The broad long-term objective of this project is to compare the adverse effects of bicalutamide monotherapy with androgen deprivation therapy (ADT) using a gonadotropin-releasing hormone (GnRH) agonist in men with nonmetastatic prostate cancer. GnRH agonists account for one-third of total Medicare expenditures for prostate cancer treatment Adverse effects of GnRH agonist include decreased bone mineral density (BMD), increased fracture risk, changes in body composition including decreased muscle size and strength. Bicalutamide (Casodex(R) is a peripherally selective, nonsteroidal antiandrogen under development as adjuvant therapy for early stage prostate cancer and as an alternative to ADT. Bicalutamide might have fewer adverse effects than GnRH agonists because it (1) increases rather than decreases serum testosterone and estrogen levels, (2) preserves patient-reported physical capacity. The specific aims of this project are to compare the effects of bicalutamide monotherapy versus GnRH agonist monotherapy on BMD and muscle size and strength. These specific aims will be accomplished using a common protocol. The study will include men with locally advanced, node-positive, or recurrent prostate cancer and no radiographic evidence of bone metastases. Subjects will be randomly assigned to leuprolide or bicalutamide (150 milligrams by mouth daily) for 12 months. The following outcomes will be evaluated at 0, 6, and 12 BMD by dual energy x-ray absorptiometry (DXA) and quantitative computed tomography (QCT), cross-sectional muscle and fat areas of the thigh and abdomen by QCT, body composition by anthropometry, bioimpedance, DXA, and isotope dilution, muscle function by maximum voluntary strength and Margada power testing, and quality of life. This project will provide definitive data about effects of GnRH agonists and bicalutamide on bone mineral density and muscle size and strength, and will impact the clinical management of men with prostate cancer. This project may demonstrate advantages of bicalutamide monotherapy or may highlight the need for development of more selective agents. In addition, this project will provide important insights into the relative contributions of testosterone and estrogen in bone metabolism, and maintenance of muscle size and strength in older men.