IS DHEA REPLACMENT THERAPY BENEFICIAL?

DHEA 替代疗法有效吗？

• 批准号: 7377195
• 负责人: JOHN O. HOLLOSZY
• 金额: $ 32.57万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377195
• 关键词: DHEA; REPLACMENT; THERAPY; BENEFICIAL

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The maor emphasis of our researh on the prevention of physical frailty and loss of independence has been on the adaptatations 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 tis 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 concentration peak at ~20 yrs of age and decline rapidly ad markedly after age 25 yr DHEA is a PPARa activator. PPARa play major roles in regulatinglipid 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 adn men on (a) truncal and visceral (b) insulin resistance and serum triglycerides, (c) muscle mass and strength, (d) bone mineral density, (e) chronic inflammation, (f) arterial-endothelium-dependent vasodilation, adn (g) sense of well being. The specific aims of this study are to test the hypothesis 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 an increasing anaolic stimuli; (d) increase bone mineral density by increasing anabolic stimuli an 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 his research is on the mechanisms responsible for the biological effects of DHEA replacement.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。我们研究的重点是预防身体脆弱和失去独立性，这是在适应性上进行的。但是，由于大多数美国人没有动力运动，因此我们已经开始评估其他维持健康和预防脆弱的方法。其中，最强大的似乎是DHEA替代疗法。在情况下，这项研究的总体目标是确定长期脱氢雌激素（DHEA）替代疗法是否具有有益的效果，可以（a）延迟脆弱和残疾的发展，（b）防止2型糖尿病和冠状动脉疾病的发展，（c）改善生命的质量，以及（d）改善了该机构的dehea机构。 DHEA和DHEA硫酸盐（DHEAS）血浆浓度在约20岁时的年龄峰值峰值，并在25岁DHEA年龄较大后迅速下降AD是PPARA激活剂。 PPARA在调节脂质代谢和控制炎症中起着重要作用。 DHEA似乎对肌肉和骨骼也具有合成代谢作用。此处提出的研究是一项随机，双盲，安慰剂对照的DHEA替代试验。它旨在确定65-75岁的DHEA更换的影响（a）截短和内脏（b）胰岛素抵抗和血清甘油三酸酯，（c）肌肉质量和力量，（d）骨矿物质密度，（e）慢性炎症，（f）Arterip-Endertim-Enpertation vasodation vasodication vasodication（d）肌肉质量和力量。这项研究的具体目的是检验以下假设：12 mo的DHEA替代将（a）通过将代谢转移到脂肪氧化并增加能量浪费，从而导致截短和内脏脂肪的显着降低； （b）降低胰岛素抵抗并降低血清甘油三酸酯； （c）通过减少分解代谢刺激增加厌氧刺激来增加肌肉质量和力量； （d）通过增加代谢性刺激增加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的细胞因子； （f）改善动脉内皮依赖性血管舒张； （g）提高一般的福祉感。他的研究的主要重点是负责DHEA替代生物学作用的机制。