Background: Growth hormone (GH) is reputed to be in widespread use in the sporting arena as a performanceenhancing agent and is on the list of banned substances published by the World Anti-Doping Agency. The detection of GH abuse poses many challenges. Unlike many substances of abuse, such as synthetic anabolic steroids, GH is a naturally occurring substance; therefore, demonstration of exogenous administration must rely on detecting concentrations in excess of an established reference interval. The purpose of this review is to discuss the methodologies being developed to detect GH abuse. Methods: We undertook a comprehensive search using multiple electronic databases and hand searches of reference lists of articles. The data for this review reflect our academic interests and experience through work on the GH-2000 and GH-2004 projects. Results: Two approaches have been taken to detect GH abuse. The first is based on assessment of the effect of exogenous GH on pituitary GH isoforms, and the second is based on measurement of markers of GH action. The advantages of each approach and the difficulties encountered with each technique, as well as future concepts in detection, are discussed. Conclusion: Although there are substantial challenges for the detection of GH, methodologies now exist to detect GH abuse with reasonable sensitivity and specificity.

The GH-2000 detection method based on IGF-I and P-III-P would be valid in all ethnic groups.

Context: The GH-2000 team proposed a method based on IGF1 and type III pro-collagen (P-III-P) to detect exogenously administered GH. As previous studies involved predominantly white European athletes, it is important to assess whether the response of these markers to recombinant human GH (rhGH) differs with ethnicity. Objective: To examine the response of serum IGF1 and P-III-P and GH-2000 score to rhGH in non-Caucasian amateur athletes. Design: Double-blind placebo-controlled rhGH administration study. Setting: Wellcome Trust Clinical Research Facility, Southampton General Hospital. Subjects: The study included 31 male and 14 female amateur athletes of different ethnicities. Intervention: The subjects were assigned to treatment with placebo or 0.1 IU/kg per day (low dose) or 0.2 IU/kg per day (high dose) rhGH for 28 days. Blood was collected weekly during treatment and on days 35, 42 and 84 during the washout period. Serum IGF1 and P-III-P were measured, and GH-2000 score was calculated. Results: IGF1, P-III-P and GH-2000 score rose in response to both low-and high-dose GH in both men and women. When compared with the Caucasian volunteers of the previous GH-2000 study, mean baseline and placebo-treated P-III-P and GH-2000 score were lower in GH-2004 men and women. Post-GH, however, peak IGF1 or P-III-P did not differ between studies but the peak GH-2000 score was lower in GH-2004 men. There was no difference between studies in the maximal change in IGF1, P-III-P and GH-2000 score in response to GH in either gender. Conclusions: These data do not support a significant ethnic effect on the peak or maximal response to rhGH.

Although there was a rise in P-III-P after injury, this was insufficient to invalidate the GH-2000 detection method based on IGF-I and P-III-P concentrations.