Longitudinal Profiling of Endogenous Steroids in Blood using the Athlete Biological Passport Approach

Context: Detection of endogenous anabolic androgenic steroids (EAAS), like testosterone (T), as doping agents has been improved with the launch of the Steroidal Module of the Athlete Biological Passport (ABP) in urine samples. Objective: To target doping practices with EAAS, particularly in individuals with low level of biomarkers excreted in urine, by including new target compounds measured in blood. Design: T and T/Androstenedione (T/A4) distributions were obtained from 4 years of anti-doping data and applied as priors to analyze individual profiles from two T administration studies in female and male subjects. Setting: Anti-doping laboratory. Elite athletes (n=823) and male and female clinical trials subjects (n=19 and 14, respectively). Intervention(s): Two open-label administration studies were carried out. One involved a control phase period followed by patch and then oral T administration in male volunteers and the other followed female volunteers during three menstrual cycles with 28 days of daily transdermal T application during the second month. Main outcome measure(s): Serum samples were analyzed for T and A4 and the performance of a longitudinal, ABP-based approach was evaluated for T and T/A4. Results: An ABP-based approach set at a 99% specificity flagged all female subjects during the transdermal T application period and 44% of subjects three days after the treatment. Testosterone showed the best sensitivity (74%) in response to transdermal T application in males. Conclusions: Inclusion of T and T/A4 as markers in the Steroidal Module can improve the performance of the ABP to identify T transdermal application, particularly in females.