Increased serum concentration of IGFBP-4 and IGFBP-5 in healthy adults during one month's treatment with supraphysiological doses of growth hormone

Objectives: To study the effects on insulin-like growth factor binding proteins (IGFBP)-4 and -5 after one month's treatment with supraphysiological doses of growth hormone (GH) in healthy, active young adults with a normal GH-IGF-I axis. Furthermore, the possible use of IGFBP-4 and IGFBP-5 as markers of GH doping is discussed. Design: Thirty healthy, physically active volunteers (15 men and 15 women), mean age 25.9 years (range 18-35), participated in this randomized, double-blind, placebo-controlled, parallel study with three groups (n = 10; 5 men and 5 women in each group). The groups comprised the following: placebo, GH 0.1 IU/kg/day [0.033 mg/kg/day] and GH 0.2 IU/kg/day [0.067 mg/kg/day]. Results: Baseline levels of IGFBP-4 were higher (+20%), while IGFBP-5 levels were lower (-37%) in women than in men. IGFBP-5 levels were positively correlated to age, but no significant correlation was found for IGFBP-4. In the pooled group with active GH treatment (n = 20), both IGFBP-4 and IGFBP-5 levels were increased vs. the placebo group from day 14 until end of treatment [day 28, IGFBP-4 (+40%, p < 0.01) and IGFBP-5 (+61%, p < 0.001)]. After inclusion of serum IGF-I as a covariate in the linear regression analysis, the associations between GH treatment and the IGFBP-4 and IGFBP-5 levels were not significant. Conclusions: This study shows that the levels of IGFBP-4 and IGFBP-5 are affected by supraphysiological GH treatment given to young, healthy, physically active adults of both genders. The present study, including relatively few subjects, does not support that IGFBP-4 and IGFBP-5 can be used as IGF-I independent markers in a forthcoming method for detecting GH doping, although, further studies are needed to investigate the potential use of IGFBP-4 and IGFBP-5 as markers of GH doping.