DHEA REPLACEMENT IN HEALTHY OLDER MEN AND WOMEN

健康老年男性和女性的 DHEA 替代

• 批准号: 6649677
• 负责人: DENISE Goldani VON MUHLEN
• 金额: $ 42.44万
• 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/6649677
• 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：(改编自调查者摘要) 主要分泌物脱氢表雄酮(DHEA)和脱氢表雄酮-硫酸酯(DHEAS) 肾上腺的产物，随着年龄的增长急剧减少，同时 与衰老相关的退行性改变和慢性病的发病。 人类的流行病学证据和大量动物研究表明 脱氢表雄酮(S)具有心脏保护、抗肥胖、抗糖尿病、增强免疫、 和防癌特性。这些观察结果导致了这项提议 将老年人的脱氢表雄酮水平恢复到年轻人的水平可能 提供保护，避免与年龄相关的健康缺陷。到目前为止，临床试验 由于样本量小，缺乏 有足够的权力，只限一个性别，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，服药时间短。这双眼双眼， 安慰剂对照随机试验将确定可接受性，益处， 每日口服50毫克脱氢表雄酮替代品一年的不良反应 男性和100名女性，年龄在55岁到85岁之间，身体健康，目前不是 使用任何激素疗法。数据将在筛查访问中收集， 基线访问，以及一年中的三次后续访问。一个 广泛的或生物学的结果将被研究，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， 和心血管危险因素。将调查脱氢表雄酮的核心影响 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 关于每个健康结果的小组将进行调整，以防止潜在的混淆 协变量，如吸烟、饮酒、锻炼、饮食 补充剂及其对性别、年龄和基线内源性脱氢表雄酮水平的影响 将对每个结果变量进行检查。脱氢表雄酮的潜在作用机制 将进行研究，包括将DHEA生物转化为活性类固醇和 类固醇代谢物，提高IGF-1的生物利用度，并抑制 IL-6的产生。此外，脱氢表雄酮的潜在不良反应 将受到系统的监控。