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首页> 美国卫生研究院文献>Frontiers in Endocrinology >UGT2B17 Genotype and the Pharmacokinetic Serum Profile of Testosterone during Substitution Therapy with Testosterone Undecanoate. A Retrospective Experience from 207 Men with Hypogonadism
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UGT2B17 Genotype and the Pharmacokinetic Serum Profile of Testosterone during Substitution Therapy with Testosterone Undecanoate. A Retrospective Experience from 207 Men with Hypogonadism

机译：十一烷酸睾丸酮替代治疗期间睾丸激素的UGT2B17基因型和药代动力学血清分布。 207例性腺功能减退男性的回顾性经验

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>Background: Testosterone (T) is mainly excreted in the urine as testosterone glucuronide (TG). This glucuronidation is partly dependent on the UGT2B17 genotype, and TG excretion is therefore lower in men having the UGT2B17 deletion. However, the possible influence of UGT2B17 genotype on serum T during androgen therapy is unknown. We retrospectively investigated the possible association between the UGT2B17 gene polymorphism and serum T levels in hypogonadal men during Testosterone undecanoate (TU) substitution therapy.>Subjects and Methods: Two hundred and seven patients treated with TU (Nebido®) were genotyped by quantitative polymerase chain reaction for the UGT2B17 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.>Results: The UGT2B17 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 UGT2B17 genotype.>Conclusion: 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 UGT2B17 genotype, which however suggest that the UGT2B17 genotype exert modest influence on the pharmacokinetic profile of T after TU treatment.
机译：>背景：睾丸激素（T）主要以尿素葡萄糖醛酸（TG）的形式排泄在尿液中。该葡萄糖醛酸化部分地取决于UGT2B17的基因型，因此在具有UGT2B17缺失的男性中TG排泄较低。然而，在雄激素治疗期间UGT2B17基因型对血清T的可能影响尚不清楚。我们回顾性研究了十一酸睾丸酮（TU）替代治疗期间性腺功能减退男性的UGT2B17基因多态性与血清T水平之间的可能关联。>受试者与方法： 207例接受TU治疗的患者（Nebido >®）通过UGT2B17缺失多态性定量聚合酶链反应进行基因分型。在第0、6和18周时，每次注射均给予1000μmgTU。在第一次和第二次注射后第2和6周，第三次注射之前以及治疗2–3年后采集血样。我们分析了T，黄体生成素（LH），性激素结合球蛋白，雌二醇，前列腺特异性抗原，血细胞比容，血红蛋白和总胆固醇的水平。>结果： UGT2B17基因型频率为： ins / ins：42％，ins / del：44％和del / del：14％。在TU治疗的最初18周内，观察到个体内和个体间血清T水平存在较大差异。不论基因型如何，注射后2周，T水平的峰值都在6.7至69.5 6nmol / l之间。在第三次注射之前，三种基因型之间的T水平没有差异，但是del / del组的LH水平明显较低。在2-3年后的随访中，注射间隔或每日T剂量与UGT2B17基因型无关。>结论：总之，我们发现血清T的个体内和个体间差异很大性腺功能减退男性的标准TU治疗方案中。根据UGT2B17基因型，仅观察到血清T和LH的细微差异，但这表明UGT2B17基因型在TU治疗后对T的药代动力学特性产生适度的影响。

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