AUTHOR=Bang Anne Kirstine , Jørgensen Niels , Rajpert-De Meyts Ewa , Juul Anders 

TITLE=UGT2B17 Genotype and the Pharmacokinetic Serum Profile of Testosterone during Substitution Therapy with Testosterone Undecanoate. A Retrospective Experience from 207 Men with Hypogonadism

JOURNAL=Frontiers in Endocrinology

VOLUME=4

YEAR=2013

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2013.00094

DOI=10.3389/fendo.2013.00094

ISSN=1664-2392

ABSTRACT=<p><bold>Background:</bold> Testosterone (T) is mainly excreted in the urine as testosterone glucuronide (TG). This glucuronidation is partly dependent on the <italic>UGT2B17</italic> genotype, and TG excretion is therefore lower in men having the <italic>UGT2B17</italic> deletion. However, the possible influence of <italic>UGT2B17</italic> genotype on serum T during androgen therapy is unknown. We retrospectively investigated the possible association between the <italic>UGT2B17</italic> gene polymorphism and serum T levels in hypogonadal men during Testosterone undecanoate (TU) substitution therapy.</p><p><bold>Subjects and Methods:</bold> Two hundred and seven patients treated with TU (Nebido<sup>®</sup>) were genotyped by quantitative polymerase chain reaction for the <italic>UGT2B17</italic> deletion polymorphism. All were given 1000 mg TU per injection at 0, 6, and 18 weeks. Blood samples were taken 2 and 6 weeks after the first and second injection, prior to the third injection, and after 2–3 years of treatment. We analyzed for the levels of T, luteinizing hormone (LH), sex-hormone-binding globulin, estradiol, prostate specific antigen, hematocrit, hemoglobin, and total cholesterol.</p><p><bold>Results:</bold> The <italic>UGT2B17</italic> genotype frequency was: ins/ins: 42%, ins/del: 44%, and del/del: 14%. During the initial 18 weeks of TU treatment, large intra- and inter-individual variations in serum T levels were observed. Large peaks in T levels, ranging from 6.7 to 69.5 nmol/l, were noted 2 weeks after injections, regardless of the genotype. T levels did not differ between the three genotypes prior to the third injection, but the del/del group had significantly lower levels of LH. At follow-up after 2–3 years, the injection interval or daily T dosage was not dependent on the <italic>UGT2B17</italic> genotype.</p><p><bold>Conclusion:</bold> In conclusion, we found large intra- and inter-individual variations in serum T during standard TU treatment regimen in hypogonadal men. Only subtle differences in serum T and LH were noted according to <italic>UGT2B17</italic> genotype, which however suggest that the <italic>UGT2B17</italic> genotype exert modest influence on the pharmacokinetic profile of T after TU treatment.</p>