Potential parameters for the detection of hGH doping

Abstract

The aim of our hGH application study with non-competitive athletes was the investigation of selected serum parameters from different processes affected by hGH. Fifteen athletes (age 21-33, mean 24) were treated with 0.06 IU hGH/kg BW per day or placebo (10 hGH, 5 placebo) respectively for 14 days. Blood samples were taken prior to, during and until 10 weeks after treatment. The concentrations of the following markers were determined in relevant serum samples: IGF-I, IGFBP-3, ALS, PIIINP, PINP, osteocalcin, and leptin. The IGF-I concentration increased rapidly within the hGH treatment group and showed significantly higher levels compared to baseline even 3 days after application. The response of the IGFBP-3 to the hGH applications was lower in comparison to IGF-I. The hGH group showed an increasing IGFBP-3 compared to baseline from day 4 till day 15. The response of PIIINP to hGH is clearly delayed compared to the IGF-I axis, but the PIIINP concentration remains on an increased level for a longer period (from day 4 until day 21). The time course and the extent of response varied strongly interindividually. PINP and osteocalcin showed only a small response to hGH applications. These parameters are characterised by a strong scattering of base values compared with the small response. In the hGH treatment group very different leptin concentrations were found at the beginning of the study, but after treatment decreasing leptin levels were observed in all cases. The determination of only one parameter will not be sufficient for detection of hGH abuse. A combination of markers by mathematical methods can be helpful to distinguish between placebo and hGH-treated athletes. By using the suggested discriminant function the data sets of hGH and placebo-treated athletes could be separated without false positive results.

Within-Subject Variability and Analytic Imprecision of Insulinlike Growth Factor Axis and Collagen Markers: Implications for Clinical Diagnosis and Doping Tests

“…Increased serum concentrations of IGF axis and collagen markers in response to GH administered to young recreational athletes (12)(13)(14)(15) have indicated the potential for these markers in detecting GH abuse in sport. Use of these markers in a GH-doping test requires estimation of between-subject variability in elite athletes to define demographically relevant reference ranges, and we have previously demonstrated the influence of demographic factors and sport type on between-subject variation in the same cohort of elite athletes (23 ).…”

“…The N-terminal propeptide of type III procollagen (PIIINP) is a marker of type III collagen turnover in connective tissue (8 ) that is used clinically to monitor growth (9 ) or clinical conditions such as liver fibrosis (10 ) and prognostically in atherosclerotic disease (11 ). The serum concentrations of these IGF axis and collagen markers also increase in response to growth hormone (GH) (12)(13)(14)(15), indicating the potential of these GH-responsive proteins in detecting exogenous GH administration (16 ).…”

Challenges in Detecting the Abuse of Growth Hormone in Sport

“…IGF-I is an ideal candidate marker because it has little diurnal or day-to-day variation (22 ), increases 1.3-to 2.3-fold in a uniform dose-dependent fashion after GH administration (28 ), and has low basal scatter (29 ) and minimal changes with exercise. Ninety-five percent of circulating IGF-I is bound to binding proteins (IGFBP-1 to -6), predominantly IGFBP-3, which modulate its actions and bioavailability (22,30 ).…”

A proteomic approach combining MS and bioinformatic analysis for the detection and identification of biomarkers of administration of exogenous human growth hormone in humans

“…The first measures the levels of the different GH isoforms (non-22 kDa versus 22 kDa), where a high ratio of 22 kDa to non-22 kDa (17 and 20 kDa) GH is used to indicate rhGH abuse [8]. The second technique is based on monitoring a number of downstream GH biomarkers, with IGF-I and procollagen III N-terminal peptide, being the most important candidates [8,[13][14][15]. One major problem with these approaches is that they are all dependent on the availability of stable and reliable immunoassays, and changes in the performance of the commercial assay kit might result in the need to re-establish the reference intervals [16].…”