Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling

Abstract

In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module.

Keywords: Doping; Steroids.

Figure 1

Target analytes of the steroid profile, their interindependence and metabolic pathway. 5α-/5β-diol, 5α/5β-androstane-3α,17β-diol; DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone.

Figure 2

Example of steroid profile generated by the Bayesian model of the ABP for the T/E ratio parameter. The blue line represents the measured T/E values, whereas the individual limits are shown by the red lines. ABP, athlete biological passport; E, epitestosterone; T, testosterone.

Figure 3

Schematic representation of the variables influencing the steroid profile in the fight against doping. ABP, athlete biological passport; GC-C-IRMS, gas chromatography and combustion coupled to isotope ratio mass spectrometry; ITP, initial testing procedure.

Figure 4

Schematic illustrations of (A) glucuronidation and (B) sulfoconjugation of testosterone. SULT, sulfotransferase enzymes; UGT, uridine diphosphate glucuronosyltransferase.