Aromatase inhibition in elderly hypogonadal men

描述（由申请人提供）：虚弱是一种常见于老年人的状况，其特征是力量下降，耐力下降，易受创伤。荷尔蒙环境的变化可能是导致身体虚弱的一个重要因素，也可能是与年龄相关的生理衰退的其他方面的一个重要因素。在男性中，性腺类固醇分泌的减少可能是特别重要的。老年男性的雄激素替代疗法可以改善虚弱的客观指标（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。芳香酶抑制剂的施用使性腺功能低下的老年男性循环睾酮水平正常化，同时适度降低雌激素水平。与传统的雄激素替代相比，这种增加雄激素产生的新方法可能具有独特的生理特性。定义这些特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性腺功能低下的老年男性虚弱的更有效和更安全的方法。本研究的目的是通过一项为期2年的随机、双盲、安慰剂对照试验，评估芳香化酶抑制对老年性腺功能低下男性人群虚弱客观指标的改善能力。此外，我们将探讨芳香酶抑制对生活质量、认知功能、心血管危险因素和前列腺相关健康的影响。通过这些评估，我们将更好地定义雌激素和雄激素在衰老生理中的相对作用，并探索老年男性性腺类固醇作用的机制。

DESCRIPTION (provided by applicant): 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 2-year randomized, double blind, placebo-controlled trial. Additionally, we will explore the effects of aromatase inhibition on quality of life, cognitive function, cardiovascular risk factors, and prostate-related health. With these assessments, we will better define the relative roles of estrogens and androgens in the physiology of aging and explore the mechanisms underlying gonadal steroid action in older men.