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Chapter 7/Androgen Excess Disorders in Women 137 13. Elchalal U, Schenker JG. The pathophysiology of ovarian hyperstimulation syndrome—views and ideas. Hum Reprod 1997;12:1129–1137. 14. Fulghesu AM, Villa P, Pavone V, et al. The impact of insulin secretion on the ovarian response to exogenous gonadotropins in polycystic ovary syndrome. J Clin Endocrinol Metab 1997;82:644–648. 15. Dale PO, Tanbo T, Haug E, Abyholm T. The impact of insulin resistance on the outcome of ovulation induction with low-dose follicle stimulating hormone in women with polycystic ovary syndrome. Hum Reprod 1998;13:567–570. 16. Dahlgren E, Friberg LG, Johansson S, et al. Endometrial carcinoma; ovarian dysfunction—a risk factor in young women. Eup J Obstet Gynecol Reprod Biol 1991;41:143–150. 17. Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab 1999:84;165–169. 18. Ehrmann DA, Barnes RB, Rosenfield RL, et al. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabet Care 1999;22:141–146. 19. Anonymous. American Diabetes Association: clinical practice recommendations 1997. Diabetes Care 1997;20(Suppl 1): S1–S70. 20. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595–1607. 21. Haffner SM, Miettinen H, Gaskill SP, Stern MP: Metabolic precursors of hypertension. The San Antonio Heart Study . Arch Intern Med 1996;156:1994–2001. 22. Lind L, Lithell H, Pollare T. Is it hyperinsulinemia or insulin resistance that is related to hypertension and other metabolic cardiovascular risk factors? J Hypertens 1993;11(Suppl): S11–S16 23. Talbott E, Clerici A, Berga SL, et al. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiology 1998;51:415–422. 24. Zimmermann S, Phillips RA, Dunaif A, et al. Polycystic ovary syndrome: lack of hypertension despite profound insulin resistance. J Clin Endocrinol Metab 1992;75:508–513. 25. Holte J, Gennarelli G, Berne C, et al. Elevated ambulatory day-time blood pressure in women with polycystic ovary syndrome: a sign of a pre-hypertensive state? Hum Reprod 1996;11:23–28. 26. Talbott EO, Guzick DS, Sutton-Tyrrell K, et al. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterio Thromb Vasc Biol (Online) 2000:20(11):2414–2421. 27. Chetkowski RJ, DeFazio J, Shamonki I, et al. The incidence of late-onset congenital adrenal hyperplasia due to 21-hydroxylase deficiency among hirsute women. J Clin Endocrinol Metab 1984;58:595–598. 28. New MI, Speiser PW. Genetics of adrenal steroid 21-hydroxylase deficiency. Endocr Rev 1986;7:331–349. 29. Azziz R, Hincapie LA, Knochenhauer ES, et al. Screening for 21-hydroxylase-deficient nonclassic adrenal hyperplasia among hyperandrogenic women: a prospective study. Fertil Steril 1999;72:915–925. 30. New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab 1983;57:320–326. 31. Speiser PW, Dupont J, Zhu D, et al. Disease expression and molecular genotype in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. J Clin Invest 1992;90:584–595. 32. Azziz R, Dewailly D, Owerbach D. Clinical review 56: nonclassic adrenal hyperplasia: current concepts. J Clin Endocrinol Metab1994;78:810–815. 33. Cizza G, Chrousos GP. Adrenocorticotrophic hormone-dependent Cushing’s syndrome. Canc Treat Res 1997;89:25–40. 34. Plotz CM, Knowlton AL, Ragan C. The natural history of Cushing’s syndrome. Am J Med 1952;13:597–605. 35. Polson DW, Adams J, Wadsworth J, et al. Polycystic ovaries—a common finding in normal women. Lancet 1988;1:870–872. 36. Farquhar CM, Birdsall M, Manning P, et al. The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust NZJ Obstet Gynaecol 1994;34:67–72. 37. Carmina E, Koyama T, Chang L., et al. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992;167:1807–1812. 38. Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol 1997;15:111–122.
138 Legro 39. Lee O, Farquhar C, Toomath R, Jepson R. Spironolactone versus placebo or in combination with steroids for hirsutism and/or acne. Cochrane Database of Systematic Reviews CD000194, 2000. 40. Rosenbaum M, Leibel RL, Hirsch J. Obesity. N Engl J Med 1997;337:396–407. 41. Pasquali R, Antenucci D, Casimirri F, et al. Clinical and hormonal characteristics of obese amenorrheic hyperandrogenic women before and after weight loss. J Clin Endocrinol Metab 1989;68:173–179. 42. Jaatinen TA, Anttila L, Erkkola R, et al. Hormonal responses to physical exercise in patients with polycystic ovarian syndrome. Fertil Steril 1993;60:262–267. 43. Braun B, Zimmermann MB, Kretchmer N. Effects of exercise intensity on insulin sensitivity in women with non-insulin-dependent diabetes mellitus. J Appl Physiol 1995;78:300–306. 44. McCann PP, Pegg AE. Ornithine decarboxylase as an enzyme target for therapy. Pharmacol Therapeut 1992;54:195–215. 45. Givens JR, Andersen RN, Wiser WL, et al. The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH, and FSH, and in stimulating plasma testosterone-binding capacity in hirsute women. Am J Obstet Gynecol 1976;124:333–339. 46. Azziz R, Ochoa TM, Bradley EL Jr, et al. Leuprolide and estrogen versus oral contraceptive pills for the treatment of hirsutism: a prospective randomized study. J Clin Endocrinol Metab 1995;80:3406–3411. 47. Heiner JS, Greendale GA, Kawakami AK, et al. Comparison of a gonadotropin-releasing hormone agonist and a low dose oral contraceptive given alone or together in the treatment of hirsutism. J Clin Endocrinol Metab 1995;80:3412–3418. 48. Elkind-Hirsch KE, Anania C, Mack M, Malinak R: Combination gonadotropin-releasing hormone agonist and oral contraceptive therapy improves treatment of hirsute women with ovarian hyperandrogenism. Fertil Steril 1995;63:970–978. 49. Carr BR, Breslau NA, Givens C, et al. Oral contraceptive pills, gonadotropin-releasing hormone agonists, or use in combination for treatment of hirsutism: a clinical research center study. J Clin Endocrinol Metab 1995;80:1169–1178. 50. Velazquez EM, Mendoza S, Hamer T, et al. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabol 1994;43:647–654. 51. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian p450c17 alpha activity and serum androgens. J Clin Endocrinol Metab 1997;82:4075–4079. 52. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med 1998;338:1876–1880. 53. Nestler JE, Jakubowicz DJ, Reamer P, et al. Ovulatory and metabolic effects of d-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999;340:1314–1320. 54. Coetzee EJ, Jackson WP. Metformin in management of pregnant insulin-independent diabetics. Diabetologia 1979;16:241–245. 55. Callahan TL, Hall JE, Ettner SL, et al. The economic impact of multiple-gestation pregnancies and the contribution of assisted-reproduction techniques to their incidence. N Engl J Med 1994;331: 244–249. 56. Coetzee EJ, Jackson WP. Pregnancy in established non-insulin-dependent diabetics. A five-and-a-half year study at Groote Schuur Hospital. S Afric Med J 1980;58:795–802. 57. Sarlis NJ, Weil SJ, Nelson LM. Administration of metformin to a diabetic woman with extreme hyperandrogenemia of nontumoral origin: management of infertility and prevention of inadvertent masculinization of a female fetus. J Clin Endocrinol Metab 1999;84:1510–1512. 58. Diamanti-Kandarakis E, Kouli C, Tsianateli T, Bergiele A. Therapeutic effects of metformin on insulin resistance and hyperandrogenism in polycystic ovary syndrome. Eur J Endocrinol 1998;138: 269–274. 59. Velazquez E, Acosta A, Mendoza SG: Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol 1997;90:392–395. 60. Vandermolen DT, Ratts VS, Evans WS, et al. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic ovary syndrome who are resistant to clomiphene citrate alone . Fertil Steril 2001;75:310–315. 61. Moghetti P, Castello R, Negri C, et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebocontrolled 6-month trial, followed by open, long-term clinical evaluation. J Clin Endocrinol Metab 2000;85:139–146.
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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
Page 97 and 98: 86 Sutton, Amory, and Clark 40. The
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
Page 147: 136 Legro is undetermined according
Page 151 and 152: 140 Legro
Page 153 and 154: 142 Wang and Swerdloff PHARMACOLOGY
Page 155 and 156: 144 Wang and Swerdloff The 17α-alk
Page 157 and 158: 146 Wang and Swerdloff Table 2 Dose
Page 159 and 160: 148 Wang and Swerdloff The steroid
Page 161 and 162: 150 Wang and Swerdloff The inabilit
Page 163 and 164: 152 Wang and Swerdloff 15. De Lorim
Page 165 and 166: 154 Wang and Swerdloff
Page 167 and 168: 156 Marcelli et al.
Page 169 and 170: 158 Marcelli et al. Differentiated
Page 171 and 172: 160 Marcelli et al. These coactivat
Page 173 and 174: 162 Marcelli et al. tigators have e
Page 175 and 176: 164 Marcelli et al. AR in Prostate
Page 177 and 178: 166 Marcelli et al. Table 1 Androge
Page 179 and 180: 168 Marcelli et al. A molecular exp
Page 181 and 182: 170 Marcelli et al. The above data
Page 183 and 184: 172 Marcelli et al. up to 9 yr late
Page 185 and 186: 174 Marcelli et al. Three major pha
Page 187 and 188: 176 Marcelli et al. vitro model of
Page 189 and 190: 178 Marcelli et al. yr, survival wa
Page 191 and 192: 180 Marcelli et al. 26. McKenna NJ,
Page 193 and 194: 182 Marcelli et al. 78. Isaacs J, C
Page 195 and 196: 184 Marcelli et al. 126. Watanabe M
Page 197 and 198: 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
Page 239 and 240:
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,
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
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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
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
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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
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
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374 Davis Table 4 Androgen Replacem
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376 Davis 8. Vierhapper H, Nowotny
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378 Davis 60. Simberg N, Titinen A,
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380 Davis
Page 393 and 394:
382 Bhasin, Woodhouse, and Storer h
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384 Table 2 Effects of Testosterone
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386 Bhasin, Woodhouse, and Storer e
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388 Bhasin, Woodhouse, and Storer F
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390 Bhasin, Woodhouse, and Storer t
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Table 3 Effects of Testosterone Sup
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Table 4 Effects of Testosterone Sup
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396 Bhasin, Woodhouse, and Storer c
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398 Bhasin, Woodhouse, and Storer C
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400 Bhasin, Woodhouse, and Storer w
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402 Bhasin, Woodhouse, and Storer 4
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404 Bhasin, Woodhouse, and Storer
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406 Amory Fig. 1. The endocrinology
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408 Amory pregnancies fathered by t
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410 Amory antagonists can suppress
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412 Amory 100-mg doses of weekly TE
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414 Amory FUTURE DIRECTIONS Given t
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416 Amory 22. Oral contraception. I
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418 Amory
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420 Anawalt inadequate androgen eff
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422 Anawalt few specialty commercia
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424 Anawalt Fig. 1. (C) Secondary h
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426 Anawalt Fig. 2. Evaluation and
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428 Anawalt All men with secondary
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430 Anawalt anemia (38). With the a
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432 Anawalt osterone levels achieve
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434 Anawalt SIDE EFFECTS OF ANDROGE
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436 Anawalt 7. Rosner W. Errors in
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438 Anawalt 59. Mackey MA, Conway A
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440 Index polycystic ovaries, 131 A
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442 Index lipoid congenital adrenal
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444 Index women, 254 dihydrotestost
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446 Index Pituitary adenoma, male h
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448 Index lipoid congenital adrenal
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