DHEA REPLACEMENT IN HEALTHY OLDER MEN AND WOMEN

健康老年男性和女性的 DHEA 替代

• 批准号: 6533877
• 负责人: DEBORAH L GOODMAN-GRUEN
• 金额: $ 74.8万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6533877
• 关键词: aging; body composition; bone density; bone metabolism; cardiovascular function; clinical research; clinical trials; cognition; dehydroepiandrosterone; emotions; hormone regulation /control mechanism; hormone therapy; human middle age (35-64); human old age (65+); human subject; human therapy evaluation; immunity; insulinlike growth factor; interleukin 6; longitudinal human study; muscle strength; quality of life; sex behavior

DESCRIPTION: (adapted from Investigator's abstract) Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory product of the adrenal gland, decrease dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidence in humans and numerous animal studies have suggested that DHEA(S) has cardioprotective, antiobesity, antidiabetic, immuno-enhancing, and cancer-preventing properties. These observations have led to the proposal that restoration of DHEA levels in older adults to those of young adults may offer protection from age-associated health deficits. To date, clinical trials of DHEA replacement have been limited due to small sample size, lack of adequate power, restriction to one gender, failure to adjust for potential confounders (baseline endogenous hormone levels and age), lack of placebo comparison groups, and short duration of administration. This double blind, placebo-controlled randomized trial will determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacements for one year in 100 men and 100 women, 55 to 85 years of age, who are healthy and not currently using any hormone therapy. Data will be collected at a screening visit, baseline visit, and at three follow-up visits over the course of one year. A wide range or biological outcomes will be studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Central effects of DHEA will be investigated by assessing changes in mood and well-being, cognitive function, and sexuality. Cross-sectional and longitudinal analyses comparing the treatment and placebo groups on each health outcome will be adjusted for potentially confounding covariates such as smoking, alcohol consumption, exercise, diet, and supplements and the influence of gender, age and baseline endogenous DHEA level on each outcome variable will be examined. Potential mechanisms of DHEA action will be studied including biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-1 bioavailability, and inhibition of IL-6 production. In addition, potential adverse effects of DHEA administration will be systematically monitored.

描述：（改编自研究者摘要） 脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS），主要分泌 肾上腺的产物，随着年龄的增长而急剧减少，同时 与衰老有关的退行性变化和慢性疾病的发生。 人类流行病学证据和大量动物研究表明， DHEA（S）具有心脏保护、抗肥胖、抗糖尿病、免疫增强 和抗癌特性。这些意见导致了一项建议， 老年人的DHEA水平恢复到年轻人的水平， 提供与年龄相关的健康缺陷的保护。迄今为止，临床试验 由于样本量小，缺乏 足够的权力，仅限于一种性别，未能适应潜力 混杂因素（基线内源性激素水平和年龄），缺乏安慰剂 对照组和短的给药时间。这双盲， 安慰剂对照随机试验将确定可接受性，益处， 和不良反应的50毫克每日口服DHEA替代一年的100 男性和100名女性，年龄在55至85岁之间，他们健康，目前没有 使用任何激素疗法。将在筛选访视时收集数据， 基线访视和一年内的三次随访访视。一 将研究广泛的生物学结局，包括骨矿物质 密度和新陈代谢，身体成分和肌肉力量，免疫功能， 和心血管风险因素。将研究DHEA的中枢作用 通过评估情绪和幸福感，认知功能和性行为的变化。 比较治疗和安慰剂的横断面和纵向分析 每个健康结局的组将针对潜在的混杂因素进行调整 协变量如吸烟、饮酒、运动、饮食和 补充剂和性别，年龄和基线内源性DHEA水平的影响 将对每个结果变量进行检查。DHEA作用的潜在机制 将进行研究，包括DHEA生物转化为活性类固醇， 类固醇代谢物，增强IGF-1生物利用度，以及抑制 IL-6产生。此外，DHEA给药的潜在副作用 将受到系统监控。