Fertility and Sterility
Volume 85, Issue 5 , Pages 1319-1340 , May 2006

Obesity and androgens: facts and perspectives

This review was partly presented as a presidential lecture at the first meeting of the Androgen Excess Society, Philadelphia, Pennsylvania, June 18, 2003.

  • Renato Pasquali, M.D.

      Affiliations

    • Corresponding Author InformationReprint requests: Renato Pasquali, M.D., Unitá Operativa di Endocrinologia, Dipartimento di Medicina Interna, Ospedale Sant’Orsola-Malpighi, Via Massarenti 9, 40138 Bologna, Italy (FAX: 0039 (0)51 6363080).

Received 1 February 2005 ,Revised 26 October 2005 ,Accepted 26 October 2005.

References 

  1. Pinkey JH , Kopelman PG . Endocrine determinant of obesity . In:  Bray GA ,  Bouchard C editor. Handbook of obesity. Etiology and pathophysiology . 2nd ed.. New York: Marcel Dekker; 2004;p. 655–670
  2. Kahn BB , Flier JS . Obesity and insulin resistance . J Clin Invest . 2000;106:473–481
  3. Wajchenberg BL . Subcutaneous and visceral adipose tissue (their relation to the metabolic syndrome) . Endocr Rev . 2000;21:697–738
  4. Pasquali R , Vicennati V . Obesity and hormonal abnormalities . In:  Bjorntorp P editors. International textbook of obesity . Chichester (UK): John Wiley & Sons; 2001;p. 225–239
  5. Pasquali R , Pelusi C , Genghini S , Cacciari M , Gambineri A . Obesity and reproductive disorders in women . Hum Reprod Update . 2003;9:1–14
  6. Hu FCW , von Eckardstein A . Androgens and coronary artery disease . Endocr Rev . 2003;24:183–217
  7. Von Shoultz B , Carlstrom K . On the regulation of sex-hormone–binding globulin. A challenge of old dogma and outlines of an alternative mechanism . J Steroid Biochem . 1989;32:327–334
  8. Tchernof A , Despres JP . Sex steroid hormones, sex hormone–binding globulin, and obesity in men and women . Horm Metab Res . 2000;32:526–536
  9. Pasquali R , Casimirri F , Platé L , Capelli M . Characterization of obese women with reduced sex hormone–binding globulin concentrations . Horm Metab Res . 1990;22:303–306
  10. Evans DJ , Hoffmann RG , Kalkhoff RK , Kissebah AH . Relationship of androgenic activity to body fat topography, fat cell morphology and metabolic aberrations in premenopausal women . J Clin Endocrinol Metab . 1983;57:304–310
  11. Samojlik E , Kirschner MA , Silber D , Schneider G , Ertel NH . Elevated production and metabolic clearance rates of androgens in morbidly obese women . J Clin Endocrinol Metab . 1984;59:949–954
  12. Kirschner MA , Samojlik E , Drejka M , Szmal E , Schneider G , Ertel N . Androgen-estrogen metabolism in women with upper body versus lower body obesity . J Clin Endocrinol Metab . 1990;70:473–479
  13. Kurtz BR , Givens JR , Komindrr S , Stevens MD , Karas JG , Bittle JB , et al.   Maintenance of normal circulating levels of Δ4-androstenedine and dehydroepiandrosterone in simple obesity despite increased metabolic clearance rates (evidence for a servo-control mechanism) . J Clin Endocrinol Metab . 1987;64:1261–1267
  14. Smith SR . The endocrinology of obesity . Endocr Metab Clin North Am . 1996;25:921–942
  15. Zumoff B , Strain G , Miller LK , Rosner W , Senie R , Seres D , et al.   Plasma free and nonsex-hormone-binding-globulin–bound testosterone are decreased in obese men in proportion to their degree of obesity . J Clin Endocrinol Metab . 1990;71:929–931
  16. Strain GW , Zumoff B , Kream J , Strain JJ , Deucher R , Rosenfeld RS , et al.   Mild hypogonadotropic hypogonadism in obese men . Metabolism . 1982;31:871–875
  17. Tchernoff A , Després J-P , Bélanger A , Dupont A , Prud’homme D , Moorjani S , et al.   Reduced testosterone and adrenal C19 steroid levels in obese men . Metabolism . 1995;44:513–519
  18. Kokkoris P , Pi-Sunyer FX . Obesity and endocrine diseases . Endrocrinol Metab Clin North Am . 2003;32:895–914
  19. Vermeulen A , Kaufman JM , Deslypere JP , Thomas G . Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men . J Clin Endocrinol Metab . 1993;76:1140–1146
  20. Giagulli Giagulli VA , Giorgino R , Vermeulen A . Origin and significance of plasma androsterone glucuronide levels (a parameter of adrenal androgen secretion and hepatic 5 alpha-reductase activity) . J Clin Endocrinol Metab . 1993;76:918–923
  21. Khaw KT , Barrett-Connor E . Lower endogenous androgens predict central adiposity in men . Ann Epidemiol . 1992;2:675–682
  22. Pasquali R , Casimirri F , Cantobelli S , Melchionda N , Morselli Labate AM , Fabbri R , et al.   Effect of obesity and body fat distribution on sex hormones and insulin in men . Metabolism . 1991;40:101–104
  23. Leenen R , van der Koy K , Seidell JC , Deurenberg P , Kopperschaar HPF . Visceral fat accumulation in relation to sex hormones in obese men and women undergoing weight loss therapy . J Clin Endocrinol Metab . 1994;78:1515–1520
  24. Plymate SR , Matej LA , Jones RE , Friedl KE . Inhibition of sex hormone–binding globulin production in the human hepatoma (Hep G2) cell line by insulin and prolactin . J Clin Endocrinol Metab . 1988;67:460–464
  25. Poretsky L , Cataldo NA , Rosenwaks Z , Giudice LC . The insulin-related ovarian regulatory system in health and disease . Endocr Rev . 1999;20:535–582
  26. Gambineri A , Pelusi C , Vicennati V , Pagotto U , Pasquali R . Obesity and the polycystic ovary syndrome . Int J Obes . 2002;26:883–896
  27. Pasquali R , Casimirri F , De Iasio R , Mesini P , Boschi S , Chierici R , et al.   Insulin regulates testosterone and sex hormone–binding globulin concentrations in adult normal weight and obese men . J Clin Endocrinol Metab . 1995;80:654–658
  28. Pitteloud N , Hardin M , Dwyer AA , Valassi E , Yialamas M , Elahi D , et al.   Increasing insulin resistance is associated with a decrease in leydig cell testosterone secretion in men . J Clin Endocrinol Metab . 2005;90:2636–2641
  29. Siiteri PK , McDonald PC . Role of extraglandular estrogen in goman endocrinology . In:  Greep PO ,  Astwood E editor. Female reproduction system . Washington (DC): American Physiological Society; 1973;p. 615; Handbook of physiology. Sect. 7: Endocrinology. Vol. 11
  30. Schneider J , Bradlow HL , Strain G , Levin J , Anderson K , Fishman J . Effect of obesity on estradiol metabolism (decreased formation of nonuterotropic metabolites) . J Clin Endocrnol Metab . 1983;56:973–978
  31. Yen SSC , Chaney C , Judd HL . Functional aberrations of the hypothalamic-pituitary system in polycystic ovary. A consideration of the pathogenesis . In:  James WHT ,  Serio M ,  Giusti G editor. The endocrine function of the human ovary . New York: Academic Press; 1976;p. 373–380
  32. McKenna TJ . Pathogenesis and treatment of polycystic ovary syndrome . N Engl J Med . 1988;318:558–562
  33. Longcope C , Kato T , Horton R . Conversion of blood androgens to estrogens in normal adult men and women . J Clin Invest . 1969;48:2191–2201
  34. Glass AR . Endocrine aspects of obesity . Endocr Metab Clin North Am . 1989;73:139–160
  35. Pasquali R , Casimirri F , Melchionda N , Fabbri R , Capelli M , Platé L , et al.   Weight loss and sex steroid metabolism in massively obese men . J Endocrinol Invest . 1988;11:205–210
  36. Strain GW , Zumoff B , Miller LK , et al.   Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men . J Clin Endocrinol Metab . 1988;66:1019–1023
  37. Blank DM , Clark RV , Heymsfield SB , Rudman DR , Blank MS . Endogenous opioids and hypogonadism in human obesity . Brain Res Bull . 1994;34:571–574
  38. Stanik S , Dornfeld LP , Maxwell MH , Viosca SP , Korenman SG . The effect of weight loss on reproductive hormones in obese men . J Clin Endocrinol Metab . 1981;53:828–832
  39. Zumoff B , Miller LK , Strain GW . Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone . Metabolism . 1999;52:1126–1128
  40. Williams T , Berelowitz M , Joffe SN , Thorner MO , Rivier J , Vale W , et al.   Impaired growth hormone response to growth hormone releasing factor in obesity (a pituitary defect reversed with weight reduction) . N Engl J Med . 1984;311:1403–1407
  41. Couse JF , Korach KH . Estrogen receptor null mice (what have we learned and where they lead us?) . Endocr Rev . 1999;20:358–417
  42. Smith EP , Boyd J , Frank GR , Takasashi H , Cohen RM , Specker B , et al.   Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man . N Engl J Med . 1994;331:1056–1061
  43. Carani C , Qin K , Simoni M , Faustini-Fustini M , Serpente S , Boyd J , et al.   Effect of testosterone and estradiol in a man with aromatase deficiency . N Engl J Med . 1997;337:91–95
  44. The Writing Group for the PEPI Trial . Effect of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopaual women . JAMA . 1996;273:199–208
  45. Jensen LB , Vestergaard P , Hermann AP , Gram J , Eiken P , Abrahamsen B , et al.   Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women (a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study) . J Bone Miner Res . 2003;18:333–342
  46. Murata Y , Robertson KM , Jones MEE , Simpson ER . Effect of estrogen deficiency in the male (the ArKO mouse model) . Mol Cell Endocrinology . 2002;193:7–12
  47. Jones MEE , Thorburn AW , Britt KL , Hewitt KN , Wreford NG , Proietto J , et al.   Aromatase deficient (ArKO) mice have a phenotype of increased adiposity . Proc Natl Acad Sci U S A . 2000;97:12735–12740
  48. Taylor JA , Lewis KJ , Lubahn DB . Estrogen receptor mutations . Mol Cell Endocrinol . 1998;145:61–66
  49. Bjorntorp P . The regulation of adipose tissue distribution in humans . Int J Obes . 1996;20:291–302
  50. Pasquali R , Vicennati V . The abdominal obesity phenotype and insulin resistance are associated with abnormalities of the hypothalamic-pituitary-adrenal axis in humans . Horm Metab Res . 2000;32:521–525
  51. Bjorntorp P . Centralization of body fat . In:  Bjorntorp P editors. International textbook of obesity . Chichester (UK): John Wiley & Sons; 2001;p. 213–224
  52. Rebuffé-Scrive M , Lundholm K , Bjorntorp P . Glucocorticoid hormone binding to human adipose tissue . Eur J Clin Invest . 1985;15:267–271
  53. Sandeep TC , Walker BR . Pathophysiology of modulation of local glucocorticoid levels by11 β −hydroxysteroid dehydrogenase . Trends Endocrinol Metab . 2001;12:446–453
  54. Tomlinson JW , Walker EA , Bujalska IJ , Draper N , Lavery GG , Cooper MS , et al.   11β-hydroxysteroid dehydrogenase type 1 (a tissue specific regulation of glucorticoid response) . Endocr Rev . 2004;25:831–866
  55. Masuzaki H , Paterson J , Shinyama H , Morton NM , Mullins JJ , Seckl JR , et al.   A transgenic model of visceral obesity and the metabolic syndrome . Science . 2001;294:2166–2170
  56. Tilbrook AJ , Turner AI , Clarke IJ . Effects of stress on reproduction in nonrodent mammals (the role of glucocorticoids and sex differences) . Rev Reprod . 2000;5:105–113
  57. Handa RJ , Burgess LH , Kerr JE , O’Keefe JA . Gonadal steroid hormone receptors and sex differences in the hypothalamo-pituitary-adrenal axis . Horm Behav . 1994;28:464–476
  58. Viau V , Meaney MJ . The inhibitory effect of testosterone on hypothalamic-pituitary-adrenal responses to stress is mediated by the medial preoptic area . J Neurosci . 1996;16:1866–1876
  59. Viau V . Functional cross-talk between the hypothalamic-pituitary-gonadal and -adrenal axes . J Neuroendocrinol . 2002;14:506–513
  60. Born J , Ditschuneit I , Schreiber M , Dodt C , Fehm HL . Effects of age and gender on pituitary-adrenocortical responsiveness in humans . Eur J Endocrinol . 1995;132:705–711
  61. Vierhapper H , Nowotny P , Waldhausl W . Production rates of testosterone in patients with Cushing’s syndrome . Metabolism . 2000;49:229–231
  62. Lado-Abeal J , Rodriguez-Arnao J , Newell-Price JD , Perry LA , Grossman AB , Besser GM , et al.   Menstrual abnormalities in women with Cushing’s disease are correlated with hypercortisolemia rather than raised circulating androgen levels . J Clin Endocrinol Metab . 1998;83:3083–3088
  63. Vicennati V , Ceroni L , Genghini S , Patton L , Pagotto U , Pasquali R . Sex difference in the relationship between the hypothalamic-pituitary-adrenal (HPA) axis and sex hormones in obesity . Obes Res . 2006;14:
  64. Moschos S , Chan JL , Mantzoros CS . Leptin and reproduction (a review) . Fertil Steril . 2002;77:433–444
  65. Mantzoros CS , Moschos S . Leptin (in search for role(s) in human physiology and pathophysiology) . Clin Endocrinol (Oxf) . 1998;49:551–567
  66. Fasshauer M , Paschke R . Regulation of adipocytokines and insulin resistance . Diabetologia . 2003;46:1594–1603
  67. Licinio J , Negrao AB , Mantzoros C , Kaklamani V , Wong ML , Bongiorno PB , et al.   Sex difference in circulating leptin pulse amplitude (clinical implications) . J Clin Endocrinol Metab . 1998;83:4140–4147
  68. Montague CT , Prins JB , Sanders l , Digby JE , O’Rahilly S . Depot- and sex specific differences in human leptin mRNA expression (implications for the control of regional fat distribution) . Diabetes . 1997;46:342–347
  69. Shimizu H , Shimomura K , Negishi M , Masumago M , Uehara Y , Sato N , et al.   Circulating concentrations of soluble leptin receptor (influence of menstrual cycle and diet) . Nutrition . 2002;18:309–312
  70. McConway MG , Johnson D , Kelly A , Griffin D , Smith J , Wallace AM . Differences in circulating concentrations of total, free and bound leptin relate to gender and body composition in adult humans . Ann Clin Biochem . 2000;37:717–723
  71. Housecknecht KL , Mantzoros CS , Kuliawat R , Hadro E , Flier JS , Kahn BB . Evidence for leptin binding to proteins in serum of rodents and humans (modulation with obesity) . Diabetes . 1996;45:1638–1643
  72. Jin L , Zhang S , Burguera BG , Couce ME , Osamura RY , Kulig E , et al.   Leptin and leptin receptor expression in rat and mouse pituitary cells . Endocrinology . 2000;141:333–339
  73. Machinal F , Dieudonne MN , Leneveu MC , Pecquery R , Guidicelli Y . In vivo and in vitro ob gene expression and leptin secretion in rat adipocytes (evidence for a regional specific regulation by sex steroid hormones) . Endocrinology . 1999;140:1567–1574
  74. Tartaglia LA . The leptin receptor . J Biol Chem . 1997;272:6093–6096
  75. Terasawa F . Cellular mechanism of pulsatile LHRH release . Gen Com Endocrinol . 1998;112:283–295
  76. Yu WH , Kimura M , Walczewska A , Kaant S , McCann SM . Role of leptin in hypothalamic-pituitary function . Proc Natl Acad Sci U S A . 1997;94:1023–1028
  77. Spicer JL , Francisco CC . The adipose obese gene product, leptin (evidence of a direct inhibitory role in ovarian function) . Endocrinology . 1997;138:3374–3379
  78. Caprio M , Isidori AM , Carta AR , Moretti C , Dufau ML , Fabbri A . Expression of functional leptin receptors in rodent Leydig cells . Endocrinology . 1999;140:4939–4947
  79. Barash IA , Cheung CC , Weigle Ds , Ren H , Kabigting EB , Kuijper JI , et al.   Leptin is a metabolic signal to the reproduction system . Endocrinology . 1996;137:3144–3147
  80. Chehab FF , Lim ME , Lu R . Correction of the sterility defect in homozygous obese female mice by treatment with the human recombinant leptin . Nat Genet . 1996;12:318–320
  81. Faroqui LS , Matarese G , Lord GM , Keogh JM , Lawrence E , Agwu C , et al.   Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency . J Clin Invest . 2002;110:1093–1103
  82. Clement K , Vaisse C , Lahlou N , Cabrol S , Pelloux V , Cassuto D , et al.   A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction . Nature . 1998;392:398–401
  83. Oral EA , Ruiz E , Andewelt A , Sebring N , Wagner AJ , Depaoli AM , et al.   Effect of leptin replacement on pituitary hormone regulation in patients with severe lipodystrophy . J Clin Endocrinol Metab . 2002;87:3110–3117
  84. Considine RV , Sinha MK , Heiman ML , Kriauciunas A , Stephens TW , Nyce MR , et al.   Serum immunoreactive leptin concentrations in normal-weight and obese humans . N Engl J Med . 1996;334:292–295
  85. Sahu A . Minireviw (a hypothalamic role in energy balance with special emphasis on leptin) . Endocrinology . 2004;145:2613–2620
  86. Vettor R , De Pergola G , Pagano C , Englaro P , Laudadio E , Giorgino F , et al.   Gender differences in serum leptin in obese people (relationship with testosterone, body fat distribution and insulin sensitivity) . Eur J Clin Invest . 1997;27:1016–1024
  87. Jockenhovel F , Blum WF , Vogel E , Englaro P , Muller-Wieland D , Reinwein D , et al.   Testosterone substitution normalizes elevated serum leptin levels in hypogonadal men . J Clin Endocrinol Metab . 1997;82:2510–2513
  88. Wabitsch M , Blum WS , Muche R , Braun M , Hube F , Rascher W , et al.   Contribution of androgens to the gender differences in leptin production in obese children and adolescents . J Clin Invest . 1997;100:808–813
  89. Rosembaum M , Nicolson M , Hirsch J , Haymsfield SB , Gallagher D , Chu F , et al.   Effects of gender, body composition, and menopause on plasma concentrations of leptin . J Clin Endocrinol Metab . 1996;81:34247
  90. Isidori AM , Caprio M , Strollo F , Moretti C , Frajese G , Isidori A , et al.   Leptin and androgens in male obesity (evidence for leptin contribution to reduced androgen levels) . J Clin Endocrinol Metab . 1999;84:3673–3680
  91. Agarwal SK , Vogel k , Weistman SR , Magoffin DA . Leptin antagonizes the insulin-like factor-1 augmentation of steroidogenesis in granulosa and theca cells of the human ovary . J Clin Endocrinol Metab . 1999;84:1072–1076
  92. Spicer JL , Francisco CC . Adipose obese gene product, leptin, inhibits bovine ovarian thecal cell steroidogenesis . Biol Reprod . 1998;58:207–212
  93. Duggal PS , Van Der Hoek KH , Milner CR , Ryan NK , Armstrong DT , Magoffin DA , et al.   The in vivo and in vitro effects of exogenous leptin on ovulation in the rat . Endocrinology . 2000;141:1971–1976
  94. Zachow RJ , Magoffin DA . Direct intraovarian effects of leptin (impairment of the synergistic action of insulin-like growth factor-I on FSH-dependent 17β-estradiol production by rat ovarian granulosa cells) . Endocrinology . 1997;1378:847–850
  95. Urbancsek J , Fedorcsak P , Klinga K , Devènyi N , Papp Z , Rabe T , et al.   Impact of obesity and leptin levels on the secretion of estradiol inhibin A and inhibin B during ovarian stimulation with gonadotropins . Gynecol Endocrinol . 2004;16:285–292
  96. Geisthovel F , Meysing A , Brabant G . C-peptide and insulin, but not c19 steroids, support the predictive value of body mass index on leptin in serum of premenopausal women . Hum Reprod . 1998;13:547–553
  97. Saad MF , Damani S , Gingerich RL , Riad-Gabriel MG , Khan A , Boyadjian R , et al.   Sexual dimorphism in plasma leptin concentration . J Clin Endocrinol Metab . 1997;82:579–584
  98. Brzechffa PR , Jakimiuk AJ , Agarwal SA , Weitsman SR , Buyalos RP , Magoffin DA . Serum immunoreactive leptin levels in women with polycystic ovary syndrome . J Clin Endocrinol Metab . 1996;81:4166–4169
  99. Vicennati V , Gambineri A , Calzoni L , Casimirri F , Macor C , Vettor R , et al.   Serum leptin in obese women with polycystic ovary syndrome is correlated with body weight and fat distribution but not with androgen and insulin levels . Metabolism . 1998;47:988–992
  100. Veldhuis JD , Pincus SM , Garcia-Rudaz MC , Ropelato MG , Escobar ME , Barontini M . Disruption of the synchronous secretion of leptin, LH, and ovarian androgens in nonobese adolescents with the polycystic ovarian syndrome . J Clin Endocrinol Metab . 2001;86:3772–3778
  101. Howard AD , Feighner SD , Cully DF , Arena JP , Liberator PA , Rosenblum CI , et al.   A receptor in pituitary and hypothalamus that function in growth hormone release . Science . 1996;273:974–977
  102. Arvat E , Di Vito L , Broglio F , Papotti M , Muccioli G , Dieguez C , et al.   Preliminary evidence that ghrelin, the natural GH secretagogue (GHS)–receptor ligand, strongly stimulates GH secretion in humans . J Endocrinol Invest . 2000;23:493–495
  103. Kojima M , Hosoda H , Date Y , Nakazato M , Matsuo H , Kangawa K . Ghrelin is a growth-hormone releasing acylated peptide from stomach . Nature . 1999;402:656–660
  104. Casanueva F , Dieguez G . Ghrelin (the link connecting growth with metabolism and energy homeostasis) . Rev Endocr Metab Dis . 2002;3:325–338
  105. Tschop M , Weyer C , Tataranni AP , Devanarayan V , Ravussin E , Heiman ML . Circulating ghrelin levels are decreased in human obesity . Diabetes . 2001;50:707–709
  106. Shiiya T , Nakazato M , Minuta M , Date Y , Mondal MS , Tanaka M , et al.   Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion . J Clin Endocrinol Metab . 2002;87:240–244
  107. Yildiz BO , Suckard MA , Wong Ml , McCann SM , Licinio J . Alterations of the dynamics of circulating ghrelin, adiponectin, and leptin in humans . Proc Natl Acad Sci U S A . 2004;101:10434–10439
  108. Cummings DE, DE , Weigle DS, Frayo RS, Breen PA, Ma MK, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery . N Engl J Med . 2002;346:1623–1630
  109. Ukkola O , Ravussin E , Jacobson P , Perisse l , Rankinen T , Tschop M , et al.   Role of ghrelin polymorphism in obesity based on three different studies . Obes Res . 2002;10:782–791
  110. Goldstone AP . Prader-Willy syndrome (advances in genetics, pathophysiology and treatment) . Trends Endocrinol Metab . 2004;15:12–20
  111. Korbonits M , Goldstone AP , Guerguiev M , Grossman AB . Ghrelin—a hormone with multiple functions . Front Neuroendocrinol . 2004;25:27–68
  112. Barkan AL , Dimaraki EV , Jessup SK , Symons KV , Ermolenko M , Jaffe CA . Ghrelin secretion in humans is sexually dymorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels . J Clin Endocrinol Metab . 2003;88:2180–2184
  113. van der Lely AJ , Thchop M , Heiman ML , Ghigo E . Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin . Endocr Rev . 2004;25:426–457
  114. Papotti M, Ghe C, Cassoni P, Catapano F, Deghenghi R, Ghigo E, et al. Growth hormone secretagogue binding sites in peripheral human tissues . J Clin Endocrinol Metab . 2000;85:3803–3807
  115. Gnanapavan S , Kola B , Bustin SA , Morris DG , McGee P , Fairclough  , et al.   The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans . J Clin Endocrinol Metab . 2002;87:2988–2991
  116. Tena-Sempere M , Barreiro ML , Gonzalez LC , Gaytan F , Zhang FP , Caminos JE , et al.   Novel expression and functional role of ghrelin in rat testis . Endocrinology . 2002;143:717–725
  117. Barreiro ML , Gaytán F , Caminos JE , Pinilla L , Casanueva FF , Aguilar E , et al.   Cellular location and hormonal regulation of ghrelin expression in rat testis . Biol Reprod . 2002;67:1768–1776
  118. Barreiro ML , Suominen JS , Gaytan F , Pinilla L , Chopin LK , Casanueva FF , et al.   Developmental, stage-specific and hormonally regulated expression of growth hormone secretagogue receptor messenger ribonucleic acid in rat testis . Biol Reprod . 2003;68:1631–1640
  119. Tanaka M , Hayashida Y , Nakao N , Nakai N , Nakashima K . Testis-specific and developmentally induced expression of a ghrelin gene–derived transcript that encodes a novel polypeptide in the mouse . Biochem Biophys Acta . 2001;1522:62–65
  120. Papotti M , Ghe C , Cassoni P , Catapano F , Deghenghi R , Ghigo E , et al.   Growth hormone secretagogue binding sites in peripheral human tissues . J Clin Endocrinol Metab . 2000;85:3803–3807
  121. Pagotto U , Gambineri A , Pelusi C , Genghini S , Cacciari M , Otto B , et al.   Testosterone replacement therapy restores normal ghrelin in hypogonadal men . J Clin Endocrinol Metab . 2003;88:4139–4143
  122. Gambineri A , Pagotto U , De Iasio R , Meriggiola MC , Costantino A , Patton L , et al.   Short-term modification of sex hormones is associated with changes in ghrelin circulating levels in healthy normal men . J Endocrinol Invest . 2005;28:241–246
  123. Caminos JE , Tena-Sempere M , Gaytan F , Sanchez-Criado JE , Barreiro ML , Nogueiras R , et al.   Expression of ghrelin in the cyclic and pregnant ovary . Endocrinology . 2003;144:1594–1602
  124. Gaytán F , Barreiro ML , Chopin LK , Herington AC , Morales C , Pinilla L , et al.   Immunolocalization of ghrelin and its functional receptor, the type 1a GH-secretagogue receptor, in the cyclic human ovary . J Clin Endocrinol Metab . 2003;88:879–887
  125. Barkan AL , Dimaraki EV , Jessup SK , Symons KV , Ermolenko M , Jaffe CA , et al.   Ghrelin secretion in humans is sexually dimorphic, suppressed by somatostatin, and not affected by the ambient growth hormone levels . J Clin Endocrinol Metab . 2003;88:2180–2184
  126. Ariyasu H , Takaya K , Tagami T , Ogawa Y , Hosoda K , Akamizu T , et al.   Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans . J Clin Endocrinol Metab . 2001;86: 4753–48
  127. Pagotto U , Gambineri A , Vicennati V , Heiman ML , Tschöp M , Pasquali R . Plasma ghrelin, obesity, and the polycystic ovary syndrome (correlation with insulin resistance and androgen levels) . J Clin Endocrinol Metab . 2002;87:5625–5629
  128. Schöfl C , Horn R , Schill T , Schlösser HW , Müller MJ , Brabant G . Circulating ghrelin levels in patients with polycystic ovary syndrome . J Clin Endocrinol Metab . 2002;87:4607–4610
  129. Gambineri A , Pagotto U , Tschöp M , Vicennati V , Manicardi E , Carcello A , et al.   Anti-androgen treatment increases circulating ghrelin levels in obese women with polycystic ovary syndrome . J Endocrinol Invest . 2003;26:493–498
  130. Moran LJ , Noakes M , Clifton PM , Wittert GA , Tomlinson L , Galletly C , et al.   Ghrelin and measures of satiety are altered in polycystic ovary syndrome but not differentially affected by diet composition . J Clin Endocrinol Metab . 2004;89:3337–3344
  131. Chamberlain NL , Driver ED , Miesfeld RL . The length and location of CAG trinucleotide repeats in the androgen receptor N-terminal domain affect transactivation function . Nucleic Acids Res . 1994;22:3181–3186
  132. Kazemi-Esfariani P , trifiro MA , Pinski L . Evidence for a repressive function of the long polyglutamine tract in the human androgen receptor (possible pathogenetic relevance for the (CAG)n-expanded neuropathies) . Hum Mol Genet . 1995;4:523–527
  133. Westberg I , Baghaei F , Rosmond R , Hellstrand M , Landen M , Jansson M , et al.   Polymorphisms of the androgen receptor gene and the estrogen beta gene are associated with androgen levels in women . J Clin Endocrinol Metab . 2001;86:2562–2568
  134. Irvine RA , Ma H , Yu MC , Ross RK , Stallcup MR , Coetzee GA . Inhibition of p160-mediated coactivation with increasing androgen receptor polyglutamide length . Hum Mol Genet . 2000;9:267–274
  135. Sato T , Matsumoto T , Yamada T , Watanabe T , Kawano H , Kato S . Late onset of obesity in male androgen receptor-deficient (AR KO) mice . Biochem Biophys Res Comm . 2003;300:167–171
  136. Krithivas K , Yurgalevitch SM , Mohr BA , Wilcox CJ , Batter SJ , Brown M , et al.   Evidence that the CAG repeat in the androgen receptor gene is associated with the age-related decline in serum androgen levels in men . J Endocrinol . 1999;162:137–142
  137. Giovannucci E , Stampfer MJ , Krithivas K , Brown M , Dahl D , Brufsky A , et al.   The CAG repeat within the androgen receptor gene and its relationship with prostate cancer . Proc Natl Acad Sci U S A . 1997;94:3320–3323
  138. Giovannucci E , Platz EA , Stampfer MJ , Giovannucci E , Platz EA , Stampfer MJ , et al.   The CAG repeat within the androgen receptor gene and benign proastate hyperplasia . Urology . 1999;53:121–125
  139. Dowsing AT , Young EL , Clarck M , McLachlan RI , de Kretser DM , Trounson AO . Linkage between male infertility and tronucleotide repeat expansion in the androgen-receptor gene . Lancet . 1999;354:640–643
  140. Gustafson DR , Wen MJ , Koppanati BM . Androgen receptor gene repeats and indices of obesity in older adults . Int J Obes . 2003;27:75–81
  141. Mifsud A , Ramirez S , Yong EL . Androgen receptor gene CAG trinucleotide repeats in anovulatoty infertility and polycystic ovaries . J Clin Endocrinol Metab . 2000;83:3484–3488
  142. The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian caucasian women with infertility related to polycystic ovary syndrome . J Clin Endocrinol Metab . 2002;87:161–165
  143. Legro RS , Shabahrami B , Lobo RA , Kovacs BW . Size polymorphism of the androgen receptor among female hispanics and correlation with androgenic characteristics . Obstet Gynecol . 1994;83:701–706
  144. Ibanez L , Ong KK , Mongan N , Jaaskelainen J , Marcos MV , Hughes IA , et al.   Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism . J Clin Endocrinol Metab . 2003;88:3333–3338
  145. Joyner J , Hutley L , Cameron D . Intrinsic regional differences in androgen receptors and dihydrotestosterone metabolism in human preadipocytes . Horm Metab Res . 2002;34:223–228
  146. Stewart PM , Shackleton CH , Beastall GH , Edwards CR . 5a-reductase activity in polycystic ovary syndrome . Lancet . 1990;335:431–433
  147. Fassnacht M , Schlenz N , Schneider SB , Wudy SA , Allolio B , Arlt W . Behind adrenal and ovarian androgen generation (increased peripheral 5a-reductase activity in women with polycystic ovary syndrome) . J Clin Endocrinol Metab . 2003;88:2760–2766
  148. Adamski J , Jacob FJ . A guide to 17 β-hydroxysteroid dehydrogenases . Mol Cell Endocrinol . 2001;171:1–4
  149. Luu-The V . Analysis and characteristics of multiple types of human 17β-hydroxysteroid dehydrogenases . J Steroid Biochem Mol Biol . 2001;76:143–151
  150. Corbould AM , Badwen MJ , Lavranos TC , Rogers RJ , Judd DJ . The effect of obesity and the ratio of type 3 17β-hydroxysteroid dehydrogenase mRNA to cytochrome P450 aromatase mRNA in subcutaneous abdominal and intra-abdominal adipose tissue in women . Int J Obes . 2002;26:165–175
  151. Dufort I , Rheault P , Huang X-F , Soucy P , Luu-The V . Characteristics of a highly labile human type 5 17β-hydroxysteroid dehydrogenase . Endocrinology . 1999;140:568–574
  152. Penning TM , Burczynski ME , Jez JM , Hung CF , Lin HK , Ma H , et al.   Human 3a-hydroxysteroid dehydrogenases isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily (functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones) . Biochem J . 2003;351:67–77
  153. Blouin K , Richard C , Belanger C , Dupont P , Daris M , Laberge P , et al.   Local androgen inactivation in abdominally visceral adipose tissue . J Clin Endocrinol Metab . 2003;88:5944–5950
  154. Quinkler M , Sinha B , Tomlinson JW , Bujalska IJ , Stewart PM , Artl W . Androgen generation in adipose tissue in women with simple obesity—a site-specific role for 17β-hydroxysteroid dehydrogenase type 5 . J Endocrinol . 2004;183:331–342
  155. Singh R , Artaza JN , Taylor WE , Gonzales-Cadavid NF , Bhasin S . Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor–mediated pathway . Endocrinology . 2003;144:5081–5088
  156. Dieudonne MN , Pecquery R , Boumedienne A , Leneveu MC , Guidicelly Y . Androgen receptors in human preadipocytes and adipocytes (regional specificities and regulation by sex steroids) . Am J Physiol . 1998;274:C1645–C1652
  157. Pasquali R , Vicennati V , Pagotto U . Endocrine determinants of fat distribution . In:  Bray G ,  Bouchard C editor. Handbook of obesity . New York: Marcel Dekker; 2003;p. 671–692
  158. Cryer A . Tissue lipoprotein lipase activity and its action in lipoprotein metabolism . J Biochem . 1981;13:525–541
  159. Ailhaud G . L’adipocyte, cellule sécrétrice et endocrine . Méd/Sci . 1998;14:858–864
  160. Kern PA . High adipose tissue lipoprotein lipase activity plays a causal role in the etiology of obesity . In:  Angel A ,  Anderson H ,  Bouchard C ,  Lau D ,  Leiter L ,  Mendelson R editor. Progress in obesity research. Proceedings of the 7th International Congress on Obesity; 1994; Toronto, Canada . London: John Libbey; 1994;p. 89–94
  161. Mayes JS , Watson Gh . Direct effect of sex steroid hormones on adipose tissue and obesity . Obes Rev . 2004;5:197–216
  162. Lonnqvist F , Thorne A , Large V , Arner P . Sex differences in visceral fat lipolysis and metabolic complications of obesity . Arterioscler Thromb Vasc Biol . 1997;17:1472–1480
  163. Bonadonna R , Bonora E . Glucose and free fatty acid metabolism in human obesity. Relationships to insulin resistance . Diabetes Rev . 1997;5:21–51
  164. Lafontan M , Berlan M . Fat cell adrenergic receptors and the control of white and brown fat cell function . J Lipid Res . 1993;34:1057–1091
  165. Reynisdottir S , Dauzats M , Thorne A , Langin D . Comparison of hormone-sensitive lipase activity in visceral and subcutaneous human adipose tissue . J Clin Endocrinol Metab . 1997;82:4162–4166
  166. Miller LK , Kral JG , Strain GW , Zumoff B . Androgen binding to ammonium sulfate precipitates of human adipose tissue cytosols . Steroids . 1990;55:410–415
  167. De Pergola G , Xu XF , Yang SM , Giorgino R , Bjorntorp P . Up-regulation of androgen receptor binding in male rat fat pad adipose precursor cells exposed to testosterone (study in a whole cell assay system) . J Steroid Biochem Mol Biol . 1990;37:553–558
  168. Dicker A , Ryden M , Naslund E , Muchlen IE , Wiren M , Lafontan M , et al.   Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots . Diabetologia . 2004;47:420–428
  169. Marin P , Oden B , Bjorntorp P . Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men (effects of androgens) . J Clin Endocrinol Metab . 1995;80:239–243
  170. Elbers JMH , Asscheman H , Seidel JC , Megens JA , Gooren LJG . Long-term testosterone administration increases visceral fat in female to male transsexuals . J Clin Endocrinol Metab . 1997;79:265–271
  171. Haarbo J , Marslew U , Gottfredsen A , Christiansen C . Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause . Metabolism . 1991;40:323–326
  172. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults . Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) . JAMA . 2001;285:2486–2497
  173. Hergenc G , Schulte H , Assmann G , von Eckardstein A . Associations of obesity markers, insulin, and sex hormones with HDL-cholesterol levels in Turkish and German individuals . Atherosclerosis . 1999;145:147–156
  174. Tsai EC , Boyko EJ , Leonetti DL , Fujimto WY . Low serum testosterone levels as a predictor of increased visceral fat in Japanese-American men . Int J Obes . 1996;24:485–491
  175. Simon D , Charles MA , Nahoul K , Orssaud G , Kremski J , Hully V , et al.   Association between plasma total testosterone and cardiovascular risk factors in healthy adult men (the TELECOM study) . J Clin Endocrinol Metab . 1997;82:682–685
  176. Malkin CJ , Pugh PJ , Jones TH , Channer KS . Testosterone for secondary prevention in men with ischaemic heart disease . Quat J Med . 2003;96:521–529
  177. Wang C , Swerdloff RS , Iranmanesh A , Dobs A , Snyder PJ , Cunningham G , et al.  Testosterone gel study group   Trasdermal testosterone gel improves sexual function, mood, muscle strength, and body composition parameters in hypogonadal men . J Clin Endocrinol Metab . 2000;85:2839–2853
  178. Marin P , Holmang S , Jonsson L , Sjostrom L , Kvist H , Holm G , et al.   The effects of testosterone treatment on body composition and metabolism in middle-aged obese men . Int J Obes . 1992;16:991–997
  179. Buchter D , Behere HM , Kliesch S , Chirazi A , Nieschlag E , Assmann G , et al.   Effect of testosterone suppression in young men by the gonadotropin releasing hormone antagonist cetrorelix on plasma lipids, lipolytic enzymes, lipid transfer proteins, insulin, and leptin . Exp Clin Endocr Diabetes . 1999;107:522–529
  180. Lindstedt G , Lundberg P , Lapidus L , Lundgren H , Bengtsson C , Bjorntorp P . Low sex hormone binding globulin concentration as an independent risk factor for development of NIDDM (12 yr follow-up of population study of women in Gotemburg) . Diabetes . 1991;40:123–128
  181. Pasquali R , Gambineri A . Role of changes in dietary habits in polycystic ovary syndrome . Reprod Biomed Online . 2004;8:431–439
  182. De Leo V , la Marca A , Petraglia F . Insulin-lowering agents in the management of polycystic ovary syndrome . Endocr Rev . 2003;24:633–667
  183. Gambineri A , Pelusi C , Genghini S , Morselli-Labate AM , Cacciari M , Pagotto U , et al.   Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome . Clin Endocrinol (Oxf) . 2004;60:241–249
  184. Holmang A , Larsson BM , Brzezinska Z , Bjorntorp P . The effects of short term testosterone exposure on insulin sensitivity in female rats . Am J Physiol . 1992;262:E851–E855
  185. Nilsson C , Niklasson M , Erikson E , Bjorntorp P , Holmag A . Imprinting of females offspring with testosterone results in insulin resistance and changes in body fat distribution at adult age in rats . J Clin Invest . 1998;101:74–78
  186. Dunaif A . Insulin resistance and the polycystic ovary syndrome (mechanisms and implications for pathogenesis) . Endocr Rev . 1997;18:774–800
  187. Legro RS . Diabetes prevalence and risk factors in polycystic ovary syndrome . Curr Opin Endocrinol Diab . 2002;9:451–458
  188. Gambineri A , Pelusi C , Manicardi E , Vicennati V , Cacciari M , Morselli-Labate AM , et al.   Glucose intolerance in a large cohort of Mediterranean women with polycystic ovary syndrome. Phenotype and associated factors . Diabetes . 2004;53:2353–2358
  189. Legro RS . Polycystic ovary syndrome and cardiovascular disease (a premature association?) . Endocr Rev . 2003;24:302–312
  190. Pasquali R , Vicennati V , Scopinaro N , Marinari G , Flamia R , Casimirri F , et al.   Achievement of near-normal body weight as the prerequisite to normalize sex hormone-binding globulin concentrations in massively obese men . Int J Obes . 1997;21:1–5
  191. Grenman S , Konnemaa T , Iryale K , Kaiola HL , Grouroos M . Sex steroid, gonadotropin, cortisol, and prolactin in healthy, massively obese women (correlation with abdominal fat cell size and effect of weight loss) . J Clin Endocrinol Metab . 1986;63:1257–1261
  192. Jakubowicz DJ , Nestler JE . 17a-hydroxyprogesterone responses to leuprolide and serum androgens in obese women with and without polycystic ovary syndrome after dietary weight loss . J Clin Endocrinol Metab . 1997;82:556–560
  193. Pasquali R , Gambineri A , Biscotti D , Vicennati V , Gagliardi L , Colitta D , et al.   Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome . J Clin Endocrinol Metab . 2000;85:2767–2774
  194. Pasquali R , Casimirri F , Colella P , Melchionda N . Body fat distribution and weight loss in obese women . Am J Clin Nutr . 1989;49:185–186
  195. Lord JM , Flight IH , Norman RJ . Metformin in polycystic ovary syndrome (systematic review and meta-analysis) . BMJ . 2003;25(327):951–953
  196. Bachamann GA , Bancroft G , Braunstein G , Burger SR , Davis l , Dennerstein I , et al.   Female androgen insufficiency (the Princeton consensus statement on definition, classification and assessment) . Fertil Steril . 2002;77:660–665
  197. Davison SL , Davis SR . Androgens in women . J Steroid Biochem Mol Biol . 2003;85:363–366
  198. Lovejoy JC , Bray GA , Bourgeois MO , Macchiavelli R , Rood JC , Greeson C , et al.   Exogenous androgens influence body composition and regional body fat distribution in obese postmenopausal women—a clinical research center study . J Clin Endocrinol Metab . 1996;81:2198–2203
  199. Davis SR , Walker KZ , Strauss BJ . Effect of estradiol with or without testosterone on body composition and relationship with lipids in postmenopausal women . Menopause . 2000;7:395–401
  200. Shifren JL , Braunstein J , Simon P , Casson JE , Buster RE , Red Burki ES , et al.   Transdermal testosterone treatment in women with impaired sexual function after oophorectomy . N Engl J Med . 2000;343:682–688
  201. Marin P . Effects of androgens in men with the metabolic syndrome . Aging Male . 1998;1:129–136
  202. Li M , Bjorntorp P . Effects of testosterone and triglycerides uptake and mobilization in different adipose tissues in male rats in vivo . Obes Res . 1995;3:113–119
  203. Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, et al. Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men . J Clin Endocrinol Metab . 2004;89:718–726
  204. Marin P , Holmang S , Gustafsson C , Jonsson L , Sjostrom L , Kvist H , et al.   Androgen treatment in abdominally obese men . Obes Res . 1993;1:245–251
  205. Alexandersen P , Christensen C . The ageing male: testosterone deficiency and testosterone replacement. An up-date . Atherosclerosis . 2004;173:157–169
  206. Svartberg J , von Muhlen D , Schirmer H , Barret-Connor E , Sundfjord J , Jorde R . Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study . Eur J Endocrinol . 2004;150:65–71
  207. Boyanow MA , Boneva Z , Christov VG . Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency . Aging Male . 2003;6:1–7
  208. Rittmaster RS . Antiandrogen treatment of polycystic ovary syndrome . Endocrinol Metab Clin North Am . 1999;28:409–421
  209. Miller JA , Jabobs HS . Treatment of hirsutism and acne with cyproterone acetate . Clin Endocrinol Metab . 1986;15:373–389
  210. Wynn V , Godsland IF , Seed M , Jacobs HS . Paradoxical effects of the antiandrogen cyproterone acetate on lipid and lipoprotein metabolism . Clin Endocrinol (Oxf) . 1986;24:183–191
  211. De Leo V , La Marca A , Lanzetta D , Cariello PL , D’Antona D , Morgante G . Effects of flutamide on pituitary and adrenal responsiveness to corticotrophin releasing factor (CRF) . Clin Endocrinol (Oxf) . 1998;49:85–89
  212. DiamantiKandarakis E , Mitrakou A , Hennes MMI , Platanissiotis D , Kaklas N , Spina J , et al.   Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome . Metabolism . 1995;44:525–531
  213. Ibánez L , Potau N , Marcos MV , De Zegher F . Treatment of hirsutism, hyperandrogenism, oligomenorrhea, dyslipidemia, and hyperinsulinism in nonobese, adolescent girls (effect of flutamide) . J Clin Endocrinol Metab . 2000;85:3251–3255
  214. Eagleson CA , Gingrich MB , Pastor CL , Azora TK , Bust CM , Evans WS , et al.   Polycystic ovarian syndrome (evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone) . J Clin Endocrinol Metab . 2000;85:4047–4052
  215. De Leo V , Lanzetta D , D’Antona D , La Marca A , Morgante G . Hormonal effects of flutamide in young women with polycystic ovary syndrome . J Clin Endocrinol Metab . 1998;83:99–102
  216. DiamantiKandarakis E , Mitrakou A , Raptis S , Tolis G , Duleba AJ . The effect of a pure antiandrogen receptor blocker, flutamide, on the lipid profile in the polycystic ovary syndrome . J Clin Endocrinol Metab . 1998;83:2699–2705
  217. Brogden RN , Clissold SP . Flutamide. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in advanced prostatic cancer . Drugs . 1989;38:185–203
  218. Ayub M , Levell MJ . Inhibition of rat testicular 17a-hydroxylase and 17,20-lyase activities by antiandrogens (flutamide, hydroxyflutamide, RU 23908, cyproterone acetate) in vitro . J Steroid Biochem . 1987;28:43–50
  219. Ibanez L , Ong K , Amin R , Dunger D , de Zegher F . Low-dose flutamide-metformin therapy reverses insulin resistance and reduces fat mass in nonobese adolescents with ovarian hyperandrogenism . J Clin Endocrinol Metab . 2003;88:2600–2606
  220. Ibanez L , de Zegher F . Flutamide-metformin therapy to reduce fat mass in hyperinsulinemic ovarian hyperandrogenism (effects in adolescents and in women on third-generation oral contraception) . J Clin Endocrinol Metab . 2003;88:4720–4724
  221. Ibanez L , de Zegher F . Ethynilestradiol-drospirenoine, fltamide-metformin, or both for adolescents and women with hyperinsulinemic hyperandrogenism (opposite effects on adipokines and body adiposity) . J Clin Endocrinol Metab . 2004;1592–1594
  222. Krattenmaker R . Drospirenone (pharmacology and pharmacokinetics of unique progestagen) . Contraception . 2000;62:29–38
  223. Dumesic DA , Abbott DH , Eisner JR , Herrmann RR , Reed JE , Welch TJ , et al.   Pituitary desensitization to gonadotropin-releasing hormone increases abdominal adiposity in hyperandrogenic anovulatory women . Fertil Steril . 1998;70:94–101

PII: S0015-0282(06)00098-7

doi: 10.1016/j.fertnstert.2005.10.054

Fertility and Sterility
Volume 85, Issue 5 , Pages 1319-1340 , May 2006

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