Context: Previous in vitro studies have demonstrated that the UDP glucuronosyltransferase (UGT) 2B15 and UGT2B17 glucuronidate androgens and their metabolites.

Objective: To determine in vivo if the UGT2B15 D⁸⁵Y and the UGT2B17 deletion polymorphisms predict androgen glucuronidation and body composition.

Participants: Two population-based cohorts including young adult (n=1068, age=18.9 years) and elderly (n=1001, age=75.3 years) men.

Main Outcome Measures: Serum and urine levels of testosterone (T) and dihydrotestosterone (DHT) measured by GC-MS and serum levels of the major glucuronidated androgen metabolites androstane-3,17-diol(androstanediol)-3glucuronide, androstanediol-17glucuronide and androsterone-glucuronide measured by LC-MS/MS. Body composition measured by DXA.

Results: Both the UGT2B15 D⁸⁵Y and the UGT2B17 deletion polymorphisms were associated with serum levels of androstanediol-17glucuronide (p<0.001) but not with levels of androstanediol-3glucuronide or androsterone-glucuronide in both cohorts. Glucuronidation of T and DHT was associated with the UGT2B17 deletion but not with the UGT2B15 D⁸⁵Y polymorphism, suggested by strong associations between the deletion polymorphism and urine levels of these two hormones. Both polymorphisms were associated with several different measures of fat mass (p<0.01). The UGT2B17 deletion polymorphism was associated with insulin sensitivity (p<0.05) as indicated by the HOMA index.

Conclusions: The UGT2B15 D⁸⁵Y and the UGT2B17 deletion polymorphisms are both predictors of the glucuronidation pattern of androgens/androgen metabolites. Our findings indicate that UGT2B17 is involved in 17 glucuronidation of mainly T but also of DHT and androstanediol and that UGT2B15 is involved in the 17 glucuronidation of androstanediol. Furthermore, these two polymorphisms are predictors of fat mass in men.