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Chapter 21/Androgens and Male Contraception 415 are, at present, impractical for widespread use. T combinations with progestins appear promising. Ongoing trials with T plus LNG, DSG, CPA, or NETE may offer a usable option for men, but difficulties in T delivery continue to hinder commercial use. Newer androgens such as injectable TU and MENT may help improve T delivery, avoid undesirable effects on the prostate, and aid in the development of a marketable contraceptive regimen. REFERENCES 1. Martin CW, Anderson RA, Cheng L, et al. Potential impact of hormonal meal contraception: crosscultural implications for development of novel male preparations. Hum Reprod 2000;15:637–645. 2. Glasier AF, Anakwe R, Everington D, et al. Would women trust their partners to use a male pill? Hum Reprod 2000;15:646–649. 3. Amory JK, Bremner WJ. The use of testosterone as a male contraceptive. Balliere’s Clin Endocrinol Metab 1998;12:471–484. 4. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men. Fertil Steril 1996;65:821–829. 5. Handelsman DJ, Farley TM, Peregoudov A,Waites GM. Factors in nonuniform induction of azoospermia by testosterone enanthate in normal men. Fertil Steril 1995;63:125–133. 6. Bagatell CJ, Bremner WJ. Androgens in men-uses and abuses. N Engl J Med 1996;334:707–714 7. World Health Organization. Contraceptive efficacy of testosterone-induced azoospermia in normal men. Lancet 1990;336:995–999. 8. Bagatell CJ, Heiman JR, Matsumoto AM, et al. Metabolic and behavioral effects of high-dose, exogenous testosterone in healthy men. J Clin Endocrinol Metab 1994;79:561–567. 9. Meriggiola MC, Marcovina S, Paulsen CA, Bremner WJ. Testosterone enanthate at the dose 200 mg/ week decreases HDL-cholesterol levels in healthy men. Int J Androl 1995;18:237–242. 10. Behre HM, Nieschlag E. Testosterone buciclate (20 Aet-1) in hypogonadal men: pharmacokinetics and pharmacodynamics of the new long-acting androgen ester. J Clin Endocrinol Metab 1992;75:1204–1210. 11. Sharma RS, Rajalakshmi M, Pal PC, et al. Evaluation of efficacy, safety, and reversibility of combination regimen of cyproterone acetate and testosterone buciclate in bonnet monkeys. Contraception 2000;62:195–201. 12. Coert A, Geelen J, de Visser J, VanderVies J. The pharmacology and metabolism of testosterone undecanoate (TU), an new orally active androgen. Acta Endocrinol (Copenh) 1975;79:789–800. 13. Zhang GY, Gu YQ, Wang XH, et al. A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men. J Androl 1998;19:761–768. 14. Behre AM, Abshagen K, Oettel M, et al. Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. Eur J Endrocrinol 1999;140:414–419. 15. Zhang GY, Gu YQ, Wang XH, et al. Injectable testosterone undecanoate for contraception in Chinese men. J Clin Endocrinol Metab 1999;84:3642–3647 16. Kamischke A, Ploger D, Venherm S, et al. Intramuscular testosterone undecanoate with or without oral levonorgestrel: a randomized placebo-controlled feasibility study for male contraception. Clin Endocrinol 2000;53:43–52. 17. Kamischke A, Venherm S, Ploger D, et al. Intramuscular testosterone undecanoate and norethisterone enanthate in a clinical trial for male contraception. J Clin Endocrinol Metab 2001;86:303–309. 18. Schurmeyer T, Knuth UA, Belkien L, Nieschlag E. Reversible azoospermia induced by the anabolic steroid 19-nortestosterone. Lancet 1984;1:417–420. 19. World Health Organization. Comparison of two androgens plus depot-medroxyprogesterone acetate for suppression to azoospermia in Indonesian men. Fertil Steril 1993;60:1062–1068. 20. Behre HM, Kliesch S, Lemcke B, et al. Suppression of spermatogenesis to azoospermia by combined administration of GnRH antagonist and 19-nortestosterone cannot be maintained by this nonaromatizable androgen alone. Hum Reprod 2001;16:2570–2577. 21. Sundaram K, Kumar N, Bardin CW. 7-Alpha-methyl-19-nortestosterone: an ideal androgen for replacement therapy. Recent Prog Horm Res 1994;49:373–376.
416 Amory 22. Oral contraception. In: Speroff L, Glass RH, Kase NG, eds. Clinical Gynecologic Endocrinology and Infertility, 6th Edition. Williams and Wilkins, Baltimore, MD, 1999, pp. 867–945. 23. Cummings DE, Kumar N, Bardin CW, et al. Prostate-sparing tissue specific effects of the potent androgen 7α-methyl-19-nortestosterone (MENT) in primates. J Clin Endocrinol Metab 1998;83: 4212–4219. 24. Suvissari J, Sundaram K, Noe G, et al. Pharmacokinetics and pharmacodynamics of 7α-methyl-19nortestosterone and intramuscular administration in healthy men. Hum Reprod 1997;12:967–973. 25. Noe G, Suvisaari J, Martin C, et al. Gonadotropin and testosterone suppression by 7α-methyl-19nortestosterone acetate administered by subdermal implant to healthy men. Hum Reprod 1999;14: 2200–2206. 26. Von Eckardstein, Nieschlag E, Croxatto H, et al. 7α-Methyl-19-nortestosterone (MENT) implants for male contraception: a dose-finding study. VIIth International Congress for Andrology, 2001, abstract 140. 27. Buchter D, Von Eckardstein S, Von Eckardstein A, et al. Clinical trial of transdermal testosterone and oral levonorgestrel for male contraception. J Clin Endocrinol Metab 1999;84:1244–1249. 28. Hair WM, Kitteridge K, O’Conner DB, Wu FC. A novel male contraceptive pill-patch combination: oral desogestrel and transdermal testosterone in the suppression of spermatogenesis in normal men. J Clin Endocrinol Metab 2001;86:5201–5209. 29. Pollanen P, Nikkanen V, Huhtaniemi I. Combination of subcutaneous levonorgestrel implants and transdermal dihydrotestosterone gel for male hormonal contraception. Int J Androl 2001;24:369–380. 30. Hamann LG, Mani NS, Davis RL, et al. Discovery of a potent, orally active, nonsteroidal androgen receptor agonist: 4-ethyl-1,2,3,4-tetrahydro-6-(trifluoromethyl)-8-pyridono[5,6-g]-quinoline (LG121071). J Med Chem 1999;42:210–212. 31. Van Dort ME, Robins DM, Wayburn F. Design, synthesis, and pharmacological characterization of 4-[4,4-dimethyl-3-(4-hydroxybutyl)-5-oxo-2-thioxo-1-imidazolidinyl]-2-iodobenzonitrile as a highaffinity nonsteroidal androgen receptor ligand. J Med Chem 2000;43:3344–3347. 32. Pavlou SN, Brewer K, Farley MG et al. Combined administration of a gonadotropin-releasing hormone antagonist and testosterone in men induces reversible azoospermia without loss of libido. J Clin Endocrinol Metab 1991;73:1360–1369. 33. Tom L, Bhasin S, Salameh W et al. Induction of azoospermia in normal men with combined Nal- Glu gonadotropin-releasing hormone and testosterone enanthate. J Clin Endocrinol Metab 1992;75: 476–483. 34. Bagatell CJ, Matsumoto AM, Christensen RB, et al. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab 1993;77:427–432. 35. Swerdloff RS, Bagatell CJ, Wang C, et al. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate (TE) is maintained by TE alone. J Clin Endocrinol Metab 1998;83:3527–3533. 36. Yeung CH, Weinbauer GF, Cooper TG. Effect of acute androgen withdrawal by GnRH antagonist on epididymal sperm motility and morphology in the cynomolgus monkey. J Androl 1999;20:72–79. 37. Rolf C, Gottschalk I, Behre HM, et al. Pharmacokinetics of new testosterone transdermal therapeutic systems in gonadotropin-releasing hormone antagonist-supressed normal men. Exp Clin Endocrinol Diabetes 1999;107:63–69. 38. Herbst KL, Anawalt BD, Amory JK, et al. Acyline: a novel GnRH antagonist in men. J Clin Endocrinol Metab 2002;87:3215–3220. 39. Cho N, Harada M, Imaeda T, et al. Discovery of a novel, potent and orally active nonpeptide antagonist of the human luteinizing hormone-releasing hormone (LHRH) receptor. J Med Chem 1998;41: 4190–4195. 40. Schearer SB, Alvarez-Sanchez F, Anselmo J et al. Hormonal contraception for men. Int J Androl 1978;2:680–695. 41. Fotherby K, Davies JE, Richards DJ, Bodin M. Effect of low doses of synthetic progestagens on testicular function. Int J Fertil 1972;17:113–119. 42. Meriggiola MC, Bremner WJ. Progestin-androgen combination regimens for male contraception. J Androl 1997;18:240–244. 43. Barfield A, Melo J, Coutinho E, et al. Pregnancies associated with sperm concentrations below 10 million/ml in clinical studies of a potential male contraceptive method, monthly depot medroxyprogesterone acetate and testosterone esters. Contraception 1977;20:121–127.
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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
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
Page 403 and 404: Table 3 Effects of Testosterone Sup
Page 405 and 406: Table 4 Effects of Testosterone Sup
Page 407 and 408: 396 Bhasin, Woodhouse, and Storer c
Page 409 and 410: 398 Bhasin, Woodhouse, and Storer C
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
Page 421 and 422: 410 Amory antagonists can suppress
Page 423 and 424: 412 Amory 100-mg doses of weekly TE
Page 425: 414 Amory FUTURE DIRECTIONS Given t
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
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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