Preventing a Decline in Physical Function in Older Androgen-Deprived Men with Structured Exercise Training

项目摘要/摘要 这项建议的总体目标是确定抗阻运动训练在预防 接受雄激素剥夺治疗(ADT)的前列腺癌(PCA)男性患者的身体功能下降。 由于睾丸激素在刺激前列腺组织中起着核心作用，ADT是治疗前列腺癌的基石。 高级别和转移性前列腺癌的男性。ADT导致去势的血清睾酮水平和这 严重的雄激素缺乏会导致瘦体重的减少和脂肪质量的增加。这些 随着瘦体重的明显减少，身体成分的紊乱在这些人中遵循着一种攻击性的过程 在开始ADT的6-8周内。这些身体成分的不利变化导致肌肉减少。 力量，反过来会导致身体机能的下降。这些不利影响具有严重的 后果：服用ADT的男性与没有服用ADT的男性相比，身体虚弱和摔倒的风险更高 接受ADT，仅接受前列腺切除术。尽管这些功能性任务有所下降，但 患者重要，对保持独立性至关重要，没有一项随机试验是 在这些男性中进行，以评估有组织的运动方案在防止 身体机能。少数先前的研究只招募了已经接受ADT和 已经遇到了严重的肌肉萎缩；因此，正如预期的那样，在 观察两组的生理功能。此外，以前的研究没有对控制组提供同样的关注。 我们提出了一项随机、对照、平行分组试验来确定6个月结构化治疗的疗效。 阻力运动训练在预防身体机能下降中的作用(按负荷阶梯评定 对于60岁及以上即将开始前列腺癌ADT的男性来说，这是一种新的治疗方法。我们还将提供 对对照组给予同等关注，使用结构化的、患者重要的、但结果无害的干预措施 (灵活性和平衡性练习)。我们还将评估运动训练对肌肉质量的效果 (DEXA扫描)、肌肉力量(1RM法)、生活质量(SF-36问卷)和疲劳(Facit-F 问卷)。这项试验的结果将为最终的干预试验奠定基础，以防止硬 接受ADT的男性的虚弱和跌倒的结果。因为脆弱会造成重大的公共卫生负担， 与功能能力和恢复力减弱有关，拟议的试验可能会有实质性的 对患者群体的整体健康和独立性的临床影响。

PROJECT SUMMARY/ABSTRACT The overall goal of this proposal is to determine the efficacy of resistance exercise training in preventing the decline in physical function in men with prostate cancer (PCa) undergoing androgen deprivation therapy (ADT). As testosterone has a central role in the stimulation of prostate tissue, ADT is the cornerstone of treatment in men with high grade and metastatic PCa. ADT results in castrate levels of serum testosterone and this profound androgen deficiency leads to a reduction in lean mass and an increase in fat mass. These perturbations in body composition follow an aggressive course in these men as loss of lean mass is evident within 6-8 weeks of starting ADT. These unfavorable changes in body composition result in decreased muscle strength, which in turn, results in a decline in physical function. These adverse effects have serious consequences as men on ADT have a higher risk of frailty and falls compared with men with PCa who do not undergo ADT and are only treated with prostatectomy. Despite declines in these functional tasks that are patient-important and critical to maintenance of independence, not a single randomized trial has been performed in these men to evaluate the efficacy of a structured exercise regimen in preventing decline in physical function. A handful of previous studies had only enrolled men who were already receiving ADT and had already encountered significant muscle atrophy; therefore, as expected, no meaningful improvements in physical function were seen. Furthermore, previous studies did not provide equal attention to control groups. We propose a randomized, controlled, parallel group trial to determine the efficacy of 6-months of structured resistance exercise training in preventing the decline in physical function (assessed by loaded stair climbing power) in men age 60 years and older who are about to begin ADT for PCa. We will also provide equal attention to the control group using structured, patient-important, but outcome innocuous interventions (flexibility and balance exercises). We will also evaluate the efficacy of exercise training on muscle mass (DEXA scan), muscle strength (1RM method), QOL (SF-36 questionnaire) and fatigue (FACIT-F questionnaire). The findings of this trial will lay the groundwork for definitive intervention trials to prevent hard outcomes of frailty and falls in men undergoing ADT. As frailty imposes a significant public health burden and is associated with diminished functional capacity and resilience, the proposed trial is likely to have a substantial clinical impact in the overall health and independence of this patient population.