Context: Testosterone abuse is conventionally assessed by the urinary testosterone/epitestosterone (T/E) ratio, levels above 4.0 being considered suspicious. The large variation in testosterone glucuronide (TG) excretion and its strong association with a deletion polymorphism in the uridine diphospho-glucuronosyl transferase (UGT) 2B17 gene challenge the accuracy of the T/E ratio test.Objective: Our objective was to investigate whether genotype-based cutoff values will improve the sensitivity and specificity of the test. Design:This was an open three-armed comparative study.Participants: A total of 55 healthy male volunteers with either two, one, or no allele [insertion/ insertion, insertion/deletion, or deletion/deletion (del/del)] of the UGT2B17 gene was included in the study.Intervention: A single im dose of 500 mg testosterone enanthate was administered.Main Outcome Measures: Urinary excretion of TG after dose and the T/E ratio during 15 d were calculated. Results:The degree and rate of increase in the TG excretion rate were highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the insertion/insertion group compared with the del/del group. Of the del/del subjects, 40% never reached the T/E ratio of 4.0 on any of the 15 d after the dose. When differentiated cutoff levels for the del/del (1.0) and the other genotypes (6.0) were applied, the sensitivity increased substantially for the del/del group, and false positives in the other genotypes were eliminated.Conclusions: Consideration of the genetic variation in disposition of androgens will improve the sensitivity and specificity of the testosterone doping test. This is of interest not only for combating androgen doping in sports, but also for detecting and preventing androgen abuse in society. (J Clin Endocrinol Metab 93: 2500 -2506, 2008) T estosterone (T) was identified as the male sex hormone in the mid-1930s. It has been clinically used for nearly seven decades (1), primarily for androgen replacement therapy in men with androgen deficiency. Over the recent decades, testosterone and other androgens have been increasingly abused for muscle building and enhancement of physical performance (2). A recent study showed that power lifters with current or previous abuse of anabolic steroids have increased cross-sectional area of muscle

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The CYP17 promoter polymorphism may partly explain high natural (>4) T/E ratios. Our data indicate that 5-androstene-3beta, 17alpha-diol is an important precursor of epitestosterone and that CYP17 is involved in its production. In addition, we found that lack of the UGT2B17 enzyme may be compensated for by increase in UGT2B15 transcription.