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).