum gonadotropin and testosterone levels in male subjects: (1) prior to, and during AAS use (six studies, n = 65 AAS users; seven studies, n = 59, evaluating gonadotropin and testosterone levels respectively); (2) during AAS use and following AAS discontinuation (four studies, n = 35; six studies, n = 39, respectively); as well as (3) prior to AAS use and following AAS discontinuation (three studies, n = 17; five studies, n = 27, respectively). During AAS intake, significant reductions in luteinizing hormone [weighted mean difference (WMD) −3.37 IU/L, 95% confidence interval (CI) −5.05 to −1.70, p < 0.001], follicle-stimulating hormone (WMD −1.73 IU/L, 95% CI −2.67 to −0.79, p < 0.001), and endogenous testosterone levels (WMD −10.75 nmol/L, 95% CI −15.01 to −6.49, p < 0.001) were reported. Following AAS discontinuation, serum gonadotropin levels gradually returned to baseline values within 13–24 weeks, whereas serum testosterone levels remained lower as compared with baseline (WMD −9.40 nmol/L, 95% CI −14.38 to −4.42, p < 0.001). Serum testosterone levels remained reduced at 16 weeks following discontinuation of AAS. In addition, AAS abuse resulted in structural and functional sperm changes, a reduction in testicular volume, gynecomastia, as well as clitoromegaly, menstrual irregularities, and subfertility.

Conclusion

The majority of AAS users demonstrated hypogonadism with persistently low gonadotropin and testosterone levels, lasting for several weeks to months after AAS withdrawal. Anabolic androgenic steroid use results in profound and prolonged effects on the reproductive system of athletes and recreational users and potentially on fertility.

Keywords

Testosterone Luteinizing Hormone Testosterone Level DHEAS Female Athlete 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Compliance with Ethical Standards

Funding

No funding was obtained for the preparation of this study.

Conflict of interest

Maria A. Christou, Panagiota A. Christou, Georgios Markozannes, Agathocles Tsatsoulis, George Mastorakos, and Stelios Tigas declare that they have no conflicts of interest; they have received no research grants or speaker honoraria from any drug company and they own no stock in any drug company.

Supplementary material

40279_2017_709_MOESM1_ESM.docx (35 kb)
Supplementary material 1 (DOCX 35 kb)
40279_2017_709_MOESM2_ESM.docx (34 kb)
Supplementary material 2 (DOCX 34 kb)
40279_2017_709_MOESM3_ESM.docx (29 kb)
Supplementary material 3 (DOCX 28 kb)
40279_2017_709_MOESM4_ESM.docx (26 kb)
Supplementary material 4 (DOCX 25 kb)
40279_2017_709_MOESM5_ESM.tiff (481 kb)
Supplementary material 5 (TIFF 481 kb)

References

  1. 1.
    Dotson JL, Brown RT. The history of the development of anabolic-androgenic steroids. Pediatr Clin North Am. 2007;54(4):761–9 xi.CrossRefPubMedGoogle Scholar
  2. 2.
    Kickman AT. Pharmacology of anabolic steroids. Br J Pharmacol. 2008;154(3):502–21.CrossRefGoogle Scholar
  3. 3.
    Stromme SB, Meen HD, Aakvaag A. Effects of an androgenic-anabolic steroid on strength development and plasma testosterone levels in normal males. Med Sci Sports. 1974;6(3):203–8.PubMedGoogle Scholar
  4. 4.
    Sagoe D, Molde H, Andreassen CS, et al. The global epidemiology of anabolic-androgenic steroid use: a meta-analysis and meta-regression analysis. Ann Epidemiol. 2014;24(5):383–98.CrossRefPubMedGoogle Scholar
  5. 5.
    Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–75.CrossRefPubMedGoogle Scholar
  6. 6.
    Rogol AD, Yesalis CE 3rd. Clinical review 31: anabolic-androgenic steroids and athletes: what are the issues? J Clin Endocrinol Metab. 1992;74(3):465–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Nieschlag E, Vorona E. Doping with anabolic androgenic steroids (AAS): adverse effects on non-reproductive organs and functions. Rev Endocr Metab Disord. 2015;16(3):199–211.CrossRefPubMedGoogle Scholar
  8. 8.
    Fronczak CM, Kim ED, Barqawi AB. The insults of illicit drug use on male fertility. J Androl. 2012;33(4):515–28.CrossRefPubMedGoogle Scholar
  9. 9.
    Nieschlag E, Vorona E. Mechanisms in endocrinology: medical consequences of doping with anabolic androgenic steroids: effects on reproductive functions. Eur J Endocrinol. 2015;173(2):R47–58.CrossRefPubMedGoogle Scholar
  10. 10.
    Kersey RD, Elliot DL, Goldberg L, et al. National Athletic Trainers’ Association position statement: anabolic-androgenic steroids. J Athl Train. 2012;47(5):567–88.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    de Souza GL, Hallak J. Anabolic steroids and male infertility: a comprehensive review. BJU Int. 2011;108(11):1860–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Maravelias C, Dona A, Stefanidou M, Spiliopoulou C. Adverse effects of anabolic steroids in athletes: a constant threat. Toxicol Lett. 2005;158(3):167–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513–54.CrossRefPubMedGoogle Scholar
  14. 14.
    Liberati A, Altman DG, Tetzlaff J, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med. 2009;151(4):W65–94.CrossRefPubMedGoogle Scholar
  15. 15.
    Higgins JP, Altman DG, Gotzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Viswanathan M, Berkman ND. Development of the RTI item bank on risk of bias and precision of observational studies. J Clin Epidemiol. 2012;65(2):163–78.CrossRefPubMedGoogle Scholar
  17. 17.
    Viswanathan M, Berkman ND, Dryden DM, Hartling L. Assessing risk of bias and confounding in observational studies of interventions or exposures: further development of the RTI Item Bank. Rockville (MD): Agency for Healthcare Research and Quality (US); 2013.Google Scholar
  18. 18.
    Fuentes JP, Armijo Olivo S, Magee DJ, Gross DP. Effectiveness of interferential current therapy in the management of musculoskeletal pain: a systematic review and meta-analysis. Phys Ther. 2010;90(9):1219–38.CrossRefPubMedGoogle Scholar
  19. 19.
    Fuentes CJ, Armijo-Olivo S, Magee DJ, Gross DP. Effects of exercise therapy on endogenous pain-relieving peptides in musculoskeletal pain: a systematic review. Clin J Pain. 2011;27(4):365–74.CrossRefGoogle Scholar
  20. 20.
    DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–88.CrossRefPubMedGoogle Scholar
  21. 21.
    Hardy RJ, Thompson SG. Detecting and describing heterogeneity in meta-analysis. Stats Med. 1998;17(8):841–56.CrossRefGoogle Scholar
  22. 22.
    Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stats Med. 2002;21(11):1539–58.CrossRefGoogle Scholar
  23. 23.
    Aakvaag A, Stromme SB. The effect of mesterolone administration to normal men on the pituitary-testicular function. Acta Endocrinol. 1974;77(2):380–6.PubMedGoogle Scholar
  24. 24.
    Holma P, Adlercreutz H. Effect of an anabolic steroid (metandienon) on plasma LH-FSH, and testosterone and on the response to intravenous administration of LRH. Acta Endocrinol. 1976;83(4):856–64.PubMedGoogle Scholar
  25. 25.
    Holma PK. Effects of an anabolic steroid (metandienone) on spermatogenesis. Contraception. 1977;15(2):151–62.CrossRefPubMedGoogle Scholar
  26. 26.
    Remes K, Vuopio P, Jarvinen M, et al. Effect of short-term treatment with an anabolic steroid (methandienone) and dehydroepiandrosterone sulphate on plasma hormones, red cell volume and 2,3-diphosphoglycerate in athletes. Scand J Clin Lab Invest. 1977;37(7):577–86.CrossRefPubMedGoogle Scholar
  27. 27.
    Hervey GR, Hutchinson I, Knibbs AV, et al. “Anabolic” effects of methandienone in men undergoing athletic training. Lancet. 1976;2(7988):699–702.CrossRefPubMedGoogle Scholar
  28. 28.
    Strauss RH, Liggett MT, Lanese RR. Anabolic steroid use and perceived effects in ten weight-trained women athletes. JAMA. 1985;253(19):2871–3.CrossRefPubMedGoogle Scholar
  29. 29.
    Gruber AJ, Pope HG Jr. Psychiatric and medical effects of anabolic-androgenic steroid use in women. Psychother Psychosom. 2000;69(1):19–26.CrossRefPubMedGoogle Scholar
  30. 30.
    Borjesson A, Garevik N, Dahl ML, et al. Recruitment to doping and help-seeking behavior of eight female AAS users. Subst Abuse Treat Prevent Policy. 2016;11:11.CrossRefGoogle Scholar
  31. 31.
    Malarkey WB, Strauss RH, Leizman DJ, et al. Endocrine effects in female weight lifters who self-administer testosterone and anabolic steroids. Am J Obstet Gynecol. 1991;165(5 Pt 1):1385–90.CrossRefPubMedGoogle Scholar
  32. 32.
    Ip EJ, Barnett MJ, Tenerowicz MJ, et al. Women and anabolic steroids: an analysis of a dozen users. Clin J Sport Med. 2010;20(6):475–81.CrossRefPubMedGoogle Scholar
  33. 33.
    Korkia P, Stimson GV. Indications of prevalence, practice and effects of anabolic steroid use in Great Britain. Int J Sports Med. 1997;18(7):557–62.CrossRefPubMedGoogle Scholar
  34. 34.
    Schurmeyer T, Knuth UA, Belkien L, Nieschlag E. Reversible azoospermia induced by the anabolic steroid 19-nortestosterone. Lancet. 1984;1(8374):417–20.CrossRefPubMedGoogle Scholar
  35. 35.
    Alen M, Reinila M, Vihko R. Response of serum hormones to androgen administration in power athletes. Med Sci Sports Exerc. 1985;17(3):354–9.PubMedGoogle Scholar
  36. 36.
    Alen M, Rahkila P, Reinila M, Vihko R. Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes. Am J Sports Med. 1987;15(4):357–61.CrossRefPubMedGoogle Scholar
  37. 37.
    Bonetti A, Tirelli F, Catapano A, et al. Side effects of anabolic androgenic steroids abuse. Int J Sports Med. 2008;29(8):679–87.CrossRefPubMedGoogle Scholar
  38. 38.
    Urhausen A, Torsten A, Wilfried K. Reversibility of the effects on blood cells, lipids, liver function and hormones in former anabolic-androgenic steroid abusers. J Steroid Biochem Mol Biol. 2003;84(2–3):369–75.CrossRefPubMedGoogle Scholar
  39. 39.
    Karila T, Hovatta O, Seppala T. Concomitant abuse of anabolic androgenic steroids and human chorionic gonadotrophin impairs spermatogenesis in power athletes. Int J Sports Med. 2004;25(4):257–63.CrossRefPubMedGoogle Scholar
  40. 40.
    Taher A-MM, Al-Sabbagh MS, Al-Khashali DK. Effects of abuse of anabolic androgenic steroids on Iraqi athletes. Iraqi J Pharm Sci. 2008;17(2):9–17.Google Scholar
  41. 41.
    Garevik N, Strahm E, Garle M, et al. Long term perturbation of endocrine parameters and cholesterol metabolism after discontinued abuse of anabolic androgenic steroids. J Steroid Biochem Mol Biol. 2011;127(3–5):295–300.CrossRefPubMedGoogle Scholar
  42. 42.
    Knuth UA, Maniera H, Nieschlag E. Anabolic steroids and semen parameters in bodybuilders. Fertil Steril. 1989;52(6):1041–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Torres-Calleja J, Gonzalez-Unzaga M, DeCelis-Carrillo R, et al. Effect of androgenic anabolic steroids on sperm quality and serum hormone levels in adult male bodybuilders. Life Sci. 2001;68(15):1769–74.CrossRefPubMedGoogle Scholar
  44. 44.
    Ruokonen A, Alen M, Bolton N, Vihko R. Response of serum testosterone and its precursor steroids, SHBG and CBG to anabolic steroid and testosterone self-administration in man. J Steroid Biochem. 1985;23(1):33–8.CrossRefPubMedGoogle Scholar
  45. 45.
    Al-Janabi AS, Kanaan ZA, Al Salih AM. Effect of anabolic-androgenic steroids on semen parameters and serum hormonal levels in Iraqi male bodybuilders. Jordan Med J. 2011;45(2):159–66.Google Scholar
  46. 46.
    Martikainen H, Alen M, Rahkila P, Vihko R. Testicular responsiveness to human chorionic gonadotrophin during transient hypogonadotrophic hypogonadism induced by androgenic/anabolic steroids in power athletes. J Steroid Biochem. 1986;25(1):109–12.CrossRefPubMedGoogle Scholar
  47. 47.
    Alen M, Suominen J. Effect of androgenic and anabolic steroids on spermatogenesis in power athletes. Int J Sports Med. 1984;5(Suppl):189–92.Google Scholar
  48. 48.
    Johnson LC, Fisher G, Silvester LJ, Hofheins CC. Anabolic steroid: effects on strength, body weight, oxygen uptake and spermatogenesis upon mature males. Med Sci Sports. 1972;4(1):43–5.PubMedGoogle Scholar
  49. 49.
    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.CrossRefPubMedGoogle Scholar
  50. 50.
    Evans NA. Gym and tonic: a profile of 100 male steroid users. Br J Sports Med. 1997;31(1):54–8.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Coward RM, Rajanahally S, Kovac JR, et al. Anabolic steroid induced hypogonadism in young men. J Urol. 2013;190(6):2200–5.CrossRefPubMedGoogle Scholar
  52. 52.
    Perry PJ, Lund BC, Deninger MJ, et al. Anabolic steroid use in weightlifters and bodybuilders: an internet survey of drug utilization. Clin J Sports Med. 2005;15(5):326–30.CrossRefGoogle Scholar
  53. 53.
    Kanayama G, Hudson JI, DeLuca J, et al. Prolonged hypogonadism in males following withdrawal from anabolic-androgenic steroids: an under-recognized problem. Addiction. 2015;110(5):823–31.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Strauss RH, Wright JE, Finerman GA, Catlin DH. Side effects of anabolic steroids in weight-trained men. Phys Sportsmed. 1983;11(12):86–98.CrossRefGoogle Scholar
  55. 55.
    Yesalis CE 3rd, Herrick RT, Buckley WE, et al. Self-reported use of anabolic-androgenic steroids by elite power lifters. Phys Sportsmed. 1988;16(12):91–100.CrossRefPubMedGoogle Scholar
  56. 56.
    Razavi Z, Moeini B, Shafiei Y, Bazmamoun H. Prevalence of anabolic steroid use and associated factors among body-builders in Hamadan, West province of Iran. J Res Health Sci. 2014;14(2):163–6.PubMedGoogle Scholar
  57. 57.
    Rahnema CD, Lipshultz LI, Crosnoe LE, et al. Anabolic steroid-induced hypogonadism: diagnosis and treatment. Fertil Steril. 2014;101(5):1271–9.CrossRefPubMedGoogle Scholar
  58. 58.
    Mastorakos G, Pavlatou M, Diamanti-Kandarakis E, Chrousos GP. Exercise and the stress system. Hormones. 2005;4(2):73–89.PubMedGoogle Scholar
  59. 59.
    Mastorakos G, Pavlatou MG, Mizamtsidi M. The hypothalamic-pituitary-adrenal and the hypothalamic- pituitary-gonadal axes interplay. Pediatr Endocrinol Rev. 2006;3(Suppl 1):172–81.PubMedGoogle Scholar
  60. 60.
    Kloner RA, Carson C 3rd, Dobs A, et al. Testosterone and cardiovascular disease. J Am Coll Cardiol. 2016;67(5):545–57.CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Department of EndocrinologyMedical School, University of IoanninaIoanninaGreece
  2. 2.Department of Hygiene and Epidemiology, Medical SchoolUniversity of IoanninaIoanninaGreece
  3. 3.Endocrine Unit, ‘Aretaieion’ Hospital, Medical SchoolNational and Kapodistrian University of AthensAthensGreece

Personalised recommendations