As men age, their muscle mass and muscle strength gradually decrease, and so does their serum testosterone concentration. Because a decrease in the serum testosterone concentration in young men is a recognized cause of decreased muscle mass and muscle strength, the decrease in testosterone with aging may be a cause of the concomitant decrease in muscle strength. We therefore propose to test the hypothesis that increasing the serum testosterone concentrations of healthy elderly men to those of healthy young men will improve their muscle strength. We plan to recruit healthy men >65 years from the life care communities and senior centers associated with the Philadelphia Gerontology Research Consortium and to screen them to include those who have a serum testosterone concentration less than mean - 1 SD of men 20-40 years old and exclude those who have diseases known to affect muscle strength and diseases that would preclude compliance with the study protocol. We estimate that we shall need to screen 300 volunteers to find 100 to begin the protocol and have 70 complete R. The estimation that 70 subjects will need to complete the protocol in order to obtain meaningful results is based on several assumptions, including the precision of the procedure, and on the judgment that an improvement of greater than or equal to 20% in muscle strength would be clinically important. The study will be double-blinded, and subjects will be randomized to either a testosterone treatment or a placebo group. Testosterone will be administered transdermally, in order to produce a physiologic pattern of serum testosterone concentration and to facilitate recruitment of subjects. The serum testosterone and SHBG concentrations will be measured throughout the study, and signs of adverse effects of testosterone will be monitored. The principal index of the effect of testosterone will be maximal strength of knee extension, as measured on a Biodex dynamometer. Any difference in maximum strength of knee extension between the testosterone and placebo groups at the end of the study will be interpreted in light of the results of measurement of maximum strength of knee flexion by Biodex dynamometer and hand strength by Jaymar dynamometer, and measurement of lean and fat soft tissue mass by dual energy x-ray absorptiometry (DEXA). We expect that the results of this study will help determine if increasing the serum testosterone concentrations of healthy elderly men will improve their muscle strength without increasing the incidence of testosterone-dependent diseases.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010954-04
Application #
2052185
Study Section
Biological and Clinical Aging Review Committee (BCA)
Project Start
1992-09-01
Project End
1999-06-30
Budget Start
1996-07-01
Budget End
1999-06-30
Support Year
4
Fiscal Year
1996
Total Cost
Indirect Cost
Name
University of Pennsylvania
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Snyder, P J (2001) Effects of age on testicular function and consequences of testosterone treatment. J Clin Endocrinol Metab 86:2369-72
Snyder, P J; Peachey, H; Berlin, J A et al. (2001) Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Am J Med 111:255-60
Snyder, P J; Peachey, H; Hannoush, P et al. (1999) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647-53
Snyder, P J; Peachey, H; Hannoush, P et al. (1999) Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84:1966-72