The long term objective of this application is to provide information about the efficacy of testosterone (T) replacement therapy, in hypogonadal elderly men, in preventing physical frailty by arresting bone density loss and increasing muscle mass, strength, and balance. Impaired muscle strength, falls, and fractures contribute to the development of physical frailty in the elderly. In young men, androgens are known to have positive effects on formation and maintenance of male muscle and bone, and T replacement therapy in young hypogonadal men has been shown to increase bone density and muscle mass. Although a significant number of elderly men are hypogonadal, little is known about the benefits and risks of androgen replacement in this population. Using a double-blind placebo controlled design, men greater than or equal to 65 years of age, who are not yet frail but have a serum T level below the normal range for young adult men, will be given T replacement for 3 years. An additional group will be given T plus a 5alpha-reductase inhibitor, which is being utilized both as a means to.elucidate the relative roles of T and dihydrotestosterone (DHT) in the androgen effects on muscle and bone, and as a means of protecting the prostate from increased androgen levels. During the 3 year treatment period, men will receive bone density measurements of the spine and hip, evaluation of biochemical parameters of bone turnover, extremity muscle strength testing, evaluation of balance, measurement of body composition, and evaluation of parameters related to potential adverse effects of androgen therapy (prostate, lipoproteins, hematocrit, and libido). The proposal specifically aims to study whether T replacement (1) has positive effects on bone and muscle by preventing bone density loss and increasing muscle mass, strength and balance, (2) has its effects without needing conversion to the other major androgen, DHT, and (3) can be given safely to elderly hypogonadal men.
| Vaughan, Camille; Goldstein, Felicia C; Tenover, J Lisa (2007) Exogenous testosterone alone or with finasteride does not improve measurements of cognition in healthy older men with low serum testosterone. J Androl 28:875-82 |
| Page, Stephanie T; Amory, John K; Bowman, F Dubois et al. (2005) Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 90:1502-10 |
| Amory, John K; Watts, Nelson B; Easley, Kirk A et al. (2004) Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab 89:503-10 |
