Elderly men have lower serum testosterone concentrations and less muscular strength than young men. In a short-term study (1 month), we administered testosterone to elderly men in doses designed to raise their testosterone concentrations to those found in young men. This treatment increased skeletal muscle strength and muscle protein synthesis. The goal of this project is to determine whether more prolonged testosterone administration (6 months) will show a continuation of an increase in muscle strength and net muscle protein synthesis. Moreover, it will assess the changes that occur in myofibrillar protein (actin and myosin) and muscle size. Elderly men (ages 60 and greater) will be recruited from 3 sources, the Geriatrics outpatient clinic, a registry of elderly volunteers maintained by the Geriatrics Division at the University of Texas Medical Branch, and the local population. They will be enrolled in a double-blinded, placebo controlled study in which testosterone enanthate is given by intramuscular injection every week for 1 month, then every 2 weeks for an additional 5 months. At baseline, 1 and 6 months, we will determine muscle strength, muscle protein synthesis and degradation, myofibrillar (actin and myosin) protein synthesis, amino acid transport and arterial-venous balance, mRNA concentrations of actin and myosin, and muscle strength. Muscle size will be determined by DEXA and MRI scan at baseline and 6 months. Careful assessment of the risks of testosterone administration in this age group will be done by measuring prostate size and urinary flow rates (baseline and 6 months), lipid concentrations, liver enzymes, CBC, blood pressure, and prostate specific antigen. This study will determine whether the long-term administration of testosterone in elderly men will increase muscle strength, net protein anabolism, and muscle size. If 6 month testosterone administration increases strength, then studies can be done to assess the functional implications of this therapy in reducing falls, increasing independence, and improving the quality of life in elderly men.
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