Is DHEA Replacement Therapy Beneficial?

描述（由申请人提供）：我们在预防身体虚弱和丧失独立性方面的研究主要侧重于对运动的适应。然而，由于大多数美国人没有运动的动力，我们已经开始评估其他保持健康和预防虚弱的方法。其中，最有效的似乎是脱氢表雄酮替代疗法。在这种背景下，本研究的总体目标是确定长期的脱氢表雄酮（DHEA）替代疗法是否具有有益的效果，可以(a)延缓虚弱和残疾的发展，（b)防止2型糖尿病和冠状动脉疾病的发展，(c)提高生活质量，以及d）获得脱氢表雄酮作用机制的信息。脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）血浆浓度在20岁左右达到峰值，25岁后迅速显著下降。脱氢表雄酮是ppar - α激活剂。ppar - α在调节脂质代谢和控制炎症中起重要作用。脱氢表雄酮似乎对肌肉和骨骼也有合成代谢作用。这里提出的研究是一项随机、双盲、安慰剂对照的DHEA替代试验。该研究旨在确定65-75岁男性和女性接受12个月脱氢表雄酮替代治疗对以下方面的影响：(a)身体和内脏脂肪，(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舒张，以及(g)幸福感。本研究的具体目的是验证以下假设：12个月的脱氢表雄酮替代将(a)通过将代谢转变为脂肪氧化和增加能量浪费，导致躯干和内脏脂肪显著减少；(b)降低胰岛素抵抗，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密度；(e)减少慢性炎症，减少外周血单核细胞促炎细胞因子的产生；(f)改善动脉内皮依赖性血管舒张；(g)提高普遍的幸福感。本研究的一个主要重点是对脱氢表雄酮替代的生物效应机制负责。

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.