Aromatase inhibition in elderly hypogonadal men

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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.