LONG TERM ADMINISTRATION OF TESTOSTERONE IN ELDERLY MEN

老年男性的血清睾酮浓度较低，肌肉力量也不如年轻男性。在一项短期研究（1个月）中，我们给老年男性注射睾酮，其剂量旨在将他们的睾酮浓度提高到年轻男性的水平。这种治疗增加了骨骼肌力量和肌肉蛋白质合成。该项目的目的是确定更长时间的睾酮治疗（6个月）是否会显示肌肉力量和净肌肉蛋白质合成的持续增加。此外，它将评估发生在肌纤维蛋白（肌动蛋白和肌球蛋白）和肌肉大小的变化。老年男性（60岁及以上）将从三个来源招募：老年门诊诊所、德克萨斯大学医学分院老年科维护的老年志愿者登记处和当地人口。他们将参加一项双盲、安慰剂对照的研究，在这项研究中，每周肌肉注射睾酮烯酸盐，持续1个月，然后每2周注射一次，再持续5个月。在基线、1和6个月时，我们将测定肌肉力量、肌肉蛋白合成和降解、肌纤维（肌动蛋白和肌球蛋白）蛋白合成、氨基酸转运和动静脉平衡、肌动蛋白和肌球蛋白mRNA浓度以及肌肉力量。肌肉大小将在基线和6个月时通过DEXA和MRI扫描确定。通过测量前列腺大小和尿流率（基线和6个月）、脂质浓度、肝酶、CBC、血压和前列腺特异性抗原，对该年龄组使用睾酮的风险进行仔细评估。这项研究将确定老年男性长期服用睾酮是否会增加肌肉力量、净蛋白质合成代谢和肌肉大小。如果6个月的睾酮治疗增加了力量，那么可以进行研究来评估这种治疗在减少跌倒、增加独立性和改善老年男性生活质量方面的功能影响。

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.