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PREFACE The products of the testes have been recognized as essential to the development and maintenance of male physique and virility since ancient times. However, only in the past few decades has the entire spectrum of influence and action of testosterone, its metabolites, and its analogs begun to be fully investigated and appreciated. As we understand more about how androgens act and how they influence a myriad of physiological functions, we are able to use androgens in a wider variety of clinical settings. Unfortunately, use is frequently accompanied by abuse; over the last 20 years, abuse of anabolic agents has become widespread in some communities of athletes, sometimes with untoward consequences. In Androgens in Health and Disease, we have brought together reviews of our latest understanding of andrology in both basic science and clinical medicine. In the first section of the book, the biology of androgens, androgen metabolites, and androgen receptors is presented from several different perspectives. We hope that clinicians as well as basic scientists will find this section useful. The next two sections explore the roles of androgens in development and in the modulation of a wide variety of physiologic systems. Although the lay public tends to view androgens primarily as agents of virility and muscularity, androgens actually regulate nearly every physiologic system in some way, as these chapters demonstrate. In the last two sections of the book, several newer uses of androgens are presented. Most endocrinologists and urologists, as well as some practitioners with broader scopes of practice, are familiar with the use of androgens in delayed puberty and in young men with acquired hypogonadism. However, fewer clinicians are aware that testosterone can be a useful adjunct to the treatment of many other disease states, particularly those in which catabolism and loss of muscle mass occur. In addition, it is becoming increasingly apparent that many older men experience “andropause,” analogous but certainly not identical to menopause. Although not appropriate for all older men, androgens may improve physical function and enhance the quality of life for many individuals. As with hormone replacement, the development of hormonal male contraception lags far behind that which is available for women. However, several recent studies have demonstrated the potential utility of androgens, often combined with other hormonal agents, in suppressing spermatogenesis consistently and reversibly. These potential indications are much more prevalent than is “classical” hypogonadism, and thus the potential future uses of androgens as therapeutic agents are extensive. The last section of the book presents recent developments in the role of androgens in regulating female physiology. Excessive androgens, either in the serum or at the tissue level, can cause a wide range of symptoms and physical findings in women, and hyperandrogenism may also be associated with an increased risk of cardiovascular disease. Conversely, androgen deficiency in women is not often recognized, but it too may impact the physical and emotional well-being of women, particularly after menopause. v
vi Preface We hope Androgens in Health and Disease will serve as a valuable resource to researchers and clinicians alike and will broaden the reader’s concept of how and why androgens exert their effects. We are grateful to all of the authors for contributing their time and expertise to this endeavor. We offer sincere thanks to Ms. Tetana Oguara for her expert and enthusiastic support in coordinating and compiling the manuscripts. Carrie Bagatell, MD William J. Bremner, MD, PhD
Page 1 and 2: CONTEMPORARY ENDOCRINOLOGY Androgen
Page 3 and 4: CONTEMPORARY ENDOCRINOLOGY P. Micha
Page 5: © 2003 Humana Press Inc. 999 River
Page 9 and 10: viii Contents 13 Androgens and Body
Page 11 and 12: x Contributors RICHARD S. LEGRO, MD
Page 13 and 14: 2 Winters and Clark
Page 15 and 16: 4 Winters and Clark chorionic gonad
Page 17 and 18: 6 Winters and Clark LH REGULATION O
Page 19 and 20: 8 Winters and Clark These enzymes a
Page 21 and 22: 10 Winters and Clark -subunit mRNA
Page 23 and 24: 12 Winters and Clark Fig. 3. A sche
Page 25 and 26: 14 Winters and Clark Table 1 Factor
Page 27 and 28: 16 Winters and Clark Table 2 Tissue
Page 29 and 30: 18 Winters and Clark 11. Thomas JL,
Page 31 and 32: 20 Winters and Clark 61. Dufau ML,
Page 33 and 34: 22 Winters and Clark 112. Raivio T,
Page 35 and 36: 24 Brown Fig. 1. Mechanism for andr
Page 37 and 38: 26 Brown increase in intracellular
Page 39 and 40: 28 Brown Fig. 2. Structural and fun
Page 41 and 42: 30 Brown Fig. 3. Amino acid sequenc
Page 43 and 44: 32 Brown tions to shuttle the AR th
Page 45 and 46: 34 Brown Fig. 4. Amino acid primary
Page 47 and 48: 36 Brown part of an inactive chroma
Page 49 and 50: 38 Brown the external genitalia is
Page 51 and 52: 40 Brown tors, as well as the trans
Page 53 and 54: 42 Brown 49. Williams SP, Sigler PB
Page 55 and 56: 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
Page 237 and 238:
226 Kenny and Raisz The level of th
Page 239 and 240:
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,
Page 259 and 260:
248 Katznelson change during treatm
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250 Katznelson testosterone or free
Page 263 and 264:
252 Katznelson disproportionate dec
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254 Katznelson have been additional
Page 267 and 268:
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
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280 Bancroft Women with Endocrine A
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282 Bancroft in response to the fil
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284 Bancroft Men are much more awar
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286 Bancroft 22. Morales A, Johnsto
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288 Bancroft 78. Hyde JS, DeLamater
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290 Bancroft 129. Appelt H, Strauss
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292 Cherrier and Craft Fig. 1. Path
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294 Cherrier and Craft ment of the
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296 Cherrier and Craft information
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298 Cherrier and Craft Fig. 3. Wech
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300 Cherrier and Craft gen excess r
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302 Cherrier and Craft occurring wi
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304 Cherrier and Craft gesting that
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306 Cherrier and Craft 39. Gouchie
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308 Cherrier and Craft 94. Kelso WM
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310 Cherrier and Craft
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312 Matsumoto
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314 Matsumoto long-term benefits an
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316 Matsumoto manifestations (7). F
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318 Formulation Usual adult dosage
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320 Matsumoto Fig. 1. Mean serum T
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322 Matsumoto dosage is increased g
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324 Matsumoto Androgel 5 g (50 mg o
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326 Matsumoto gen receptor and tiss
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328 Matsumoto such as hepatic cirrh
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330 Matsumoto occasionally, more se
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332 Matsumoto 27. Bhasin S, Bremner
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334 Matsumoto 77. Dobs AS, Meikle A
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336 Richmond and Rogol PHYSIOLOGY O
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338 Richmond and Rogol activity (28
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340 Richmond and Rogol increase lin
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342 Richmond and Rogol curve, the h
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344 Richmond and Rogol Permanent hy
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346 Richmond and Rogol 46. Stanhope
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348 Tenover In aging men, the combi
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350 Tenover Table 1 Changes in Andr
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352 Tenover studies in which eugona
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354 Tenover Table 3 Testosterone Th
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356 Tenover Table 5 ART in Older Me
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358 Tenover be overcome with either
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360 Tenover Laboratory tests should
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362 Tenover 40. Kohrt WM, Malley MT
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364 Tenover 95. Mooradian AD, Morle
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366 Davis Table 1 Proposed Androgen
Page 379 and 380:
368 Davis transdermal testosterone
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370 Davis increase in circulating t
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372 Davis (93). Most recently, Zhou
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374 Davis Table 4 Androgen Replacem
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376 Davis 8. Vierhapper H, Nowotny
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378 Davis 60. Simberg N, Titinen A,
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380 Davis
Page 393 and 394:
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
Page 417 and 418:
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
Page 455 and 456:
444 Index women, 254 dihydrotestost
Page 457 and 458:
446 Index Pituitary adenoma, male h
Page 459 and 460:
448 Index lipoid congenital adrenal
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