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Androgen deprivation therapy is a common treatment in men with prostate cancer that may cause fatigue, functional decline, increased body fatness, and loss of lean body tissue. These physical changes can negatively affect health-related quality of life. Resistance exercise may help to counter some of these side effects by reducing fatigue, elevating mood, building muscle mass, and reducing body fat.In a two-site study, 155 men with prostate cancer who were scheduled to receive androgen deprivation therapy for at least 3 months after recruitment were randomly assigned to an intervention group that participated in a resistance exercise program three times per week for 12 weeks (82 men) or to a waiting list control group (73 men). The primary outcomes were fatigue and disease-specific quality of life as assessed by self-reported questionnaires after 12 weeks. Secondary outcomes were muscular fitness and body composition.Men assigned to resistance exercise had less interference from fatigue on activities of daily living (P = .002) and higher quality of life (P = .001) than men in the control group. Men in the intervention group demonstrated higher levels of upper body (P = .009) and lower body (P < .001) muscular fitness than men in the control group. The 12-week resistance exercise intervention did not improve body composition as measured by changes in body weight, body mass index, waist circumference, or subcutaneous skinfolds.Resistance exercise reduces fatigue and improves quality of life and muscular fitness in men with prostate cancer receiving androgen deprivation therapy. This form of exercise can be an important component of supportive care for these patients.