Androgens in Health and Disease.pdf - E Library

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Chapter 15/Androgens and Cognition 297 Aging Effects on Androgens Serum levels of total T and bioavailable T (T that is not bound to sex hormone-binding globulin) decrease with age in men (66,67). Although this decrease is gradual, it can result in decreased muscle mass, osteoporosis, decreased sexual activity, and changes in cognition (66,68–71). Androgen-replacement therapy in normal older men has demonstrated benefits on bone mass, muscle strength, and sexual functioning (72,73). However, these benefits may result from direct effects of T or from increased estradiol levels following aromatization of T. Recent evidence in the case of a patient with genetic aromatase deficiency suggests that bone mass changes and other physiological effects in men may, in fact, be attributable to changes in estradiol levels rather than to direct T effects (74). In addition to peripheral physiological effects, age-related declines in T levels may affect cognitive abilities. In healthy older men, endogenous T levels are significantly correlated with both visual and verbal memory and verbal fluency (0.53, 0.52 and 0.45, respectively) (75). In a large, epidemiological cohort of healthy older males, the Ranch- Bernardo study, bioavailable T was significantly and positively correlated with verbal memory and a common cognitive screening test (76). These associations were independent of age, education, body mass index, alcohol use, cigarette smoking, and depression. Thus, the association was not simply a reflection of health status. Testosterone Replacement in Older Men Although studies examining exogenous T administration in older men have produced mixed results, carefully designed prosposective studies with sensitive neuropsychological batteries tend to show significant effects. Sih et al. (1997), using a double-blind, placebo-controlled design, gave older, hypogonadal men biweekly injections of 200 mg T cypionate for 12 mo (77). Fifteen men were randomly assigned to receive placebo and 17 men were randomly assigned to receive testosterone. The men were in good general health with a mean age of 68 yr. Tests of verbal and visual memory were administered prior to treatment and again after 6 mo. Although grip strength improved, memory measures remained unchanged. However, several reasons may account for lack of significant findings in this study. First, T levels did not change significantly from baseline levels during the course of T administration. Second, it is unclear when cognitive testing occurred relative to the T injection. Thus, cognitive testing may have occurred during times of trough T levels. In contrast, Janowsky et al. (1994) (78) found improvements in spatial abilities in a double-blind study using daily 15-mg T skin patches. In this study, 56 healthy older men (mean age: 67 yr) participated and were randomized to placebo or T for 3 mo of treatment. Participants were administered a battery of tests measuring semantic knowledge, constructional ability, verbal memory, fine motor coordination and divided attention prior to and after 3 mo of treatment. The treatment group demonstrated improvement on a measure of visuoconstructional ability (see Fig. 3). More recently, Janowsky et al. (2000) found that T enanthate injections, 150 mg/weekly, improved spatial working memory in a group of healthy older males (see Fig. 4) (79). These improvements were evident compared to an age-matched placebo group and exceeded practice effects demonstrated by young men (without T treatment). Working memory refers to one’s ability to maintain information in mind while simultaneously manipulating or updating the information as needed. It is the mind’s scratchpad; therefore, improvements in working memory can affect a number of cognitive and day-to-day tasks.
298 Cherrier and Craft Fig. 3. Wechsler Adult Intelligence Scale—Revised Block Design subtest performance (total score) by a testosterone-supplemented group of healthy older eugonadal men (solid circles) and a placebo group (open circles) at Session 1 (baseline) and Session 2 (12 wk of daily 15-mg T skin patch use). The T-treated group demonstrated a significant improvement from baseline compared to placebo, as evidenced by a significant group by test session interaction F(1,54) = 5.33, p = 0.025. (From ref. 78, reproduced with permission.) Fig. 4. Change in performance after 1 mo of placebo or hormone supplementation (150 mg intramuscular T enanthate weekly for men and 0.625 mg/d conjugated estrogen daily for women) in older subjects (stripped bars) or no treatment in the younger subjects (open bars). Older men on T supplementation showed an improvement in performance (fewer errors). Younger subjects showed the expected improvement on the task because of practice, whereas older subjects, without hormone supplementation or with estrogen supplementation did not. Brackets show standard error of the mean. (From ref. 79, reproduced with permission.)
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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
Page 257 and 258: 246 Katznelson Fig. 1. Body weight,
Page 259 and 260: 248 Katznelson change during treatm
Page 261 and 262: 250 Katznelson testosterone or free
Page 263 and 264: 252 Katznelson disproportionate dec
Page 265 and 266: 254 Katznelson have been additional
Page 267 and 268: 256 Katznelson 18. Marin P, Lonn L,
Page 269 and 270: 258 Katznelson 71. Davis SR, McClou
Page 271 and 272: 260 Bancroft Androgen Deficiency an
Page 273 and 274: 262 Bancroft studies had presented
Page 275 and 276: 264 Bancroft Bagatell et al. (36) g
Page 277 and 278: 266 Bancroft much larger group of a
Page 279 and 280: 268 Bancroft In a report of a serie
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Page 283 and 284: 272 Bancroft Particularly confusing
Page 285 and 286: 274 Bancroft 4. Studies using place
Page 287 and 288: 276 Bancroft either E and T or plac
Page 289 and 290: 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
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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
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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 and 342: 330 Matsumoto occasionally, more se
Page 343 and 344: 332 Matsumoto 27. Bhasin S, Bremner
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
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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
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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
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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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