Is DHEA Replacement Therapy Beneficial?

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一直是运动的适应性。然而，由于大多数美国人没有锻炼的动力，我们已经开始评估其他保持健康和预防虚弱的方法。在这些疗法中，最有效的似乎是脱氢表雄酮替代疗法。在这种背景下，这项研究的总体目标是确定长期脱氢表雄酮(DHEA)替代疗法是否具有以下有益效果：(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生；(C)提高生活质量；以及(D)获得有关DHEA作用机制的信息。脱氢表雄酮和脱氢表雄酮硫酸盐(DHEAS)的血浆浓度在20岁左右达到峰值，并在25岁后迅速显著下降。DHEA是一种PPAR-α激活剂。PPAR-α在调节脂代谢、控制炎症等方面发挥着重要作用。脱氢表雄酮似乎也对肌肉和骨骼有合成代谢作用。这项研究是一项随机、双盲、安慰剂对照的脱氢表雄酮替代试验。它旨在确定65-75岁的女性和男性服用12mo脱氢表雄酮对(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)骨密度、(E)慢性炎症、(F)动脉-内皮依赖性血管扩张和(G)幸福感的影响。本研究的具体目的是检验以下假设：(A)通过将代谢转变为脂肪氧化和增加能量消耗，12个月的DHEA将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，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，增加骨密度；(E)减少慢性炎症，减少外周血单核细胞产生促炎细胞因子；(F)改善动脉内皮依赖的血管扩张；以及(G)改善总体幸福感。这项研究的一个主要重点是DHEA替代的生物学效应的机制。

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.