Androgens and doping tests: genetic variation and pit-falls.

Area of Science:

• Pharmacogenetics
• Sports Science
• Anti-Doping Research

Background:

• Drug disposition, including anabolic androgenic steroids, exhibits significant inter-individual variability.
• Genetic factors are the primary drivers of this variation in drug metabolism and response.
• This variability likely extends to the efficacy of doping agents used in sports.

Purpose of the Study:

• To investigate the role of genetic variability in the disposition and efficacy of anabolic androgenic steroids.
• To explore the implications of genetic variability on testosterone doping detection.
• To propose improvements to current doping control strategies based on genetic insights.

Main Methods:

• Analysis of genetic factors influencing metabolic pathways of testosterone and its derivatives.
• Review of existing data on inter- and intra-ethnic variations in testosterone glucuronidation and excretion.
• Evaluation of testosterone enanthate hydrolysis and bioactivation variability.
• Assessment of current doping control methodologies, including population-based cut-off levels.

Main Results:

• Genetic variability substantially influences the disposition and efficacy of testosterone, a common doping agent.
• Significant inter- and intra-ethnic variations exist in testosterone metabolism and excretion.
• Testosterone enanthate's hydrolysis and bioactivation show genetic variability, leading to 2-3 fold differences in excretion and serum levels.
• Current population-based cut-off levels for testosterone:epitestosterone ratios may be inadequate.

Conclusions:

• Genetic information should be integrated into doping control programs to enhance accuracy.
• Replacing population-based cut-offs with Bayesian interpretation of individual test results, combined with genetic data, improves test sensitivity.
• This integrated approach can reduce false positives/negatives and the need for costly follow-up tests, aligning with World Anti-Doping Agency goals.