Detection of Growth Hormone Doping in Sport Using Growth Hormone-Responsive Markers

  • Anne E. Nelson
  • Ken K. Y. Ho
Part of the Endocrine Updates book series (ENDO, volume 29)


There is anecdotal evidence that growth hormone (GH) is widely abused, reportedly often in combination with anabolic steroids at high doses for several months. Development of a robust test for GH has been challenging. There are wide physiological fluctuations in circulating GH concentrations and the recombinant human 22 kDa GH used in doping is indistinguishable analytically from endogenous GH. The GH-responsive markers approach to detect GH doping is based on the measurement of serum proteins, such as insulin-like growth factor (IGF) and collagen peptides, that have more stable concentrations and longer half-lives than GH. Age and gender are the major determinants of variability for IGF-I and the collagen markers. A test based on these markers must take age into account for men and women and ethnicity is unlikely to be a confounder for IGF-I and the collagen markers. Extensive data from administration studies are now available to validate the use of GH-responsive marker and a test based on this approach will likely use a combination of markers. This approach extends the time window of detection of GH and to detect abuse of other forms of GH and GH secretagogues. Implementation of a test based on GH-responsive markers is now largely dependent on overcoming hurdles including availability of standardized assays with assured supplies of antibodies.


Growth Hormone Anabolic Steroid Elite Athlete Anabolic Androgenic Steroid Collagen Marker 
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.



Research by the authors has been supported by the World Anti-Doping Agency and by the Australian Government through the Anti-Doping Research Program (ADRP) of the Department of Communications, Information Technology and the Arts.


  1. 1.
    Nelson AE, Ho KK. A robust test for growth hormone doping--present status and future prospects. Asian J Androl. 2008;10(3):416–25.CrossRefPubMedGoogle Scholar
  2. 2.
    Nelson AE, Meinhardt U, Hansen JL, et al. Pharmacodynamics of growth hormone abuse biomarkers and the influence of gender and testosterone: a randomized double-blind placebo-controlled study in young recreational athletes. J Clin Endocrinol Metab. 2008;93(6):2213–22.CrossRefPubMedGoogle Scholar
  3. 3.
    Nelson AE, Howe CJ, Nguyen TV, et al. Influence of demographic factors and sport type on growth hormone-responsive markers in elite athletes. J Clin Endocrinol Metab. 2006;91(11):4424–32.CrossRefPubMedGoogle Scholar
  4. 4.
    Bamberger M, Yaeger D. Over the edge: special report. Sports Illus. 1997;86:64.Google Scholar
  5. 5.
    Rickert VI, Pawlak-Morello C, Sheppard V, Jay MS. Human growth hormone: a new substance of abuse among adolescents? Clin Pediatr (Phila). 1992;31(12):723–6.CrossRefGoogle Scholar
  6. 6.
    National Collegiate Athletic Association. NCAA study of substance use of college student-athletes. 2006 (Accessed 2008: Scholar
  7. 7.
    Saugy M, Robinson N, Saudan C, Baume N, Avois L, Mangin P. Human growth hormone doping in sport. Br J Sports Med. 2006;40(Suppl 1):i35–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Parkinson AB, Evans NA. Anabolic androgenic steroids: a survey of 500 users. Med Sci Sports Exerc. 2006;38(4):644–51.CrossRefPubMedGoogle Scholar
  9. 9.
    Perry PJ, Lund BC, Deninger MJ, Kutscher EC, Schneider J. Anabolic steroid use in weightlifters and bodybuilders: an internet survey of drug utilization. Clin J Sport Med. 2005;15(5):326–30.CrossRefPubMedGoogle Scholar
  10. 10.
    Weissberger AJ, Ho KY, Stuart MC. Quanepsication of urinary growth hormone (GH) excretion by centrifugal ultrafiltration and radioimmunoassay: appraisal of the relationship between 24 h urinary GH and mean 24 h serum GH levels in normal and abnormal states of GH secretion. Clin Endocrinol (Oxf). 1989;30(6):687–98.CrossRefGoogle Scholar
  11. 11.
    Flanagan DE, Taylor MC, Parfitt V, Mardell R, Wood PJ, Leatherdale BA. Urinary growth hormone following exercise to assess growth hormone production in adults. Clin Endocrinol (Oxf). 1997;46(4):425–9.CrossRefGoogle Scholar
  12. 12.
    Saugy M, Cardis C, Schweizer C, Veuthey JL, Rivier L. Detection of human growth hormone doping in urine: out of competition tests are necessary. J Chromatogr B Biomed Appl. 1996;687(1):201–11.CrossRefPubMedGoogle Scholar
  13. 13.
    Kazlauskas R, Howe C, Trout G. Strategies for rhEPO detection in sport. Clin J Sport Med. 2002;12(4):229–35.CrossRefPubMedGoogle Scholar
  14. 14.
    Holl RW, Schwarz U, Schauwecker P, Benz R, Veldhuis JD, Heinze E. Diurnal variation in the elimination rate of human growth hormone (GH): the half-life of serum GH is prolonged in the evening, and affected by the source of the hormone, as well as by body size and serum estradiol. J Clin Endocrinol Metab. 1993;77(1):216–20.CrossRefPubMedGoogle Scholar
  15. 15.
    Giustina A, Veldhuis JD. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998;19(6):717–97.CrossRefPubMedGoogle Scholar
  16. 16.
    Gibney J, Healy ML, Sonksen PH. The growth hormone/insulin-like growth factor-I axis in exercise and sport. Endocr Rev. 2007;28(6):603–24.CrossRefPubMedGoogle Scholar
  17. 17.
    Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994;42(4–5):140–4.CrossRefPubMedGoogle Scholar
  18. 18.
    Jones JI, Clemmons DR. Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 1995;16(1):3–34.PubMedGoogle Scholar
  19. 19.
    Ohlsson C, Bengtsson BA, Isaksson OG, Andreassen TT, Slootweg MC. Growth hormone and bone. Endocr Rev. 1998;19(1):55–79.CrossRefPubMedGoogle Scholar
  20. 20.
    Seibel MJ. Molecular markers of bone turnover: biochemical, technical and analytical aspects. Osteoporos Int. 2000;11(Suppl 6):S18–29.CrossRefPubMedGoogle Scholar
  21. 21.
    McHugh CM, Park RT, Sonksen PH, Holt RI. Challenges in detecting the abuse of growth hormone in sport. Clin Chem. 2005;51(9):1587–93.CrossRefPubMedGoogle Scholar
  22. 22.
    Sonksen PH. Insulin, growth hormone and sport. J Endocrinol. 2001;170(1):13–25.CrossRefPubMedGoogle Scholar
  23. 23.
    Wallace JD, Cuneo RC, Baxter R, et al. Responses of the growth hormone (GH) and insulin-like growth factor axis to exercise, GH administration, and GH withdrawal in trained adult males: a potential test for GH abuse in sport. J Clin Endocrinol Metab. 1999;84(10):3591–601.CrossRefPubMedGoogle Scholar
  24. 24.
    Wallace JD, Cuneo RC, Lundberg PA, et al. Responses of markers of bone and collagen turnover to exercise, growth hormone (GH) administration, and GH withdrawal in trained adult males. J Clin Endocrinol Metab. 2000;85(1):124–33.CrossRefPubMedGoogle Scholar
  25. 25.
    Juul A. Serum levels of insulin-like growth factor I and its binding proteins in health and disease. Growth Horm IGF Res. 2003;13(4):113–70.CrossRefPubMedGoogle Scholar
  26. 26.
    Szulc P, Seeman E, Delmas PD. Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int. 2000;11(4):281–94.CrossRefPubMedGoogle Scholar
  27. 27.
    Crofton PM, Wade JC, Taylor MR, Holland CV. Serum concentrations of carboxyl-terminal propeptide of type I procollagen, amino-terminal propeptide of type III procollagen, cross-linked carboxyl-terminal telopeptide of type I collagen, and their interrelationships in schoolchildren. Clin Chem. 1997;43(9):1577–81.PubMedGoogle Scholar
  28. 28.
    Healy ML, Dall R, Gibney J, et al. Toward the development of a test for growth hormone (GH) abuse: a study of extreme physiological ranges of GH-dependent markers in 813 elite athletes in the postcompetition setting. J Clin Endocrinol Metab. 2005;90(2):641–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Erotokritou-Mulligan I, Bassett EE, Cowan DA, et al. Influence of ethnicity on IGF-I and procollagen III peptide (P-III-P) in elite athletes and its effect on the ability to detect GH abuse. Clin Endocrinol (Oxf). 2009;70(1):161–8.CrossRefGoogle Scholar
  30. 30.
    Nguyen TV, Nelson AE, Howe CJ, et al. Within-subject variability and analytic imprecision of insulin like growth factor axis and collagen markers: implications for clinical diagnosis and doping tests. Clin Chem. 2008;54(8):1268–76.CrossRefPubMedGoogle Scholar
  31. 31.
    Holt RI, Erotokritou-Mulligan I, Ridley SA, et al. A determination of the pre-analytical storage conditions for insulin like growth factor-I and type III procollagen peptide. Growth Horm IGF Res. 2009;19(1):43–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Dall R, Longobardi S, Ehrnborg C, et al. The effect of four weeks of supraphysiological growth hormone administration on the insulin-like growth factor axis in women and men. GH-2000 Study Group. J Clin Endocrinol Metab. 2000;85(11):4193–200.CrossRefPubMedGoogle Scholar
  33. 33.
    Longobardi S, Keay N, Ehrnborg C, et al. Growth hormone (GH) effects on bone and collagen turnover in healthy adults and its potential as a marker of GH abuse in sports: a double blind, placebo-controlled study. The GH-2000 Study Group. J Clin Endocrinol Metab. 2000;85(4):1505–12.CrossRefPubMedGoogle Scholar
  34. 34.
    Kniess A, Ziegler E, Kratzsch J, Thieme D, Muller RK. Potential parameters for the detection of hGH doping. Anal Bioanal Chem. 2003;376(5):696–700.CrossRefPubMedGoogle Scholar
  35. 35.
    Sartorio A, Agosti F, Marazzi N, et al. Combined evaluation of resting IGF-I, N-terminal ­propeptide of type III procollagen (PIIINP) and C-terminal cross-linked telopeptide of type I collagen (ICTP) levels might be useful for detecting inappropriate GH administration in athletes: a preliminary report. Clin Endocrinol (Oxf). 2004;61(4):487–93.CrossRefGoogle Scholar
  36. 36.
    Ehrnborg C, Ohlsson C, Mohan S, Bengtsson BA, Rosen T. Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month’s treatment with supraphysiological doses of growth hormone. Growth Horm IGF Res. 2007;17(3):234–41.CrossRefPubMedGoogle Scholar
  37. 37.
    Powrie JK, Bassett EE, Rosen T, et al. Detection of growth hormone abuse in sport. Growth Horm IGF Res. 2007;17(3):220–6.CrossRefPubMedGoogle Scholar
  38. 38.
    Erotokritou-Mulligan I, Bassett EE, Kniess A, Sonksen PH, Holt RI. Validation of the growth hormone (GH)-dependent marker method of detecting GH abuse in sport through the use of independent data sets. Growth Horm IGF Res. 2007;17(5):416–23.CrossRefPubMedGoogle Scholar
  39. 39.
    Nelson AE, Howe CJ, Nguyen TV, et al. Erythropoietin administration does not influence the GH--IGF axis or makers of bone turnover in recreational athletes. Clin Endocrinol (Oxf). 2005;63(3):305–9.CrossRefGoogle Scholar
  40. 40.
    Kurdy NM, Bowles S, Marsh DR, Davies A, France M. Serology of collagen types I and III in normal healing of tibial shaft fractures. J Orthop Trauma. 1998;12(2):122–6.CrossRefPubMedGoogle Scholar
  41. 41.
    Stoffel K, Engler H, Kuster M, Riesen W. Changes in biochemical markers after lower limb fractures. Clin Chem. 2007;53(1):131–4.CrossRefPubMedGoogle Scholar
  42. 42.
    Erotokritou-Mulligan I, Bassett EE, Bartlett C, et al. The effect of sports injury on insulin-like growth factor-I and type 3 procollagen: implications for detection of growth hormone abuse in athletes. J Clin Endocrinol Metab. 2008;93(7):2760–3.CrossRefPubMedGoogle Scholar
  43. 43.
    Bidlingmaier M, Strasburger CJ. Technology insight: detecting growth hormone abuse in athletes. Nat Clin Pract Endocrinol Metab. 2007;3(11):769–77.CrossRefPubMedGoogle Scholar
  44. 44.
    Vignali DA. Multiplexed particle-based flow cytometric assays. J Immunol Methods. 2000;243(1–2):243–55.CrossRefPubMedGoogle Scholar
  45. 45.
    Kirsch S, Widart J, Louette J, Focant JF, De Pauw E. Development of an absolute quanepsication method targeting growth hormone biomarkers using liquid chromatography coupled to isotope dilution mass spectrometry. J Chromatogr A. 2007;1153(1–2):300–6.CrossRefPubMedGoogle Scholar
  46. 46.
    Han B, Copeland M, Geiser AG, et al. Development of a highly sensitive, high-throughput, mass spectrometry-based assay for rat procollagen type-I N-terminal propeptide (PINP) to measure bone formation activity. J Proteome Res. 2007;6(11):4218–29.CrossRefPubMedGoogle Scholar
  47. 47.
    Sharpe K, Ashenden MJ, Schumacher YO. A third generation approach to detect erythropoietin abuse in athletes. Haematologica. 2006;91(3):356–63.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Pituitary Research Unit, Department of EndocrinologyGarvan Institute of Medical Research (AN, KH), St. Vincent’s Hospital (KH)SydneyAustralia

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