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

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。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缺乏症。 此外，我们的工作已经证明，共同管理的5a还原酶抑制剂度他雄胺与口服T增加血清T水平，同时降低血清DHT水平的影响，可能会改善长期的安全性雄激素治疗。口服睾酮的一个障碍是要求睾酮在油中施用。本提案的目的是：1）确定口服睾酮（T）的两种较新制剂之一，同时通过度他雄胺降低5 α，是否可以导致血清T水平，从而允许在治疗T缺乏男性中使用口服T。在这项研究中，我们将给16名正常男性口服T，他们自己的T生产已经被促性腺激素释放激素激动剂Lupron暂时关闭。Lupron给药后两周，受试者将接受两种不同制剂的一系列剂量或口服T。他们也将服用度他雄胺。我们希望确定口服T和度他雄胺的联合给药是否可以产生一种可用的T治疗形式，该形式允许T的益处而没有DHT的缺点。本试验的主要生物学终点将是血清T升高，同时监测肝功能或一般健康状况的任何不良变化。

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.