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Chapter 22/Androgens in Primary Care 427 Table 4 Common Causes of Secondary Hypogonadism Prepubertal onset (small testes) Kallmann’s syndrome Idiopathic hypogonadotropic hypogonadism Pituitary tumor (craniopharyngioma) Uremia Severe systemic illness Cranial irradiation Hyperprolactinemia Postpubertal onset (normal testes) Acquired idiopathic hypogonadotropic hypogonadism Pituitary macroadenomas Uremia Severe systemic illness Cranial irradiation Hyperprolactinemia Hemochromatosis Cushing’s syndrome Cirrhosis Morbid obesity Table 5 Drugs Commonly Associated with Male Hypogonadism Primary hypogonadism Decreased Leydig cell production of testosterone Corticosteroids Ethanol Ketoconazole (high dosages) Decreased conversion of testosterone to dihydrotestosterone Finasteride (rarely cause decreased libido and erectile dysfunction) Androgen-receptor blockade Spironolactone Flutamide Cimetidine Cyproterone Secondary hypogonadism Decreased pituitary secretion of gonadotropins Corticosteroids Ethanol GnRH analogs (e.g., Lupron) Estrogens Medications that raise prolactin levels (psychotropic drugs, metoclopramide, opiates) After secondary hypogonadism has been confirmed with repeat biochemical testing, common causes of gonadotropin deficiency should be excluded. Common causes include idiopathic hypogonadotropic hypogonadism, hyperprolactinemia, Cushing’s syndrome, pituitary macroadenomas (>1 cm 2 ), hemochromatosis, and drugs (see Tables 4 and 5).
428 Anawalt All men with secondary hypogonadism should be evaluated with a serum prolactin level and iron studies to exclude hyperprolactinemia and hemochromatosis. The recommended screening test for hemochromatosis is serum transferrin saturation (serum iron concentration divided by total iron-binding capacity, multiplied by 100). Iron saturation less than 45% excludes hemochromatosis as a cause of male hypogonadism, and virtually all men who are homozygotic for hemochromatosis will have an iron saturation greater than 62% (14,15). Because serum iron concentration and transferrin saturation are increased by meals, the specificity of transferrin saturation for hemochromatosis is better when the patient is fasting. The possibility of Cushing’s syndrome should be evaluated by history and physical examination (careful examination of the skin for decreased thickness, easy bruisability, violaceous striae, and evaluation of the musculoskeletal system for weakness and osteoporosis). If indicated, Cushing’s syndrome may be screened for with a 24-h collection for urinary free cortisol or an overnight low-dose dexamethasone suppression test. Men with secondary hypogonadism who are younger than age 50 and who do not have hemochromatosis should have an imaging study of the pituitary to exclude a large, compressive pituitary macroadenoma. Either a computed tomography (CT) or magnetic resonance imaging (MRI) scan would suffice, but CT is less expensive. MRI is clearly superior when smaller pituitary lesions need to be evaluated. Because men older than age 65 yr often have low or low-normal serum testosterone and gonadotropin levels without any pituitary disease, it would not be cost-effective to do imaging studies on all of them. If prolactin levels are normal and thyroid function tests do not suggest a pituitary source of hypothyroidism (low serum T4 plus low or inappropriately normal thyroid-stimulating hormone [TSH]), an imaging study may be waived unless the patient complains of frequent headaches or visual disturbances that might suggest a sellar mass. Men with secondary hypogonadism with very low serum testosterone levels ( 65 yr) with Low-Normal Serum Testosterone Levels Serum testosterone levels decline in aging men because of a dual defect in the hypothalamus and in the testes. Aging is associated with the aberrant secretion of gonadotropin-releasing hormone (GnRH) and a blunted response of the Leydig cell to gonadotropin stimulation (26–28). Pituitary gonadotropin function is spared in older men as the gonadotropes continue to produce LH normally when stimulated by GnRH (27,29,30). More than 20% of all men ≥ 60 yr have serum total- and free-testosterone levels below the threshold of hypogonadism for healthy young men (2). Most of these men will have normal serum gonadotropin levels and thus have a biochemical profile
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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
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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
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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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Page 391 and 392: 380 Davis
Page 393 and 394: 382 Bhasin, Woodhouse, and Storer h
Page 395 and 396: 384 Table 2 Effects of Testosterone
Page 397 and 398: 386 Bhasin, Woodhouse, and Storer e
Page 399 and 400: 388 Bhasin, Woodhouse, and Storer F
Page 401 and 402: 390 Bhasin, Woodhouse, and Storer t
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Page 405 and 406: Table 4 Effects of Testosterone Sup
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Page 411 and 412: 400 Bhasin, Woodhouse, and Storer w
Page 413 and 414: 402 Bhasin, Woodhouse, and Storer 4
Page 415 and 416: 404 Bhasin, Woodhouse, and Storer
Page 417 and 418: 406 Amory Fig. 1. The endocrinology
Page 419 and 420: 408 Amory pregnancies fathered by t
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Page 423 and 424: 412 Amory 100-mg doses of weekly TE
Page 425 and 426: 414 Amory FUTURE DIRECTIONS Given t
Page 427 and 428: 416 Amory 22. Oral contraception. I
Page 429 and 430: 418 Amory
Page 431 and 432: 420 Anawalt inadequate androgen eff
Page 433 and 434: 422 Anawalt few specialty commercia
Page 435 and 436: 424 Anawalt Fig. 1. (C) Secondary h
Page 437: 426 Anawalt Fig. 2. Evaluation and
Page 441 and 442: 430 Anawalt anemia (38). With the a
Page 443 and 444: 432 Anawalt osterone levels achieve
Page 445 and 446: 434 Anawalt SIDE EFFECTS OF ANDROGE
Page 447 and 448: 436 Anawalt 7. Rosner W. Errors in
Page 449 and 450: 438 Anawalt 59. Mackey MA, Conway A
Page 451 and 452: 440 Index polycystic ovaries, 131 A
Page 453 and 454: 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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