Genetic Variations in UDP-Glucuronosyl Transferase 2B17: Implications for Testosterone Excretion Profiling and Doping Control Programs

The use of drugs and ergogenic substances to aug-ment athletic performance, commonly referred to as doping, has evolved along with sporting events. An-cient Olympic athletes consumed mushrooms, plants, and herbs in an attempt to gain a competitive edge. ThemodernOlympicGamesmade their debut in 1896, and mixtures of cocaine, ephedrine, and strychnine were used to enhance performance. Anabolic andro-genic steroids (substances similar to the hormone testosterone) were used after World War II by Soviet athletes to increase muscle mass and power in weight-lifting and bodybuilding events. Anabolic androgenic steroids rapidly spread to athletes in other sporting events and are still a problem in today’s sports world. To deal with the problem of doping in sports, the International Olympic Committee established a Med-ical Commission. The first list of prohibited sub-stances was created in 1967; drug testing was imple-mented at Olympic Games the following year. In 1999, an independent international organization, the World Anti-Doping Agency (WADA), was created to combat doping in sports and provide unified standards for doping control. THE T/E RATIO TO SCREEN FOR TESTOSTERONE USE Anabolic androgenic steroids are themost abused class of prohibited substances, with testosterone accounting for many positive cases. Testosterone abuse is prob-lematic because synthetic testosterone is indistin-guishable from endogenous testosterone by routine screening methods such as gas chromatography–mass spectrometry. In the 1980s, it was discovered that tes-tosterone use alters the ratio of testosterone glucuro-nide to epitestosterone glucuronide (T/E ratio)1 in urine. Epitestosterone is a naturally occurring biologi-cally inactive epimer of testosterone that remains rela-tively constant in urine. A population-based T/E ratio cutoff of 6.0 was initially used to indicate synthetic tes-tosterone use; the T/E ratio cutoff was lowered to 4.0 in 2005. Based on data from several laboratories, the av-erage T/E ratio ranges from 0.9 to 1.6 for healthy male adolescents andmen. At the UCLAOlympic Analytical Laboratory, we found that the average T/E ratio during a 31-month period was 1.1 (median 0.9%). The distri