Testosterone supplementation therapy for older men: Potential benefits and risks

Journal of the American Geriatrics Society

Volumn 51, Issue 1, 2003, Pages 101-115

  Gruenewald, David A ^a,b   Matsumoto, Alvin M ^a  

^a UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

^b VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

Author keywords

Aging; Androgens; Hormone replacement therapy; Hypogonadism; Testosterone

Indexed keywords

PROSTATE SPECIFIC ANTIGEN; TESTOSTERONE;

AFFECTIVE PSYCHOSIS; AGED; AGING; ANDROGEN THERAPY; ARTICLE; COGNITION; DRUG EFFICACY; DRUG SAFETY; ERECTILE DYSFUNCTION; FUNCTIONAL ASSESSMENT; HEART MUSCLE ISCHEMIA; HEMATOCRIT; HORMONE DEFICIENCY; HORMONE SUBSTITUTION; HUMAN; LEAN BODY WEIGHT; LIBIDO; MALE; MUSCLE ATROPHY; MUSCLE STRENGTH; PHYSICAL ACTIVITY; QUALITY OF LIFE; RISK BENEFIT ANALYSIS; SEXUAL FUNCTION; TESTOSTERONE BLOOD LEVEL;

AGED; AGING; BODY COMPOSITION; BONE DENSITY; COGNITION; CORONARY DISEASE; GONADAL STEROID HORMONES; HAND STRENGTH; HUMANS; HYPOGONADISM; MALE; MYOCARDIAL ISCHEMIA; OUTCOME ASSESSMENT (HEALTH CARE); TESTOSTERONE;

EID: 0037241928     PISSN: 00028614     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1601-5215.2002.51018.x     Document Type: Article

References (98)

1. Tenover JL. Male hormone replacement therapy including "andropause". Endocrinol Metab Clin North Am 1998;27:969-987.
2. Swerdloff RS, Wang C. Androgen deficiency and aging in men. West J Med 1993;159:579-585.
3. Tenover JS. Male hormonal changes with aging. In: Morley JE, Korenman SG, eds. Endocrinology and Metabolism in the Elderly. Cambridge, MA: Blackwell Scientific Publications, 1992, pp 243-261.
4. Vermeulen A, Rubens R, Verdonck L. Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab 1972;34:730-735.
5. Gray A, Berlin JA, McKinlay JB er al. An examination of research design effects on the association of testosterone and male aging: Results of a meta-analysis. J Clin Epidemiol 1991;44:671-684.
6. Zmuda JM, Cauley JA, Kriska A et al. Longitudinal relation between endogenous testosterone and cardiovascular risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997;146:609-617.
7. Morley JE, Kaiser FE, Perry HM III et al. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 1997;46:410-413.
8. Harman SM, Metter EJ, Tobin JD et al. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724-731.
9. Rudman D, Mattson DE, Nagraj HS et al. Plasma testosterone in nursing home men. J Clin Epidemiol 1988;41:231-236.
10. Kosasih JB, Abbasi AA, Rudman D. Serum insulin-like growth factor-I and serum testosterone status of elderly men in an inpatient rehabilitation unit. Am J Med Sci 1996;311:169-173.
11. Binkley N, Drinka PJ, Schultz S et al. Clinical prediction of testosterone deficiency in male nursing home residents. Nurs Home Med 1995;3:295-299.
12. Bhasin S, Storer TW, Berman N et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1-7.
13. Snyder PJ, Peachey H, Berlin JA et al. Effects of testosterone replacement in hypogonadal men. J Clin Endocrinol Metab 2000;85:2670-2677.
14. Behre HM, Kliesch S, Leifke E et al. Long-term effect of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 1997;82:2386-2390.
15. Katznelson L, Finkelstein JS, Schoenfeld DA et al. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996;81:4358-4365.
16. Anderson FH, Francis RM, Faulkner K. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Bone 1996;18:171-177.
17. Stanley HL, Schmitt BP, Poses RM et al. Does hypogonadism contribute to the occurrence of a minimal trauma hip fracture in elderly men? J Am Geriatr Soc 1991;39:766-771.
18. Jackson JA, Riggs MW, Spiekerman AM. Testosterone deficiency as a risk factor for hip fractures in men: A case-control study. Am J Med Sci 1992;304:4-8.
19. Abbasi AA, Rudman D, Wilson CR et al. Observations on nursing home residents with a history of hip fracture. Am J Med Sci 1995;310:229-234.
20. Tenover JS. Testosterone and the aging male. J Androl 1997;18:103-106.
21. Gouchie C, Kimura D. The relationship between testosterone levels and cognitive ability patterns. Psychoneuroendocrinology 1991;16:323-334.
22. O'Carroll R, Shapiro C, Bancroft J. Androgens, behaviour and nocturnal erection in hypogonadal men: The effects of varying the replacement dose. Clin Endocrinol (Oxf) 1985;23:527-538.
23. Burris AS, Banks SM, Carter CS et al. A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl 1992;13:297-304.
24. Cappa SF, Guariglia C, Papagno C et al. Patterns of lateralization and performance levels for verbal and spatial tasks in congenital androgen deficiency. Behav Brain Res 1988;31:177-183.
25. Davidson JM, Camargo CA, Smith ER. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab 1979;48:955-958.
26. Skakkebaek NE, Bancroft J, Davidson DW et al. Androgen replacement with oral testosterone undecanoate in hypogonadal men: A double blind controlled study. Clin Endocrinol (Oxf) 1981;14:49-61.
27. Kwan M, Greenleaf WJ, Mann J et al. The nature of androgen action on male sexuality: A combined laboratory-self-report study on hypogonadal men. J Clin Endocrinol Metab 1983;57:557-562.
28. Wang C, Swerdloff RS, Iranmanesh A et al. Transdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men. J Clin Endocrinol Metab 2000;85:2839-2853.
29. Morley JE, Kaiser F, Raum WJ et al. Potentially predictive and manipulable blood serum correlates of aging in the healthy human male: Progressive decreases in bioavailable testosterone, dehydroepiandrosterone sulfate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci U S A 1997;94:7537-7542.
30. Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: The Rancho Bernardo Study. J Clin Endocrinol Metab 1999;84:573-577.
31. Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999;84:3681-3685.
32. Phillips GB, Pinkernell BH, Jing TY. The association of hypotestosteronemia with coronary artery disease in men. Arterioscler Thromb 1994;14:701-706.
33. Alexandersen P, Haarbo J, Christiansen C. The relationship of natural androgens to coronary heart disease in males: A review. Atherosclerosis 1996;125:1-13.
34. Yue P, Chatterjee K, Beale C et al. Testosterone relaxes rabbit coronary arteries and aorta. Circulation 1995;91:1154-1160.
35. Chou TM, Sudhir K, Hutchison SJ et al. Testosterone induces dilation of canine coronary conductance and resistance arteries in vivo. Circulation 1996;94:2614-2619.
36. Bhasin S, Bagatell CJ, Bremner WJ et al. Issues in testosterone replacement in older men. J Clin Endocrinol Metab 1998;83:3435-3448.
37. Bross R, Javanbakht M, Bhasin S. Anabolic interventions for aging-associated sarcopenia. J Clin Endocrinol Metab 1999;84:3420-3430.
38. Tenover JL. Experience with testosterone replacement in the elderly. Mayo Clin Proc 2000;75(Suppl.):S77-S82.
39. Jadad AR, Moore RA, Carroll D et al. Assessing the quality of reports of randomized clinical trials: Is blinding necessary? Control Clin Trials 1996;17:1-12.
40. Dobs AS, Hoover DR, Chen MC et al. Pharmacokineric characteristics, efficacy, and safety of buccal testosterone in hypogonadal males: A pilot study. J Clin Endocrinol Metab 1998;83:33-39.
41. O'Carroll R, Bancroft J. Testosterone therapy for low sexual interest and erectile dysfunction in men: A controlled study. Br J Psychiatry 1984;145:146-151.
42. Sih R, Morley JE, Kaiser FE et al. Testosterone replacement in older hypogonadal men: A 12-month randomized controlled trial. J Clin Endocrinol Metab 1997;82:1661-1667.
43. Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992;75:1092-1098.
44. Snyder PJ, Peachey H, Hannoush P et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999;84:2647-2653.
45. Marin P, Holmang S, Gustafsson C et al. Androgen treatment of abdominally obese men. Obesity Res 1993;1:245-251.
46. Munzer T, Harman SM, Hees P et al. Effects of GH and/or sex steroid administration on abdominal subcutaneous and visceral fat in healthy aged women and men. J Clin Endocrinol Metab 2001;86:3604-3610.
47. Ivey FM, Harman SM, Hurley BF et al. Effects of GH and/or sex steroid administration on thigh muscle and fat by magnetic resonance imaging (MRI) in healthy elderly men and women [Abstract]. In: Proceedings of the Endocrine Society 81st Annual Meeting, June 12-15, 1999. San Diego, CA. Bethesda, MD: Endocrine Society Press, 1999, p 390.
48. Blackman MR, Christmas C, O'Connor KG et al. Effects of growth hormone and/or sex steroid administration on body composition in healthy elderly women and men [Abstract]. In: Proceedings of the Endocrine Society 81st Annual Meeting, June 12-15, 1999. San Diego, CA. Bethesda, MD: Endocrine Society Press, 1999, p 391.
49. Kenny AM, Prestwood KM, Gruman CA et al. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. J Gerontol A Biol Sci Med Sci 2001;56A:M266-M272.
50. Bebb R, Anawalt B, Wade J et al. A randomized, double blind, placebo controlled trial of testosterone undecanoate administration in aging hypogonadal men: Effects on bone density and body composition [Abstract]. In: Proceedings of the Endocrine Society 83rd Annual Meeting, June 20-23, 2001. Denver, CO. Bethesda, MD: Endocrine Society Press, 2001, pp 100-101.
51. Brill K, Weltman A, Gentili A et al. Single and joint impact of one month of transdermal testosterone (T) and/or recombinant human growth hormone (rhGH) supplementation on body composition, strength, balance, function, and muscle IGF-I and androgen gene expression in healthy older men: A prospective randomized double-blind crossover study [Abstract]. In: Proceedings of the Endocrine Society 82nd Annual Meeting, June 21-24, 2000. Toronto, Canada. Bethesda, MD: Endocrine Society Press, 2000, p 398.
52. Clague JE, Wu FC, Horan MA. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Int J Androl 1999;22:261-265.
53. Snyder PJ, Peachey H, Hannoush P et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84:1966-1972.
54. Edmond J, Busby-Whitehead MJ, Harman SM et al. Effects of growth hormone and/or sex steroid administration on aerobic capacity in healthy elderly women and men [Abstract]. In: Proceedings of the Endocrine Society 81st Annual Meeting, June 12-15, 1999. San Diego, CA. Bethesda, MD: Endocrine Society Press, 1999, p 392.
55. Amory JK, Chansky HC, Anawalt BD et al. Supraphysiologic androgen administration in elderly men undergoing joint replacement surgery [Abstract]. In: J Androl (Suppl.). Proceedings of the 7th International Congress of Andrology. June 15-19, 2001. Montreal, Canada. Lawrence, KS: Allen Press, 2001, p 175.
56. Bakhshi V, Elliott M, Gentili A et al. Testosterone improves rehabilitation outcomes in ill older men. J Am Geriatr Soc 2000;48:550-553.
57. Gentili A, Mulligan T, Godschalk M et al. Testosterone supplementation increases growth hormone secretion in older men [Abstract]. In. Proceedings of the Endocrine Society 82nd Annual Meeting, June 21-24, 2000. Toronto, Canada. Bethesda, MD: Endocrine Society Press, 2000, p 470.
58. Nankin HR, Lin T, Osterman J. Chronic testosterone cypionate therapy in men with secondary impotence. Fertil Steril 1986;46:300-307.
59. Benkert O, Witt W, Adam W et al. Effects of testosterone undecanoate on sexual potency and the hypothalamic-pituitary-gonadal axis of impotent males. Arch Sex Behav 1979;8:471-479.
60. Schiavi RC, White D, Mandeli J et al. Effect of testosterone administration on sexual behavior and mood in men with erectile dysfunction. Arch Sex Behav 1997;26:231-241.
61. Holmang S, Marin P, Lindstedt G et al. Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum prostate-specific antigen concentrarion in eugonadal middle-aged men. Prostate 1993;23: 99-106.
62. Tenover JS. Effect of testosterone (T) and 5-alpha-reductase inhibitor (5-ARI) administration on the responses to a sexual function questionnaire in older men [Abstract]. J Androl 1992;13:50.
63. Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men. Behav Neurosci 1994;108:325-332.
64. Janowsky JS, Chavez B, Orwoll E. Sex steroids modify working memory. J Cogn Neurosci 2000;12:407-414.
65. Cherrier MM, Asthana S, Plymate S et al. Testosterone supplementation improves spatial and verbal memory in healthy older men. Neurology 2001;57: 80-88.
66. Wolf OT, Preut R, Hellhammer DH et al. Testosterone and cognition in elderly men: A single testosterone injection blocks the practice effect in verbal fluency, but has no effect on spatial or verbal memory. Biol Psychiatry 2000;47:650-654.
67. Christmas C, Harman SM, Munzer T et al. Effects of growth hormone and/or sex steroid administration on serum lipid profiles in healthy elderly women and men [Abstract]. In: Proceedings of the Endocrine Society 81st Annual Meeting, June 12-15, 1999. San Diego, CA. Bethesda, MD: Endocrine Society Press, 1999, p 394.
68. Uyanik BS, Ari Z, Gumus B et al. Beneficial effects of testosterone undecanoate on the lipoprotein profiles in healthy elderly men. A placebo controlled study. Jpn Heart J 1997;38:73-82.
69. Marin P, Oden B, Bjorntorp P. Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: Effects of androgens. J Clin Endocrinol Metab 1995;80:239-243.
70. Webb CM, Adamson DL, de Zeigler D et al. Effect of acute testosterone on myocardial ischemia in men with coronary artery disease. Am J Cardiol 1999;83:437-439.
71. Rosano GM, Leonardo F, Pagnotta P et al. Acute anti-ischemic effect of testosterone in men with coronary artery disease. Circulation 1999;99:1666-1670.
72. English KM, Steeds RP, Jones TH et al. Low-dose transdermal testosterone therapy improves angina threshold in men with chronic stable angina. Circulation 2000;102:1906-1911.
73. Jaffe MD. Effect of testosterone cypionate on postexercise ST segment depression. Br Heart J 1977;39:1217-1222.
74. Sigler LH, Tulgan J. Treatment of angina pectoris by testosterone propionate. N Y State J Med 1943;43:1424-1428.
75. Ong PJL, Patrizi G, Chong WCF et al. Testosterone enhances flow-mediated brachial artery reactivity in men with coronary artery disease. Am J Cardiol 2000;85:269-272.
76. Harman SM, Pabst KM, Munzer T et al. Adverse effects observed in healthy women and men over 65 years of age treated with GH and sex steroid hormone replacement [Abstract]. In: Proceedings of the Endocrine Society 82nd Annual Meeting, June 21-24, 2000. Toronto, Canada. Bethesda, MD: Endocrine Society Press, 2000, p 395.
77. Drinka PJ, Jochen AL, Cuisinier M et al. Polycythemia as a complication of testosterone replacement therapy in nursing home men with low tesrosterone levels. J Am Geriatr Soc 1995;43:899-901.
78. Bagatell CJ, Knopp RH, Vale WW et al. Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels. Ann Intern Med 1992;116:967-973.
79. Bagatell CJ, Heiman JR, Matsumoto AM et al. Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J Clin Endocrinol Metab 1994;79:561-567.
80. Matsumoto AM, Sandblom RE, Schoene RB et al. Testosterone replacement in hypogonadal men. Effects on obstructive sleep apnea, respiratory drives, and sleep. Clin Endocrinol (Oxf) 1985;22:713-721.
81. Swerdloff RS, Bhasin S, Blackman MR et al. Summary of the Consensus Session From the 1st Annual Andropause Consensus 2000 Meeting; 28-30 April, 2000 Beverly Hills, CA. Bethesda, MD. Endocrine Society Press, 2000, pp. 1-6.
82. Cook DJ, Mulrow CD, Haynes RB. Systematic reviews. Synthesis of best evidence for clinical decisions. Ann Intern Med 1997;126:376-380.
83. McAlister FA, Clark HD, van Walraven C et al. The medical review article revisited: Has the science improved? Ann Intern Med 1999;131:947-951.
84. Rosenfeld RM. How to systematically review the medical literature. Otolaryngol Head Neck Surg 1996;115:53-63.
85. Ly LP, Jiminez M, Zhuang TN et al. 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 2001;86:4078-4088.
86. Khan KS, Daya S, Jadad AR. The importance of quality of primary studies in producing unbiased systematic reviews. Arch Intern Med 1996;156:661-666.
87. Snyder PH, Peachey H, Berlin JA et al. Effect of transdermal testosterone treatment on serum lipid and apolipoprotein levels in men more than 65 years of age. Am J Med 2001;111:255-260.
88. Bhasin S, Buckwalter JG. Testosterone supplementation in older men: A rational idea whose time has not yet come. J Androl 2001;22:718-731.
89. Vermeulen A. Androgen replacement therapy in the aging male - a critical evaluation. J Clin Endocrinol Metab 2001;86:2380-2390.
90. Matsumoto AM. Andropause: Clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A Biol Sci Med Sci 2002;57A:M76-M99.
91. Morley JE, Charlton E, Patrick P et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000;49:1239-1242.
92. Christmas C, O'Connor KG, Harman SM et al. Growth hormone and sex steroid effects on bone metabolism and bone mineral density in healthy aged women and men. J Gerontol Biol Sci Med Sci 2002;57A:M12-M18.
93. Ferrando AA, Sheffield-Moore M, Yeckel CW et al. Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. Am J Physiol Endocrinol Metab 2002;282:E601-E607.
94. Gentili A, Mulligan T, Godschalk M et al. Unequal impact of short-term testosterone repletion on the somatotropic axis of young and older men. J Clin Endocrinol Metab 2002;87:825-834.
95. Amory JK, Chansky HA, Chansky KL et al. Preoperative supraphysiological testosterone in older men undergoing knee replacement surgery. J Am Geriatr Soc 2002;50:1698-1701.
96. Kenny AM, Bellantonio S, Gruman CA et al. Effects of transdermal testosterone on cognitive function and health perception in older men with low bioavailable testosterone levels. J Gerontol Biol Sci Med Sci 2002;57A:M321-M325.
97. Thompson PD, Ahlberg AW, Moyna NM et al. Effect of inrravenous testosrerone on myocardial ischemia in men with coronary artery disease. Am Heart J 2002;143:249-256.
98. Kenny AM, Presrwood KM, Gruman CA et al. Effects of transdermal testosterone on lipids and vascular reactivity in older men with low bioavailable testosterone levels. J Gerontol Biol Sci Med Sci 2002;57A:M460-M465.