The role of insulin resistance in polycystic ovary syndrome

Endocrinologist

Volumn 6, Issue 4, 1996, Pages 307-321

  Legro, Richard S ^a,b   Dunaif, Andrea ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

^b PENN STATE MILTON S HERSHEY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANOVULATION; AUTOPHOSPHORYLATION; CUSHING SYNDROME; DISEASE ASSOCIATION; ENZYME DEFICIENCY; FEMALE; GLUCOSE TOLERANCE; HORMONAL THERAPY; HORMONE ACTION; HUMAN; HYPERANDROGENISM; INSULIN RESISTANCE; INSULIN SENSITIVITY; NON INSULIN DEPENDENT DIABETES MELLITUS; OBESITY; OVARY POLYCYSTIC DISEASE; REVIEW; STEROIDOGENESIS; WEIGHT REDUCTION;

EID: 0029836518     PISSN: 10512144     EISSN: None     Source Type: Journal    
DOI: 10.1097/00019616-199607000-00007     Document Type: Review

References (125)

1. Dunaif A, Givens JR, Haseltine F, Merriam GR, editors: Polycystic Ovary Syndrome, Cambridge, MA, Blackwell Scientific 1992.
2. Chang RJ, editor: Proceedings of the Serono Symposia on Polycystic Ovary Syndrome. Springer Verlag, New York 1996.
3. Polson DW, Wadsworth J, Adams J, Franks S: Polycystic ovaries - a common finding in normal women. Lancet 1988; 1: 870-72.
4. Goldzieher JW, Axelrod LR: Clinical and biochemical features of polycystic ovarian disease. Fertil Steril 1963; 14: 631-53.
5. Givens JR: Polycystic ovaries - a sign, not a diagnosis. Semin Reprod Endocrinol 1984; 2: 271-80.
6. Adams J, Franks S, Poison DW, et al.: Multifollocular ovaries: clinical and endocrine features and response to pulsatile gonadotrophin-releasing hormone. Lancet 1985; 2: 1375-8.
7. Farquhar CM, Birdsall M, Manning P, Mitchell JM, France JT: The prevalence of polycystic ovaries on ultrasound scanning in a population of randomly selected women. Aust N Z J Obstet Gynaecol 1994; 34: 67-72.
8. Clayton RN, Ogden V, Hodgkinson J, et al.: How common are polycystic ovaries in normal women and what is their significance for the fertility of the population? Clin Endocrinol (Oxf) 1992; 32: 127-34.
9. Carey AH, Chan KL, Short F, White D, Williamson R, Franks S: Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol (Oxf) 1993; 38: 653-9.
10. Broster LR: Eight years' experience with adrenal gland. Arch Surg 1937; 34: 761-91.
11. Chrousos GP, Loriaux DL, Mann DL, et al.: Late-onset 21-hydroxylase deficiency mimicking idiopathic hirsutism or polycystic ovarian disease. Ann Intern Med 1982; 96: 143-8.
12. Gabrilove JL, Sharma DC, Dorman RI: Adrenocortical 11-β-hydroxylase deficiency and virilism first manifest in the adult woman. N Eng J Med 1965; 272: 1189-94.
13. Axelrod LR, Goldzieher JW, Ross SD: Concurrent 3-β-hydroxysteroid dehydrogenase deficiency in adrenal and sclerocystic ovary. Acta Endocrinol 1965; 48: 392-412.
14. Pang S, Softness B, Sweeney WJ, New MI: Hirsutism, polycystic ovarian disease, and ovarian 17-ketosteroid reductase deficiency. N Eng J Med 1987; 316: 1295-301.
15. Conte FA, Grumbach MM, Ito Y, Fisher CR, Simpson ER: A syndrome of female pseudohermaphrodism, hypergonadotropic hypogonadism, and multicystic ovaries associated with missense mutations in the gene encoding aromatase. J Clin Endocrinol Metab 1994; 78: 1287-92.
16. Dunaif A, Scully RE, Andersen RN, Chapin DS, Crowley WF Jr: The effects of continuous androgen secretion on the hypothalamic-pituitary axis in women: evidence from a luteinized thecoma of the ovary. J Clin Endocrinol Metab 1984; 59: 389-93.
17. Givens JR, Kerber IJ, Wiler WL, Anderson RN, Coleman SA, Fish SA: Remission of acanthosis nigricans associated with polycystic ovarian disease and a stroma luteoma. J Clin Endocrinol Metab 1974; 38: 347-55.
18. Kase N, Kowal J, Perloff W, Soffer LJ: In vitro production of androgens by a virilizing adrenal denoma and associated polycystic ovaries. Acta Endocrinol 1963; 44: 15-9.
19. Futterweit W, Deligdisch L: Histopathological effects of exogenously administered testosterone in 19 female-to-male transsexuals. J Clin Endocrinol Metab 1986; 62: 16-21.
20. Pache RD, Chadha S, Gooren LJG, et al.: Ovarian morphology in long-term androgen-treated female-to-male transsexuals. A human model for the study of polycystic ovarian syndrome. Histopathology 1991; 19: 445-52.
21. Balen AH, Schacter ME, Montgomery D, Reid RW, Jacobs HS: Polycystic ovaries are a common finding in untreated female-to-male transsexuals. Clin Endocrinol (Oxf) 1993; 38: 325-9.
22. Pache TD, Fauser BC: Polycystic ovaries in female-to-male transsexuals. Clin Endocrinol (Oxf) 1993; 39: 702-3.
23. Lobo RA: The syndrome of hyperandrogenic chronic anovulation. In Infertility, Contraception, and Reproductive Endocrinology, 3rd Ed., edited by Mishell DR Jr, Davajan V, Lodu RA, Boston, Blackwell Scientific 1991.
24. Krook A, Kumar S, Laing I, Bouldton AJ, Wass JA, O'Rahilly S: Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes 1994; 43: 357-68.
25. Dunaif A, Green G, Phelps RG, Lebwohl M, Futterweit W, Lewy L: Acanthosis nigricans, insulin action, and hyperandrogenism: clinical, histological, and biochemical findings. J Clin Endocrinol Metab 1991; 73: 590-5.
26. Lee PJ, Patel A, Hindmarsh PC, Mowat AP, Leonard JV: The prevalence of polycystic ovaries in the hepatic glycogen storage diseases: its association with hyperinsulinism. Clin Endocrinol (Oxf) 1995; 42: 601-3.
27. Bartuska DG, Eskin BA, Smith EM, Dacou C, Dratman MB: Brain damage, hypertrichosis, and polycystic ovaries. Clinical evaluation of seven cases. Am J Obstet Gynecol 1967; 99: 387-9.
28. Isojaervi JI, Laatikainen TJ, Pakarinen AJ, Juntnen KT, Myllylae W: Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 1993; 329: 1383-8.
29. Luciano AA, Chapler FK, Sherman BM: Hyperprolactinemia in polycystic ovary syndrome. Fertil Steril 1984; 41: 719-25.
30. Kuroda S, Yonekawa Y, Kawano T: Pituitary prolactinoma associated with polycystic ovary - case report. Neurol Med Chir (Tokyo) 1991; 31: 736-9.
31. Perricone R, Pasetto N, DeCarolis C, et al.: Cystic ovaries in women affected with hereditary angioedema. Clin Exp Immunol 1992; 90: 401-4.
32. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A: Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab 1987; 65: 499-507.
33. Robinson S, Kiddy D, Gelding SV, et al: The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries. Clin Endocrinol (Oxf) 1993; 39: 351-5.
34. Carmina E, Koyama T, Chang L, Stancyzk FZ, Lobo RA: Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992; 167: 1807-12.
35. Moller DE, Flier JS: Insulin resistance - mechanisms, syndromes, and implications. N Engl J Med 1991; 325: 938-48.
36. Defronzo RA, Tobin JD, Andres R: Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 239: E214-23.
37. Bergman RN, Prager R, Aage V, Olefsky JM: Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest 1987; 79: 790-80.
38. Bergman RN, Beard JC, Chen M: The minimal modeling method. Assessment of insulin sensitivity and beta-cell function in vivo. In Methods in Diabetes Research, edited by Clark WL, pp. 15-34, New York, Wiley 1986.
39. Finegood DT, Dunaif A: Beta-cell dysfunction in the absence of glucose intolerance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 8: 942-7.
40. Pederson O, Hjollund E, Lindskov HO: Insulin binding and action on fat cells from young healthy females and males. Am J Physiol 1982; 243: E158-67.
41. Foley JE: Mechanisms of impaired insulin action in isolated adipocytes from obese and diabetic subjects. Diabetes Metab Rev 1988; 4: 487-505.
42. Harris MI, Hadden WC, Knowler WC, Bennett PH: Prevalence of diabetes and impaired glucose tolerance and plasma glucose levels in U.S. population aged 20-74 yr. Diabetes 1987; 36: 523-34.
43. DeFronzo RA: The triumvirate. Beta cell, muscle, liver. A collusion responsible for NIDDM. Diabetes 1988; 37: 667-87.
44. Taylor SI, Kadowaki T, Kadowaki H, et al.: Mutations in insulin-receptor gene in insulin-resistant patients. Diabetes Care 1990; 13: 257-79.
45. Dahlgren E, Johansson S, Lindstedt G, et al.: Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones. Fertil Steril 1992; 57: 505-13.
46. Quintana B, Chinchilli V, Sieber J, Fultz P, George N, Dunaif A: High risk of glucose intolerance (GI) in women with oligomenorrhea (oligo) or with polycystic ovary syndrome (PCOS) (abstract OR3-5). Proceedings of the 77th Annual Meeting of The Endocrine Society, p. 50, June 1995, Washington, DC.
47. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T: Evidence for distinctive and intrinsic defects in insulin action in the polycystic ovary syndrome. Diabetes 1992; 41: 1257-66.
48. Dunaif A, Futterweit W, Segal KR, Dobrjansky A: Profound peripheral insulin resistance, independent of obesity, in the polycystic ovary syndrome. Diabetes 1989; 38: 1165-74.
49. Dunaif A, Sorbara L, Delson R, Green G: Ethnicity and polycystic ovary syndrome are associated with independent and additive decreases in insulin action in Caribbean Hispanic women. Diabetes 1993; 442: 1462-8.
50. Ovensen P, Moller J, Ingerslev HJ, et al.: Normal basal and insulin-stimulated fuel metabolism in lean women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1993; 77: 1636-40.
51. Osei K, Schuster DP: Ethnic differences in secretion, sensitivity, and hepatic extraction of insulin in black and white Americans. Diabet Med 1994; 11: 755-62.
52. Norman RJ, Mahabeer S, Masters S: Ethnic differences in insulin and glucose response to glucose between white and Indian women with polycystic ovary syndrome. Fertil Steril 1995; 63: 58-62.
53. O'Meara NM, Blackman JD, Ehrmann DA, et al: Defects in beta-cell function in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1993; 76: 1241-7.
54. Ehrmann DA, Sturis J, Byrne MM, Karrison T, Rosenfield RL, Polonsky KS: Insulin secretory defects in polycystic ovary syndrome. Relationship to insulin sensitivity and family history of non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 96: 520-7.
55. Weber RF, Pache TD, Jacobs ML, Loriaux DL, Fauser BC, Birkenhager JC: The relation between clinical manifestations of polycystic ovary syndrome and beta-cell function. Clin Endocrinol (Oxf) 1993; 38: 295-300.
56. Holte J, Bergh T, Brne C, Berglund L, Lithell H: Enhanced early insulin response to glucose in relation to insulin resistance in women with polycystic ovary syndrome and normal glucose tolerance. J Clin Endocrinol Metab 1994; 78: 1052-8.
57. Ciaraldi TP, El-Roeiy A, Madar Z, Reichart D, Olefsky JM, Yen SS: Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab 1992; 75: 577-83.
58. Dunaif A, Xia J, Book C-B, Schenker E, Tang Z: Excessive insulin receptor serine phosphorylation in cultured fibroblasts and in skeletal muscle: a potential mechanism for insulin resistance in the polycystic ovary syndrome. J Clin Invest 1995; 96: 801-10.
59. Caro J, Dohm LG, Pories WJ, Sinha MK: Cellular alterations in liver, skeletal muscle, and adipose tissue responsible for insulin resistance in obesity and type II diabetes. Diabetes Metab Rev 1989; 5: 655-9.
60. Rosenbaum D, Haber RS, Dunaif A: Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. Am J Physiol 1993; 264: E197-202.
61. Bollage GE, Roth RA, Beaudoin J, Mochly-Rosen D, Koshland DE Jr: Protein kinase C directly phosphorylates the insulin receptor in vitro and reduces its tyrosine kinase activity. Proc Natl Acad Sci U S A 1986; 83: 5822-34.
62. Takayama S, White MF, Kahn CR: Phorbol ester-induced serine phosphorylation of the insulin receptor decreases its tyrosine kinase activity. J Biol Chem 1988; 263: 3440-7.
63. Legro R, Fox J, Dunaif A: Insulin resistance is a potential phenotypic marker for familial polycystic ovary syndrome (PCOS) (abstract 136). Proceedings of the 50th Annual Meeting of The American Fertility Society, November 1994, San Antonio, TX.
64. Sorbara LR, Tang Z, Cama Z, et al.: Absence of insulin receptor gene mutations in three women with the polycystic ovary syndrome. Metabolism 1994; 43: 1568-74.
65. Maddux BA, Sbraccia P, Kumakura S, et al.: Membrane glycoprotein PC-I and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995; 373: 448-51.
66. Nuutila P, Knuuti MJ, Maki M, et al.: Gender and insulin sensitivity in the heart and in skeletal muscles. Studies using positron emission tomography. Diabetes 1995; 44: 31-6.
67. Foley JE, Kashiwagi A, Chang H, et al.: Sex differences in insulin-stimulated glucose transport in rat and human adipocytes. Am J Physiol 1984; 246: E211-5.
68. Taylor SI, Cama A, Accili D, et al.: Mutations in the insulin receptor gene. Endocr Rev 1992; 13: 566-95.
69. Godsland IF, Walton C, Felton C, Proudler A, Patel A, Wynn V: Insulin resistance, secretion, and metabolism in users of oral contraceptives. J Clin Endocrinol Metab 1992; 74: 64-70.
70. Cohen JC, Hickman R: Insulin resistance and diminished glucose tolerance in power lifters ingesting anabolic steroids. J Clin Endocrinol Metab 1987; 64: 960-3.
71. Polderman KH, Gooren JG, Asscherman H, Bakker A, Heine RJ: Induction of insulin resistance by androgens and estrogens. J Clin Endocrinol Metab 1994; 79: 265-71.
72. Dunaif A, Green G, Futterweit W, Dobrjansky A: Suppression of hyperandrogenism does not improve peripheral or hepatic insulin resistance in the polycystic ovary syndrome. J Clin Endocrinol Metab 1990; 70: 699-704.
73. Elkind-Hirsch KE, Valdes CT, Malinak LR: Insulin resistance improves in hyperandrogenic women treated with Lupron. Fertil Steril 1993; 60: 634-41.
74. Moghetti P, Tosi F, Castello R, et al.: The insulin resistance in women with hyperandrogenism is partially reversed by antiandrogen treatment: evidence that androgens impair insulin action in women. J Clin Endocrinol Metab 1996; 81: 952-60.
75. Buffington CK, Givens JR, Kitabchi AE: Opposing actions of dehydroepiandrosterone and testosterone on insulin sensitivity. Diabetes 1992; 40: 693-700.
76. Mortola JF, Yen SC: The effects of oral dehydroepiandrosterone on endocrine and metabolic parameters in postmenopausal women. J Clin Endocrinol Metab 1990; 71: 696-704.
77. Nestler JE, Barlascini CO, Clore JN, Blackard WG: Dehydroepiandrosterone reduces serum low-density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1988; 66: 57-61.
78. Dunaif A: Insulin resistance and ovarian hyperandrogenism. Endocrinologist 1992; 2: 248-60.
79. Willis D, Mason H, Gilling-Smith C, Franks S: Modulation by insulin of follicle-stimulating hormone and luteinizing hormone actions in human granulosa cells of normal and polycystic ovaries. J Clin Endocrinol Metab 1996; 81: 302-9.
80. Fox JH, Licholai T, Green G, Dunaif A: Differential effects of oral glucose-mediated vs. intravenous hyperinsulinemia on circulating androgen levels in women. Fertil Steril 1993; 60: 994-1000.
81. Adashi EY, Hsueh AJ, Yen SS: Insulin enhancement of luteinizing hormone andfollicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981; 108: 1441-9.
82. Dunaif A, Graf M: Insulin administration alters gonadal steroid metabolism independent of changes in gonadotropin secretion in insulin-resistant women with the polycystic ovary syndrome. J Clin Invest 1989; 83: 23-9.
83. Nestler JE, Singh R, Matt DW, Clore JN, Blackard WG: Suppression of serum insulin level by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy, normal, nonobese women. Am J Obstet Gynecol 1990; 163: 1243-6.
84. Prelevic GM, Wurzburger MI, Balint-Peric L, Nesic JS: Inhibitory effect of sandostatin on secretion of luteinizing hormone and ovarian steroids in polycystic ovary syndrome. Lancet 1990; 336: 900-3.
85. Velasquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ: Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43: 647-54.
86. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R: The insulin sensitizing agent troglitazone. A novel therapy of the polycystic ovary syndrome. J Clin Endocrinol Metab (in press).
87. Nestler JE, Strauss JR III: Insulin as an effector of human ovarian and adrenal steroid metabolism. Endocrinol Metab Clin North Am 1991; 20: 807-32.
88. Beer NA, Jakubowicz DJ, Ber RM, Nestler JE: Disparate effects of insulin reduction with diltiazem on serum dehydroepiandrosterone sulfate levels in obese hypertensive men and women. J Clin Endocrinol Metab 1994; 79: 1077-81.
89. Nestler JE, Kahwash Z: Sex-specific action of insulin to acutely increase the metabolic clearance rate of dehydroepiandrosterone in humans. J Clin Invest 1994; 94: 1484-9.
90. Plymate SR, Hoop RC, Jones RE, Matej LA: Regulation of sex hormone-binding globulin production by growth factors. Metabolism 1990; 39: 967-70.
91. Nestler JE: Sex hormone-binding globulin: a marker for hyperinsulinemia and/or insulin resistance? (editorial). J Clin Endocrinol Metab 1993; 76: 273-4.
92. Legro RS: The genetics of polycystic ovary syndrome. Am J Med 1995; 18: S9-16.
93. 3 receptor polymorphisms is associated with hyperandrogenic chronic anovulation and clomiphene citrate failure among female Hispanics. Fertil Steril 1995; 63: 779-84.
94. Carey AH, Waterworth D, Patel K, et al.: Polycystic ovaries and premature male pattern baldness are associated with one allele of the steroid metabolism gene CYP17. Hum Mol Genet 1994; 3: 1873-6.
95. Jahanfar S, Eden JA, Warren P, Seppala M, Nguyen TV: A twin study of polycystic ovary syndrome. Fertil Steril 1995; 63: 478-86.
96. Jackson RL, Dockerty MB: The Stein-Levanthal syndrome: analysis of 43 cases with special reference to association with endometrial carcinoma. Am J Obstet Gynecol 1950; 73: 161-73.
97. Coulam CB, Annegers JF, Kranz JS: Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol 1983; 1: 61:403-7.
98. Dahlgren E, Friberg LG, Johansson S, Lindstroem B, Oden A, Samsioe G: Endometrial carcinoma: ovarian dysfunction - a risk factor in young women. Eur J Obstet Gynecol 1991; 41: 143-50.
99. Secreto G, Toniolo P, Berrino F, et al.: Increased androgenic activity and breast cancer risk in premenopausal women. Cancer Res 1984; 44: 5902-5.
100. Secreto G, Toniolo P, Berrino F, et al.: Serum and urinary androgens and risk of breast cancer in postmenopausal women. Cancer Res 1991; 51: 2572-6.
101. Bruning PF, Bonfrer JM, van Noord PA, Hart AA, de Jong-Bakker M, Nooijen WJ: Insulin resistance and breast cancer risk. Int J Cancer 1992; 52: 511-6.
102. Gammon MD, Thompson WD: Polycystic ovaries and the risk of breast cancer. Am J Epidemiol 1991; 134: 818-24.
103. LaRosa JC: Androgens and women's health: genetic and epidemiologic aspects of lipid metabolism. Am J Med 1995; 98: S22-6.
104. Wild RA, Painter PC, Coulson PB, Carruth LB, Ranney GB: Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1985; 61: 945-51.
105. Graf M, Brown V, Richards C, Meissner L, Dunaif A: The independent effects of hyperandrogenemia, hyperinsulinemia, and obesity in lipid and lipoprotein profiles in women. Clin Endocrinol (Oxf) 1990; 33: 119-31.
106. Wild RA: Obesity, lipids, cardiovascular risk, and androgen excess. Am J Med 1995; 98: S27S-32.
107. DeFronzo RA, Ferrannini E: Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 1991; 14: 173-94.
108. Zimmerman S, Phillips RA, Wikenfeld C, et al.: Polycystic ovary syndrome: lack of hypertension despite insulin resistance. J Clin Endocrinol Metab 1992; 75: 508-13.
109. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A: Polycystic ovary syndrome and risk for myocardial infarction. Acta Obstet Gynecol Scand 1992; 71: 599-603.
110. Talbott E, Guzick D, Clerici A, et al.: Coronary heart disease risk factors in women with polycystic ovary syndrome. Arterio Thromb Vas Bio 1995; 15: 821-6.
111. Parra A, Ramirez A, Espinosa de los Monteras A: Fasting glucose/insulin ratio. An index to differentiate normal from hyperinsulinemic women with polycystic ovary syndrome. Rev Invest Clin 1994; 46: 363-8.
112. Laakso M: How good a marker is insulin level for insulin resistance? Am J Epidemiol 1993; 137: 959-65.
113. Haffner SM, Mykkaenen, Valdez RA, et al.: Disproportionately increased proinsulin levels are associated with the insulin resistance syndrome. J Clin Endocrinol Metab 1994; 79: 1806-10.
114. Bates GW, Whitworth NS: Effect of body weight reduction of plasma androgens in obese, infertile women. Fertil Steril 1982; 38: 406-9.
115. 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: 173-9.
116. Kiddy DS, Hamilton-Fairley D, Bush A, et al.: Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992; 36: 105-11.
117. Andersen P, Selifeflot, Abdelnoor M, et al.: Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 1995; 44: 611-6.
118. Bailey CJ: Metformin - an update. Gen Pharmacol 1993; 24: 1299-309.
119. Velasquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ: Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism 1994; 43: 647-54.
120. Korytkowski MT, Mokan M, Horwitz MJ, Berga SL: Metabolic effects of oral contraceptives in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1995; 80: 3327-34.
121. Godsland IF, Walton C, Felton C, Proudler A, Patel A, Wynn V: Insulin resistance, secretion, and metabolism in users of oral contraceptives. J Clin Endocrinol Metab 1992; 74: 64-70.
122. Fahmy K, Abdel-Razik M, Shaaraway M, et al.: Effect of long-acting progestagen-only injectable contraceptives on carbohydrate metabolism and its hormonal profile. Contraception 1991; 44: 419-30.
123. Ramsay LE, Yeo WW, Jackson PR: Influence of diuretics, calcium antagonists, and alpha blockers on insulin sensitivity and glucose tolerance in hypertensive patients. J Cardiovasc Physiol 1992; 20S: 49-54.
124. Diamanti-Kandarakis E, Mitrakou A, Hermes MM, et al.: Insulin sensitivity and antiandrogenic therapy in women with polycystic ovary syndrome. Metabolism 1995; 44: 525-31.
125. Elkind-Hirsch KE, Sherman LD, Malinak R: Hormone replacement therapy alters insulin sensitivity in young women with premature ovarian failure. J Clin Endocrinol Metab 1993; 76: 472-5.