Applying metabolomics to detect growth hormone administration in athletes: proof of concept.

Growth hormone (GH), an endogenous peptide regulating anabolism and lipolysis in humans, is known to be abused by the athletes to improve their performances. Despite the development of two distinct screening methods, few positive cases have been reported by the anti-doping authorities, probably due to the GH quick turnover and the masking effects of age, ethnicity and sex. Apart from growth regulation, GH is known to affect several metabolic pathways in humans including ketosis, amino-acids uptake and proteins breakdown. It is reasonable to imagine to observe its markers of effects through the leading tool on metabolism study, metabolomics. In this proof-of-concept study, a cohort of well-trained volunteers has been split in two equal groups and administered with micro-doses of EPO or EPO + GH every second day for two weeks. Urine and plasma samples have been collected before, during and after the treatment and analyzed using metabolomics and lipidomics approaches. The results show that, applying a direct discriminant analysis on the treated groups, it is possible to distinguish the treatments, and to use this difference to classify them correctly. High intragroup variability is observed, due to the subject-specific effect of the hormones. Through time 0 centering the data, a longitudinally tracking of the group was performed and higher difference was observed between the groups, including a perfect classification of the samples before and after the treatments.