Drugs & Aging

, Volume 15, Issue 2, pp 131–142

Risks Versus Benefits of Testosterone Therapy in Elderly Men

Review Article

Abstract

‘Andropause’, like menopause, has received significant attention in recent years. It results in a variety of symptoms experienced by the elderly. Many of these symptoms are nonspecific and vague. For this reason, many authors have questioned the value of androgen replacement in this population. Also in dispute is the normal cutoff level for testosterone beyond which therapy should be initiated, and whether to measure free or total testosterone. Testosterone levels decline with age, with the lowest level seen in men older than 70 years. This age-related decline in testosterone levels is both central (pituitary) and peripheral (testes) in origin. With aging, there is also a loss of circadian rhythm of testosterone secretion and a rise in sex hormone binding globulin (SHBG) levels. Total testosterone level is the best screening test for patients with suspected hypogonadism. If the total testosterone concentration is low, free testosterone levels should be obtained. Prostate cancer remains an absolute contraindication to androgen therapy. Testosterone replacement results in an improvement in muscle strength and bone mineral density. Similar effects are observed on the haematopoietic system. Data on cognition and lipoprotein profiles are conflicting. Androgen therapy can result in polycythemia and sleep apnoea. These adverse effects can be deleterious in men with compromised cardiac reserve. We recommend that elderly men with symptoms of hypogonadism and a total testosterone level <300 ng/dl should be started on testosterone replacement. This review discusses the pros and cons of testosterone replacement in hypogonadal elderly men and attempts to answer some of the unanswered questions. Furthermore, emphasis is made on the regular follow-up of these patients to prevent the development of therapy-related complications.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Jeffcoate SL, Brocks RV, Lin NY, et al. Androgen production in hypogonadal men. J Endocrinol 1967; 37: 401–11PubMedCrossRefGoogle Scholar
  2. 2.
    Wheeler MJ. Determination of bio-available testosterone. Ann Clin Biochem 1995; 32: 345–57PubMedGoogle Scholar
  3. 3.
    Ekins R. Measurement of free hormones in blood. Endocr Rev 1990; 11: 5–46PubMedCrossRefGoogle Scholar
  4. 4.
    Meikel CM. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989; 10: 232–74CrossRefGoogle Scholar
  5. 5.
    Bremner WJ, Vitiello V, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983; 56: 1278–81PubMedCrossRefGoogle Scholar
  6. 6.
    Vermeulen A, Rubens R, Verdonck L. Testosterone secretion and metabolism in male senescence. J Clin Endocrinol Metab 1972; 34: 730–5PubMedCrossRefGoogle Scholar
  7. 7.
    Stearns EL, MacDonell JA, Kauffman BJ, et al. Declining testicular function with aging: hormonal and clinical correlates. Am J Med 1974; 57: 761–6PubMedCrossRefGoogle Scholar
  8. 8.
    Baker HWG, Burger HG, de Kretser DM, et al. Endocrinology of aging: pituitary testicular axis. Clin Endocrinol (Oxf) 1976; 5: 349–72CrossRefGoogle Scholar
  9. 9.
    Vermeulen A. Androgens in the aging male. J Clin Endocrinol Metab 1991; 73: 221–4PubMedCrossRefGoogle Scholar
  10. 10.
    Gray A, Feldman HA, McKinley JB, et al. Age, disease and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J Clin Endocrinol Metab 1991; 73: 1016–25PubMedCrossRefGoogle Scholar
  11. 11.
    Purifoy FE, Koopmans LH, Mayes DM. Age differences in serum androgen levels in normal adult males. Hum Biol 1981; 57: 71Google Scholar
  12. 12.
    Deslypere JP, Vermeulen A. Leydig cell function in normal men: effect of age, life-style, residence, diet, and activity. J Clin Endocrinol Metab 1984; 59: 955–62PubMedCrossRefGoogle Scholar
  13. 13.
    Morley JE, Kaiser FE, Perry III HM, et al. Longitudinal changes in testosterone, LH, and FSH in healthy older men. Metabolism 1997; 46(4): 410–3PubMedCrossRefGoogle Scholar
  14. 14.
    Harman SM, Tsitouras PD. Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and leydig cell response to human chorionic gonadotropin. J Clin Endocrinol Metab 1980; 51: 35–40PubMedCrossRefGoogle Scholar
  15. 15.
    Tenover JS, Matsumoto AM, Plymate SR, et al. The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphine citrate. J Clin Endocrinol Metab 1987; 65: 1118–26PubMedCrossRefGoogle Scholar
  16. 16.
    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 insulinlike growth factor 1 to growth hormone. Proc Natl Acad Sci 1997; 94: 7537–42PubMedCrossRefGoogle Scholar
  17. 17.
    Sniffen RC. The testes. I. The normal testes. Arch Pathol 1950; 50: 259–84Google Scholar
  18. 18.
    Tillinger KG. Testicular morphology. Acta Endocrinol Suppl (Copenh) 1957; Suppl. 30: 1–192Google Scholar
  19. 19.
    Harbitz TB. Morphometric study of Leydig cells in elderly men with special reference to the histology of the prostate. Acta Pathol Microbiol Scand 1973; 81: 301–13Google Scholar
  20. 20.
    Neaves WB, Johnson L, Porter JC, et al. Leydig cell numbers, daily sperm production and serum gonadotrophin levels in aging men. J Clin Endocrinol Metab 1984; 59: 756–63PubMedCrossRefGoogle Scholar
  21. 21.
    Sasano M, Ishyo S. Vascular patterns of the human testes with special reference to its senile changes. Tohoku J Exp Med 1969; 99: 269–80PubMedCrossRefGoogle Scholar
  22. 22.
    Suoranta H. Changes in small blood vessels of the adult human testes in relation to age and some pathological conditions. Virchows Arch Pathol Anat Physiol Klin Med 1971; 352: 765–81Google Scholar
  23. 23.
    Vermeulen A, Desylpere JP. Intratesticular unconjugated steroids in elderly men. J Steroid Biochem 1986; 24: 1079–89PubMedCrossRefGoogle Scholar
  24. 24.
    Desylpere JP, Vermeulen A. Leydig cell function in normal men: effect of age, lifestyle, residence, diet and activity. J Clin Endocrinol Metab 1989; 68: 68–72CrossRefGoogle Scholar
  25. 25.
    Vermeulen A, Desylpere JP, Kaufman JM. Influence of antiopioids and luteinizing hormone pulsatility in aging men. J Clin Endocrinol Metab 1989; 68: 68–72PubMedCrossRefGoogle Scholar
  26. 26.
    Winters SJ, Sherins RJ, Troen P. The gonadotropin suppressive activity of androgens is increased in elderly men. Metabolism 1984; 33: 1052–9PubMedCrossRefGoogle Scholar
  27. 27.
    Desylpere JP, Kaufman JM, Vermeulen T, et al. Influence of age on pulsatile luteinizing hormone release and responsiveness of the ganadotrophs to sex hormone feedback in men. J Clin Endocrinol Metab 1987; 64: 68–73CrossRefGoogle Scholar
  28. 28.
    McConnell JD. Prostatic growth: new insights into hormonal regulation. Br J Urol 1995; 76Suppl. 1: 5–10PubMedGoogle Scholar
  29. 29.
    Horton R. Benign prostatic hyperplasia: a disorder of androgen metabolism in the male. J Am Geriatr Soc 1984; 32: 380–85PubMedGoogle Scholar
  30. 30.
    Wilson JD. Recent studies on the mechanism of action of testosterone. N Engl J Med 1972; 287: 1284–94PubMedCrossRefGoogle Scholar
  31. 31.
    Rogers C, Coffey D, Cunha G, et al. Benign prostatic hyperplasia. Vol. II. Bethesda (MD): US Department of Health and Human Service. NIH publication no: 87-2881Google Scholar
  32. 32.
    McConnell JD. The pathophysiology of BHP. J Androl 1991; 12: 356–63PubMedGoogle Scholar
  33. 33.
    Liao S, Fang S. Receptor proteins for androgens and the mode of action of androgens on gene transcription in ventral prostate. Vitam Horm 1969; 27: 17–26PubMedCrossRefGoogle Scholar
  34. 34.
    Hulka BS, Hammond JE, DiFerdinando G, et al. Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls. Prostate 1987; 11: 171–82PubMedCrossRefGoogle Scholar
  35. 35.
    Carter HB, Pearson JD, Metter EJ, et al. Longitudinal evaluation of serum androgen levels in men with and without prostate cancer. Prostate 1995; 27: 25–31PubMedCrossRefGoogle Scholar
  36. 36.
    Gann PH, Hennekens CH, Longcope C, et al. A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate 1995; 26: 40–9PubMedCrossRefGoogle Scholar
  37. 37.
    McConnell JD, Wilson JD, George FW, et al. Finasteride, an inhibitor of 5-alpha reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992; 74: 505–8PubMedCrossRefGoogle Scholar
  38. 38.
    Ekman P. A risk benefit assessment of treatment with Finasteride in benign prostatic hyperplasia. Drug Saf 1998; 18(3): 161–70PubMedCrossRefGoogle Scholar
  39. 39.
    Stone NN, Clejan SJ. Response of prostate volume, prostate specific antigen, and testosterone to flutamide in men with benign prostatic hyperplasia. J Androl 1991; 12: 376–80PubMedGoogle Scholar
  40. 40.
    Peters CA, Walsh PC. The effect of nafarelin acetate, a luteinizing-hormone-releasing hormone agonist, on benign prostatic hyperplasia. N Engl J Med 1987; 317: 599–604PubMedCrossRefGoogle Scholar
  41. 41.
    Tenover JS. Effects of testosterone supplementation in the aging male. J Clin Endocrinol Metab 1992; 75: 1092–8PubMedCrossRefGoogle Scholar
  42. 42.
    Hartnell J, Korenman SG, Viosca SP. Results of testosterone enanthate therapy for hypogonadism in older men. Proceedings of the 72nd Annual Meeting of The Endocrine Society; 1990 Jun; 428Google Scholar
  43. 43.
    Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab 1997; 82: 3793–6PubMedCrossRefGoogle Scholar
  44. 44.
    Behre HM, Bohmeyer J, Nieschlag E. Prostate volume in testosterone treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol 1994; 40: 341–9CrossRefGoogle Scholar
  45. 45.
    Meikle AW, Arver S, Dobs AS, et al. Prostate size in hypogonadal men treated with a nonscrotal permeation-enhanced testosterone transdermal system. Urology 1997; 49: 191–6PubMedCrossRefGoogle Scholar
  46. 46.
    Marin P, Holmang S, Gustafsson C, et al. Androgen treatment of abdominally obese men [abstract]. Obes Res 1993; 1: 245PubMedGoogle Scholar
  47. 47.
    Orwoll E, Oviatt S, Biddle J, et al. Transdermal testosterone supplementation in normal older men [abstract no. 1071]. Programs and Abstracts of the 74th Annual Meeting of the Endocrine Society; 1992 Jun 24–27; San Antonio, 319Google Scholar
  48. 48.
    Melton III LJ. Epidemiology of fractures. In: Riggs BL, Melton III LJ, editors. Osteoporosis, etiology, diagnosis, and management. New York: Raven Press, 1988: 133–54Google Scholar
  49. 49.
    Genant HK, Cann CE, Pozzi-Mucelli S, et al. Vertebral mineral determination by quantitative CT: clinical feasibility and normative data [abstract]. J Comput Assist Tomogr 1981; 7: 554CrossRefGoogle Scholar
  50. 50.
    Meier DE, Orwoll ES, Jones JM. Marked disparity between trabecular and cortical bone loss with age in healthy men. Ann Intern Med 1984; 101: 605–12PubMedGoogle Scholar
  51. 51.
    Riggs BL, Wahner HW, Dunn WL, et al. Differential changes in bone mineral density of the appendicular and axial skeleton with aging: relationship to spin osteoporosis. J Clin Invest 1981; 67: 328–35PubMedCrossRefGoogle Scholar
  52. 52.
    Orwoll ES, Oviatt S, McClung MR, et al. The rate of bone mineral loss in normal men and the effects of calcium and cholecalciferol supplementation. Ann Intern Med 1990; 112: 29–34PubMedGoogle Scholar
  53. 53.
    Drinka PJ, Bauwens SF. Male osteopenia: a brief review. J Am Geriatr Soc 1987; 35: 258–61PubMedGoogle Scholar
  54. 54.
    Seeman E, Melton LJ, O’Fallon WM, et al. Risk factors for spinal osteoporosis in men. Am J Med 1983; 75: 977–83PubMedCrossRefGoogle Scholar
  55. 55.
    Smith DAS, Walker MS. Changes in plasma steroids and bone density in Klinefelter’s syndrome. Calcif Tissue Res 1977; 22: 225–8PubMedCrossRefGoogle Scholar
  56. 56.
    Lewinnek GE, Kelsey J, White AA, et al. The significance and a comparative analysis of the epidemiology of hip fractures. Clin Orthoped 1980; 152: 35–43Google Scholar
  57. 57.
    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(1): 4–8PubMedCrossRefGoogle Scholar
  58. 58.
    Ongphiphadhanakul B, Rajatanavin R, Chailurkit L, et al. Serum testosterone and its relation to bone mineral density and body composition in normal males. Clin Endocrinol 1995; 43: 727–33CrossRefGoogle Scholar
  59. 59.
    Finkelstein JS, Klibanski A, Neer RM, et al. Increases in bone density during treatment of men with idiopathic hypogonadotropic hypogonadism. J Clin Endocrinol Metab 1989; 69: 776–83PubMedCrossRefGoogle Scholar
  60. 60.
    Goldray D, Weisman Y, Jaccard N, et al. Decreased bone density in elderly men treated with gonadotropin-releasing hormone agonist decapeptyl (D-Trp6-GnRH). J Clin Endocrinol Metab 1993; 76: 288–90PubMedCrossRefGoogle Scholar
  61. 61.
    Stepan JJ, Lachman M, Zverina J, et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodelling. J Clin Endocrinol Metab 1989; 69: 523–7PubMedCrossRefGoogle Scholar
  62. 62.
    Greenspan SL, Oppenheim DS, Klibanski A. Importance of gonadal steroids to bone mass in men with hyperprolactinemic hypogonadism. Ann Intern Med 1989; 110: 526–31PubMedGoogle Scholar
  63. 63.
    Albright F, Reifenstein EC. Metabolic bone disease: osteoporosis. In: Williams, editor. The parathyroid glands and metabolic bone disease. Baltimore (MD): Williams and Wilkins, 1948: 145Google Scholar
  64. 64.
    Lafferty FW, Spencer GE, Pearson OH. Effects of androgens, estrogens and high calcium intakes on bone formation and resorption in osteoporosis. Am J Med 1964; 36: 514–28PubMedCrossRefGoogle Scholar
  65. 65.
    Oppenheim D, Klibanski A. Osteopenia in men with acquired hypogonadism: improvement with testosterone replacement [abstract no. 585]. Programs and Abstracts of the 71st Meeting of The Endocrine Society; 1989 Jun: 289Google Scholar
  66. 66.
    Morley JE, Perry HM, Kaiser FE, et al. Effects of testosterone replacement therapy in old hypogonadal males: a preliminary study. J Am Geriatr Soc 1993; 41: 149–52PubMedGoogle Scholar
  67. 67.
    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: 4358–65PubMedCrossRefGoogle Scholar
  68. 68.
    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: 2386–90PubMedCrossRefGoogle Scholar
  69. 69.
    Kochakian CD. Comparison of protein anabolic property of various androgens in the castrated rat. Am J Physiol 1950; 60: 553–8Google Scholar
  70. 70.
    Forbes GB, Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 1970; 19: 653–63PubMedCrossRefGoogle Scholar
  71. 71.
    Kallman DA, Plato CA, Tobin JD. The role of muscle loss in the age-related decline of grip strength: cross-sectional and longitudinal perspectives. J Gerontol 1990; 45: M82–8PubMedGoogle Scholar
  72. 72.
    Shimokata H, Tobin JD, Muller DC, et al. Studies in the distribution of body fat. I. Effects of age, sex, and obesity. J Gerontol 1989; 44: M66–73PubMedGoogle Scholar
  73. 73.
    Seidell JC, Bjorntorp P, Sjostrom L, et al. Visceral fat accumulation in men is positively associated with insulin, glucose and C-peptide levels, but negatively with testosterone levels. Metabolism 1990; 39: 897–901PubMedCrossRefGoogle Scholar
  74. 74.
    Marin P, Oden B, Bjorntop 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: 239–43PubMedCrossRefGoogle Scholar
  75. 75.
    Rogers MA, Evans WJ. Changes in skeletal muscle with aging: effects of exercise training. Exerc Sport Sci Rev 1993; 21: 65–102PubMedCrossRefGoogle Scholar
  76. 76.
    Spencer H, Lewin I, Friedland JA. Actions of androgens and related substances on mineral metabolism and bone [abstract]. Pharmacol Ther 1976; 1: 207Google Scholar
  77. 77.
    Bergamini E. Testosterone and sugar transport in levator ani muscle of rat. Biochim Biophys Acta 1969; 193: 193–202PubMedCrossRefGoogle Scholar
  78. 78.
    Breuer CB, Florini JR. Effects of ammonium sulphate, growth hormone and testosterone propionate on ribonucleic acid polymerase and chromatin activities in rat skeletal muscle. Biochemistry 1966; 5: 3857–65CrossRefGoogle Scholar
  79. 79.
    Powers ML, Florini JR. A direct effect of testosterone on muscle cells in tissue culture. Endocrinology 1975; 97: 1043–7PubMedCrossRefGoogle Scholar
  80. 80.
    Bhasin S, Storer TW, Berman N, et al. Anabolic effects of androgens: testosterone increases lean body mass, muscle size and strength in hypogonadal men [abstract]. The 19th Annual Meeting of the American Society of Andrology; 1994 Nov: 40Google Scholar
  81. 81.
    Friedl KE, Dettori JR, Hannan CJ, et al. Comparison of the effects of high dose testosterone and 19-nortestosterone to a replacement dose of testosterone on strength and body composition in normal men. J Steroid Biochem Molec Biol 1991; 40: 607–12PubMedCrossRefGoogle Scholar
  82. 82.
    Griggs RC, Kingston W, Jozefowics RF, et al. Effect of testosterone on muscle mass and muscle protein synthesis. J Appl Physiol 1989; 66: 498–503PubMedGoogle Scholar
  83. 83.
    Young NR, Baker HWG, Liu G, et al. Body composition and muscle strength in healthy men receiving testosterone enanthate for contraception. J Clin Endocrinol Metab 1993; 77: 1028–32PubMedCrossRefGoogle Scholar
  84. 84.
    Wang C, Eyre DR, Clark R, et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men: a clinical research center study. J Clin Endocrinol Metab 1996; 81: 3654–62PubMedCrossRefGoogle Scholar
  85. 85.
    Bhasin S, Storer T, Strakora J, et al. Testosterone increases lean body mass, muscle size and strength in hypogonadal men [abstract]. Clin Res 1994; 42: 74AGoogle Scholar
  86. 86.
    Wong FHW, Pun KK, Wang C. Loss of bone mass in patients with Kleinfelter’s syndrome despite sufficient testosterone replacement. Osteoporos Int 1993; 7: 281–7Google Scholar
  87. 87.
    Brodsky IG, Balagopal P, Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research study. J Clin Endocrinol Metab 1996; 81: 3469–75PubMedCrossRefGoogle Scholar
  88. 88.
    Urban RJ, Bodenburg YH, Gilkison C, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 1995; 269: E820–26PubMedGoogle Scholar
  89. 89.
    Sih R, Morley JE, Kaiser FE, et al. Testosterone replacement in older hypogonadal men: a 12-month randomised controlled trial. J Clin Endocrinol Metab 1997; 82: 1661–7PubMedCrossRefGoogle Scholar
  90. 90.
    De Pergola G, Xu X, Yang S, et al. Upregulation of androgen receptor binding in male rat fat adipose precursor cells exposed to testosterone: study in a whole cell assay system. J Steroid Biochem Mol Biol 1990; 37: 553–8PubMedCrossRefGoogle Scholar
  91. 91.
    Xu X, De Pergola G, Bjorntorp P. The effects of androgens on the regulation of lipolysis in adipose precursor cells. Endocrinology 1990; 126: 1229–34PubMedCrossRefGoogle Scholar
  92. 92.
    US Department of Health, Education and Welfare. The prevalence study. In: Lipid Research Group. The Lipids Research Clinics population studies data book. Vol. 1. Bethesda (MD): US Department of Health, Education and Welfare, 1979. NIH publication no: 79-1527Google Scholar
  93. 93.
    Heiss G, Johnson NJ, Reiland S, et al. The epidemiology of plasma high density lipoproteins cholesterol levels. Circulation 1980; 62Suppl. 4: 116Google Scholar
  94. 94.
    Bagatell CJ, Bremner WJ. Androgen and progestagen effects on plasma lipids. Prog Cardiovasc Dis 1995; 38: 255–71PubMedCrossRefGoogle Scholar
  95. 95.
    von Eckardstein A, Kliesch S, Nieschlag E, et al. Suppression of endogenous testosterone in young men increases serum levels of high density lipoprotein subclass lipoprotein A-1 and lipoprotein(a). J Clin Endocrinol Metab 1997; 82: 3367–72CrossRefGoogle Scholar
  96. 96.
    Hauner H, Stangl K, Burger K, et al. Sex hormone concentrations in men with angiographically assessed coronary artery disease: relationship to obesity and body fat distribution. Klin Wochenschr 1991; 69(14): 664–8PubMedCrossRefGoogle Scholar
  97. 97.
    Barrett-Connor EL. Testosterone and risk factors for cardiovascular disease in men. Diabete Metab 1995; 21(3): 156–61PubMedGoogle Scholar
  98. 98.
    Dai WS, Gutai JP, Kuller LH, et al. Relation between plasma high-density lipoprotein cholesterol and sex hormone concentrations in men. Am J Cardiol 1984; 53(9): 1259–63PubMedCrossRefGoogle Scholar
  99. 99.
    Zmuda JM, Cauley JA, Kriska A, et al. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men: a 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997; 146(8): 609–17PubMedCrossRefGoogle Scholar
  100. 100.
    Zhao Sp, Li XP. The association of low plasma testosterone level with coronary artery disease in Chinese men. Int J Cardiol 1998; 63(2): 161–4PubMedCrossRefGoogle Scholar
  101. 101.
    Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med 1992; 117(10): 807–11PubMedGoogle Scholar
  102. 102.
    Khaw KT, Barrett-Connor E. Endogenous sex hormones, high density lipoprotein cholesterol, and other lipoprotein fractions in men. Arterioscler Thromb 1991; 11(3): 489–94PubMedCrossRefGoogle Scholar
  103. 103.
    Freedman DS, O’Brian TR, Flanders WD, et al. Relation of serum testosterone levels to high density lipoprotein cholesterol and other characteristics in men. Arterioscler Thromb 1991; 11(2): 307–15PubMedCrossRefGoogle Scholar
  104. 104.
    Arver S, Dobs AS, Meikle AW, et al. Long-term efficacy and safety of a permeation-enhanced testosterone transdermal system in hypogonadal men. Clin Endocrinol 1997; 47: 727–37CrossRefGoogle Scholar
  105. 105.
    Ellvin FM, Plunkett-Reid K, Rumilla AE. The long-term beneficial effect of low-dose testosterone in the aging male [abstract]. Proceedings of the 79th Annual Meeting of the Endocrine Society: 1997 Jun 11–14; Minneapolis, 236Google Scholar
  106. 106.
    Zgliczynski S, Ossowski M, Slowinska-Srzednicka J, et al. Effect of testosterone replacement therapy on lipids and lipoproteins in hypogonadal and elderly men. Arteriosclerosis 1996; 121(1): 35–43CrossRefGoogle Scholar
  107. 107.
    Gardner FH, Besa EC. Physiologic mechanisms and the hematopoeitic effects of the androstanes and their derivatives. Curr Top Hematol 1983; 4: 123–95PubMedGoogle Scholar
  108. 108.
    Krabbe S, Christensen T, Worm J, et al. Relationship between haemoglobin and serum testosterone in normal children and adolescents and in boys with delayed puberty. Acta Paediatr Scand 1978; 67: 655–8PubMedCrossRefGoogle Scholar
  109. 109.
    Vahlquist B. The cause of the sexual differences in erythrocyte, hemoglobin and serum iron levels in human adults. Blood 1950; 5: 874–5PubMedGoogle Scholar
  110. 110.
    Williamson CS. Influence of age and sex on hemoglobin: a spectrophotometric analysis of nine hundred and nineteen cases. Arch Intern Med 1916; 18: 505–28CrossRefGoogle Scholar
  111. 111.
    McCullagh EP, Jones R. Effect of androgens on blood counts of men. J Clin Endocrinol 1942; 2: 243–51CrossRefGoogle Scholar
  112. 112.
    Hamilton JB, Bunch LD, Mestler GE, et al. Effect of castration in men upon blood sedimentation rate, hematocrit and hemoglobin. J Clin Endocrinol Metab 1964; 24: 506–11PubMedCrossRefGoogle Scholar
  113. 113.
    Garry PJ, Goodwin JS, Hunt WC. Iron status and anemia in the elderly: new findings and a review of previous studies. J Am Geriatr Soc 1983; 31: 389–99PubMedGoogle Scholar
  114. 114.
    Kennedy BJ, Gilbertsen AS. Increased erythropoiesis induced by androgenic hormone therapy. N Engl J Med 1957; 256: 719–26PubMedCrossRefGoogle Scholar
  115. 115.
    Krauss DJ, Taub HA, Lantinga LJ, et al. Risks of blood volume changes in hypogonadal men treated with testosterone enanthate for erectile impotence. J Urol 1991; 146: 1566–70PubMedGoogle Scholar
  116. 116.
    Drinka PJ, Jochen AL, Cuisinier M, et al. Polycythemia as a complication of testosterone replacement therapy in nursing home men with low testosterone levels. J Am Geriatr Soc 1995; 43: 899–901PubMedGoogle Scholar
  117. 117.
    Bhasin S, Bagatell CJ, Bremner WJ, et al. Issues in testosterone replacement in older men. J Clin Endocrinol Metab 1998; 83: 3435–48PubMedCrossRefGoogle Scholar
  118. 118.
    Morley JE, Kaiser FE. Sexual function with advancing age. Med Clin North Am 1989; 73: 1483–95PubMedGoogle Scholar
  119. 119.
    Bhasin S. Androgen treatment of hypogonadal men. J Clin Endocrinol Metab 1992; 74: 1221–5PubMedCrossRefGoogle Scholar
  120. 120.
    Davidson JM, Chen JJ, Crapo L, et al. Hormonal changes and sexual function in aging men. J Clin Endocrinol Metab 1983; 57: 71–7PubMedCrossRefGoogle Scholar
  121. 121.
    Feldman HA, Goldstein I, Hatzichristou DG, et al. Impotence and its medical and psychological correlates: results of the Massachussetts Male Aging Study. J Urol 1994; 151: 54–61PubMedGoogle Scholar
  122. 122.
    Bancroft J, Wu FCW. Changes in erectile responsiveness during androgen replacement therapy. Arch Sex Behav 1983; 12: 59–66PubMedCrossRefGoogle Scholar
  123. 123.
    Davidson JM, Camargo CA, Smith ER. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab 1979; 48: 955–8PubMedCrossRefGoogle Scholar
  124. 124.
    Kwan M, Greenleaf WJ, Mann J, et al. The nature of androgen action on male sexuality: a combined laboratory-self report study in hypogonadal men. J Clin Endocrinol Metab 1983; 57: 557–62PubMedCrossRefGoogle Scholar
  125. 125.
    Carani C, Bancroft J, Granata A, et al. Testosterone and erectile function, nocturnal penile tumescence and rigidity, and erectile response to visual erotic stimuli in hypogonadal and eugonadal men. Psychoneuroendocrinology 1992; 17(6): 647–54PubMedCrossRefGoogle Scholar
  126. 126.
    Clopper RR, Voorhess ML, MacGillivray MH, et al. Psycho-sexual behavior in hypopituitary men: a controlled comparison of gonadotropin and testosterone replacement. Psychoneuroendocrinology 1993; 18(2): 149–61PubMedCrossRefGoogle Scholar
  127. 127.
    Salmimies P, Kockott G, Pirke KM. Effects of testosterone replacement on sexual behavior in hypogonadal men. Arch Sex Behav 1982; 11(4): 345–53PubMedCrossRefGoogle Scholar
  128. 128.
    Arver S, Dobs AS, Meikle AW, et al. Improvement of sexual function in testosterone deficient men treated for one year with a permeation enhanced testosterone transdermal system. J Urol 1996; 155: 1604–8PubMedCrossRefGoogle Scholar
  129. 129.
    Morales A, Johnston B, Heaton JPW, et al. Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapeutic outcomes. J Urol 1997; 157: 849–54PubMedCrossRefGoogle Scholar
  130. 130.
    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: 297–304PubMedGoogle Scholar
  131. 131.
    Nielson J, Pelsen B, Sorensen K. Follow-up of 30 Klinefelter males treated with testosterone. Clin Genet 1988; 33: 262–9CrossRefGoogle Scholar
  132. 132.
    O’Carroll R, Shapiro C, Bancroft J. Androgens, behavior and nocturnal erection in hypogonadal men: the effects of varying the replacement dose. Clin Endocrinol 1985; 23: 527–38CrossRefGoogle Scholar
  133. 133.
    Albeaux-Fernet M, Bohler CC, Karpas AE. Testicular function in the aging male. In: Greenblatt RB, editor. Aging-geriatric endocrinology. Vol 5. New York: Raven Press, 1978: 210Google Scholar
  134. 134.
    Benton AL, Eslinger PJ, Danasio AR. Normative observations on neuropsychological test performance in old age. J Clin Neuropsychol 1981; 3: 33–42PubMedCrossRefGoogle Scholar
  135. 135.
    Koss E, Haxby JW, DeCarli C, et al. Patterns of performance preservation and loss in healthy aging. Dev Psychol 1991; 7: 99–107Google Scholar
  136. 136.
    Janowsky JS, Oviatt SK, Carpenter JS, et al. Testosterone administration enhances spatial cognition in older men [abstract no. 340.12]. Programs and Abstracts of the Society for Neuroscience Annual Meeting; 1991 Nov: 868Google Scholar
  137. 137.
    Vogel W, Klaiber EL, Broverman DM. The role of the gonadal steroid hormones in psychiatric depression in men and women. Prog Neuropsychopharmacol 1978; 2: 487–90CrossRefGoogle Scholar
  138. 138.
    Schiavi RC, White D, Mandeli J, et al. Effect of testosterone administration on sexual behaviour and mood in men with erectile dysfunction. Arch Sex Behav 1997; 26(3): 231–41PubMedCrossRefGoogle Scholar
  139. 139.
    Block AJ, Boysen PG, Wynne JW, et al. Sleep apnea, hypopnea and oxygen desaturation in normal subjects: a strong male predominance. N Engl J Med 1979; 300: 513–7PubMedCrossRefGoogle Scholar
  140. 140.
    Block AJ, Wynne JW, Boysen PG. Sleep-disordered breathing and nocturnal oxygen desaturation in postmenopausal women. Am J Med 1980; 69: 75–9PubMedCrossRefGoogle Scholar
  141. 141.
    Matsumoto AM, Sandblom RE, Schoene RB, et al. Testosterone replacement in hypogonadal men: effects on obstructive sleep apnoea, respiratory drives, and sleep. Clin Endocrinol 1985; 22(6): 713–21CrossRefGoogle Scholar

Copyright information

© Adis International Limited 1999

Authors and Affiliations

  1. 1.Division of Endocrinology and MetabolismJohns Hopkins UniversityBaltimoreUSA

Personalised recommendations