IGF-I, IGFBP-2 and –3: do they have a role as test for rhGH abuse in trained males?

PURPOSE: Although the illegal use of recombinant human growth hormone (rhGH) to enhance performance is increasing among athletes, no official test for its detection has yet been implemented. The aim of this work was to study how prolonged rhGH administration in trained subjects influences the insulin-like growth factor (IGF) system, in order to evaluate new methods in antidoping tests. METHODS: Morning serum growth hormone (GH), IGF-I, IGF binding protein (BP)-2, IGFBP-3, IGF-I/IGFBP-2, and IGFBP-3/IGFBP-2 ratios were evaluated before, during (8th and 15th days), and at the end and after cessation (+3, +6, +9, +12, and +15 d) of a 3-wk treatment with different doses of rhGH (0.09 IU.kg BW(-1).d(-1) for 6 or 3 d a week, i.e., the A and B trials, respectively) in seven well-trained subjects not involved in competitive sports. The blood collections pre- and during treatment were performed immediately before the daily rhGH dose. RESULTS: In both trials, significant increases of IGF-I (higher in the A trial) and IGFBP-3 serum concentrations during rhGH administration were observed. Serum IGFBP-3 remained significantly increased in the A trial 3 d after treatment cessation. In the A trial only, two subjects had IFG-I concentrations exceeding the upper limit of the reference range. No modifications of serum GH, IGFBP-2 and IGF-I/IGFBP-2, and IGFBP-3/IGFBP-2 ratios were observed. The z-score evaluation for IGFBP-3 detected GH exposure in 100% of subjects only at end treatment in A trial. CONCLUSION: Although IGF-I and IGFBP-3 seem potentially the most specific markers of rhGH assumption, our data suggest that for antidoping purposes a single evaluation of their absolute serum concentration is not a sufficiently secure method to detect rhGH abuse in all subjects, especially in the case of low rhGH doses.