Aromatase inhibition in elderly hypogonadal men

老年性腺功能减退男性的芳香酶抑制

• 批准号: 7265218
• 负责人: BENJAMIN Z LEDER
• 金额: $ 35.26万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7265218
• 关键词: Age; Aging; Androgens; Aromatase Inhibition; Aromatase Inhibitors; Behavior; Behavioral; Biochemical Markers; Biological; Body Composition; Bone Density; Cardiovascular system; Cessation of life; Clinical; Cognition; Condition; Decreased Libido; Development; Disease Marker; Elderly; Elderly man; Estradiol; Estrogens; Fatty acid glycerol esters; Feedback; Femur; Goals; Gonadal Steroid Hormones; Health; Heart Diseases; Hip region structure; Hormonal; Hyperplasia; Hypogonadism; Hypothalamic structure; Impaired cognition; Inflammatory; Injury; Lead; Lipids; Malignant neoplasm of prostate; Measures; Mediating; Mediator of activation protein; Memory; Methods; Muscle; Osteogenesis; Physiological; Physiology; Pilot Projects; Pituitary Gland; Placebos; Population; Preparation; Principal Investigator; Production; Property; Prostate; Quality of life; Questionnaires; Randomized; Relative (related person); Replacement Therapy; Research Personnel; Risk; Role; Safety; Serum; Sex Functioning; Sexuality; Standards of Weights and Measures; Symptoms; Testosterone; Thick; Trauma; Ultrasonography; Vertebral column; Woman; X-Ray Computed Tomography; age related; anastrozole; bone loss; bone metabolism; cardiovascular risk factor; cognitive function; cytokine; double-blind placebo controlled trial; frailty; improved; male; men; neurocognitive test; novel; older men; osteoporosis with pathological fracture; prevent; programs; psychologic; radius bone structure; sarcopenia; serum PSA; size; substantia spongiosa

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.

描述（由申请人提供）：虚弱是一种常见于老年人的病症，其特征是力量下降、耐力下降和容易受到创伤。荷尔蒙环境的变化可能是导致虚弱以及与年龄相关的生理衰退的其他方面的重要因素。对于男性来说，性腺类固醇分泌的下降可能特别重要。老年男性的雄激素替代疗法可以改善虚弱的客观指标（例如身体成分、力量、骨矿物质密度），并可能改善生活质量、性功能和认知。然而，雄激素替代方法并不是最佳的，并且无法将雄激素的直接影响与雌激素代谢物的影响分开。芳香酶抑制剂的给药可以使性腺功能减退的老年男性的循环睾酮水平正常化，同时适度降低雌激素水平。因此，与传统雄激素替代疗法相比，这种增加雄激素产生的新方法可能具有独特的生理特性。定义这些特性将使我们能够阐明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减退男性虚弱的更有效和更安全的方法。该提案的目标是通过一项为期 2 年的随机、双盲、安慰剂对照试验，评估芳香酶抑制改善老年性腺功能减退男性人群虚弱客观指标的能力。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学中的相对作用，并探索老年男性性腺类固醇作用的机制。