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This version published online on November 23, 2004
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2004-1184
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Submitted on June 21, 2004
Accepted on November 12, 2004

Older Men are as Responsive as Young Men to the Anabolic Effects of Graded Doses of Testosterone on the Skeletal Muscle

Shalender Bhasin MD*, Linda Woodhouse MS, CPT, Richard Casaburi Ph.D., MD, Atam B. Singh MD, Ricky Phong Mac M.D., Martin Lee Ph.D., Kevin E. Yarasheski Ph.D., Indrani Sinha-Hikim Ph.D., Connie Dzekov, Jeanne Dzekov B.S., Lynne Magliano M.S., and Thomas W. Storer Ph.D.

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059; Division of Respiratory Diseases, Pulmonary Physiology, and Critical Care Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502; Laboratory for Exercise Science, El Camino College, Torrance, CA; Division of Endocrinology, Metabolism, & Lipid Research, Washington University School of Medicine, St. Louis, MO 63110 01-1184 Version 3

* To whom correspondence should be addressed.
Shalender Bhasin, E-mail: sbhasin{at}ucla.edu

Although testosterone levels and muscle mass decline with age, many older men have serum testosterone level in the normal range, leading to speculation whether older men are less sensitive to testosterone. We determined the responsiveness of androgen-dependent outcomes to graded testosterone doses in older men, and compared it to that of young men. The participants in this randomized, double-blind, trial were 60 ambulatory, healthy, older men, 60-75 yr of age, who had normal serum testosterone levels. Their responses to graded doses of testosterone were compared with previous data in 61, 19-35 yr old men. The participants received a long-acting GnRH agonist to suppress endogenous testosterone production and 25, 50, 125, 300, or 600 mg testosterone enanthate weekly for 20 weeks. Fat free (FFM) and fat mass, muscle strength, sexual function, mood, visuospatial cognition, hormone levels, and safety measures were evaluated before, during and after treatment. Of 60 older men who were randomized, 52 completed the study. After adjusting for testosterone dose, changes in serum total testosterone (change -6.8, -1.9, +16.1, +49.5, and +101.9 nmol/L, at 25, 50, 125, 300 at 600 mg*wk-1, respectively) and hemoglobin (change -3.6, +9.9, +20.9, +12.6, +29.4 g/L at 25, 50, 125, 300, and 600 mg*wk-1, respectively) levels were dose-related in older men and significantly greater in older men than young men (each P < 0.0001). The changes in FFM (-0.3, +1.7, +4.2, +5.6, +7.3 kg, respectively in five ascending dose groups) and muscle strength in older men were correlated with testosterone dose and concentrations, and were not significantly different in young and older men. Changes in fat mass correlated inversely with testosterone dose (r0.54, P < 0.001) and were significantly different in young and older men (P < 0.0001); young men receiving 25 and 50 mg doses gained more fat mass than older men (P < 0.0001). Sexual function, mood, and visuospatial cognition did not change significantly in either group. Frequency of hematocrit >54%, leg edema, and prostate events was numerically higher in older men than in young men. Conclusion. Older men are as responsive as young men to testosterone's anabolic effects; however, older men have lower testosterone clearance rates, higher increments in hemoglobin, and a higher frequency of adverse effects. Although substantial gains in muscle mass and strength can be realized in older men with supraphysiological testosterone doses, these high doses are associated with high frequency of adverse effects. The best trade-off was achieved with a testosterone dose (125 mg) that was associated with high normal testosterone levels, low frequency of adverse events and significant gains in fat-free mass and muscle strength.




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