Combined administration of microdoses of growth hormone and erythropoietin: Effects on performance and evaluation of GH detection capability using anti-doping methods.
EPO microdoses
GH microdoses
detection
doping
effects
Journal
Drug testing and analysis
ISSN: 1942-7611
Titre abrégé: Drug Test Anal
Pays: England
ID NLM: 101483449
Informations de publication
Date de publication:
Nov 2019
Nov 2019
Historique:
received:
06
03
2019
revised:
01
07
2019
accepted:
04
07
2019
pubmed:
14
7
2019
medline:
13
5
2020
entrez:
14
7
2019
Statut:
ppublish
Résumé
The combination of growth hormone (GH) and recombinant erythropoietin (rEPO) is thought to be used particularly in endurance sports. Our objective was to reproduce a 2-week administration of rEPO microdoses alone or in combination with GH microdoses (three times a week) on healthy and athletic male subjects and to evaluate if GH had any additional effects compared to EPO treatment alone. The effects of the treatments on hematological parameters and VO2max were studied as well as the detection of GH in serum. While the rEPO microdose regimen was associated with a significant increase in reticulocytes, no clear elevation in hemoglobin concentration (HGB) was observed. Using a correction by plasma volume did not reveal more effects of EPO on HGB. Our results did not show any additional effect when the GH microdoses were co-administered. In addition, no clear increase in VO2max was observed after treatment, with an elevation in only half the subjects in both groups (EPO and EPO+GH). A clear effect of GH on insulin-like growth factor I (IGF-I) was seen but it was lower on procollagen III amino-terminal propeptide (P-III-NP). GH detection using the direct isoform test identified only one subject 24 hours after receiving GH. The GH biomarker test combining IGF-I and P-III-NP was not able to detect the GH administration. However, a longitudinal follow-up of the intraindividual variations showed a significant increase in IGF-I 24 and 48 hours after GH administration in most subjects, while the effect of GH microdoses on P-III-NP was less straightforward.
Substances chimiques
Erythropoietin
11096-26-7
Growth Hormone
9002-72-6
Oxygen
S88TT14065
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1698-1713Subventions
Organisme : AFLD scientific comity (COS)
ID : 2016
Organisme : French Anti-Doping Agency
ID : own resources
Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
Martin L, Ashenden M, Bejder J, et al. New insights for identification of doping with recombinant human erythropoietin micro-doses after high hydration. Drug Test Anal. 2016;8(11-12):1119-1130.
Marchand A, Buisson C, Martin L, Martin JA, Molina A, Ressiot D. Report on an anti-doping operation in Guadeloupe: high number of positive cases and inferences about doping habits. Drug Test Anal. 2017;9(11-12):1753-1761.
Sohmiya M, Ishikawa K, Kato Y. Stimulation of erythropoietin secretion by continuous subcutaneous infusion of recombinant human GH in anemic patients with chronic renal failure. Eur J Endocrinol. 1998;138(3):302-306.
Sohmiya M, Kato Y. Effect of long-term administration of recombinant human growth hormone (rhGH) on plasma erythropoietin (EPO) and haemoglobin levels in anaemic patients with adult GH deficiency. Clin Endocrinol (Oxf). 2001;55(6):749-754.
Åstrand P-O, Rodahl K, Dahl H, Strømme SB. Textbook of work physiology: physiological bases of exercise. Champaign (Ill): Human Kinetics; 2003:1-649.
Lobigs LM, Garvican-Lewis LA, Vuong VL, et al. Validation of a blood marker for plasma volume in endurance athletes during a live-high train-low altitude training camp. Drug Test Anal. 2018;10(7):1176-1183.
Lobigs LM, Sottas PE, Bourdon PC, et al. The use of biomarkers to describe plasma-, red cell-, and blood volume from a simple blood test. Am J Hematol. 2017;92(1):62-67.
Lobigs LM, Sottas PE, Bourdon PC, et al. A step towards removing plasma volume variance from the Athlete's biological passport: the use of biomarkers to describe vascular volumes from a simple blood test. Drug Test Anal. 2018;10(2):294-300.
TD2015GH. Human Growth Hormone (hGH) isoform differential immunoassays for doping control analyses v1.0. www.wada-ama.org. 2015.
GuidelinesHuman Growth Hormone (hGH) Biomarkers test for doping control analyses v. 2.0. www.wada-ama.org. 2016.
Bidlingmaier M, Suhr J, Ernst A, et al. High-sensitivity chemiluminescence immunoassays for detection of growth hormone doping in sports. Clin Chem. 2009;55(3):445-453.
Erotokritou-Mulligan I, Guha N, Stow M, et al. 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. 2012;22(2):53-58.
Erotokritou-Mulligan I, Holt RI, Sonksen PH. Growth hormone doping: a review. Open Access J Sports Med. 2011;2:99-111.
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):3591-3601.
Grant MB, Schmetz I, Russell B, Harwood HJ Jr, Silverstein J, Merimee TJ. Changes in insulin-like growth factors I and II and their binding protein after a single intramuscular injection of growth hormone. J Clin Endocrinol Metab. 1986;63(4):981-984.
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):124-133.
Sgro P, Sansone M, Sansone A, Romanelli F, Di Luigi L. Effects of erythropoietin abuse on exercise performance. Phys Sportsmed. 2018;46(1):105-115.
Ashenden M, Gough CE, Garnham A, Gore CJ, Sharpe K. Current markers of the athlete blood passport do not flag microdose EPO doping. Eur J Appl Physiol. 2011;111(9):2307-2314.
Clark B, Woolford SM, Eastwood A, Sharpe K, Barnes PG, Gore CJ. Temporal changes in physiology and haematology in response to high- and micro-doses of recombinant human erythropoietin. Drug Test Anal. 2017;9(10):1561-1571.
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-i39.
Lehtihet M, Bhuiyan H, Dalby A, Ericsson M, Ekstrom L. Longitudinally monitoring of P-III-NP, IGF-I and GH-2000 score increase the probability to detect 2 weeks administration of low doses recombinant growth hormone compared to GH-2000 decision limit and GH isoform test and micro RNA markers. Drug Test Anal. 2019;11(3):411-421.
Jelkmann W. Erythropoietin. Front Horm Res. 2016;47:115-127.
Garvican LA, Saunders PU, Cardoso T, et al. Intravenous iron supplementation in distance runners with low or suboptimal ferritin. Med Sci Sports Exerc. 2014;46(2):376-385.
Bennett H, Parfitt G, Davison K, Eston R. Validity of submaximal step tests to estimate maximal oxygen uptake in healthy adults. Sports Med. 2016;46(5):737-750.
Beedie CJ, Foad AJ. The placebo effect in sports performance: a brief review. Sports Med. 2009;39(4):313-329.
Di Luigi L, Guidetti L. IGF-I, IGFBP-2, and −3: do they have a role in detecting rhGH abuse in trained men? Med Sci Sports Exerc. 2002;34(8):1270-1278.
Pawlikowska-Haddal A, Cohen P, Cook DM. How useful are serum IGF-I measurements for managing GH replacement therapy in adults and children? Pituitary. 2012;15(2):126-134.
Gupta V. Adult growth hormone deficiency. Indian J Endocrinol Metab. 2011;15(Suppl 3):S197-S202.
Voss SC, Robinson N, Alsayrafi M, et al. The effect of a period of intense exercise on the marker approach to detect growth hormone doping in sports. Drug Test Anal. 2014;6(6):582-586.
Hartman ML, Veldhuis JD, Thorner MO. Normal control of growth hormone secretion. Horm Res. 1993;40(1-3):37-47.