Single and combined effects of growth hormone and testosterone administration on measures of body composition, physical performance, mood, sexual function, bone turnover, and muscle gene expression in healthy older men

Journal of Clinical Endocrinology and Metabolism

Volumn 87, Issue 12, 2002, Pages 5649-5657

  Brill, Kimberly T ^a   Weltman, Arthur L ^a   Gentili, Angela ^c   Patrie, James T ^a   Fryburg, David A ^a   Hanks, John B ^b   Urban, Randall J ^d   Veldhuis, Johannes D ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

^b UNIVERSITY OF VIRGINIA   (United States)

^c VIRGINIA COMMONWEALTH UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d University of Texas Medical Branch School of Medicine   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; ESTRADIOL; HUMAN GROWTH HORMONE; MYOSTATIN; OSTEOCALCIN; SOMATOMEDIN C; TESTOSTERONE;

AGED; ARTICLE; BODY COMPOSITION; BODY FAT; BODY MASS; BONE TURNOVER; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; ESTRADIOL BLOOD LEVEL; GROWTH HORMONE BLOOD LEVEL; HORMONAL THERAPY; HUMAN; HUMAN EXPERIMENT; HUMAN TISSUE; MALE; MOOD; NORMAL HUMAN; PHYSICAL ACTIVITY; PHYSICAL PERFORMANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SEXUAL FUNCTION; STRENGTH; TREATMENT OUTCOME; WALKING;

AFFECT; AGED; BODY COMPOSITION; BONE REMODELING; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; ESTRADIOL; GENE EXPRESSION; HUMAN GROWTH HORMONE; HUMANS; INSULIN-LIKE GROWTH FACTOR I; MALE; MIDDLE AGED; MUSCLE, SKELETAL; MUSCULOSKELETAL EQUILIBRIUM; PHYSICAL FITNESS; RECOMBINANT PROTEINS; SEX HORMONE-BINDING GLOBULIN; SEXUAL BEHAVIOR; TESTOSTERONE;

EID: 0036924729     PISSN: 0021972X     EISSN: None     Source Type: Journal    
DOI: 10.1210/jc.2002-020098     Document Type: Article

References (61)

1. Iranmanesh A, Lizzarlde G, Veldhuis JD 1991 Age and relative adiposity are specific negative determinants of the frequency and amplitude of growth hormone (GH) secretory burst and half-life of endogenous GH in healthy men. J Clin Endocrinol Metab 73:1081-1088
2. Veldhuis JD, Iranmanesh A, Weltman A 1997 Elements in the pathophysiology of diminished growth hormone (GH) secretion in aging humans. Endocrine 7:41-48
3. Veldhuis JD, Liem AY, South S, Weltman A, Weltman J, Clemmons DA, Abbott R, Mulligan T, Johnson ML 1995 Differential impact of age, sex steroid hormones, and obesity on basal vs. pulsatile growth hormone secretion in men assessed in an ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 80:3209-3222
4. Baker HW, Burger HG, de Krester DM, Hudson B, O'Connor S, Wang C, Mirovics A, Court J, Dunlop M, Rennie GC 1967 Changes in the pituitary testicular system with age. Clin Endocrinol (Oxf) 5:349-372
5. Snyder PJ 2001 Effects of age on testicular function and consequences of testosterone treatment. J Clin Endocrinol Metab 86:2369-2372
6. Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR 2001 Longitudinal effects of aging on serum total and free testosterone levels in healthy men. J Clin Endocrinol Metab 86:724-731
7. Davidson J, Chen JJ, Crapo L, Gary GD, Greenleaf WJ, Catania JA 1983 Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab 57:71-77
8. Desylpere JP, Vermuelen A 1984 Leydig cell function in normal men: Effect of age, lifestyle, residency, diet and activity. J Clin Endocrinol Metab 59:955-962
9. Kaiser FE, Viosca SP, Morley JE, Mooradian AD, Davis SS, Korenman SG 1988 Impotence and aging: Clinical and hormonal factors. J Am Geriatr Soc 36:511-519
10. Nankin HR, Calkin JG 1986 Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab 63:1418-1420
11. Stearns EL, MacDonnel JA, Kaufman BL, Padua R, Lucman TS, Winter JS, Faiman C 1974 Declining testicular function with age: Hormonal and clinical correlates. Am J Med 57:761-766
12. Veldhuis JD, Urban RJ, Lizzarlde G, Johnson ML, Iranmanesh A 1995 Attenuation of luteinizing hormone secretory burst amplitude is a proximal basis for hypoandrogenism of healthy aging in men. J Clin Endocrinol Metab 80:3025-3031
13. Wallymahed ME, Foy P, Shaw D, Hutcheon R, Edwards RH, MacFarlane IA 1997 Quality of life, body composition and muscle strength in adult growth hormone deficiency: The influence of growth hormone replacement therapy for up to 3 years. Clin Endocrinol (Oxf) 47:439-446
14. Woodhouse LJ, Asa SL, Thomas SG, Ezzat S 1999 Measures of submaximal aerobic performance evaluate and predict functional response to growth hormone (GH) treatment in GH-deficient adults. J Clin Endocrinol Metab 84:4570-4577
15. Welle S, Thornton C, Statt M, McHenry B 1996 Growth hormone increases muscle mass and strength but does not rejuvenate myofibrillar protein in healthy subjects over 60 years old. J Clin Endocrinol Metab 81:3239-3243
16. Papadakis MA, Grady D, Black D, Tierney MJ, Gooding GA, Schambelan M, Grunfeld C 1996 Growth hormone replacement in healthy older men improves body composition but not functional ability. Ann Intern Med 124:708-716
17. Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE 1990 Effects of human growth hormone in men over 60 years old. N Engl J Med 323:1-6
18. Rudman D, Feller AG, Nagraj HS, Cohn L, Shetty KR, Rudman IW, Draper MW 1991 Effects of growth hormone on body composition in elderly men. Horm Res 36(Suppl 1):73-81
19. Marcus R, Butterfield G, Holloway L, Gilliland L, Baylink DJ, Hintz RL, Sherman BM 1990 Effects of short term administration of recombinant human growth hormone to elderly people. J Clin Endocrinol Metab 70:519-527
20. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Diewati A, Santanna J, Rosen CJ, Strom BL 1999 Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647-2653
21. Snyder PJ, Peachey H, Berlin JA, Hannoush P, Haddad G, Diewati A, Santanna J, Loh L, Lenrow DA, Holmes JH, Kapoor SC, Atkinson LE, Strom BL 2000 Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 85:2670-2677
22. Bhasin S, Storer TW, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee WP, Bunnell TJ, Casaburi R 1997 Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 82: 407-413
23. Tenover JC 1992 Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 75:1092-1098
24. Wang C, Eyre DR, Clark R, Kleinberg D, Newman C, Iranmanesh A, Veldhuis J, Dudley RE, Berman N, Davidson T, Barstow TJ, Sinow R, Alexander G, Swerdloff RS 1996 Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption and increases bone formation markers in hypogonadal men. J Clin Endocrinol Metab 8:3654-3662
25. Wang C, Swerdloff RS, Iranmanesh A, Dobs A, Snyder PJ, Cunningham G, Matsumoto AM, Weber T, Berman N 2000 Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 85:2839-2853
26. Griggs RC, Kingston W, Jozefowicz RF, Herr BE, Forbes G, Halliday D 1989 Effect of testosterone on muscle mass and muscle protein synthesis. J App1 Physiol 66:498-503
27. Johannsson G, Grimby G, Sunnerhagen KS, Bengston BA 1997 Two years of growth hormone treatment increase isometric and isokinetic muscle strength in GH deficient adults. J Clin Endocrinol Metab 82:2877-2884
28. Urban RJ, Bodenburg YH, Gilkison C, Foxworth J, Coggan AR, Wolfe RR, Ferando A 1995 Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 269:820-826
29. Sih R, Morley JE, Kaiser FE, Perry 3rd HM, Patrick P, Ross C 1997 Testosterone replacement in older hypogonadal men: A 12-month randomized controlled trial. J Clin Endocrinol Metab 82:1661-1667
30. Urban RJ, Gilkison C, Jiang J, Marcell T, Tipton K, Sheffield-Moore M, Yeckel CW, Lieberman S, Ferrando AA, Testosterone administration to older men for six months increases skeletal muscle strength, net muscle protein balance, and the expression of intramuscular IGF-I transcripts. Program of the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000, p 393 (Abstract 1628)
31. Morley JE, Perry 3rd HM, Kaiser FE, Kraenzle D, Jensen J, Houston K, Mattammal M, Perry Jr HM 1993 Effects of testosterone replacement therapy in old hypogonadal males: A preliminary study. J Am Geriatr Soc 41:149-152
32. Behre HM, Kleish S, Leife E, Link TM, Nieschlag E 1997 Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 82:2386-2390
33. Hajjar RR, Kaiser FE, Morley JE 1997 Outcomes of long-term testosterone replacement in older hypogonadal men: A retrospective analysis. J Clin Endocrinol Metab 82:3793-3796
34. Salehian B, Wang C, Alexander G, Davidson T, McDonald V, Berman N, Dudley RE, Ziel F, Swerdloff RS 1995 Pharmacokinetics, bioefficacy, and safety of sublingual testosterone cyclodextrin in hypogonadal men: Comparison to testosterone enanthate. J Clin Endocrinol Metab 80:3567-3575
35. Vermeulen A 2001 Androgen replacement therapy in the aging male-a critical evaluation. J Clin Endocrinol Metab 86:2380-2390
36. Borst SE, Millard WJ, Lowenthal DT 1994 Growth hormone, exercise and aging: The future of therapy of the frail elderly. J Am Geriatr Soc 42:528-535
37. Bengtsson BA, Abs R, Monson J, Wuster C, Wilton P, No increased mortality in growth-hormone treated adults. Experience from KIMS. Program of the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000, p 472 (Abstract 1951)
38. Hartman M, Crowe B, Melmed S, Kleinberg D, Chipman JJ, Safety of GH replacement therapy for adult GH deficiency (GHD): Comparison of adverse event profiles in treated and untreated patients. Program of the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000, p 471 (Abstract 1950)
39. Harman SM, Pabst KM, Munzer T, Christmas C, O'Connor KG, Bellantoni MF, Busby-Whitehead MJ, Stevens TM, Sorkin JD, Blackman MR, Adverse effects observed in healthy women and men over 65 years of age treated with GH and sex-steroid hormone replacement. Program of the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000, p 395 (Abstract 1635)
40. Roch GC, Landis JR, Freeman JL, Freeman DH, Lehnen RG 1977 A general methodology for the analysis of experiments with repeated measurements of chronological data. Biometrics 33:133-158
41. Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS 1996 Testosterone replacement therapy improves mood in hypogonadal men-a clinical research center study. J Clin Endocrinol Metab 81:3578-3583
42. Veldhuis JD, Johnson ML 1986 Cluster analysis: A simple, versatile and robust algorithm for endocrine pulse detection. Am J Physiol 250:E486-E493
43. Katch FI, Micheal ED, Horvath SM 1967 Estimation of body volume by underwater weighing: Description of a simple method. J Appl Physiol 23: 811-813
44. Dempster P, Aitkens S 1995 A new air displacement method for the determination of human body composition. Med Sci Sport Exerc 27:1692-1697
45. Wilmore JH 1969 A simple method for the determination of residual lung volume. J Appl Physiol 27:96-100
46. Brozek J, Grande F, Anderson JT, Keys A 1963 Densitometric analysis of body composition of men from girth measurements: Revisions of some quantitative assumptions. Ann N Y Acad Sci 110:113-140
47. Lam P, Jimenez M, Zhaung TN, Celermajer DS, Conway AJ, Handelsman DJ 2001 A double-blind, placebo controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab 86:4078-4088
48. Munzer T, Harman SM, Hees P, Shapiro E, Christmas C, Bellantoni MF, Stevens TE, O'Connor KG, Pabst KM, St Clair C, Sorkin JD, Blackman MR 2001 Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 86:3604-3610
49. Deijen JB, de Boer H, van der Veen EA 1998 Cognitive changes during growth hormone replacement in adult men. Psychoneuroendocrinology 23:45-55
50. Vermeulen A 1991 Androgens in the aging male. J Clin Endocrinol Metab 73:221-224
51. Hayes VY, Urban RJ, Jiang J, Marcell TJ, Helgeson K, Mauras N 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 86:2211-2219
52. Kenny AM, Prestwood, KM, Gruman CA, Marcello KM, Raisz LG 2001 Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 56:M266-M272
53. Falahati-Nini A, Riggs BL, Atkinson EJ, O'Fallon WM, Eastell R, Khosla S 2000 Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 106:1553-1560
54. De Rosa M, Paesano L, Nuzzo V, Zarrilli S, Del Puente A, Oriente P, Lupoli G 2001 Bone mineral density and bone markers in hypogonadotrophic hypogonadal men after prolonged testosterone treatment. J Endocrinol Invest 24:246-252
55. Wuster C, Abs R, Bengsston BA, Bennmarker H, Feldt-Rasmussen U, Hernberg-Stahl E, Monson JP, Westberg B, Wilton P; The KIMS Study Group and the KIMS International Board. Pharmacia & Upjohn International Metabolic Database 2001 The influence of growth hormone deficiency, growth hormone replacement therapy, and other aspects of hypopituitarism on fracture rate and bone mineral density. J Bone Miner Res 16:398-405
56. Nilsson AG 2000 Effects of growth hormone replacement therapy on bone markers and bone mineral density in growth hormone deficient adults. Horm Res 54:52-57
57. Gurlek A, Gedik O 2001 Endogenous sex steroid, GH, and IGF-I levels in normal elderly men: Relationship with bone mineral density and markers of bone turnover. J Endocrinol Invest 24:408-414
58. Drake WM, Rodriguez-Arnao J, James IT, James IT, Coyte D, Spector TD, Besser GM, Monson JP 2001 The influence of gender on the short and long-term effects of growth hormone replacement on bone metabolism and bone mineral density in hypopituitary adults: A 5-year study. Clin Endocrinol (Oxf) 54:525-532
59. Sartorio A, Ortolani S, Galbaiti E, Conte G, Vangeli V, Arosia M, Poretti S, Faglia G 2001 Effects of 12-month GH treatment on bone metabolism and bone mineral density in adults with adult-onset GH deficiency. J Endocrinol Invest 24:224-230
60. Gonzalez-Cadavid NF, Taylor WE, Yarasheski K, Sinha-Hikim I, Ma K, Ezzat S, Shen R, Lalani R, Asa S, Mamita M, Nair G, Arver S, Bhasin S 1998 Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting. Proc Natl Acad Sci USA 95:14938-14943
61. Blackman MR, Bellantoni MF, Busby-Whitehead J, Stevens T, O'Connor KG, Jayme J, Christmas C, Munzer T, Edmond J, Marcell TJ, Cottrell E, Stewart K, Tobin JD, Roy TA, Shapiro E, Hees P, Hurley B, Ivey FM, St Clair C, Pabst K, Sorkin JD, Harman SM, Growth hormone and sex steroid treatment of the elderly. Program of the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000, p 47 (Abstract 215)