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Chapter 4/Dihydrotestosterone and 5α-Reductase 85 15. Imperato-McGinley J, Peterson RE, Gautier T, et al. Androgens and the evolution of male-gender identity among male pseudohermaphrodites with 5alpha-reductase deficiency. N Engl J Med 1979;300(22):1233–1237. 16. Randall VA, Hibberts NA, Thornton MJ, et al. The hair follicle: a paradoxical androgen target organ. Horm Res 2000;54(5–6):243–250. 17. Price VH, Menefee E, Sanchez M, et al. Changes in hair weight and hair count in men with androgenetic alopecia after treatment with finasteride, 1 mg, daily. J Am Acad Dermatol 2002;46(4):517–523. 18. Steers WD. 5Alpha-reductase activity in the prostate. Urology 2001;58(6 Suppl 1):17–24; discussion, 24. 19. Frade Costa EM, Prado Arnhold IJ, Inacio M, et al. Normal bone density in male pseudohermaphroditism due to 5alpha- reductase 2 deficiency. Rev Hosp Clin Fac Med Sao Paulo 2001;56(5): 139–142. 20. Matsumoto AM, Tenover L, McClung M, et al. The long-term effect of specific type II 5alphareductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial. J Urol 2002;167(5):2105–2108. 21. Miller EA, Ellis WJ, Endocrine aspects of benign prostatic hyperplasia. In: Becker, KL, ed. Principles and Practice of Endocrinology and Metabolism, 3rd Edition, Lippencott Williams & Wilkins, Philadelphia, PA, 2001, pp. 1207–1212. 22. McConnell JD. The pathophysiology of benign prostatic hyperplasia. J Androl 1991;12(6):356–363. 23. Huggins C, Clark PJ. Quantitative studies of prostatic secretion: II. The effect of castration and of estrogen injection on the normal and on the hyperplastic prostate glands of dogs. J Exp Med 1940;72:747–761. 24. Huggins C, Stevens RA. The effect of castration on benign hypertrophy of the prostate in man. J Urol 1940;43:705–714. 25. Imperato-McGinley J, Guerrero L, Gautier T, et al. Steroid 5alpha-reductase deficiency in man: an inherited form of male pseudohermaphroditism. Science 1974;186(4170):1213–1215. 26. Walsh PC, Madden JD, Harrod MJ, et al. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. N Engl J Med 1974;291(18):944–949. 27. Imperato-McGinley J, Gautier T, Zirinsky K, et al. Prostate visualization studies in males homozygous and heterozygous for 5 alpha-reductase deficiency. J Clin Endocrinol Metab 1992;75(4):1022–1026. 28. Fratianni CM, Imperato-McGinley J. The syndrome of 5a-reductase deficiency. Endocrinologist 1994;4:302–314. 29. Rittmaster RS. 5Alpha-reductase inhibitors. J Androl 1997;18(6):582–587. 30. Geller J. Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. J Clin Endocrinol Metab 1990;71(6):1552–1555. 31. McConnell JD, Wilson JD, George FW, et al. Finasteride, an inhibitor of 5 alpha-reductase, suppresses prostatic dihydrotestosterone in men with benign prostatic hyperplasia. J Clin Endocrinol Metab 1992;74(3):505–508. 32. Steiner MS. Review of peptide growth factors in benign prostatic hyperplasia and urological malignancy. J Urol 1995;153(4):1085–1096. 33. Culig Z, Hobisch A, Cronauer MV, et al. Regulation of prostatic growth and function by peptide growth factors. Prostate 1996;28(6):392–405. 34. McConnell JD, Barry MJ, Bruskewitz RC, et al., Benign prostatic hyperplasia: diagnosis and treatment. In: Clinical Practice Guideline, No. 8. Agency for Health Care Policy and Research, Public Health Service, US Department of Health and Human Services, Rockville, MD, 1994. 35. Jacobsen SJ, Girman CJ, Lieber MM. Natural history of benign prostatic hyperplasia. Urology 2001;58(6 Suppl 1):5–16; discussion, 16. 36. Span PN, Voller MC, Smals AG, et al. Selectivity of finasteride as an in vivo inhibitor of 5alphareductase isozyme enzymatic activity in the human prostate. J Urol 1999;161(1):332–337. 37. Uygur MC, Arik AI, Altug U, et al. Effects of the 5 alpha-reductase inhibitor finasteride on serum levels of gonadal, adrenal, and hypophyseal hormones and its clinical significance: a prospective clinical study. Steroids 1998;63(4):208–213. 38. Clifford GM, Farmer RD. Medical therapy for benign prostatic hyperplasia: a review of the literature. Eur Urol 2000;38(1):2–19. 39. Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med 1992;327(17):1185–1191.
86 Sutton, Amory, and Clark 40. The Finasteride Study Group. Finasteride (MK-906) in the treatment of benign prostatic hyperplasia. Prostate 1993;22(4):291–299. 41. Lepor H, Williford WO, Barry MJ, et al. The efficacy of terazosin, finasteride, or both in benign prostatic hyperplasia. Veterans Affairs Cooperative Studies Benign Prostatic Hyperplasia Study Group. N Engl J Med 1996;335(8):533–539. 42. Boyle P, Gould AL, Roehrborn CG. Prostate volume predicts outcome of treatment of benign prostatic hyperplasia with finasteride: meta-analysis of randomized clinical trials. Urology 1996; 48(3):398–405. 43. Roehrborn CG, Boyle P, Bergner D, et al. Serum prostate-specific antigen and prostate volume predict long-term changes in symptoms and flow rate: results of a four-year, randomized trial comparing finasteride versus placebo. PLESS Study Group. Urology 1999;54(4):662–669. 44. McConnell JD, Bruskewitz R, Walsh P, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med 1998;338(9):557–563. 45. Roehrborn CG, McConnell JD, Lieber M, et al. Serum prostate-specific antigen concentration is a powerful predictor of acute urinary retention and need for surgery in men with clinical benign prostatic hyperplasia. PLESS Study Group. Urology 1999;53(3):473–480. 46. Andersen JT, Nickel JC, Marshall VR, et al. Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia. Urology 1997; 49(6):839–845. 47. Rittmaster RS, Norman RW, Thomas LN, et al. Evidence for atrophy and apoptosis in the prostates of men given finasteride. J Clin Endocrinol Metab 1996;81(2):814–819. 48. Saez C, Gonzalez-Baena AC, Japon MA, et al. Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression. Prostate 1998;37(2):84–90. 49. Thomas LN, Wright AS, Lazier CB, et al. Prostatic involution in men taking finasteride is associated with elevated levels of insulin-like growth factor-binding proteins (IGFBPs)-2, -4, and -5. Prostate 2000;42(3):203–210. 50. Beisland HO, Binkowitz B, Brekkan E, et al. Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia. Eur Urol 1992;22(4):271–277. 51. Ekman P. Maximum efficacy of finasteride is obtained within 6 months and maintained over 6 years. Follow-up of the Scandinavian Open-Extension Study. The Scandinavian Finasteride Study Group. Eur Urol 1998;33(3):312–317. 52. Marks LS, Partin AW, Dorey FJ, et al. Long-term effects of finasteride on prostate tissue composition. Urology 1999;53(3):574–580. 53. Glassman DT, Chon JK, Borkowski A, et al. Combined effect of terazosin and finasteride on apoptosis, cell proliferation, and transforming growth factor-beta expression in benign prostatic hyperplasia. Prostate 2001;46(1):45–51. 54. Saez C, Gonzalez-Baena AC, Japon MA, et al. Expression of basic fibroblast growth factor and its receptors FGFR1 and FGFR2 in human benign prostatic hyperplasia treated with finasteride. Prostate 1999;40(2):83–88. 55. Debruyne FM, Jardin A, Colloi D, et al. Sustained-release alfuzosin, finasteride and the combination of both in the treatment of benign prostatic hyperplasia. European ALFIN Study Group. Eur Urol 1998;34(3):169–175. 56. Barry MJ, Roehrborn CG. Benign prostatic hyperplasia. Br Med J 2001;323(7320):1042–1046. 57. Michel MC, Bressel HU, Mehlburger L, et al. Tamsulosin: real life clinical experience in 19,365 patients. Eur Urol 1998;34(Suppl 2):37–45. 58. Dutkiewics S. Efficacy and tolerability of drugs for treatment of benign prostatic hyperplasia. Int Urol Nephrol 2001;32(3):423–432. 59. McConnell JD. Long term effects of medical therapy on the progression of BPH: results from the MTOPS trial. J Urol 2002;167(Suppl 4):265 (abstract). 60. Roehrborn CG, Boyle P, Nickel CJ, et al. Efficacy and safety of dual inhibitor of 5 alpha reductase types 1 and 2 (dutasteride) in men with benign prostatic hyperplasia (BPH). Urology 2002;60: 434–441. 61. Cancer Facts and Figures. American Cancer Society, Atlanta, GA, 2001, p. 5. 62. Seidenfeld J, Samson DJ, Hasselblad V, et al. Single-therapy androgen suppression in men with advanced prostate cancer: a systematic review and meta-analysis. Ann Intern Med 2000;132(7): 566–577.
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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
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
Page 57 and 58: 46 Plymate Table 1 Classification o
Page 59 and 60: 48 Plymate In addition to the direc
Page 61 and 62: 50 Plymate LABORATORY FINDINGS In p
Page 63 and 64: 52 Plymate those manifesting as phe
Page 65 and 66: 54 Plymate result in some improveme
Page 67 and 68: 56 Plymate If both testosterone and
Page 69 and 70: 58 Plymate Persistent Müllerian Du
Page 71 and 72: 60 Plymate INFERTILITY RESULTING FR
Page 73 and 74: 62 Plymate unaffected, contralatera
Page 75 and 76: 64 Plymate SECONDARY HYPOGONADISM H
Page 77 and 78: 66 Plymate Other syndromes manifest
Page 79 and 80: 68 Plymate period after the burn. I
Page 81 and 82: 70 Plymate These findings suggest t
Page 83 and 84: 72 Plymate 49. Goebelsmann U, Horto
Page 85 and 86: 74 Plymate 104. Yoshimoto Y, Moride
Page 87 and 88: 76 Plymate
Page 89 and 90: 78 Sutton, Amory, and Clark levels
Page 91 and 92: 80 Sutton, Amory, and Clark cebo in
Page 93 and 94: 82 Sutton, Amory, and Clark Finaste
Page 95: 84 Sutton, Amory, and Clark through
Page 99 and 100: 88 Sutton, Amory, and Clark 88. Rob
Page 101 and 102: 90 Lindzey and Korach Fig. 1. Cellu
Page 103 and 104: 92 Lindzey and Korach estrogen sign
Page 105 and 106: 94 Lindzey and Korach TESTIS AND DU
Page 107 and 108: 96 Lindzey and Korach sufficient to
Page 109 and 110: 98 Lindzey and Korach Seminal Vesic
Page 111 and 112: 100 Lindzey and Korach 17. Krege JH
Page 113 and 114: 102 Lindzey and Korach 68. Chang WY
Page 115 and 116: 104 McPhaul on the Y chromosome det
Page 117 and 118: 106 106 McPhaul
Page 119 and 120: 108 McPhaul number of alleles, dele
Page 121 and 122: 110 McPhaul The first mutation of t
Page 123 and 124: 112 McPhaul gene. In vitro studies
Page 125 and 126: 114 McPhaul risk of impaired sperma
Page 127 and 128: 116 McPhaul carrying a single mutan
Page 129 and 130: 118 McPhaul REFERENCES 1. Koopman P
Page 131 and 132: 120 McPhaul 45. Weidemann W, Peters
Page 133 and 134: 122 McPhaul 92. Koivisto P, Kononen
Page 135 and 136: 124 Legro Fig. 1. The spectrum of p
Page 137 and 138: 126 Legro Virilization presents wit
Page 139 and 140: 128 Legro Fig. 3. The paradox of an
Page 141 and 142: 130 Legro small high-density athero
Page 143 and 144: 132 Legro Table 2 Syndromes or Dise
Page 145 and 146: 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
Page 171 and 172:
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
Page 241 and 242:
230 Kenny and Raisz 51. Morishima A
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232 Kenny and Raisz 103. Snyder PJ,
Page 245 and 246:
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
Page 251 and 252:
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
Page 261 and 262:
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
Page 279 and 280:
268 Bancroft In a report of a serie
Page 281 and 282:
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
Page 303 and 304:
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
Page 329 and 330:
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
Page 353 and 354:
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
Page 359 and 360:
348 Tenover In aging men, the combi
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350 Tenover Table 1 Changes in Andr
Page 363 and 364:
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
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
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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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
Page 419 and 420:
408 Amory pregnancies fathered by t
Page 421 and 422:
410 Amory antagonists can suppress
Page 423 and 424:
412 Amory 100-mg doses of weekly TE
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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 and 438:
426 Anawalt Fig. 2. Evaluation and
Page 439 and 440:
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
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
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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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