Exercise Training, Erectile Dysfunction, and Prostate Cancer

描述（由申请人提供）：根治性前列腺切除术常用于治疗临床诊断为局限性前列腺癌的男性。不幸的是，这种治疗方式经常导致勃起功能障碍（ED）， 29%至75%的男性在前列腺切除术后出现这种疾病。ED非常重要，因为它是生活质量（QOL）的一个强有力的预测指标，可能是潜在或未来心血管疾病（CVD）的替代标志物，CVD是临床上诊断为局限性前列腺癌的男性死亡的一个越来越重要的原因。尽管如此，目前可用于解决这一临床破坏性问题的干预措施是有限的。本提案整合了来自泌尿外科、血管生物学、心血管医学和运动肿瘤学等不同学科的研究，以确定有氧运动训练对ED的影响，以及可能强调运动对临床局限性前列腺癌根治性前列腺切除术男性ED影响的假定作用机制。我们提出了一项双中心、前瞻性随机试验，以确定有氧运动训练对50例接受根治性前列腺癌临床局限性前列腺癌患者ED的影响。该项目有三个具体目标：(1)确定有监督的有氧运动训练与常规护理对临床局限性前列腺癌根治性前列腺切除术男性ED发生率的影响；(2)确定有氧运动训练与等候名单对照对患者症状（即性功能、尿失禁和生活质量）变化的影响，以及接受5型磷酸二酯酶（PDE-5）抑制剂治疗的男性人数和治疗剂量的影响。(3)确定有氧运动训练与等候名单控制对运动训练与ED之间关系的假定生物学机制变化的影响[即CVD危险因素（心肺健康、血脂、血压、c反应蛋白、身体成分）、心功能、阴茎和肱动脉内皮功能]。获得这些数据将使我们能够设计一项足够有力的III期随机对照试验，以检查运动对前列腺癌患者ED和其他生存问题的疗效。此外，从这项研究中获得的机制信息将有助于设计健康男性和患有慢性疾病的ED患者的运动和其他CAM干预措施。因此，这项研究的发现可能对美国大量男性具有重要意义。公共卫生相关性：根治性前列腺切除术常用于治疗临床诊断为局限性前列腺癌的男性。不幸的是，这种治疗方式经常导致勃起功能障碍（ED）， 29%至75%的男性在前列腺切除术后出现这种疾病。ED非常重要，因为它是生活质量的一个强有力的预测指标，可能是潜在或未来心血管疾病的替代标志物。本研究将首次探讨有氧运动训练对临床局限性前列腺癌患者行根治性前列腺切除术后ED的影响。这项研究的发现可能对大量患有前列腺癌的男性和患有其他临床疾病的男性（即肥胖、II型糖尿病、心力衰竭等）具有重要意义。

DESCRIPTION (provided by applicant): Radical prostatectomy is frequently used to treat men diagnosed with clinically localized prostate cancer. Unfortunately, this treatment modality often leads to erectile dysfunction (ED), with 29% to 75% of men experiencing this disorder following prostatectomy. ED is of major importance since it is a strong predictor of quality of life (QOL) and may be a surrogate marker of underlying or future cardiovascular disease (CVD) which is an increasingly important cause of mortality among men diagnosed with clinically localized prostate cancer. Despite this, current available interventions to address this clinically devastating problem are limited. This proposal integrates research from the diverse disciplines of urology, vascular biology, cardiovascular medicine, and the emerging field of exercise oncology to determine the effects of aerobic exercise training on ED and the postulated mechanisms of action that may underline the effects of exercise on ED among men undergoing radical prostatectomy for clinically localized prostate cancer. We propose a dual-site, prospective randomized trial to determine the effects of aerobic exercise training on ED among 50 sedentary men undergoing radical prostatectomy for clinically localized prostate cancer. This project has three specific aims: (1) determine the effects of supervised aerobic exercise training versus usual care on incidence of ED among men undergoing radical prostatectomy for clinically localized prostate cancer, (2) determine the effects of aerobic exercise training versus wait-list control on changes in patient symptoms (i.e., sexual functioning, urinary incontinence, and QOL) and the number of men receiving phosphodiesterases type-5 (PDE-5) inhibitor therapy as well as therapy dose, and (3) determine the effects of aerobic exercise training versus wait-list control on changes in postulated biologic mechanisms that may underlie the relationship between exercise training and ED [i.e., CVD risk factors (cardiorespiratory fitness, lipid profile, blood pressure, c-reactive protein, body composition), cardiac function, and penile and brachial artery endothelial function]. Acquisition of this data will allow us to design an adequately powered phase III RCT examining the efficacy of exercise on ED and other survivorship issues among men with prostate cancer. In addition, mechanistic information gained from this study will help the design of exercise and other CAM interventions among healthy men and those with chronic disease experiencing ED. As such, the findings of this study could have important implications for a substantial number of men in United States. PUBLIC HEALTH RELEVANCE: Radical prostatectomy is frequently used to treat men diagnosed with clinically localized prostate cancer. Unfortunately, this treatment modality often leads to erectile dysfunction (ED), with 29% to 75% of men experiencing this disorder following prostatectomy. ED is of major importance since it is a strong predictor of quality of life and may be a surrogate marker of underlying or future cardiovascular disease. This study, will for the first time, examine the effects of aerobic exercise training on ED among men undergoing radical prostatectomy for clinically localized prostate cancer. The findings of this study could have important implications for a substantial number of men with prostate cancer and men with other clinical disorders which suffer ED (i.e., obesity, type II diabetes, heart failure, etc).