ANASTROZOLE ADMINISTRATION IN ELDERLY HYPOGONADAL MEN

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 虚弱是一种在老年人中常见的状况，其特征在于力量降低、耐力下降和易受创伤。激素环境的变化可能是虚弱发展以及与年龄相关的生理衰退的其他方面的重要因素。在男性中，性腺类固醇分泌的下降可能特别重要。 雄激素替代治疗可改善老年男性的虚弱程度（如身体成分、力量、骨密度），并可改善生活质量、性功能和认知能力。 然而，雄激素替代方法不是最佳的，并且不能将雄激素的直接作用与雌激素代谢物的作用分开。 芳香化酶抑制剂管理正常化循环睾酮水平在性腺功能减退的老年男性，同时适度降低雌激素水平。因此，这种增加雄激素产生的新方法与传统的雄激素替代相比可能具有独特的生理特性。定义这些特性将使我们能够澄清雄激素和雌激素在衰老男性生理学中的相对作用。 此外，芳香化酶抑制剂可能被证明是一种更有效和更安全的手段，恢复雄激素水平和预防老年性腺功能减退男性的虚弱。本提案的目的是通过一项为期1年的随机、双盲、安慰剂对照试验，评估芳香化酶抑制剂改善老年性腺功能减退男性人群虚弱的客观指标的能力。

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.