Is DHEA Replacement Therapy Beneficial?

DHEA 替代疗法有益吗？

• 批准号: 7116819
• 负责人: JOHN O. HOLLOSZY
• 金额: $ 53.21万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-15 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7116819
• 关键词: bioenergetics; blood chemistry; cardiovascular disorder risk; chemoprevention; clinical research; clinical trials; dehydroepiandrosterone; disease /disorder prevention /control; electrocardiography; enzyme linked immunosorbent assay; hormone therapy; human old age (65+); human subject; human therapy evaluation; inflammation; lipid metabolism; longitudinal human study; magnetic resonance imaging; mass spectrometry; muscle strength; noninsulin dependent diabetes mellitus; patient oriented research; quality of life; triglycerides; urinalysis; vasodilation

DESCRIPTION (provided by applicant): The major emphasis of our research on the prevention of physical frailty and loss of independence has been on the adaptations to exercise. However, because most Americans are not motivated to exercise, we have started to evaluate other approaches to maintenance of health and prevention of frailty. Of these, the most powerful appears to be DHEA replacement therapy. In this context, the overall goals of this study are to determine whether long term dehydroepiandrosterone (DHEA) replacement therapy has beneficial effects that could (a) delay the development of frailty and disability, (b) protect against development of type 2 diabetes and coronary artery disease, (c) improve quality of life, and d) obtain information on the mechanisms of DHEA action. DHEA and DHEA sulfate (DHEAS) plasma concentrations peak at about 20 yr of age and decline rapidly and markedly after age 25 yr. DHEA is a PPAR-alpha activator. PPAR-alpha plays major roles in regulating lipid metabolism and controlling inflammation. DHEA also appears to have anabolic effects on muscle and bone. The study proposed here is a randomized, double blind, placebo-controlled trial of DHEA replacement. It is designed to determine the effects of 12 mo of DHEA replacement in 65-75 yr old women and men on (a) truncal and visceral fat, (b) insulin resistance and serum triglycerides, (C) muscle mass and strength, (d) bone mineral density, (e) chronic inflammation, (f) arterial-endothelium-dependent vasodilation, and (g) sense of well being. The specific aims of this study are to test the hypotheses that 12 mo of DHEA replacement will (a) Result in significant decreases in truncal and visceral fat by shifting metabolism to fat oxidation and increasing energy wastage; (b) Decrease insulin resistance and decrease serum triglycerides; (c) Increase muscle mass and strength, by decreasing catabolic stimuli and increasing anabolic stimuli; (d) Increase bone mineral density by increasing anabolic stimuli and decreasing catabolic stimuli; (e) Reduce chronic inflammation and decrease pro-inflammatory cytokine production by peripheral blood mononuclear cells; (f) Improve arterial endothelium dependent vasodilation; and (g) Improve general sense of well being. A major emphasis of this research is on the mechanisms responsible for the biological effects of DHEA replacement.

描述（由申请人提供）：我们对预防身体虚弱和丧失独立性的研究的主要重点是对运动的适应。然而，由于大多数美国人没有锻炼的动机，我们已经开始评估其他方法来维持健康和预防虚弱。其中，最强大的似乎是DHEA替代疗法。在这种情况下，本研究的总体目标是确定长期脱氢表雄酮（DHEA）替代疗法是否具有有益效果，可以（a）延迟虚弱和残疾的发展，（B）防止2型糖尿病和冠状动脉疾病的发展，（c）改善生活质量，和d）获得有关DHEA作用机制的信息。DHEA和DHEA硫酸盐（DHEAS）血浆浓度在20岁左右达到峰值，25岁后迅速显著下降。DHEA是一种PPAR-alpha激活剂。PPAR-alpha在调节脂质代谢和控制炎症中起主要作用。脱氢表雄酮似乎也有肌肉和骨骼合成代谢的影响。本研究是一项随机、双盲、安慰剂对照的DHEA替代试验。其目的是确定在65-75岁的女性和男性中12个月的DHEA替代对（a）躯干和内脏脂肪，（B）胰岛素抵抗和血清甘油三酯，（C）肌肉质量和强度，（d）骨矿物质密度，（e）慢性炎症，（f）动脉内皮依赖性血管舒张，和（g）健康感的影响。本研究的具体目的是检验以下假设：12个月的DHEA替代将（a）通过将代谢转移到脂肪氧化和增加能量消耗而导致躯干和内脏脂肪的显著减少;（B）降低胰岛素抵抗和降低血清甘油三酯;（c）通过减少分解代谢刺激和增加合成代谢刺激而增加肌肉质量和力量;（d）通过增加合成代谢刺激和减少分解代谢刺激来增加骨矿物质密度;（e）减少慢性炎症和减少外周血单核细胞产生的促炎细胞因子;（f）改善动脉内皮依赖性血管舒张;和（g）改善总体健康感。这项研究的一个主要重点是负责DHEA替代的生物学效应的机制。