ORAL ANDROGENS IN MAN-3: PK OF ORAL TESTOSTERONE BY ALPHA5-DUTASTERIDE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。我们的工作已经证明口服睾酮(T)治疗可以导致血清T水平，这将允许使用口服T治疗T缺乏。此外，我们的研究表明，5a还原酶抑制剂度他雄胺与口服T联合使用可增加血清T水平，同时降低血清DHT水平，这可能提高雄激素治疗的长期安全性。口服睾酮的一个障碍是睾酮必须以油的形式给药。目前这项建议的目的是：1)确定两种口服睾酮(T)的新配方中的一种是否能同时通过杜他雄胺降低5a，从而提高血清睾酮水平，从而允许使用口服睾酮治疗睾酮缺乏症。在这项研究中，我们将给16名正常男性口服睾酮，这些男性自身的睾酮分泌因服用促性腺激素释放激素激动剂鲁普酮而暂时停止。在给药两周后，受试者将接受两种不同制剂或口服t的一系列剂量，他们也将服用杜他雄胺。我们希望确定口服T和度他雄胺的联合施用是否可以产生一种可用的T治疗形式，允许T治疗的好处而没有双氢睾酮的缺点。该试验的主要生物学终点是血清T的升高，同时监测肝功能或一般健康的任何不良变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our work has demonstrated that oral testosterone (T) therapy can result in serum T levels that would allow for the use of oral T in the treatment of T deficiency. Moreover, our work has demonstrated that the co-administration of the 5a reductase inhibitor dutasteride with oral T increases serum T levels while decreasing serum DHT levels-an effect that may improve the long-term safety profile of androgen therapy. One impediment to oral testosterone is the requirement that the testosterone be administered in oil. The objective of this current proposal is to: 1) ascertain if one of two newer formulations of oral testosterone (T) with concomitant 5a reduction by dutasteride can result in serum T levels that may allow for the use of oral T in the treatment of men with T deficiency. In this study, we will be administering oral T to 16 normal men whose own production of T has been temporarily shut down by the administration of the gonadotropin-releasing hormone agonist Lupron. Two weeks after Lupron administration, subjects will receive a series of doses of two different formulations or oral T. They will also be taking dutasteride. We wish to determine if the co-administration of oral T and dutasteride can result in a usable form of T therapy that allows for the benefits of T without the drawbacks of DHT. The primary biological end points in this trial will be elevations in serum T while monitoring for any adverse changes in liver function or general health.