Is DHEA Replacement Therapy Beneficial?

DHEA 替代疗法有益吗？

• 批准号: 6778242
• 负责人: JOHN O. HOLLOSZY
• 金额: $ 54.55万
• 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 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6778242
• 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）：我们关于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力，我们已开始评估其他维持健康和预防虚弱的方法。其中，最有效的似乎是 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作用，可以 (a) 延缓虚弱和残疾的发展，(b) 预防 2 型糖尿病和冠状动脉疾病的发展，(c) 提高生活质量，以及 d) 获得有关 DHEA 作用机制的信息。 DHEA 和硫酸 DHEA (DHEAS) 血浆浓度在 20 岁左右达到峰值，并在 25 岁后迅速显着下降。 DHEA 是一种 PPAR-α 激活剂。 PPAR-α 在调节脂质代谢和控制炎症方面发挥着重要作用。 DHEA 似乎还对肌肉和骨骼具有合成代谢作用。这里提出的研究是一项 DHEA 替代的随机、双盲、安慰剂对照试验。它旨在确定 65-75 岁女性和男性补充 12 个月的 DHEA 对 (a) 躯干和内脏脂肪、(b) 胰岛素抵抗和血清甘油三酯、(C) 肌肉质量和力量、(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) 幸福感的影响。本研究的具体目的是测试以下假设：12 个月的 DHEA 替代品将 (a) 通过将代谢转变为脂肪氧化并增加能量浪费，导致躯干和内脏脂肪显着减少； (b) 降低胰岛素抵抗并降低血清甘油三酯； (c) 通过减少分解代谢刺激和增加合成代谢刺激来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) 减少慢性炎症并减少外周血单核细胞产生促炎细胞因子； (f) 改善动脉内皮依赖性血管舒张； (g) 提高总体幸福感。这项研究的重点是 DHEA 替代的生物效应机制。