This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Because testosterone promotes the growth of prostate tumors, androgen deprivation therapy (ADT) to suppress testosterone secretion is commonly used in men with advanced prostate cancer to improve survival. There is emerging evidence that initiating ADT in earlier stages of disease severity may also confer benefits on disease progression and survival. However, these potential benefits are countered by deleterious effects of ADT on body composition and quality of life. The effects of ADT on body composition include: 1) a reduction in bone mass that markedly increases risk for osteoporosis; 2) a loss of muscle mass that increases risk for physical disability and amplifies risk for osteoporosis; and 3) an increase in body fat level that increases risk for heart disease and diabetes. The negative effects of ADT on quality of life include not only sexual dysfunction, but also fatigue, perception of lower physical functioning, reduced vitality, and impaired sense of well-being. Drug therapies are available that show promise in reducing bone loss in response to ADT; their effectiveness in preventing osteoporotic fractures remains to be proven. However, these drugs target only bone, and would not be expected to counteract the loss of muscle, increase in fat, or decline in quality of life that occurs with ADT.Exercise training is the only therapeutic strategy that has the potential to favorably influence quality of life and all the aspects of body composition that are negatively affected by ADT. Specifically, resistance exercise training (i.e., weight lifting) has been shown to increase bone and muscle mass and decrease fat mass in healthy older men and women. It cannot be assumed that exercise will definitely be beneficial in men undergoing ADT, because testosterone levels may be an important determinant of the adaptive response to exercise. Therefore, the objective of the proposed studies is to determine whether resistance exercise training is effective in preventing bone and muscle loss and fat gain in men with prostate cancer undergoing ADT. This will be accomplished by randomly assigning eligible volunteers to participate in either a supervised, progressive resistance exercise training program or a walking exercise program. The intervention period for each exercise program will be 1 year. The walking program was chosen as the control against which to compare resistance exercise training because walking does not build muscle or bone mass. Also, participation in regular exercise is recommended for all men undergoing ADT and walking is the most common form of exercise. A walking program is therefore most likely to reflect usual care.We predict that resistance exercise training will be more effective than walking exercise in preserving bone and muscle mass, but that both forms of exercise will be effective in preventing fat gain during ADT. We will also determine the effects of both exercise programs on physical functional abilities and on quality of life. If this feasibility study demonstrates that exercise training is effective in counteracting some of the deleterious effects of ADT in men with prostate cancer, larger randomized controlled trials can be designed to determine whether exercise improves survival by reducing, for example, the incidence of osteoporotic fracture or non-cancer-related mortality.
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