The Dehydroepiandrosterone And WellNess (DAWN) study: research design and methods.
The Dehydroepiandrosterone And WellNess (DAWN) study: research design and methods.
复制标题
脱氢表雄酮与健康 (DAWN) 研究：研究设计和方法。
DOI：
10.1016/j.cct.2006.04.009
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发表时间：
2007
影响因子：
2.2
通讯作者：
Barrett-Connor,Elizabeth
中科院分区：
文献类型：
--
作者：
vonMuhlen,Denise;Laughlin,GailA;Kritz-Silverstein,Donna;Barrett-Connor,Elizabeth
脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）是肾上腺的主要分泌产物，其水平随着年龄的增长而急剧下降，同时伴随着与衰老相关的退行性变化和慢性疾病的发生。人类和动物研究的流行病学证据表明，DHEA（S）可能具有心脏保护、抗肥胖、抗糖尿病和免疫增强特性。这些观察结果导致了这样的建议，即DHEA恢复到年轻成人水平可能对年龄相关疾病产生有益影响。由于样本量小、持续时间短、仅限于一种性别、未能根据基线内源性激素水平和年龄进行调整或缺乏安慰剂比较组，大多数DHEA替代治疗的临床试验都受到限制。我们设计了一项双盲、安慰剂对照的随机试验，以确定110名男性和115名女性（年龄在55至85岁之间）每天口服50 mg DHEA替代一年的可接受性、益处和不良反应，这些患者健康且目前未使用激素治疗。研究了广泛的生物学结局，包括骨矿物质密度和代谢、身体成分和肌肉力量、免疫功能和心血管危险因素。在基线和3次随访门诊访视时测量类固醇激素水平、骨标志物、细胞因子和IGF-I、IGF结合蛋白系统。评估了情绪和幸福感、认知功能和性行为的变化。获得关于潜在混杂协变量的信息，如吸烟、饮酒、运动、饮食和膳食补充剂，并监测DHEA给药的潜在不良反应。本研究能够检查DHEA管理对老年男性和女性健康的益处，以及性别，年龄和基线内源性DHEA水平对每个结果变量的影响。还可以评估DHEA作用的潜在机制，包括DHEA生物转化为活性类固醇和类固醇代谢物、IGF-I生物利用度的增强和IL-6产生的抑制。
Levels of dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEAS), the major secretory products of the adrenal gland, decline dramatically with age, concurrent with the onset of degenerative changes and chronic diseases associated with aging. Epidemiological evidences in humans and animal studies suggest that DHEA(S) may have cardioprotective, antiobesity, antidiabetic, and immuno-enhancing properties. These observations led to the proposal that restoration of DHEA to young adult levels may have beneficial effects on age-related conditions. Most clinical trials of DHEA replacement have been limited due to small samples and short duration, restriction to one sex, failure to adjust for baseline endogenous hormone level and age, or lack of placebo comparison groups. We designed a double blind, placebo-controlled randomized trial to determine the acceptability, benefits, and adverse effects of 50 mg daily oral DHEA replacement for one year in 110 men and 115 women, aged 55 to 85, who were healthy and not currently using hormone therapy. A wide range of biological outcomes were studied including bone mineral density and metabolism, body composition and muscle strength, immune function, and cardiovascular risk factors. Steroid hormone levels, bone markers, cytokines, and the IGF-I, IGF binding protein system were measured at baseline and at 3 follow-up clinic visits. Changes in mood and well-being, cognitive function, and sexuality were assessed. Information on potentially confounding covariates such as smoking, alcohol consumption, exercise, diet and dietary supplements were obtained, and potential adverse effects of DHEA administration were monitored. This study enables an examination of the benefits of DHEA administration on the health of older men and women, and the influence of gender, age, and baseline endogenous DHEA level on each outcome variable. Potential mechanisms of DHEA action, including the biotransformation of DHEA to active steroids and steroid metabolites, enhancement of IGF-I bioavailability, and inhibition of IL-6 production can also be evaluated.