title: Biochemical markers of insulin-like growth factor-I misuse in athletes: the response of serum IGF-I, procollagen type III amino-terminal propeptide, and the GH-2000 score to the administration of rhIGF-I/rhIGF binding protein-3 complex.
abstract: BACKGROUND
  The GH-2000 and GH-2004 research groups developed a method for detecting GH misuse in athletes based on the measurement of serum IGF-I and procollagen type III amino-terminal propeptide (P-III-NP). There are reports that IGF-I is also misused by athletes, but currently there is no internationally recognized test designed to detect recombinant human IGF-I misuse.
  
  
  OBJECTIVE
  The objective of the study was to examine the response of serum IGF-I, P-III-NP, and the GH-2000 score to recombinant human (rh) IGF-I/rhIGF binding protein-3 (IGFBP-3) administration in recreational athletes.
  
  
  METHODS
  This was a randomized, double-blind, placebo-controlled rhIGF-I/rhIGFBP-3 administration study at Southampton General Hospital (Southampton, United Kingdom).
  
  
  METHODS
  Fifty-six recreational athletes (26 women, 30 men) participated in the study.
  
  
  METHODS
  Participants were randomized to treatment with low-dose (30 mg/d) or high-dose (60 mg/d) rhIGF-I/rhIGFBP-3 complex or placebo for 28 days. Blood was collected throughout the drug administration and washout periods. Serum IGF-I and P-III-NP were measured using commercial immunoassays and GH-2000 scores were calculated.
  
  
  RESULTS
  IGF-I, P-III-NP, and the GH-2000 score rose in response to both low- and high-dose rhIGF-I/rhIGFBP-3 administration. The relative maximum response of IGF-I (approximately 4-fold increase in women and men) was greater than that of P-III-NP (40%-50% increase in women, 35%-50% increase in men). The GH-2000 formulae, which incorporate IGF-I and P-III-NP results, detected up to 61% of women and 80% of men in the rhIGF-I/rhIGFBP-3 groups but, using IGF-I concentrations alone, the sensitivity increased to 94% in both women and men during the administration period.
  
  
  CONCLUSIONS
  The rise in P-III-NP after rhIGF-I/rhIGFBP-3 administration is small compared with that after rhGH administration. Although rhIGF-I/rhIGFBP-3 administration can be detected using the GH-2000 score method, a test based on serum IGF-I alone provides better sensitivity.
authors.affiliation: Human Development and Health Academic Unit (N.G., I.E.-M., S.P.N., M.F., P.H.S., R.I.G.H.), Faculty of Medicine, University of Southampton, Southampton SO16 6YD, United Kingdom; Drug Control Centre (C.B., D.A.C.), Department of Forensic and Analytical Science, King's College London, London SE1 9NH, United Kingdom; and School of Mathematics, Statistics, and Actuarial Science (E.E.B.), University of Kent, Canterbury, Kent CT2 7NZ, United Kingdom.
authors.forename: Nishan
authors.initials: N
authors.lastname: Guha
authors.forename: Ioulietta
authors.initials: I
authors.lastname: Erotokritou-Mulligan
authors.forename: Christiaan
authors.initials: C
authors.lastname: Bartlett
authors.forename: Simon P
authors.initials: SP
authors.lastname: Nevitt
authors.forename: Michael
authors.initials: M
authors.lastname: Francis
authors.forename: E Eryl
authors.initials: EE
authors.lastname: Bassett
authors.forename: David A
authors.initials: DA
authors.lastname: Cowan
authors.forename: Peter H
authors.initials: PH
authors.lastname: Sönksen
authors.forename: Richard I G
authors.initials: RI
authors.lastname: Holt
mesh_terms: D000293:Adolescent; D000328:Adult; D056352:Athletes; D054316:Biomarkers, Pharmacological / Q000097:blood*; D004300:Doping in Sports; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000008:administration & dosage*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000097:blood*; D011347:Procollagen / Q000097:blood*; D011994:Recombinant Proteins / Q000008:administration & dosage*; D012107:Research Design; D015813:Substance Abuse Detection / Q000379:methods*; D006113:United Kingdom; D055815:Young Adult
chemical_list: D054316:Biomarkers, Pharmacological; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D011347:Procollagen; D011994:Recombinant Proteins; C041876:procollagen Type III-N-terminal peptide; D007334:Insulin-Like Growth Factor I