Endocrine Abstracts (2013) 32 P973 | DOI: 10.1530/endoabs.32.P973

UGT2B17 genotype and pharmacokinetic profile of testosterone during substitution therapy in men with hypogonadism

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

Department of Growth and Reproduction, Rigshospitalet, Copenhagen, 2100 Ø, Denmark.

Introduction: The UGT2B17 gene encodes a glucuronidase which is important for the urinary excretion of testosterone. Recent studies have shown that a common deletion polymorphism in UGT2B17 is strongly associated with significant lower levels of excreted urinary testosterone in men. The objective of this study was to investigate the association of the UGT2B17 gene polymorphism and the dosages of testosterone substitution in male patients with frank hypogonadism.

Material and methods: Two hundred and twenty-eight men treated with Testosterone undecanoate (TU)(Nebido) were retrospectively included. All men were given 1000 mg TU per injection at 0, 6 and 18 weeks. Blood samples were drawn at 0, 2, 6, 12 and 18 weeks after baseline. Sexual hormones were analysed by standard assays, and UGT2B17 genotype was determined by quantitative PCR on isolated DNA from peripheral blood.

Results: Of 13.6% had a homozygote deletions (del/del), 45.0% were heterozygote (del/ins) and 41.2% were homozygotes for the wildtype (ins/ins). Before the 3rd injection (18 weeks), nadir serum testosterone levels did not differ between the three groups in total (P=0.065): median 13.2, 12.7 and 14.0 nmol/l in del/del, del/ins and ins/ins groups, respectively. Estradiol levels tended to be higher in the del/del group (66.5 pmol/l) than in the two other groups (ins/del: 54 pmol/l and ins/ins: 52 pmol/l), although differences did not reach statistical significance. LH, SHBG, the free androgen index (FAI), total cholesterol or haemoglobin did not differ between groups.

At follow-up 2–3 years after initiation of treatment all patients had individual treatment regimes, but no association to genotype was detected.

Conclusion: Nadir serum testosterone levels were not significantly influenced by UGT2B17 genotype in hypogonadal men given standard treatment with TU. Thus, there is no need to consider this genotype as a marker of dosage or interval when initiating testosterone treatment.

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