Bioavailability of testosterone enanthate dependent on genetic variation in the phosphodiesterase 7B but not on the uridine 5′-diphospho-glucuronosyltransferase (UGT2B17) gene

Objective To study the disposition of serum testosterone and seven of its metabolites before and after 2 days of an intramuscular dose (500 mg) of testosterone enanthate in relation to the phosphodiesterase (PDE7B) and the uridine 5'-diphospho-glucuronosyltransferase (UGT2B17) genotypes. Methods Patients were genotyped for UGT2B17 deletion polymorphism and single nucleotide polymorphisms in the PDE7B gene. The involvement of PDE7B in hydrolysis of enanthate was assessed in human liver homogenates. Results Genetic variation in the PDE7B gene was found to be associated with the serum level of testosterone. Individuals homozygous for PDE7B rs7774640 G allele had a smaller increase (2.5-fold) in the serum testosterone levels compared with carriers of the A allele (3.9-fold, P = 0.0006). In addition, genetic variation in the PDE7B gene significantly influences the testosterone/epitestosterone ratio, a biomarker of testosterone doping. Our in-vitro incubation studies confirmed that PDE7B serves as a catalyst of the hydrolysis of testosterone enanthate. The UGT2B17 deletion polymorphism did not show any significant association with serum testosterone levels or the other androgen metabolites investigated. Conclusion We have shown that PDE7B is involved in the hydrolysis of testosterone enanthate and that genetic variation in the PDE7B gene is a determinant of the systemic levels of testosterone after administration of testosterone enanthate. It is reasonable to believe that the genetic variation in testosterone bioavailability may be correlated to varying effects of this androgen, whether it is used for replacement therapy or abused in doping. Thus our results may be important to consider in doping test programmes and in therapeutics with androgens and other esterified drugs. Pharmacogenetics and Genomics 21: 325-332 (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Pharmacogenetics and Genomics 2011, 21: 325-332