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The Journal of Clinical Endocrinology & Metabolism Vol. 82, No. 2 407-413
Copyright © 1997 by The Endocrine Society

Reproductive Endocrinology

Testosterone Replacement Increases Fat-Free Mass and Muscle Size in Hypogonadal Men1

Shalender Bhasin, Thomas W. Storer, Nancy Berman, Kevin E. Yarasheski, Brenda Clevenger, Jeffrey Phillips, W. Paul Lee, Thomas J. Bunnell and Richard Casaburi

Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science (S.B., B.C.), Los Angeles, California 90059; the Departments of Medicine, Pediatrics, and Radiology, Harbor-University of California-Los Angeles Medical Center (N.B., J.P., W.P.L., R.C.), Torrance, California 90509; Stable Isotope Laboratory, Washington University School of Medicine (K.E.Y.), St. Louis, Missouri 63110; and El Camino College (T.W.S., T.J.B.), Torrance, California 90504

Address all correspondence and requests for reprints to: Shalender Bhasin, M.D., Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, and University of California School of Medicine, 1621 East 120th Street, Los Angeles, California 90059.

Testosterone-induced nitrogen retention in castrated male animals and sex-related differences in the size of the muscles in male and female animals have been cited as evidence that testosterone has anabolic effects. However, the effects of testosterone on body composition and muscle size have not been rigorously studied. The objective of this study was to determine the effects of replacement doses of testosterone on fat-free mass and muscle size in healthy hypogonadal men in the setting of controlled nutritional intake and exercise level.

Seven hypogonadal men, 19–47 yr of age, after at least a 12-week washout from previous androgen therapy, were treated for 10 weeks with testosterone enanthate (100 mg/week) by im injections. Body weight, fat-free mass measured by underwater weighing and deuterated water dilution, and muscle size measured by magnetic resonance imaging were assessed before and after treatment. Energy and protein intake were standardized at 35 Cal/kg·day and 1.5 g/kg·day, respectively.

Body weight increased significantly from 79.2 ± 5.6 to 83.7 ± 5.7 kg after 10 weeks of testosterone replacement therapy (weight gain, 4.5 ± 0.6 kg; P = 0.0064). Fat-free mass, measured by underwater weighing, increased from 56.0 ± 2.5 to 60.9 ± 2.2 kg (change, +5.0 ± 0.7 kg; P = 0.0004), but percent fat did not significantly change. Similar increases in fat-free mass were observed with the deuterated water method. The cross-sectional area of the triceps arm muscle increased from 2421 ± 317 to 2721 ± 239 mm2 (P = 0.045), and that of the quadriceps leg muscle increased from 7173 ± 464 to 7720 ± 454 mm2 (P = 0.0427), measured by magnetic resonance imaging. Muscle strength, assessed by one repetition maximum of weight-lifting exercises increased significantly after testosterone treatment. L-[1-13C]Leucine turnover, leucine oxidation, and nonoxidative disappearance of leucine did not significantly change after 10 weeks of treatment. There was no significant change in hemoglobin, hematocrit, creatinine, and transaminase levels.

Replacement doses of testosterone increase fat-free mass and muscle size and strength in hypogonadal men. Whether androgen replacement in wasting states characterized by low testosterone levels will have similar anabolic effects remains to be studied.




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[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
T. A. Roy, M. R. Blackman, S. M. Harman, J. D. Tobin, M. Schrager, and E. J. Metter
Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men
Am J Physiol Endocrinol Metab, August 1, 2002; 283(2): E284 - E294.
[Abstract] [Full Text] [PDF]

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J. A. Carson, W. J. Lee, J. McClung, and G. A. Hand
Steroid receptor concentration in aged rat hindlimb muscle: effect of anabolic steroid administration
J Appl Physiol, July 1, 2002; 93(1): 242 - 250.
[Abstract] [Full Text] [PDF]

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P. Y. Liu, S. M. Wishart, and D. J. Handelsman
A Double-Blind, Placebo-Controlled, Randomized Clinical Trial of Recombinant Human Chorionic Gonadotropin on Muscle Strength and Physical Function and Activity in Older Men with Partial Age-Related Androgen Deficiency
J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3125 - 3135.
[Abstract] [Full Text] [PDF]

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I. Sinha-Hikim, J. Artaza, L. Woodhouse, N. Gonzalez-Cadavid, A. B. Singh, M. I. Lee, T. W. Storer, R. Casaburi, R. Shen, and S. Bhasin
Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy
Am J Physiol Endocrinol Metab, July 1, 2002; 283(1): E154 - E164.
[Abstract] [Full Text] [PDF]

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 ChestHome page
J. Weisberg, J. Wanger, J. Olson, B. Streit, C. Fogarty, T. Martin, and R. Casaburi
Megestrol Acetate Stimulates Weight Gain and Ventilation in Underweight COPD Patients*
Chest, April 1, 2002; 121(4): 1070 - 1078.
[Abstract] [Full Text] [PDF]

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 ChestHome page
D. M. Biskobing
COPD and Osteoporosis
Chest, February 1, 2002; 121(2): 609 - 620.
[Abstract] [Full Text] [PDF]

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 Journals of Gerontology Series A: Biological Sciences and Medical SciencesHome page
A. M. Matsumoto
Andropause: Clinical Implications of the Decline in Serum Testosterone Levels With Aging in Men
J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2002; 57(2): M76 - 99.
[Full Text]

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 Recent Prog Horm ResHome page
C. M. Kuhn
Anabolic Steroids
Recent Prog. Horm. Res., January 1, 2002; 57(1): 411 - 434.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
S. Bhasin, L. Woodhouse, R. Casaburi, A. B. Singh, D. Bhasin, N. Berman, X. Chen, K. E. Yarasheski, L. Magliano, C. Dzekov, et al.
Testosterone dose-response relationships in healthy young men
Am J Physiol Endocrinol Metab, December 1, 2001; 281(6): E1172 - E1181.
[Abstract] [Full Text] [PDF]

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A. Vermeulen
Androgen Replacement Therapy in the Aging Male--A Critical Evaluation
J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2380 - 2390.
[Full Text] [PDF]

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A. W. van den Beld, F. H. de Jong, D. E. Grobbee, H. A. P. Pols, and S. W. J. Lamberts
Measures of Bioavailable Serum Testosterone and Estradiol and Their Relationships with Muscle Strength, Bone Density, and Body Composition in Elderly Men
J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3276 - 3282.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
P. J. Snyder, H. Peachey, J. A. Berlin, P. Hannoush, G. Haddad, A. Dlewati, J. Santanna, L. Loh, D. A. Lenrow, J. H. Holmes, et al.
Effects of Testosterone Replacement in Hypogonadal Men
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2670 - 2677.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
C. Wang, R. S. Swerdloff, A. Iranmanesh, A. Dobs, P. J. Snyder, G. Cunningham, A. M. Matsumoto, T. Weber, and N. Berman the Testosterone Gel Study Group
Transdermal Testosterone Gel Improves Sexual Function, Mood, Muscle Strength, and Body Composition Parameters in Hypogonadal Men
J. Clin. Endocrinol. Metab., August 1, 2000; 85(8): 2839 - 2853.
[Abstract] [Full Text]

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 ChestHome page
R. Casaburi
Skeletal Muscle Function in COPD
Chest, May 1, 2000; 117 (2009): 267S - 271S.
[Abstract] [Full Text] [PDF]

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 BMJHome page
D. C Gould, R. Petty, and H. S Jacobs
For and against: The male menopause---does it exist? • For • Against
BMJ, March 25, 2000; 320(7238): 858 - 861.
[Full Text]

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 JAMAHome page
S. Bhasin, T. W. Storer, M. Javanbakht, N. Berman, K. E. Yarasheski, J. Phillips, M. Dike, I. Sinha-Hikim, R. Shen, R. D. Hays, et al.
Testosterone Replacement and Resistance Exercise in HIV-Infected Men With Weight Loss and Low Testosterone Levels
JAMA, February 9, 2000; 283(6): 763 - 770.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
B. B. Rasmussen, E. Volpi, D. C. Gore, and R. R. Wolfe
Androstenedione Does Not Stimulate Muscle Protein Anabolism in Young Healthy Men
J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 55 - 59.
[Abstract] [Full Text]

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 JPEN J Parenter Enteral NutrHome page
S. Bhasin and M. Javanbakht
Can Androgen Therapy Replete Lean Body Mass and Improve Muscle Function in Wasting Associated With Human Immunodeficiency Virus Infection?
JPEN J Parenter Enteral Nutr, November 1, 1999; 23(6_suppl): S195 - S201.
[Abstract] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
R. Bross, M. Javanbakht, and S. Bhasin
Anabolic Interventions for Aging-Associated Sarcopenia
J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3420 - 3430.
[Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
P. J. Snyder, H. Peachey, P. Hannoush, J. A. Berlin, L. Loh, D. A. Lenrow, J. H. Holmes, A. Dlewati, J. Santanna, C. J. Rosen, et al.
Effect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2647 - 2653.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
M. Sheffield-Moore, R. J. Urban, S. E. Wolf, J. Jiang, D. H. Catlin, D. N. Herndon, R. R. Wolfe, and A. A. Ferrando
Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men
J. Clin. Endocrinol. Metab., August 1, 1999; 84(8): 2705 - 2711.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
F. R. Sattler, S. V. Jaque, E. T. Schroeder, C. Olson, M. P. Dube, C. Martinez, W. Briggs, R. Horton, and S. Azen
Effects of Pharmacological Doses of Nandrolone Decanoate and Progressive Resistance Training in Immunodeficient Patients Infected with Human Immunodeficiency Virus
J. Clin. Endocrinol. Metab., April 1, 1999; 84(4): 1268 - 1276.
[Abstract] [Full Text]

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 Am. J. Respir. Crit. Care Med.Home page
Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease . A Statement of the American Thoracic Society and European Respiratory Society
Am. J. Respir. Crit. Care Med., April 1, 1999; 159(4): S2 - 40.
[Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
J. M. H. Elbers, H. Asscheman, J. C. Seidell, and L. J. G. Gooren
Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals
Am J Physiol Endocrinol Metab, February 1, 1999; 276(2): E317 - E325.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
A. A. Ferrando, K. D. Tipton, D. Doyle, S. M. Phillips, J. Cortiella, and R. R. Wolfe
Testosterone injection stimulates net protein synthesis but not tissue amino acid transport
Am J Physiol Endocrinol Metab, November 1, 1998; 275(5): E864 - E871.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Bhasin
VIII. Conclusion--Research Design Issues in Examining the Effects of Testosterone Supplementation in Older Men
J. Clin. Endocrinol. Metab., October 1, 1998; 83(10): 3445 - 3448.
[Full Text]

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 J. Clin. Endocrinol. Metab.Home page
S. Bhasin, T. W. Storer, N. Asbel-Sethi, A. Kilbourne, R. Hays, I. Sinha-Hikim, R. Shen, S. Arver, and G. Beall
Effects of Testosterone Replacement with a Nongenital, Transdermal System, Androderm, in Human Immunodeficiency Virus-Infected Men with Low Testosterone Levels
J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3155 - 3162.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
V. Luukkaa, U. Pesonen, I. Huhtaniemi, A. Lehtonen, R. Tilvis, J. Tuomilehto, M. Koulu, and R. Huupponen
Inverse Correlation between Serum Testosterone and Leptin in Men
J. Clin. Endocrinol. Metab., September 1, 1998; 83(9): 3243 - 3246.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
K. Miller, C. Corcoran, C. Armstrong, K. Caramelli, E. Anderson, D. Cotton, N. Basgoz, L. Hirschhorn, R. Tuomala, D. Schoenfeld, et al.
Transdermal Testosterone Administration in Women with Acquired Immunodeficiency Syndrome Wasting: A Pilot Study
J. Clin. Endocrinol. Metab., August 1, 1998; 83(8): 2717 - 2725.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
N. Mauras, V. Hayes, S. Welch, A. Rini, K. Helgeson, M. Dokler, J. D. Veldhuis, and R. J. Urban
Testosterone Deficiency in Young Men: Marked Alterations in Whole Body Protein Kinetics, Strength, and Adiposity
J. Clin. Endocrinol. Metab., June 1, 1998; 83(6): 1886 - 1892.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
M. Christopher, F. L. Hew, M. Oakley, C. Rantzau, and F. Alford
Defects of Insulin Action and Skeletal Muscle Glucose Metabolism in Growth Hormone-Deficient Adults Persist after 24 Months of Recombinant Human Growth Hormone Therapy
J. Clin. Endocrinol. Metab., May 1, 1998; 83(5): 1668 - 1681.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
I. Sinha-Hikim, S. Arver, G. Beall, R. Shen, M. Guerrero, F. Sattler, C. Shikuma, J. C. Nelson, B.-M. Landgren, N. A. Mazer, et al.
The Use of a Sensitive Equilibrium Dialysis Method for the Measurement of Free Testosterone Levels in Healthy, Cycling Women and in Human Immunodeficiency Virus-Infected Women
J. Clin. Endocrinol. Metab., April 1, 1998; 83(4): 1312 - 1318.
[Abstract] [Full Text]

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 J. Clin. Endocrinol. Metab.Home page
S. Arslanian and C. Suprasongsin
Testosterone Treatment in Adolescents with Delayed Puberty: Changes in Body Composition, Protein, Fat, and Glucose Metabolism
J. Clin. Endocrinol. Metab., October 1, 1997; 82(10): 3213 - 3220.
[Abstract] [Full Text] [PDF]

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 J. Clin. Endocrinol. Metab.Home page
S. Bhasin and J. S. Tenover
Age-Associated Sarcopenia--Issues in the Use of Testosterone as an Anabolic Agent in Older Men
J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1659 - 1660.
[Full Text] [PDF]

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 Am. J. Physiol. Endocrinol. Metab.Home page
A. A. Ferrando, M. Sheffield-Moore, C. W. Yeckel, C. Gilkison, J. Jiang, A. Achacosa, S. A. Lieberman, K. Tipton, R. R. Wolfe, and R. J. Urban
Testosterone administration to older men improves muscle function: molecular and physiological mechanisms
Am J Physiol Endocrinol Metab, March 1, 2002; 282(3): E601 - E607.
[Abstract] [Full Text] [PDF]


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