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This version published online on March 11, 2008
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2008-0218
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Submitted on January 28, 2008
Accepted on March 5, 2008

Doping Test Results Dependent on Genotype of UGT2B17, the Major Enzyme for Testosterone Glucuronidation

Jenny Jakobsson Schulze*, Jonas Lundmark, Mats Garle, Ilona Skilving, Lena Ekström, and Anders Rane

Department of Laboratory Medicine, Karolinska Institutet at Division of Clinical Pharmacology, Karolinska University Hospital, SE-141 86 Stockholm, Sweden

* To whom correspondence should be addressed. E-mail: jenny.schulze{at}ki.se.

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 UGT2B17 gene challenge the accuracy of the T/E ratio test.

Objective: To investigate whether genotype based cut-off values will improve the sensitivity and specificity of the test.

Design: Open 3-armed comparative study.

Participants: 55 healthy male volunteers with either two, one or no allele (ins/ins, ins/del or del/del) of the UGT2B17 gene.

Intervention: A single intramuscular dose of 500 mg testosterone enanthate.

Main outcome measures: Urinary excretion of TG after dose and the T/E ratio during 15 days.

Results: The degree and rate of increase in TG excretion rate was highly dependent on the UGT2B17 genotype with a 20-fold higher average maximum increase in the ins/ins group compared to the del/del group. Forty percent of the del/del subjects never reached the T/E ratio of 4.0 on any of the 15 days after the dose. When differentiated cut-off 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.

Conclusion: 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 combatting androgen doping in sports, but also for detecting and preventing androgen abuse in the society.
Key words: UGT2B17 deletion polymorphism • T/E ratio • testosterone doping • testosterone enanthate • glucuronidation • urinary excretion




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