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Endocrine

, Volume 43, Issue 2, pp 303–313 | Cite as

Hormones as doping in sports

  • Leonidas H. DuntasEmail author
  • Vera Popovic
Review

Abstract

Though we may still sing today, as did Pindar in his eighth Olympian Victory Ode, “… of no contest greater than Olympia, Mother of Games, gold-wreathed Olympia…”, we must sadly admit that today, besides blatant over-commercialization, there is no more ominous threat to the Olympic games than doping. Drug-use methods are steadily becoming more sophisticated and ever harder to detect, increasingly demanding the use of complex analytical procedures of biotechnology and molecular medicine. Special emphasis is thus given to anabolic androgenic steroids, recombinant growth hormone and erythropoietin as well as to gene doping, the newly developed mode of hormones abuse which, for its detection, necessitates high-tech methodology but also multidisciplinary individual measures incorporating educational and psychological methods. In this Olympic year, the present review offers an update on the current technologically advanced endocrine methods of doping while outlining the latest procedures applied—including both the successes and pitfalls of proteomics and metabolomics—to detect doping while contributing to combating this scourge.

Keywords

Doping Anabolic androgenic steroids Erythropoietin Growth hormone Olympic games 

Notes

Conflict of interest

There is no conflict of interest.

References

  1. 1.
    D.H. Catlin, T.H. Murray, Performance-enhancing drugs, fair competition, and Olympic sport. J. Am. Med. Assoc. 276(3), 231–237 (1996)CrossRefGoogle Scholar
  2. 2.
    L.H. Duntas, C. Parisis, Doping: a challenge to the endocrinologist. A reappraisal in view of the Olympic games of 2004. Hormones (Athens) 2(1), 35–42 (2003)Google Scholar
  3. 3.
    P.L. Toutain, Veterinary medicines and competition animals: the question of medication versus doping control. Handb. Exp. Pharmacol. 199, 315–339 (2010)PubMedCrossRefGoogle Scholar
  4. 4.
    H.M. Prendergast, T. Bannen, T.B. Erickson, K.R. Honore, The toxic torch of the modern Olympic games. Vet. Hum. Toxicol. 45(2), 97–102 (2003)PubMedGoogle Scholar
  5. 5.
    M. Thevis, P. Hemmersbach, H. Geyer, W. Schänzer, Doping in disabled sports. Doping control activities at the Paralympic games 1984–2008 and in Germany 1992–2008. Med. Klin. (Munich) 104(12), 918–924 (2009)CrossRefGoogle Scholar
  6. 6.
    M. Thevis, T. Kuuranne, H. Geyer, W. Schänzer, Annual banned-substance review: analytical approaches in human sports drug testing. Drug Test Anal. 4(1), 2–16 (2012)PubMedCrossRefGoogle Scholar
  7. 7.
    M. Kamber, Development of the role of national anti-doping organisations in the fight against doping: from past to future. Forensic Sci. Int. 213(1–3), 3–9 (2011)PubMedCrossRefGoogle Scholar
  8. 8.
    L. Di Luigi, F. Romanelli, P. Sgrò, A. Lenzi, Andrological aspects of physical exercise and sport medicine. Endocrine 59(6):503–508 [Epub ahead of print] (2012)Google Scholar
  9. 9.
    C. Saudan, N. Baume, N. Robinson, L. Avois, P. Mangin, M. Saugy, Testosterone and doping control. Br. J. Sports Med. 40, i21–i24 (2006)PubMedCrossRefGoogle Scholar
  10. 10.
    E.T. Keller, W.B. Ershler, C. Chang, The androgen receptor: a mediator of diverse responses. Front. Biosci. 1(1), d59–d71 (1996)PubMedGoogle Scholar
  11. 11.
    C.A. Heinlein, C. Chang, Androgen receptor (AR) coregulators: an overview. Endocr. Rev. 23(2), 175–200 (2002)PubMedCrossRefGoogle Scholar
  12. 12.
    A.B. Cadwallaber, C.S. Lim, D.E. Rollins, F. Botrè, The androgen receptor and its use in biological assays: looking toward effect-based testing and its applications. J. Anal. Toxicol. 35(9), 594–607 (2011)CrossRefGoogle Scholar
  13. 13.
    F. Sjöqvist, M. Garle, A. Rane, Use of doping agents, particularly anabolic steroids, in sports and society. Lancet 371(9627), 1872–1882 (2008)PubMedCrossRefGoogle Scholar
  14. 14.
    NIDA, National Institute on Drug Abuse Research Report Series: Anabolic Steroid Abuse (NIDA, Bethesda, 2006)Google Scholar
  15. 15.
    C.J. Bagatell, W.J. Bremner, Androgens in men—uses and abuses. N. Engl. J. Med. 334(11), 707–714 (1996)PubMedCrossRefGoogle Scholar
  16. 16.
    R.C. Hall, R.C. Hall, Abuse of supraphysiologic doses of anabolic steroids. South. Med. J. 98(5), 550–555 (2005)PubMedCrossRefGoogle Scholar
  17. 17.
    F. Hartgens, H. Kuipers, Effects of androgenic–anabolic steroids in athletes. Sports Med. 34(8), 513–554 (2004)PubMedCrossRefGoogle Scholar
  18. 18.
    A.H. Beckett, D.A. Cowan, Misuse of drugs in sport. Br. J. Sports Med. 12(4), 185–194 (1978)PubMedCrossRefGoogle Scholar
  19. 19.
    O.J. Pozo, P. Van Eenoo, K. Deventer, L. Lootens, S. Grimalt, J.V. Sancho, F. Hernández, P. Meuleman, G. Leroux-Roels, F.T. Delbeke, Detection and structural investigation of metabolites of stanozolol in human urine by liquid chromatography tandem mass spectrometry. Steroids 74(10–11), 837–852 (2009)PubMedGoogle Scholar
  20. 20.
    A. Brinkmann, G.G. Kuiper, W. de Boer, E. Mulder, J. Bolt, G.J. Van Steenbrugge, H.J. van der Molen, Characterization of androgen receptors after photoaffinity labelling with [3H]methyltrienolone (R1881). J. Steroid Biochem. 24(1), 245–249 (1986)PubMedCrossRefGoogle Scholar
  21. 21.
    L.M. Irving, M. Wall, D. Neumark-Sztainer, M. Story, Steroid use among adolescents: findings from project EAT. J. Adolesc. Health 30(4), 243–252 (2002)PubMedCrossRefGoogle Scholar
  22. 22.
    G. Kanayama, J.I. Hudson, H.G. Jr, Pope, long-term psychiatric and medical consequences of anabolic–androgenic steroid abuse: a looming public health concern? Drug Alcohol Depend. 98(1–2), 1–12 (2008)PubMedCrossRefGoogle Scholar
  23. 23.
    T.A. Pagonis, N.V. Angelopoulos, G.N. Koukoulis, C.S. Hadjichristodoulou, Psychiatric side effects induced by supraphysiological doses of combinations of anabolic steroids correlate to the severity of abuse. Eur. Psychiatry 21(8), 551–562 (2006)PubMedCrossRefGoogle Scholar
  24. 24.
    M. Montisci, R. El Mazloum, G. Cecchetto, C. Terranova, S.D. Ferrara, G. Thiene, C. Basso, Anabolic androgenic steroids abuse and cardiac death in athletes: morphological and toxicological findings in four fatal cases. Forensic Sci. Int. 217(1–3), e13–e18 (2012)PubMedCrossRefGoogle Scholar
  25. 25.
    G. Lippi, G. Banfi, Doping and thrombosis in sports. Semin. Thromb. Hemost. 37(8), 918–928 (2011)PubMedCrossRefGoogle Scholar
  26. 26.
    U. Mareck, H. Geyer, G. Opfermann, M. Thevis, W. Schänzer, Factors influencing the steroid profile in doping control analysis. J. Mass Spectrom. 43(7), 877–891 (2008)PubMedCrossRefGoogle Scholar
  27. 27.
    J.P. Danaceau, M.S. Morrison, M.H. Slawson, Quantitative confirmation of testosterone and epitestosterone in human urine by LC/Q-ToF mass spectrometry for doping control. J. Mass Spectrom. 43(7), 993–1000 (2008)PubMedCrossRefGoogle Scholar
  28. 28.
    B. Maralikova, W. Weinmann, Confirmatory analysis for drugs of abuse in plasma and urine by high-performance liquid chromatography-tandem mass spectrometry with respect to criteria for compound identification. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 811(1), 21–30 (2004)PubMedGoogle Scholar
  29. 29.
    R. Aguilera, C.K. Hatton, D.H. Catlin, Detection of epitestosterone doping by isotope ratio mass spectrometry. Clin Chem. 48(4), 629–636 (2002)PubMedGoogle Scholar
  30. 30.
    I. Athanasiadou, Y.S. Angelis, E. Lyris, A. Vonaparti, N.S. Thomaidis, M.A. Koupparis, C. Georgakopoulos, Two-step derivatization procedures for the ionization enhancement of anabolic steroids in LC–ESI–MS for doping control analysis. Bioanalysis 4(2), 167–175 (2012)PubMedCrossRefGoogle Scholar
  31. 31.
    M. Thevis, A. Thomas, M. Kohler, S. Beuck, I. Möller, M. Schäfer, G. Rodchenkov, S. Yin, J.A. Loo, H. Geyer, W. Schänzer, Mass spectrometry-based characterization of new drugs and methods of performance manipulation in doping control analysis. Eur. J. Mass Spectrom. 16(3), 301–312 (2010)CrossRefGoogle Scholar
  32. 32.
    H.M. Pereira, M.C. Padilha, F.R. Neto, Tetrahydrogestrinone analysis and designer steroids revisited. Bioanalysis 1(8), 1475–1489 (2009)PubMedCrossRefGoogle Scholar
  33. 33.
    P. Teale, J. Scarth, S. Hudson, Impact of the emergence of designer drugs upon sports doping testing. Bioanalysis 4(1), 71–88 (2012)PubMedCrossRefGoogle Scholar
  34. 34.
    M.K. Parr, G. Opfermann, H. Geyer, F. Westphal, F.D. Sönnichsen, J. Zapp, D. Kwiatkowska, W. Schänzer, Seized designer supplement named “1-androsterone”: identification as 3β-hydroxy-5α-androst-1-en-17-one and its urinary elimination. Steroids 76(6), 540–547 (2011)PubMedCrossRefGoogle Scholar
  35. 35.
    C. Gómez, O.J. Pozo, H. Geyer, J. Marcos, M. Thevis, W. Schänzer, J. Segura, R. Ventura, New potential markers for the detection of boldenone misuse. Steroid Biochem. Mol. Biol. 132(3–5):239–246 (2012) [Epub ahead of print]Google Scholar
  36. 36.
    S. Guddat, G. Fußhöller, H. Geyer, A. Thomas, H. Braun, N. Haenelt, A. Schwenke, C. Klose, M. Thevis, W. Schänzer, Clenbuterol: regional food contamination a possible source for inadvertent doping in sports. Drug Test Anal. 4(6), 534–538 (2012)PubMedCrossRefGoogle Scholar
  37. 37.
    E. Strahm, P.E. Sottas, C. Schweizer, M. Saugy, J. Dvorak, C. Saudan, Steroid profiles of professional soccer players: an international comparative study. Br. J. Sports Med. 43(14), 1126–1130 (2009)PubMedCrossRefGoogle Scholar
  38. 38.
    J.J. Schulze, J. Lundmark, M. Garle, I. Skilving, L. Ekström, A. Rane, Doping test results dependent on genotype of uridine diphospho-glucuronosyl transferase 2B17, the major enzyme for testosterone glucuronidation. J. Clin. Endocrinol. Metab. 93(7), 2500–2506 (2008)PubMedCrossRefGoogle Scholar
  39. 39.
    A. Rane, L. Ekström, Androgens and doping tests: genetic variation and pit-falls. Br. J. Clin. Pharmacol. 74(1), 3–15 (2012)PubMedCrossRefGoogle Scholar
  40. 40.
    J.J. Schulze, J. Lundmark, M. Garle, L. Ekström, P.E. Sottas, A. Rane, Substantial advantage of a combined Bayesian and genotyping approach in testosterone doping tests. Steroids 74(3), 365–368 (2009)PubMedCrossRefGoogle Scholar
  41. 41.
    C. Quan, F. Su, H. Wang, H. Li, Development of anabolic–androgenic steroids purity certified reference materials for anti-doping. Steroids 76(14), 1527–1534 (2011)PubMedCrossRefGoogle Scholar
  42. 42.
    J.C. Rijk, A. Lommen, M.L. Essers, M.J. Groot, J.M. Van Hende, T.G. Doeswijk, M.W. Nielen, Metabolomics approach to anabolic steroid urine profiling of bovines treated with prohormones. Anal. Chem. 81(16), 6879–6888 (2009)PubMedCrossRefGoogle Scholar
  43. 43.
    K.K. Ho, Diagnosis and management of adult growth hormone deficiency. Endocrine 12(2), 189–196 (2000)PubMedCrossRefGoogle Scholar
  44. 44.
    J. Gibney, J.D. Wallace, T. Spinks, L. Schnorr, A. Lanicar, R.C. Cuneo, S. Lockhart, K.G. Burnand, F. Salomon, P.H. Sonksen, D. Russell-Jones, The effects of 10 years of recombinant human growth hormone (GH) in adult GH-deficient patients. J. Clin. Endocrinol. Metab. 84(8), 2596–2602 (1999)PubMedCrossRefGoogle Scholar
  45. 45.
    G. Götherström, B.A. Bengtsson, I. Bosaeus, G. Johansson, J. Svensson, A 10-year, prospective study of the metabolic effects of growth hormone replacement in adults. J. Clin. Endocrinol. Metab. 92(4), 1442–1445 (2007)PubMedCrossRefGoogle Scholar
  46. 46.
    W.M. Widdowson, J. Gibney, The effect of growth hormone replacement on exercise capacity in patients with GH deficiency: a metaanalysis. J. Clin. Endocrinol. Metab. 93(11), 4413–4417 (2008)PubMedCrossRefGoogle Scholar
  47. 47.
    W.M. Widdowson, J. Gibney, The effect of growth hormone (GH) replacement on muscle strength in patients with GH-deficiency: a meta-analysis. Clin. Endocrinol. (Oxf) 72(6), 787–792 (2010)CrossRefGoogle Scholar
  48. 48.
    M. Gola, S. Bonadonna, M. Doga, A. Giustina, Clinical review: growth hormone and cardiovascular risk factors. J. Clin. Endocrinol. Metab. 90(3), 1864–1870 (2005)PubMedCrossRefGoogle Scholar
  49. 49.
    H. Liu, D.M. Bravata, I. Olkin, A. Friedlander, V. Liu, B. Roberts, E. Bendand, O. Saynina, S.R. Salpeter, A.M. Garber, A.R. Hoffman, Systematic review: the effects of growth hormone on athletic performance. Ann. Intern. Med. 148(10), 747–758 (2008)PubMedGoogle Scholar
  50. 50.
    K.E. Yarasheski, J.J. Zachweija, T.J. Angelopoulos, D.M. Bier, Short-term growth hormone treatment does not increase muscle protein synthesis in experienced weight lifters. J. Appl. Physiol. 74(6), 3073–3076 (1993)PubMedGoogle Scholar
  51. 51.
    A.L. Carrel, D.B. Allen, Effects of growth hormone on body composition and bone metabolism. Endocrine 12(2), 163–172 (2000)PubMedCrossRefGoogle Scholar
  52. 52.
    V. Birzniece, U.J. Meinhart, M.A. Umpleby, D.J. Hanlesman, K.K. Ho, Interaction between testosterone and growth hormone on whole-body protein anabolism occurs in the liver. J. Clin. Endocrinol. Metab. 96(4), 1060–1067 (2011)PubMedCrossRefGoogle Scholar
  53. 53.
    V. Birzniece, A.E. Nelson, K.K. Ho, Growth hormone administration: is it safe and effective for athletic performance. Endocrinol. Metab. Clin. North Am. 39(1), 11–23 (2010)PubMedCrossRefGoogle Scholar
  54. 54.
    A. Berggren, C. Ehrnborg, T. Rosén, L. Ellegård, B.A. Bengtsson, K. Caidahl, Short-term administration of supraphysiological recombinant human growth hormone (GH) does not increase maximum endurance exercise capacity in healthy, active young men and women with normal GH-insulin-like growth factor I axes. J. Clin. Endocrinol. Metab. 90(6), 3268–3273 (2005)PubMedCrossRefGoogle Scholar
  55. 55.
    U. Meinhardt, A.E. Nelson, J.L. Hansen, V. Birniece, D. Clifford, K.C. Leung, K. Graham, K.K. Ho, The effects of growth hormone on body composition and physical performance in recreational athletes: a randomized trial. Ann. Int. Med. 152(9), 568–577 (2010)PubMedGoogle Scholar
  56. 56.
    S. Longobardi, N. Keay, C. Ehrnborg, A. Cittadini, T. Rosén, R. Dall, M.A. Boroujerdi, E.E. Basset, M.L. Healy, C. Pentecost, J.D. Wallace, J. Powrie, J.O. Jorgensen, L. Saccà, 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. 85(4), 1505–1512 (2000)PubMedCrossRefGoogle Scholar
  57. 57.
    M. Volterrani, P. Desenzani, R. Lorusso, A. d’Aloia, F. Manelli, A. Giustina, Haemodynamic effects of intravenous growth hormone in congestive heart failure. Lancet 349(9058), 1067–1068 (1997)PubMedCrossRefGoogle Scholar
  58. 58.
    M. Saugy, N. Robinson, C. Saudan, N. Baume, L. Avois, P. Mangin, Human growth hormone doping in sport. Br. J. Sports Med. 40(Suppl 1), i35–i39 (2006)PubMedCrossRefGoogle Scholar
  59. 59.
    K.K. Ho, A.E. Nelson, Growth hormone in sports: detecting the doped or duped. Horm. Res. Paediatr. 76(Suppl 1), 84–90 (2011)PubMedCrossRefGoogle Scholar
  60. 60.
    I. Erotokritou-Mulligan, N. Guha, M. Stow, E.E. Bassett, C. Bartlett, D.A. Cowan, P.H. Sönksen, R.I. Holt, The development of decision limits for the implementation of the GH-2000 detection methodology using current commercial insulin-like growth factor-I and amino-terminal pro-peptide of type III collagen assays. Growth Horm. IGF Res. 22(2), 53–58 (2012)PubMedCrossRefGoogle Scholar
  61. 61.
    L. Di Luigi, A.E. Rigamonti, F. Agosti, M. Mencarelli, P. Sgrò, N. Marazzi, S.G. Cella, E.E. Müller, A. Sartorio, Combined evaluation of resting IGF1, N-terminal propeptide of type III procollagen and C-terminal cross-linked telopeptide of type I collagen levels might be useful for detecting inappropriate GH administration in female athletes. Eur. J. Endocrinol. 160(5), 753–758 (2009)PubMedCrossRefGoogle Scholar
  62. 62.
    A. Sartorio, F. Agosti, N. Marazzi, N.A. Maffiuletti, S.G. Cella, A.E. Rigamonti, L. Guidetti, L. Di Luigi, E.E. Müller, 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) 61(4), 487–493 (2004)CrossRefGoogle Scholar
  63. 63.
    J.D. Wallace, R.C. Cuneo, M. Bidlingmaier, P.A. Lundberg, L. Carlsson, C.L. Boguszewski, J. Hay, M.L. Healy, R. Napoli, R. Dall, T. Rosén, C.J. Strasburger, The response of molecular isoforms of growth hormone to acute exercise in trained adult males. J. Clin. Endocrinol. Metab. 86(1), 200–206 (2001)PubMedCrossRefGoogle Scholar
  64. 64.
    J.D. Wallace, R.C. Cuneo, M. Bidlingmaier, P.A. Lundberg, L. Carlsson, C.L. Boguszewski, J. Hay, M. Boroujerdi, A. Cittadini, R. Dall, T. Rosén, C.J. Strasburger, Changes in non-22-kilodalton (kDa) isoforms of growth hormone (GH) after administration of 22-kDa recombinant human GH in trained adult males. J. Clin. Endocrinol. Metab. 86(4), 1731–1737 (2001)PubMedCrossRefGoogle Scholar
  65. 65.
    M. Bidlingmaier, Z. Wu, C.J. Strasburger, Test method: GH. Baillieres. Best Pract. Res. Clin. Endocrinol. Metab. 14(1), 99–109 (2000)CrossRefGoogle Scholar
  66. 66.
    M. Irie, M. Ueki, Y. Kishikawa, M. Nishii, M. Kawahara, 20 K-GH and its use in detecting GH abuse. Growth Horm. IGF Res. 19(4), 352–356 (2009)PubMedCrossRefGoogle Scholar
  67. 67.
    A. Keller, Z. Wu, J. Kratzsch, E. Keller, W.F. Blum, A. Kniess, R. Preiss, J. Teichert, C.J. Strasburger, M. Bidlingmaier, Pharmacokinetics and pharmacodynamics of GH: dependence on route and dosage of administration. Eur. J. Endocrinol. 156(6), 647–653 (2007)PubMedCrossRefGoogle Scholar
  68. 68.
    O. Barroso, P. Schamasch, O. Rabin, Detection of GH abuse in sport: past, present and future. Growth Horm. IGF Res. 19(4), 369–374 (2009)PubMedCrossRefGoogle Scholar
  69. 69.
    N. Guha, I. Erotokritou-Mulligan, C. Bartlett, A.D. Cowan, E.E. Bassett, M. Stow, P.H. Sönksen, R.I. Holt, The effects of a freeze-thaw cycle and pre-analytical storage temperature on the stability of insulin-like growth factor-I and pro-collagen type III N-terminal propeptide concentrations: implications for the detection of growth hormone misuse in athletes. Drug Test Anal. 4(6), 455–459 (2012)PubMedCrossRefGoogle Scholar
  70. 70.
    I. Erotokritou-Mulligan, E. Basset, D.A. Cowan, C. Bartlett, P. Milward, A. Sartorio, P.H. Sönksen, R.I. Holt, The use of growth hormone (GH)-dependent markers in the detection of GH abuse in sport: physiological intra-individual variation of IGF-I, type 3 pro-collagen (P-III-P) and the GH-2000 detection score. Clin. Endocrinol. (Oxf.) 72(4), 520–526 (2010)CrossRefGoogle Scholar
  71. 71.
    G. Such-Sanmartín, J. Bosch, J. Segura, R. Gutiérrez-Gallego, Growth hormone abuse and biological passport: is mannan-binding lectin a complementary candidate? Clin. J. Sport Med. 21(5), 441–443 (2011)PubMedCrossRefGoogle Scholar
  72. 72.
    N. Guha, I. Erotokritou-Mulligan, C. Burford, G. Stobridge, J. Brigg, T. Drake, E.E. Basset, D. Cowan, C. Bartlett, P.H. Sönksen, R.I. Holt, Serum insulin-like growth factor-I and pro-collagen type III N-terminal peptide in adolescent elite athletes: implications for the detection of growth hormone abuse in sport. J. Clin. Endocinol. Metab. 95(6), 2969–2976 (2010)CrossRefGoogle Scholar
  73. 73.
    A.E. Nelson, U. Meinhardt, J.L. Hansen, I.H. Walker, G. Stone, C.J. Howe, K.C. Leung, M.J. Siebel, R.C. Baxter, D.J. Handelsman, R. Kazlauskas, K.K. Ho, 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. 93(6), 2213–2222 (2008)PubMedCrossRefGoogle Scholar
  74. 74.
    C.J. Mitchell, A.E. Nelson, M.J. Cowley, W. Kaplan, G. Stone, S.K. Sutton, A. Lau, C.M. Lee, K.K. Ho, Detection of growth hormone doping by gene expression profiling of peripheral blood. J. Clin. Endocrinol. Metab. 94(12), 4703–4709 (2009)PubMedCrossRefGoogle Scholar
  75. 75.
    J. Ding, E.O. List, S. Okada, J.J. Kopchick, Perspective: proteomic approach to detect biomarkers of human growth hormone. Growth Horm. IGF Res. 19(4), 399–407 (2009)PubMedCrossRefGoogle Scholar
  76. 76.
    A. Thomas, M. Kohler, W. Schänzer, P. Delahaut, M. Thevis, Determination of IGF-1 and IGF-2, their degradation products and synthetic analogues in urine by LC–MS/MS. Analyst 136(5), 1003–1012 (2011)PubMedCrossRefGoogle Scholar
  77. 77.
    F. Boyard-Kieken, G. Dervilly-Pinel, P. Garcia, A.C. Paris, M.A. Popot, B. le Bizec, Y. Bonnaire, Comparison of different liquid chromatography stationary phases in LC-HRMS metabolomics for the detection of recombinant growth hormone doping control. J. Sep. Sci. 34(24), 3493–3501 (2011)PubMedCrossRefGoogle Scholar
  78. 78.
    J.M.J. García, E.T. Sánchez, D.O. Hidalgo, E.A. Conejo, Erythropoietin pharmacology. Clin. Transl. Oncol. 9(11), 715–722 (2007)CrossRefGoogle Scholar
  79. 79.
    R.L. Wilber, Detection of DNA-recombinant human epoetin-alfa as a pharmacological ergogenic aid. Sports Med. 32(2), 125–142 (2002)PubMedCrossRefGoogle Scholar
  80. 80.
    W. Jelkmann, Use of recombinant human erythropoietin as an antianemic and performance enhancing drug. Curr. Pharm. Biotechnol. 1(1), 11–31 (2000)PubMedCrossRefGoogle Scholar
  81. 81.
    J. Mørkeberg, Detection of autologous blood transfusions in athletes: a historical perspective. Transfus. Med. Rev. 26(3), 199–208 (2012)PubMedCrossRefGoogle Scholar
  82. 82.
    S. Giraud, N. Robinson, P. Mangin, M. Saugy, Scientific and forensic standards for homologous blood transfusion anti-doping analyses. Forensic Sci. Int. 179(1), 22–33 (2012)Google Scholar
  83. 83.
    S. Elliott, E. Pham, I.C. Macdougall, Erythropoietins: a common mechanism of action. Exp. Haematol. 36(12), 1573–1584 (2008)CrossRefGoogle Scholar
  84. 84.
    J.M. Topf, CERA: third-generation erythropoiesis-stimulating agent. Expert Opin. Pharmacother. 9(5), 839–849 (2008)PubMedCrossRefGoogle Scholar
  85. 85.
    G. Lippi, M. Franchini, G.L. Salvagno, G.C. Guidi, Biochemistry, physiology, and complications of blood doping: facts and speculation. Crit. Rev. Clin. Lab. Sci. 43(4), 349–391 (2006)PubMedCrossRefGoogle Scholar
  86. 86.
    M. Tsivou, H.A. Dimopoulou, I.P. Leontiou, D.G. Georgakopoulos, M.A. Koupparis, J. Atta-Politou, C.G. Georgakopoulos, Stabilization of human urine doping control samples: III. Recombinant human erythropoietin. Clin. Chim. Acta. 411(5–6), 448–452 (2010)PubMedCrossRefGoogle Scholar
  87. 87.
    J.A. Pascual, V. Belalcazar, C. de Bolos, R. Gutiérrez, E. Llop, J. Segura, Recombinant erythropoietin and analogues: a challenge for doping control. Ther. Drug Monit. 26(2), 175–179 (2004)PubMedCrossRefGoogle Scholar
  88. 88.
    E. Diamanti-Kandarakis, P.A. Konstantinopoulos, J. Papailiou, S.A. Kandarakis, A. Andreopoulos, G.P. Sykiotis, Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era. Sports Med. 35(10), 831–840 (2005)PubMedCrossRefGoogle Scholar
  89. 89.
    C. Lundby, P. Robach, B. Saltin, The evolving science of detection of ‘blood doping’. Br. J. Pharmacol. 165(5), 1306–1315 (2012)PubMedCrossRefGoogle Scholar
  90. 90.
    C. Reichel, The overlooked difference between human endogenous and recombinant erythropoietins and its implication for sports drug testing and pharmaceutical drug design. Drug Test Anal. 3(11–12), 883–891 (2011)PubMedCrossRefGoogle Scholar
  91. 91.
    C. Reichel, SARCOSYL-PAGE: a new electrophoretic method for the separation and immunological detection of PEGylated proteins. Methods Mol. Biol. 865, 65–79 (2012)CrossRefGoogle Scholar
  92. 92.
    C. Reichel, M. Thevis, Detection of EPO-Fc fusion protein in human blood: screening and confirmation protocols for sports drug testing. Drug Test Anal. doi: 10.1002/dta.1381 (2012) [Epub ahead of print]
  93. 93.
    M. Lönnberg, M. Andrén, G. Birgegård, M. Drevin, M. Garle, J. Carlson, Rapid detection of erythropoiesis-stimulating agents in urine and serum. Anal. Biochem. 420(2), 101–114 (2012)PubMedCrossRefGoogle Scholar
  94. 94.
    C. Reichel, OMICS-strategies and methods in the fight against doping. Forensic Sci. Int. 213(1–3), 20–34 (2011)PubMedCrossRefGoogle Scholar
  95. 95.
    H. Schwarzenbach, Impact of physical activity and doping on epigenetic gene regulation. Drug Test Anal. 3(10), 682–687 (2011)PubMedCrossRefGoogle Scholar
  96. 96.
    WADA, The 2008 Prohibited List (WADA, Montreal, 2008)Google Scholar
  97. 97.
    C.F. Argüelles, E. Hernández-Zamora, Gene doping: gene transfer and possible molecular detection. Gac. Med. Mex. 143(2), 169–172 (2007)PubMedGoogle Scholar
  98. 98.
    R.S. Oliveira, T.F. Collares, K.R. Smith, T.V. Collares, F.K. Seixas, The use of genes for performance enhancement: doping or therapy? Braz. J. Med. Biol. Res. 44(12), 1194–1201 (2011)PubMedCrossRefGoogle Scholar
  99. 99.
    H.E. Montgomery, R. Marshall, H. Hemingway, S. Myerson, P. Clarkson, C. Dollery, M. Hayward, D.E. Holliman, M. Jubb, M. World, E.L. Thomas, A.E. Brynes, N. Saeed, M. Barnard, J.D. Bell, K. Prasad, M. Rayson, P.J. Talmud, S.E. Humphries, Human gene for physical performance. Nature 393(6682), 221–222 (1998)PubMedCrossRefGoogle Scholar
  100. 100.
    N.C. Sharp, The human genome and sport, including epigenetics, gene doping, and athleticogenomics. Endocrinol. Metab. Clin. North Am. 39(1), 201–215 (2010)PubMedCrossRefGoogle Scholar
  101. 101.
    E.W.Neuberger, M. Jurkiewicz, D.A. Moser, P. Simon, Detection of EPO gene doping in blood. Drug Test Anal. doi: 10.1002/dta.1347 (2012) [Epub ahead of print]
  102. 102.
    A. Baoutina, I.E. Alexander, J.E. Rasko, K.R. Emslie, Potential use of gene transfer in athletic performance enhancement. Mol. Ther. 15(10), 1751–1766 (2007)PubMedCrossRefGoogle Scholar
  103. 103.
    M.M. Mansour, H.M. Azzazy, The hunt for gene dopers. Drug Test Anal. 1(7), 311–322 (2009)PubMedCrossRefGoogle Scholar
  104. 104.
    W. Ni, C. Le Guiner, P. Moullier, R.O. Snyder, Development and utility of an internal threshold control (ITC) real-time PCR assay for exogenous DNA detection. PLoS One 7(5), e36461 (2012) [Epub ahead of print]Google Scholar
  105. 105.
    C. D’Angelo, C. Tamburrini, Addict to win? A different approach to doping. J. Med. Ethics 36(11), 700–707 (2010)PubMedCrossRefGoogle Scholar
  106. 106.
    G. Lippi, G. Banfi, M. Franchini, G.C. Guidi, New strategies for doping control. J. Sports Sci. 26(5), 441–445 (2008)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Endocrine Unit, Evgenidion HospitalUniversity of AthensAthensGreece
  2. 2.Clinic for EndocrinologyClinical Center of SerbiaBelgradeSerbia

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