ANASTROZOLE ADMINISTRATION IN ELDERLY HYPOGONADAL MEN

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 虚弱是一种在老年人中常见的情况，其特征是力量减少，耐力下降，容易受到创伤。荷尔蒙环境的变化可能是导致虚弱和其他与年龄相关的生理衰退的重要因素。在男性中，性腺类固醇分泌的下降可能是特别重要的。老年男性的雄激素替代疗法改善了身体虚弱的客观指标(例如身体成分、力量、骨密度)，并可能改善生活质量、性功能和认知能力。然而，雄激素替代方法并不是最优的，无法将雄激素的直接影响与雌激素代谢物的影响分开。芳香酶抑制剂的应用使性腺功能减退的老年男性血液中的睾酮水平恢复正常，同时适度降低雌激素水平。因此，与传统的雄激素替代方法相比，这种增加雄激素产生的新方法可能具有独特的生理特性。定义这些属性将使我们能够澄清雄激素和雌激素在男性衰老生理中的相对作用。此外，芳香酶抑制可能被证明是恢复雄激素水平和预防老年性腺功能低下男性虚弱的更有效和更安全的方法。这项建议的目的是通过一项为期一年的随机、双盲、安慰剂对照试验，评估芳香酶抑制作用改善性腺功能低下的老年男性人群的客观指标的能力。

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. Frailty is a condition, common in the elderly, characterized by reduced strength, decreased endurance, and vulnerability to trauma. Changes in the hormonal milieu may be an important contributor to the development of frailty as well as to other aspects of age-related physiologic decline. In men, the decline in gonadal steroid secretion may be of particular importance. Androgen replacement therapy in older men improves objective measures of frailty (e.g. body composition, strength, bone mineral density) and may improve quality of life, sexual function, and cognition as well. Androgen replacement methods are not optimal, however, and fail to separate the direct effects of androgens from the effects of estrogenic metabolites. Aromatase inhibitor administration normalizes circulating testosterone levels in hypogonadal older men while reducing estrogen levels modestly. This novel method of increasing androgen production may thus have unique physiologic properties compared to those of traditional androgen replacement. Defining these properties will allow us to clarify the relative roles of androgens and estrogens in aging male physiology. Furthermore, aromatase inhibition may prove to be a more efficacious and safer means of restoring androgen levels and preventing frailty in elderly hypogonadal men. The goal of this proposal is to assess the ability of aromatase inhibition to improve objective measures of frailty in an older hypogonadal male population via a 1-year randomized, double blind, placebo-controlled trial.