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Chapter 16/Androgen Treatment of the Hypogonadal Male 331 REFERENCES 1. Amory JK, Anawalt BD, Paulsen CA, Bremner WJ. Klinefelter’s syndrome. Lancet 2000;356:333–335. 2. Matsumoto AM. The testis. In: Felig P, Frohman LA, eds. Endocrinology and Metabolism, 4th Edition. McGraw-Hill, New York, 2001, pp. 635–705. 3. Bhasin S, Storer TW, Asbel-Sethi N, et al. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab 1998;83:3155–3162. 4. Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998; 129:18–26. 5. Grinspoon S, Corcoran C, Stanley T, et al. Effects of hypogonadism and testosterone administration on depression indices in HIV-infected men. J Clin Endocrinol Metab 2000;85:60–65. 6. Handelsman DJ, Liu PY. Androgen therapy in chronic renal failure. Baillieres Clin Endocrinol Metab 1998;12:485–500. 7. Matsumoto AM. Andropause: clinical implications of the decline in serum testosterone levels with aging in men. J Gerontol A: Biol Sci Med Sci 2002;57:M76–M99. 8. Reid IR, Wattie DJ, Evans MC, Stapleton JP. Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 1996;156:1173–1177. 9. Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metab 1983;56:1278–1281. 10. Giraudi G, Cenderelli G, Migliardi M. Effect of tracer binding to serum proteins on the reliability of a direct free testosterone assay. Steroids 1988;52:423–424. 11. Rosner W. Errors in the measurement of plasma free testosterone. J Clin Endocrinol Metab 1997;82:2014–2015. 12. Rosner W. An extraordinarily inaccurate assay for free testosterone is still with us. J Clin Endocrinol Metab 2001;86:2903. 13. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–3672. 14. Winters SJ, Kelley DE, Goodpaster B. The analog free testosterone assay: are the results in men clinically useful? Clin Chem 1998;44:2178–2182. 15. Spratt DI, O’Dea LS, Schoenfeld D, et al. Neuroendocrine-gonadal axis in men: frequent sampling of LH, FSH, and testosterone. Am J Physiol 1988;254:E658–E666. 16. Matsumoto AM. Clinical use and abuse of androgens and antiandrogens. In: Becker KL, ed. Principles and Practice of Endocrinology and Metabolism, 3rd Edition. Lippincott Williams & Wilkins, Philadelphia, PA, 2001, pp. 1181–1200. 17. 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. 18. Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose–response relationships in healthy young men. Am J Physiol Endocrinol Metab 2001;281:E1172–E1181. 19. Buena F, Swerdloff RS, Steiner BS, et al. Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range. Fertil Steril 1993;59:1118–1123. 20. Singh AB, Hsia S, Alaupovic P, et al. The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab 2002;87:136–143. 21. Nankin HR. Hormone kinetics after intramuscular testosterone cypionate. Fertil Steril 1987;47:1004–1009. 22. Snyder PJ, Lawrence DA. Treatment of male hypogonadism with testosterone enanthate. J Clin Endocrinol Metab 1980;51:1335–1339. 23. Swerdloff RS, Wang C, Cunningham G, et al. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab 2000;85:4500–4510. 24. Gooren LJ. A ten-year safety study of the oral androgen testosterone undecanoate. J Androl 1994;15: 212–215. 25. Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab 1996;81:3578–3583. 26. 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;81:3654–3662.
332 Matsumoto 27. Bhasin S, Bremner WJ. Clinical review 85: Emerging issues in androgen replacement therapy. J Clin Endocrinol Metab 1997;82:3–8. 28. De Luca F, Argente J, Cavallo L, et al. Management of puberty in constitutional delay of growth and puberty. J Pediatr Endocrinol Metab 2001;14:953–957. 29. Houchin LD, Rogol AD. Androgen replacement in children with constitutional delay of puberty: the case for aggressive therapy. Baillieres Clin Endocrinol Metab 1998;12:427–440. 30. Soliman AT, Khadir MM, Asfour M. Testosterone treatment in adolescent boys with constitutional delay of growth and development. Metabolism 1995;44:1013–1015. 31. Amory JK, Matsumoto AM. The therapeutic potential of testosterone patches. Expert Opin Invest Drugs 1998;7:1977–1988. 32. Cunningham GR, Cordero E, Thornby JI. Testosterone replacement with transdermal therapeutic systems. Physiological serum testosterone and elevated dihydrotestosterone levels. JAMA 1989;261: 2525–2530. 33. Findlay JC, Place V, Snyder PJ. Treatment of primary hypogonadism in men by the transdermal administration of testosterone. J Clin Endocrinol Metab 1989;68:369–373. 34. Findlay JC, Place VA, Snyder PJ. Transdermal delivery of testosterone. J Clin Endocrinol Metab 1987;64:266–268. 35. Behre HM, von Eckardstein S, Kliesch S, Nieschlag E. Long-term substitution therapy of hypogonadal men with transscrotal testosterone over 7–10 years. Clin Endocrinol (Oxf) 1999;50:629–635. 36. 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. 37. 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. 38. de Lignieres B. Transdermal dihydrotestosterone treatment of “andropause.” Ann Med 1993;25: 235–241. 39. Kunelius P, Lukkarinen O, Hannuksela ML, et al. The effects of transdermal dihydrotestosterone in the aging male: a prospective, randomized, double blind study. J Clin Endocrinol Metab 2002;87:1467–1472. 40. Ly LP, Jimenez 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. 41. Meikle AW, Arver S, Dobs AS, et al. Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site-a clinical research center study. J Clin Endocrinol Metab 1996;81:1832–1840. 42. Meikle AW, Mazer NA, Moellmer JF, et al. Enhanced transdermal delivery of testosterone across nonscrotal skin produces physiological concentrations of testosterone and its metabolites in hypogonadal men. J Clin Endocrinol Metab 1992;74:623–628. 43. 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 (Oxf) 1997;47:727–737. 44. 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 A: Biol Sci Med Sci 2002;57:M321–M325. 45. 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;56: M266–M272. 46. Brocks DR, Meikle AW, Boike SC, et al. Pharmacokinetics of testosterone in hypogonadal men after transdermal delivery: influence of dose. J Clin Pharmacol 1996;36:732–739. 47. Bennett NJ. A burn-like lesion caused by a testosterone transdermal system. Burns 1998;24:478–480. 48. Jordan WP Jr. Allergy and topical irritation associated with transdermal testosterone administration: a comparison of scrotal and nonscrotal transdermal systems. Am J Contact Dermatitis 1997;8:108–113. 49. Parker S, Armitage M. Experience with transdermal testosterone replacement therapy for hypogonadal men. Clin Endocrinol (Oxf) 1999;50:57–62. 50. Wilson DE, Kaidbey K, Boike SC, Jorkasky DK. Use of topical corticosteroid pretreatment to reduce the incidence and severity of skin reactions associated with testosterone transdermal therapy. Clin Ther 1998;20:299–306. 51. Singh AB, Norris K, Modi N, et al. Pharmacokinetics of a transdermal testosterone system in men with end stage renal disease receiving maintenance hemodialysis and healthy hypogonadal men. J Clin Endocrinol Metab 2001;86:2437–2445.
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CONTEMPORARY ENDOCRINOLOGY Androgen
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CONTEMPORARY ENDOCRINOLOGY P. Micha
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© 2003 Humana Press Inc. 999 River
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vi Preface We hope Androgens in Hea
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viii Contents 13 Androgens and Body
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x Contributors RICHARD S. LEGRO, MD
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2 Winters and Clark
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4 Winters and Clark chorionic gonad
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6 Winters and Clark LH REGULATION O
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8 Winters and Clark These enzymes a
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10 Winters and Clark -subunit mRNA
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12 Winters and Clark Fig. 3. A sche
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14 Winters and Clark Table 1 Factor
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16 Winters and Clark Table 2 Tissue
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18 Winters and Clark 11. Thomas JL,
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20 Winters and Clark 61. Dufau ML,
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22 Winters and Clark 112. Raivio T,
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24 Brown Fig. 1. Mechanism for andr
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26 Brown increase in intracellular
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28 Brown Fig. 2. Structural and fun
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30 Brown Fig. 3. Amino acid sequenc
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32 Brown tions to shuttle the AR th
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34 Brown Fig. 4. Amino acid primary
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36 Brown part of an inactive chroma
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38 Brown the external genitalia is
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40 Brown tors, as well as the trans
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42 Brown 49. Williams SP, Sigler PB
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44 Brown 100. Gregory CW, He B, Joh
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46 Plymate Table 1 Classification o
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48 Plymate In addition to the direc
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50 Plymate LABORATORY FINDINGS In p
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52 Plymate those manifesting as phe
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54 Plymate result in some improveme
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56 Plymate If both testosterone and
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58 Plymate Persistent Müllerian Du
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60 Plymate INFERTILITY RESULTING FR
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62 Plymate unaffected, contralatera
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64 Plymate SECONDARY HYPOGONADISM H
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66 Plymate Other syndromes manifest
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68 Plymate period after the burn. I
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70 Plymate These findings suggest t
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72 Plymate 49. Goebelsmann U, Horto
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74 Plymate 104. Yoshimoto Y, Moride
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76 Plymate
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78 Sutton, Amory, and Clark levels
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80 Sutton, Amory, and Clark cebo in
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82 Sutton, Amory, and Clark Finaste
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84 Sutton, Amory, and Clark through
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86 Sutton, Amory, and Clark 40. The
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88 Sutton, Amory, and Clark 88. Rob
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90 Lindzey and Korach Fig. 1. Cellu
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92 Lindzey and Korach estrogen sign
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94 Lindzey and Korach TESTIS AND DU
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96 Lindzey and Korach sufficient to
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98 Lindzey and Korach Seminal Vesic
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100 Lindzey and Korach 17. Krege JH
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102 Lindzey and Korach 68. Chang WY
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104 McPhaul on the Y chromosome det
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106 106 McPhaul
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108 McPhaul number of alleles, dele
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110 McPhaul The first mutation of t
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112 McPhaul gene. In vitro studies
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114 McPhaul risk of impaired sperma
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116 McPhaul carrying a single mutan
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118 McPhaul REFERENCES 1. Koopman P
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120 McPhaul 45. Weidemann W, Peters
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122 McPhaul 92. Koivisto P, Kononen
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124 Legro Fig. 1. The spectrum of p
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126 Legro Virilization presents wit
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128 Legro Fig. 3. The paradox of an
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130 Legro small high-density athero
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132 Legro Table 2 Syndromes or Dise
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134 Legro Insulin-Sensitizing Agent
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136 Legro is undetermined according
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138 Legro 39. Lee O, Farquhar C, To
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140 Legro
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142 Wang and Swerdloff PHARMACOLOGY
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144 Wang and Swerdloff The 17α-alk
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146 Wang and Swerdloff Table 2 Dose
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148 Wang and Swerdloff The steroid
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150 Wang and Swerdloff The inabilit
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152 Wang and Swerdloff 15. De Lorim
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154 Wang and Swerdloff
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156 Marcelli et al.
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158 Marcelli et al. Differentiated
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160 Marcelli et al. These coactivat
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162 Marcelli et al. tigators have e
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164 Marcelli et al. AR in Prostate
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166 Marcelli et al. Table 1 Androge
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168 Marcelli et al. A molecular exp
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170 Marcelli et al. The above data
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172 Marcelli et al. up to 9 yr late
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174 Marcelli et al. Three major pha
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176 Marcelli et al. vitro model of
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178 Marcelli et al. yr, survival wa
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180 Marcelli et al. 26. McKenna NJ,
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182 Marcelli et al. 78. Isaacs J, C
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184 Marcelli et al. 126. Watanabe M
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186 Marcelli et al. 177. Kousteni S
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188 Marcelli et al. 231. Colombel M
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190 Marcelli et al.
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192 Wu and von Eckardstein contrace
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194 Wu and von Eckardstein beam com
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196 Wu and von Eckardstein excess o
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198 Wu and von Eckardstein Endogeno
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Table 3 Change in Lipids in Hypogon
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Table 3 (continued) ∆LDL ∆HDL
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204 Wu and von Eckardstein THE HEMO
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206 Wu and von Eckardstein In vivo
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208 Wu and von Eckardstein (uptake
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210 Wu and von Eckardstein 4. Bhasi
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212 Wu and von Eckardstein 57. Barr
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214 Wu and von Eckardstein 107. Fra
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216 Wu and von Eckardstein 152. Zmu
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218 Wu and von Eckardstein 201. Cho
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220 Wu and von Eckardstein 250. Eic
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222 Kenny and Raisz with a cartilag
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224 Kenny and Raisz METABOLISM OF A
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226 Kenny and Raisz The level of th
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228 Kenny and Raisz REFERENCES 1. G
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230 Kenny and Raisz 51. Morishima A
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232 Kenny and Raisz 103. Snyder PJ,
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234 Basaria and Dobs losses in wome
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236 Basaria and Dobs 15 dialysis pa
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238 Basaria and Dobs duced remissio
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240 Basaria and Dobs hematocrit lev
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242 Basaria and Dobs 40. Sanchez-Me
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244 Katznelson in men with testoste
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246 Katznelson Fig. 1. Body weight,
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248 Katznelson change during treatm
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250 Katznelson testosterone or free
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252 Katznelson disproportionate dec
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254 Katznelson have been additional
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256 Katznelson 18. Marin P, Lonn L,
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258 Katznelson 71. Davis SR, McClou
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260 Bancroft Androgen Deficiency an
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262 Bancroft studies had presented
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264 Bancroft Bagatell et al. (36) g
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266 Bancroft much larger group of a
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268 Bancroft In a report of a serie
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270 Bancroft onset was related to a
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272 Bancroft Particularly confusing
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274 Bancroft 4. Studies using place
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276 Bancroft either E and T or plac
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278 Bancroft cytotoxic therapy supp
Page 291 and 292: 280 Bancroft Women with Endocrine A
Page 293 and 294: 282 Bancroft in response to the fil
Page 295 and 296: 284 Bancroft Men are much more awar
Page 297 and 298: 286 Bancroft 22. Morales A, Johnsto
Page 299 and 300: 288 Bancroft 78. Hyde JS, DeLamater
Page 301 and 302: 290 Bancroft 129. Appelt H, Strauss
Page 303 and 304: 292 Cherrier and Craft Fig. 1. Path
Page 305 and 306: 294 Cherrier and Craft ment of the
Page 307 and 308: 296 Cherrier and Craft information
Page 309 and 310: 298 Cherrier and Craft Fig. 3. Wech
Page 311 and 312: 300 Cherrier and Craft gen excess r
Page 313 and 314: 302 Cherrier and Craft occurring wi
Page 315 and 316: 304 Cherrier and Craft gesting that
Page 317 and 318: 306 Cherrier and Craft 39. Gouchie
Page 319 and 320: 308 Cherrier and Craft 94. Kelso WM
Page 321 and 322: 310 Cherrier and Craft
Page 323 and 324: 312 Matsumoto
Page 325 and 326: 314 Matsumoto long-term benefits an
Page 327 and 328: 316 Matsumoto manifestations (7). F
Page 329 and 330: 318 Formulation Usual adult dosage
Page 331 and 332: 320 Matsumoto Fig. 1. Mean serum T
Page 333 and 334: 322 Matsumoto dosage is increased g
Page 335 and 336: 324 Matsumoto Androgel 5 g (50 mg o
Page 337 and 338: 326 Matsumoto gen receptor and tiss
Page 339 and 340: 328 Matsumoto such as hepatic cirrh
Page 341: 330 Matsumoto occasionally, more se
Page 345 and 346: 334 Matsumoto 77. Dobs AS, Meikle A
Page 347 and 348: 336 Richmond and Rogol PHYSIOLOGY O
Page 349 and 350: 338 Richmond and Rogol activity (28
Page 351 and 352: 340 Richmond and Rogol increase lin
Page 353 and 354: 342 Richmond and Rogol curve, the h
Page 355 and 356: 344 Richmond and Rogol Permanent hy
Page 357 and 358: 346 Richmond and Rogol 46. Stanhope
Page 359 and 360: 348 Tenover In aging men, the combi
Page 361 and 362: 350 Tenover Table 1 Changes in Andr
Page 363 and 364: 352 Tenover studies in which eugona
Page 365 and 366: 354 Tenover Table 3 Testosterone Th
Page 367 and 368: 356 Tenover Table 5 ART in Older Me
Page 369 and 370: 358 Tenover be overcome with either
Page 371 and 372: 360 Tenover Laboratory tests should
Page 373 and 374: 362 Tenover 40. Kohrt WM, Malley MT
Page 375 and 376: 364 Tenover 95. Mooradian AD, Morle
Page 377 and 378: 366 Davis Table 1 Proposed Androgen
Page 379 and 380: 368 Davis transdermal testosterone
Page 381 and 382: 370 Davis increase in circulating t
Page 383 and 384: 372 Davis (93). Most recently, Zhou
Page 385 and 386: 374 Davis Table 4 Androgen Replacem
Page 387 and 388: 376 Davis 8. Vierhapper H, Nowotny
Page 389 and 390: 378 Davis 60. Simberg N, Titinen A,
Page 391 and 392: 380 Davis
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382 Bhasin, Woodhouse, and Storer h
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384 Table 2 Effects of Testosterone
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386 Bhasin, Woodhouse, and Storer e
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388 Bhasin, Woodhouse, and Storer F
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390 Bhasin, Woodhouse, and Storer t
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Table 3 Effects of Testosterone Sup
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Table 4 Effects of Testosterone Sup
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396 Bhasin, Woodhouse, and Storer c
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398 Bhasin, Woodhouse, and Storer C
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400 Bhasin, Woodhouse, and Storer w
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402 Bhasin, Woodhouse, and Storer 4
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404 Bhasin, Woodhouse, and Storer
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406 Amory Fig. 1. The endocrinology
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408 Amory pregnancies fathered by t
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410 Amory antagonists can suppress
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412 Amory 100-mg doses of weekly TE
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414 Amory FUTURE DIRECTIONS Given t
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416 Amory 22. Oral contraception. I
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418 Amory
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420 Anawalt inadequate androgen eff
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422 Anawalt few specialty commercia
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424 Anawalt Fig. 1. (C) Secondary h
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426 Anawalt Fig. 2. Evaluation and
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428 Anawalt All men with secondary
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430 Anawalt anemia (38). With the a
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432 Anawalt osterone levels achieve
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434 Anawalt SIDE EFFECTS OF ANDROGE
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436 Anawalt 7. Rosner W. Errors in
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438 Anawalt 59. Mackey MA, Conway A
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440 Index polycystic ovaries, 131 A
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442 Index lipoid congenital adrenal
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444 Index women, 254 dihydrotestost
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446 Index Pituitary adenoma, male h
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448 Index lipoid congenital adrenal
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