Testosterone Trial

描述(由申请人提供)：随着男性年龄的增长，他们会经历许多情况，如行动不便、与年龄相关的记忆障碍和活力低下，导致日常生活活动能力下降，跌倒倾向增加，独立性降低。他们还会经历贫血、骨质疏松症、代谢综合征和性功能减退。导致所有这些情况的一个原因是血清睾酮浓度较低。随着男性年龄的增长，他们的血清睾酮水平会下降，通常与患有脑下垂体和睾丸疾病的年轻男性的水平相当。当年轻男性由于垂体或睾丸疾病而出现睾丸素水平低下时，他们会经历类似的后果，包括肌肉质量和力量减少，性动力减弱，认知障碍，精力不足，以及贫血、骨质疏松症和代谢综合征。当这些男性接受睾丸激素治疗时，所有这些异常都会得到改善。我们提出的概念是，除了年龄之外，明确的低睾酮浓度会使男性容易患上这些老年性疾病，而睾酮治疗会改善这些疾病。 因此，我们建议进行一组密切协调的四项随机、安慰剂对照临床试验，以检验如下假设：对于血清睾酮浓度明显较低(250 ng/dL)、行动不便、与年龄相关的记忆障碍、活力低下或性功能减退的症状和客观证据的65岁男性，睾酮治疗一年将比安慰剂治疗显示出更有利的这些参数的变化。我们将在18个地点选择1200名男性，随机让他们接受睾酮或安慰剂凝胶治疗，为期一年。这四项试验的主要终点将是六分钟步行距离(行动不便)、韦克斯勒记忆量表修订的段落回忆(与年龄相关的记忆障碍)、面部疲劳量表(活力)和加州大学洛杉矶分校7天性功能问卷(性功能)。所有试验的衡量标准将包括患者对变化问题的全球评估、日常生活能力、跌倒、PHQ-9和积极和消极影响量表，以及对包括前列腺癌在内的不良事件的评估。将通过电子束CT评估男性亚组的心血管疾病；通过定量CT评估脊柱的体积骨密度；以及贫血。 这项研究的潜在意义在于，它应该最终确定，对睾酮浓度较低的老年男性进行睾酮治疗是否会改善他们的身体、性和认知功能和活力。这项研究还将提供初步数据，帮助确定是否有必要对睾酮对临床心脏病、骨折风险和前列腺癌风险的影响进行长期试验。

DESCRIPTION (provided by applicant): As men age, they experience many conditions, such as mobility disability, age-associated memory impairment, and low vitality, that result in decreased ability to perform activities of daily living, increased propensity to fall, and decreased independence. They also experience anemia, osteoporosis and metabolic syndrome and decreased sexual function. One cause that could contribute to all of these conditions is a low serum testosterone concentration. As men age, their serum testosterone falls, often to levels comparable to those of younger men who have diseases of the pituitary and testes. When young men develop low testosterone due to pituitary or testicular disease, they experience similar consequences, including decreased muscle mass and strength, decreased sexual drive, impaired cognition, and low energy, as well as anemia, osteoporosis and the metabolic syndrome. When these men are treated with testosterone, all of these abnormalities improve. The concept we propose is that an unequivocally low testosterone concentration for no apparent reason other than age predisposes a man to have these geriatric conditions and that testosterone treatment will improve them. We therefore propose a closely coordinated set of four, randomized, placebo-controlled clinical trials to test the hypotheses that testosterone treatment for one year of men >65 years who have unequivocally low serum testosterone concentrations (<250 ng/dL) and both symptoms and objective evidence of mobility disability, age-associated memory impairment, low vitality, or diminished sexual function will show more favorable changes in these parameters than placebo treatment. We shall select 1200 men at 18 sites and randomize them to receive testosterone or placebo gel for one year. Primary end points for these four trials will be six minute walking distance (mobility disability), paragraph recall by the Wechsler Memory Scale Revised (age-associated memory impairment), Facit-fatigue scale (vitality) and UCLA 7-day sexual function questionnaire (sexual function). Measures across all trials will include patient global assessment of change questions, activities of daily living, falls, PHQ-9 and Positive and Negative Affect scales, as well as assessment of adverse events, including prostate diseases. Subsets of men will be assessed for cardiovascular disease by electron beam CT; volumetric bone density of the spine by quantitative CT; and anemia. The potential significance of this study is that it should determine, finally, if testosterone treatment of older men with low testosterone concentrations will improve their physical, sexual and cognitive function and vitality. This study will also provide preliminary data that will help determine if a longer-term trial of the effects of testosterone on clinical heart disease, fracture risk and prostate risk is warranted.