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Chapter 18/Androgens in Older Men 361 13. Baker HWG, Burger HG, deKretser DM, et al. Changes in the pituitary–testicular system with age. Clin Endocrinol (Oxf) 1976;5:349–372. 14. Nieschlag E, Lammers U, Freischem CW, et al. Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 1982;55:676–681. 15. Mulligan T, Iranmanesh A, Hohnson ML, et al. Aging alters feed-forward and feedback linkings between LH and testosterone in healthy men. Am J Physiol 1997;273:R1407–R1413. 16. Marrama P, Montanini V, Celani MR, et al. Decrease in luteinizing hormone biological activity/ immunoactivity ratio in elderly men. Maturitas 1984;5:223–231. 17. Tenover JS, Matsumoto AM, Plymate SR, Bremner WJ. The effects of aging in normal men on bioavailable testosterone and luteinizing hormone secretion: response to clomiphene citrate. J Clin Endocrinol Metab 1987;5:1118–1126. 18. Bannister P, Oakes J, Sheridan P, Mosowsky MS. Sex hormone changes in chronic liver disease: a matched study of alcoholic versus non-alcoholic liver disease. Q J Med 1987;240:305–313. 19. Kley HK, Niederau C, Stremmel W, et al. Conversion of androgens to estrogens in idiopathic hemochromatosis: comparison with alcoholic liver disease. J Clin Endocrinol Metab 1985;61:1–6. 20. Turner HE, Wass JAH. Gonadal function in men with chronic illness. Clin Endocrinol (Oxf) 1997;47: 379–403. 21. Pont A, Graybill JR, Craven PC, et al. High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med 1984;144:2150–2153. 22. Lardinois CK, Mazzaferri EL. Cimetidine blocks testosterone synthesis. Arch Intern Med 1985;145: 920–922. 23. MacAdams, MR, White RH, Chipps BE. Reduction of serum testosterone levels during chronic glucocorticoid therapy. Ann Intern Med 1986;104:648–651. 24. Gaigulli VA, Kauman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Clin Endocrinol Metab 1994;79:997–1000. 25. van den Beld AW, deJong FH, Grobbee DE, et al. Measures of bio-available serum testosterone and estradiol and their relationship with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab 2000;85:3276–3282. 26. Nilsson P, Moller L, Solkad K. Adverse effects of psychosocial stress on gonadal function and insulin levels in middle aged males. J Intern Med 1995;237:479–486. 27. Khosla S, Melton LJ, Atkinson EJ, et al. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men: a key role for bio-available estrogen. J Clin Endocrinol Metab 1998;83:2266–2275. 28. Nankin HR, Calkins JH. Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab 1986;63:418–420. 29. Tenover JS, Matsumoto AM, Clifton DK, Bremner WJ. Age-related alterations in the circadian rhythms of pulsatile luteinizing hormone and testosterone secretion in healthy elderly men. J Gerontol Med Sci 1988;43:M163–M169. 30. Morley JE, Charlton E, Patrick P, et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000;49:1239–1242. 31. Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999;84:3666–3672. 32. Haren M, Nordin BEC, Pearce CEM, et al. The calculation of bioavailable testosterone. In: Robaire R, Chemes H, Morales CA, eds. Andrology in the 21st Century. Medimond Medical Publishing, Englewood, NJ, 2001, pp. 209–215. 33. Forbes GB, Reina JC. Adult lean body mass declines with age: some longitudinal observations. Metabolism 1970;19:653–663. 34. Melton LJ, Khosla S, Riggs BL. Epidemiology of sarcopenia. Mayo Clin Proc 2000;75(Suppl):S10–S13. 35. Lexell J, Henriksson-Larsen K, Wimblod B, Sjostrom M. Distribution of different fiber types in human skeletal muscles: effects of aging studied in whole muscle cross section. Muscle Nerve 1983;6:588–595. 36. Larsson LG, Grimby G, Karlsson J. Muscle strength and speed of movement in relation to age and muscle morphology. J Appl Physiol 1979;46:451–456. 37. Wolfson L. Judge J, Whipple R, King M. Strength is a major factor in balance, gait, and the occurrence of falls. J Gerontol 1995;50:A64–A67. 38. Bhasin S, Storer TW, Berman N, et al. Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 1997;82:407–413. 39. Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1–7
362 Tenover 40. Kohrt WM, Malley MT, Dalsky GP, Holloszy JO. Body composition of healthy sedentary and trained, young and older men and women. Med Sci Sports Exerc 1992;24:832–837. 41. Bjorntorp P. Visceral obesity: a civilisation syndrome. Obes Res 1993;1:206–222. 42. Vermeulen A, Goemaere S, Kaufman J. Sex hormones, body composition and aging. Aging Male 1999;2:8–15. 43. Seidell JC, Bjorntorp P, Sjostrom L, et al. Visceral fat accumulation in men is positively associated with insulin, glucose and C-peptide levels, but negatively with testosterone levels. Metabolism 1990;39:897–901. 44. Orwoll ES, Klein RF. Osteoporosis in men. Endocr Rev 1995;16:87–116. 45. Gallagher JC, Melton LJ, Riggs BL, et al. Epidemiology of fractures of the proximal femur in Rochester, Minnesota. Clin Orthoped 1980;150:163–168. 46. Magaziner J, Simonsick EM, Kashner TM, et al. Survival experience of aged hip fracture patients. Am J Public Health 1989;79:274–235. 47. Stanley HL, Schmitt BP, Poses RM, Deiss WP. Does hypogonadism contribute to the occurrence of minimal trauma hip fracture in elderly men? J Am Geriatr Soc 1991;39:766–771. 48. Stephan JJ, Lachman M, Zverina J, et al. Castrated men exhibit bone loss: effect of calcitonin treatment on biochemical indices of bone remodeling. J Clin Endocrinol Metab 1989;69:523–527. 49. Goldray D, Weisman Y, Jaccard N, et al. Decreased bone density in elderly men treated with the gonadotropin-releasing hormone agonist decapeptyl (D-Tryp 6 -GnRH). J Clin Endocrinol Metab 1993;76:288–290. 50. Finkelstein JS, Klibanski A, Neer RM, et al. Osteoporosis in men with idiopathic hypogonadaotropic hypogonadism. Ann Intern Med 1987;106:354–361. 51. Behre HM, Kliesch S. Leifke E, et al. Long-term effects of testosterone therapy on bone mineral density in hypogonadal men. J Clin Endocrinol Metab 1997;82:2386–2390. 52. Schiavi RC. Androgens and sexual function in men. In: Oddens BJ, Vermeulen A, eds. Androgens and the Aging Male. Parthenon, New York, 1996, pp. 111–128. 53. Korenman SG, Morley JE, Mooradian AD, et al. Secondary hypogonadism in older men: its relation to impotence. J Clin Endocrinol Metab 1990;71:963–969. 54. Kwan M, Greenleaf WJ, Mann J, et al. The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men. J Clin Endocrinol Metab 1983;57:557–562. 55. Carani C, Zini D, Baldini A, et al. Effects of androgen treatment in impotent men with normal and low levels of free testosterone. Arch Sex Behav 1990:19:223–234. 56. Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab 1996;81:3578–3583. 57. Margolese HC. The male menopause and mood: testosterone decline and depression in the aging male—is there a link? J Geriatr Psychiatry Neurol 2000;13:93–101. 58. Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab 1999;84:573–577. 59. Janowsky JS, Oviatt SK, Orwoll ES. Testosterone influences spatial cognition in older men. Behav Neurosci 1994;108:325–332. 60. Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999;84:3681–3685. 61. Shahidi NT. Androgens and erythropoiesis. N Engl J Med 1971;289:72–80. 62. Claustres M, Sultan C. Androgen and erythropoiesis: evidence for an androgen receptor in erythroblasts from human bone marrow cultures. Horm Res 1988;29:17–22. 63. Vahlquist B. The cause of the sexual differences in erythrocyte, hemoglobin and serum iron levels in human adults. Blood 1950;5:874–875. 64. McCullagh EP, Jones R. Effect of androgens on the blood count of men. J Clin Endocrinol 1942;2: 243–247. 65. Matsumoto AM. Effects of chronic testosterone administration in normal men: safety and efficacy of high dosage testosterone and parallel dose-dependent suppression of luteinizing hormone, follicle stimulating hormone, and sperm production. J Clin Endocrinol Metab 1990;70:282–287. 66. Garry PJ, Goodwin JS, Hunt WC. Iron status and anemia in the elderly. J Am Geriatr Soc 1983;31: 389–394. 67. Kirkland RT, Keenan BS, Probstfield JL, et al. Decrease in plasma high density lipoprotein cholesterol at puberty in boys with delayed adolescence. Correlation with plasma testosterone levels. JAMA 1987;27:502–507.
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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
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
Page 333 and 334: 322 Matsumoto dosage is increased g
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
Page 359 and 360: 348 Tenover In aging men, the combi
Page 361 and 362: 350 Tenover Table 1 Changes in Andr
Page 363 and 364: 352 Tenover studies in which eugona
Page 365 and 366: 354 Tenover Table 3 Testosterone Th
Page 367 and 368: 356 Tenover Table 5 ART in Older Me
Page 369 and 370: 358 Tenover be overcome with either
Page 371: 360 Tenover Laboratory tests should
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
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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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