Elderly men have lower serum testosterone concentrations and less muscular strength than young men. In a short-term study (1 mo), the investigators 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 new project is to determine whether more prolonged testosterone administration (1 yr) 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 (age 60+ yr) 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 2 weeks for 1 year. At 1, 3, 6, and 12 months, muscle strength, muscle protein synthesis and degradation, myofibrillar (actin and myosin) protein synthesis, and mRNA concentrations of the structural proteins actin and myosin will be determined. At 6 and 12 months, muscle size will be determined. Careful assessment of the risks of testosterone administration in this age group will be done by measuring prostate size and urinary flow rates, 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, size, and net protein anabolism. If prolonged 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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG011000-03
Application #
2899762
Study Section
Special Emphasis Panel (ZRG4-GRM (01))
Program Officer
Lymn, Richard W
Project Start
1997-04-01
Project End
2001-03-31
Budget Start
1999-04-01
Budget End
2001-03-31
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Copland, John A; Davies, Peter J; Shipley, Gregory L et al. (2003) The use of DNA microarrays to assess clinical samples: the transition from bedside to bench to bedside. Recent Prog Horm Res 58:25-53
Ferrando, Arny A; Sheffield-Moore, Melinda; Paddon-Jones, Douglas et al. (2003) Differential anabolic effects of testosterone and amino acid feeding in older men. J Clin Endocrinol Metab 88:358-62
Ferrando, Arny A; Sheffield-Moore, Melinda; Yeckel, Catherine W et al. (2002) Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 282:E601-7
Bamman, M M; Shipp, J R; Jiang, J et al. (2001) Mechanical load increases muscle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab 280:E383-90
Hayes, V Y; Urban, R J; Jiang, J et al. (2001) Recombinant human growth hormone and recombinant human insulin-like growth factor I diminish the catabolic effects of hypogonadism in man: metabolic and molecular effects. J Clin Endocrinol Metab 86:2211-9
Sheffield-Moore, M; Urban, R J; Wolf, S E et al. (1999) Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab 84:2705-11
Mauras, N; Hayes, V; Welch, S et al. (1998) Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab 83:1886-92