| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science (S.B., L.W., A.B.S., R.P.M., M.L., I.S.-H., C.D., J.D., L.M., T.W.S.), Los Angeles, California 90059; Division of Respiratory Diseases, Pulmonary Physiology, and Critical Care Medicine, Harbor-University of California-Los Angeles Medical Center (R.C.), Torrance, California 90502; Laboratory for Exercise Science, El Camino College (T.W.S.), Torrance, California 90502; and Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine (K.E.Y.), St. Louis, Missouri 63110
Address all correspondence and requests for reprints to: Dr. Shalender Bhasin, Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, University of California, Los Angeles, California 90059. 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 about 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 in 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 men, 19–35 yr old. 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 wk. Fat-free mass, 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/liter at 25, 50, 125, 300, and 600 mg/wk, respectively) and hemoglobin (change, –3.6, +9.9, +20.9, +12.6, and +29.4 g/liter at 25, 50, 125, 300, and 600 mg/wk, 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, and +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 (r = –0.54; P < 0.001) and were significantly different in young vs. older men (P < 0.0001); young men receiving 25- and 50-mg doses gained more fat mass than older men (P < 0.0001). Mood and visuospatial cognition did not change significantly in either group. Frequency of hematocrit greater than 54%, leg edema, and prostate events were numerically higher in older men than in young men. 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 a 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.
This article has been cited by other articles:
 |
|
 |
|
  J. F. Yarrow, C. F. Conover, A. V. Purandare, A. M. Bhakta, N. Zheng, B. Conrad, M. K. Altman, S. E. Franz, T. J. Wronski, and S. E. Borst Supraphysiological testosterone enanthate administration prevents bone loss and augments bone strength in gonadectomized male and female rats Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1213 - E1222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. C. Clark and T. M. Manini Sarcopenia != Dynapenia J. Gerontol. A Biol. Sci. Med. Sci., August 1, 2008; 63(8): 829 - 834. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. MacLean, W. S. M. Chiu, A. J. Notini, A.-M. Axell, R. A. Davey, J. F. McManus, C. Ma, D. R. Plant, G. S. Lynch, and J. D. Zajac Impaired skeletal muscle development and function in male, but not female, genomic androgen receptor knockout mice FASEB J, August 1, 2008; 22(8): 2676 - 2689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Brown Skeletal muscle and bone: effect of sex steroids and aging Advan Physiol Educ, June 1, 2008; 32(2): 120 - 126. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Knapp, T. W. Storer, K. L. Herbst, A. B. Singh, C. Dzekov, J. Dzekov, M. LaValley, A. Zhang, J. Ulloor, and S. Bhasin Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss Am J Physiol Endocrinol Metab, June 1, 2008; 294(6): E1135 - E1143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Coviello, B. Kaplan, K. M. Lakshman, T. Chen, A. B. Singh, and S. Bhasin Effects of Graded Doses of Testosterone on Erythropoiesis in Healthy Young and Older Men J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 914 - 919. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Fukui, M. Tanaka, G. Hasegawa, T. Yoshikawa, and N. Nakamura Association Between Serum Bioavailable Testosterone Concentration and the Ratio of Glycated Albumin to Glycated Hemoglobin in Men With Type 2 Diabetes Diabetes Care, March 1, 2008; 31(3): 397 - 401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Functional Outcomes for Clinical Trials in Frail Older Persons: Time To Be Moving: Working Group on Functional Outcome Measures for Clinical Trials J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2008; 63(2): 160 - 164. [Full Text] [PDF]
|
|
|
|
|
|
C. A. Allan, B. J. G. Strauss, H. G. Burger, E. A. Forbes, and R. I. McLachlan Testosterone Therapy Prevents Gain in Visceral Adipose Tissue and Loss of Skeletal Muscle in Nonobese Aging Men J. Clin. Endocrinol. Metab., January 1, 2008; 93(1): 139 - 146. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zitzmann and E. Nieschlag Androgen Receptor Gene CAG Repeat Length and Body Mass Index Modulate the Safety of Long-Term Intramuscular Testosterone Undecanoate Therapy in Hypogonadal Men J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3844 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. E. Borst, C. F. Conover, C. S. Carter, C. M. Gregory, E. Marzetti, C. Leeuwenburgh, K. Vandenborne, and T. J. Wronski Anabolic effects of testosterone are preserved during inhibition of 5{alpha}-reductase Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E507 - E514. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. L. Nielsen, C. Hagen, K. Wraae, K. Brixen, P. H. Petersen, E. Haug, R. Larsen, and M. Andersen Visceral and Subcutaneous Adipose Tissue Assessed by Magnetic Resonance Imaging in Relation to Circulating Androgens, Sex Hormone-Binding Globulin, and Luteinizing Hormone in Young Men J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2696 - 2705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B Yeap, O. P Almeida, Z. Hyde, P. E Norman, S A P. Chubb, K. Jamrozik, and L. Flicker In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health in Men Study Eur. J. Endocrinol., May 1, 2007; 156(5): 585 - 594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Ries, G. S. Bauldoff, B. W. Carlin, R. Casaburi, C. F. Emery, D. A. Mahler, B. Make, C. L. Rochester, R. ZuWallack, and C. Herrerias Pulmonary Rehabilitation: Joint ACCP/AACVPR Evidence-Based Clinical Practice Guidelines Chest, May 1, 2007; 131(5_suppl): 4S - 42S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ostrowski, J. E. Kuhns, J. A. Lupisella, M. C. Manfredi, B. C. Beehler, S. R. Krystek Jr., Y. Bi, C. Sun, R. Seethala, R. Golla, et al. Pharmacological and X-Ray Structural Characterization of a Novel Selective Androgen Receptor Modulator: Potent Hyperanabolic Stimulation of Skeletal Muscle with Hypostimulation of Prostate in Rats Endocrinology, January 1, 2007; 148(1): 4 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A M Solomon and P M G Bouloux Modifying muscle mass - the endocrine perspective. J. Endocrinol., November 1, 2006; 191(2): 349 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. T. Villareal and J. O. Holloszy DHEA enhances effects of weight training on muscle mass and strength in elderly women and men Am J Physiol Endocrinol Metab, November 1, 2006; 291(5): E1003 - E1008. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Orwoll, L. C. Lambert, L. M. Marshall, J. Blank, E. Barrett-Connor, J. Cauley, K. Ensrud, S. R. Cummings, and for the Osteoporotic Fractures in Men Study Group Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med, October 23, 2006; 166(19): 2124 - 2131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.-M. Axell, H. E. MacLean, D. R. Plant, L. J. Harcourt, J. A. Davis, M. Jimenez, D. J. Handelsman, G. S. Lynch, and J. D. Zajac Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice Am J Physiol Endocrinol Metab, September 1, 2006; 291(3): E506 - E516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Sinha-Hikim, M. Cornford, H. Gaytan, M. L. Lee, and S. Bhasin Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and Satellite Cells in Community-Dwelling Older Men J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 3024 - 3033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ferrucci, M. Maggio, S. Bandinelli, S. Basaria, F. Lauretani, A. Ble, G. Valenti, W. B. Ershler, J. M. Guralnik, and D. L. Longo Low testosterone levels and the risk of anemia in older men and women. Arch Intern Med, July 10, 2006; 166(13): 1380 - 1388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhasin, G. R. Cunningham, F. J. Hayes, A. M. Matsumoto, P. J. Snyder, R. S. Swerdloff, and V. M. Montori Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 1995 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Handelsman The Rationale for Banning Human Chorionic Gonadotropin and Estrogen Blockers in Sport J. Clin. Endocrinol. Metab., May 1, 2006; 91(5): 1646 - 1653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. Giannoulis, P. H. Sonksen, M. Umpleby, L. Breen, C. Pentecost, M. Whyte, C. V. McMillan, C. Bradley, and F. C. Martin The Effects of Growth Hormone and/or Testosterone in Healthy Elderly Men: A Randomized Controlled Trial J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 477 - 484. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. B. O'Donnell, T. G. Travison, S. S. Harris, J. L. Tenover, and J. B. McKinlay Testosterone, Dehydroepiandrosterone, and Physical Performance in Older Men: Results from the Massachusetts Male Aging Study J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 425 - 431. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Laghi Low Testosterone in Chronic Obstructive Pulmonary Disease: Does It Really Matter? Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1069 - 1070. [Full Text] [PDF]
|
|
|
|
|
|
T. N. Zhuang, L. P. Ly, R. G. Cumming, and D. J. Handelsman Growth and Development during Early Manhood as Determinants of Prostate Size in Later Life J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6055 - 6063. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Van Vliet, M. A. Spruit, G. Verleden, A. Kasran, E. Van Herck, F. Pitta, R. Bouillon, and M. Decramer Hypogonadism, Quadriceps Weakness, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease Am. J. Respir. Crit. Care Med., November 1, 2005; 172(9): 1105 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Kaufman and A. Vermeulen The Decline of Androgen Levels in Elderly Men and Its Clinical and Therapeutic Implications Endocr. Rev., October 1, 2005; 26(6): 833 - 876. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. B. Gray, A. B. Singh, L. J. Woodhouse, T. W. Storer, R. Casaburi, J. Dzekov, C. Dzekov, I. Sinha-Hikim, and S. Bhasin Dose-Dependent Effects of Testosterone on Sexual Function, Mood, and Visuospatial Cognition in Older Men J. Clin. Endocrinol. Metab., July 1, 2005; 90(7): 3838 - 3846. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
