Skip to main content
SpringerLink
Log in

Insulin Resistance Effects on Sex Hormones and Ovulation in the Polycystic Ovary Syndrome

  • Chapter
Insulin Resistance

Part of the book series: Contemporary Endocrinology ((COE,volume 12))

Abstract

The polycystic ovary syndrome (PCOS) is a prevalent disorder affecting an estimated 6% (range, 4–10%) of women of reproductive age. It is the most common cause of female infertility in the United States, and arguably the most common endocrinopathy affecting premenopausal women. PCOS is characterized by chronic anovulation and hyperandrogenism, and its diagnosis requires the exclusion of other disorders that can mimic PCOS (e.g., congenital or nonclassical adrenal hyperplasia).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Chang RJ, Nakamura RM, Judd HL, Kaplan SA. Insulin resistance in nonobese patients with polycystic ovarian disease. J Clin Endocrinol Metab 1983; 57: 356–359.

    Article  PubMed  CAS  Google Scholar 

  2. Geffner ME, Kaplan SA, Bersch N, Golde DW, Landaw EM, Chang RZ. Persistence of insulin resistance in polycystic ovarian disease after inhibition of ovarian steroid secretion. Fertil Steril. 1986; 45: 327–333.

    PubMed  CAS  Google Scholar 

  3. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenemic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987; 65: 499–507.

    Article  PubMed  CAS  Google Scholar 

  4. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989; 38: 1165–1174.

    Article  PubMed  CAS  Google Scholar 

  5. 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.

    Article  PubMed  CAS  Google Scholar 

  6. Carmina E, Ditkoff EC, Malizia G, Vijod AG, Janni A, Lobo RA. Increased circulating levels of immunoreactive beta-endorphin in polycystic ovary syndrome is not caused by increased pituitary secretion. Am J Obstet Gynecol. 1992; 167: 1819–1824.

    Article  PubMed  CAS  Google Scholar 

  7. Ciaraldi TP, el Roeiy A, Madar Z, Reichart D, Olefsky JM, Yen SSC. Cellular mechanisms of insulin resistance in polycystic ovarian syndrome. J Clin Endocrinol Metab. 1992; 75: 577–583.

    Article  PubMed  CAS  Google Scholar 

  8. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992; 41: 1257–1266.

    Article  PubMed  CAS  Google Scholar 

  9. 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: 197–202.

    Google Scholar 

  10. Dunaif A, Xia J, Book CB, 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: 801–810.

    Article  PubMed  CAS  Google Scholar 

  11. 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-insulindependent diabetes mellitus. J Clin Invest 1995; 96: 520–527.

    Article  PubMed  CAS  Google Scholar 

  12. Apter D, Butzow T, Laughlin GA, Yen SS. Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism. J Clin Endocrinol Metab 1995; 80: 2966–2973.

    Article  PubMed  CAS  Google Scholar 

  13. Carmina E, Koyama T, Chang L, Stanczyk FZ, Lobo RA. Does ethnicity influence the prevalence of adrenal hyperandrogenism and insulin resistance in polycystic ovary syndrome? Am J Obstet Gynecol 1992; 167: 1807–1812.

    Article  PubMed  CAS  Google Scholar 

  14. Speiser PW, Serrat J, New MI, Gertner JM. Insulin insensitivity in adrenal hyperplasia due to nonclassical steroid 21-hydroxylase deficiency. J Clin Endocrinol Metab 1992; 75: 1421–1424.

    Article  PubMed  CAS  Google Scholar 

  15. Richards GE, Cavallo A, Meyer WJ III, Prince MJ, Peters EJ, Stuart CA, Smith ER. Obesity, acanthosis nigricans, insulin resistance, and hyperandrogenemia: pediatric perspective and natural history. J Pediatr 1985; 107: 893–897.

    Article  PubMed  CAS  Google Scholar 

  16. Moller DE, Flier JS. Detection of an alteration in the insulin-receptor gene in a patient with insulin resistance, acanthosis nigricans, and the polycystic ovary syndrome (Type A insulin resistance). N Engl J Med 1988; 319: 1526–1529.

    Article  PubMed  CAS  Google Scholar 

  17. Jahanfar S, Eden JA, Warren P, Seppala M, Nguyen TV. A twin study of polycystic ovary syndrome. Fertil Steril 1995; 63: 478–486.

    PubMed  CAS  Google Scholar 

  18. Campbell PJ, Gerich JE. Impact of obesity on insulin action in volunteers with normal glucose tolerance: demonstration of a threshold for the adverse effect of obesity. J Clin Endocrinol Metab 1990; 70: 1114–1118.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang LH, Rodriguez H, Ohno S, Miller WL. Serine phosphorylation of human P450c17 increases 17,20-lyase activity: implications for adrenarche and the polycystic ovary syndrome. Proc Natl Acad Sci USA 1995; 92: 10619–10623.

    Article  PubMed  CAS  Google Scholar 

  20. Barbieri RL, Makris A, Randall RW, Daniels G, Kristner RW, Ryan KJ. Insulin stimulates androgen accumulation in incubations of ovarian stroma obtained from women with hyperandrogenism. J Clin Endocrinol Metab 1986; 62: 904–910.

    Article  PubMed  CAS  Google Scholar 

  21. Bergh C, Carlsson B, Olsson JH, Selleskog U, Hillensjo T. Regulation of androgen production in cultured human thecal cells by insulin-like growth factor I and insulin. Fertil Steril 1993; 59: 323–331.

    PubMed  CAS  Google Scholar 

  22. Nestler JE, Jakubowicz DJ, de Vargas AF, Brik C, Quintero N, Medina F. Insulin stimulates testosterone biosynthesis by human thecal cells from women with polycystic ovary syndrome by activating its own receptor and using inositolglycan mediators as the signal transduction system. J Clin Endocrinol Metab 1998; 83: 2001–2005.

    Article  PubMed  CAS  Google Scholar 

  23. Cara JF, Rosenfield RL. Insulin-like growth factor I and insulin potentiate luteinizing hormone-induced androgen synthesis by rat ovarian thecal-interstitial cells. Endocrinology 1988; 123: 733–739.

    Article  PubMed  CAS  Google Scholar 

  24. Cara JF, Fan J, Azzarello J, Rosenfield RL. Insulin-like growth factor-I enhances luteinizing hormone binding to rat ovarian theca-interstitial cells. J Clin Invest 1990; 86: 560–565.

    Article  PubMed  CAS  Google Scholar 

  25. DeClue TJ, Shah SC, Marchese M, Malone JI. Insulin resistance and hyperinsulinemia induce hyperandrogenism in a young Type B insulin-resistant female. J Clin Endocrinol Metab 1991; 72: 1308–1311.

    Article  PubMed  CAS  Google Scholar 

  26. Nestler JE, Barlascini CO, Matt DW, Steingold KA, Plymate SR, Clore JN, Blackard WG. Suppression of serum insulin by diazoxide reduces serum testosterone levels in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab 1989; 68: 1027–1032.

    Article  PubMed  CAS  Google Scholar 

  27. Nestler JE, Singh R, Matt DW, Clore JN, Blackard WG. Suppression of serum insulin by diazoxide does not alter serum testosterone or sex hormone-binding globulin levels in healthy non-obese women. Am J Obstet Gynecol 1990; 163: 1243–1246.

    Article  PubMed  CAS  Google Scholar 

  28. Ehrmann DA, Rosenfield RL, Barnes RB, Brigell DF, Sheikh Z. Detection of functional ovarian hyperandrogenism in women with androgen excess. N Engl J Med 1992; 327: 157–162.

    Article  PubMed  CAS  Google Scholar 

  29. Rosenfield RL, Barnes RB, Ehrmann DA. Studies of the nature of 17- hydroxyprogesterone hyperresonsiveness to gonadotropin-releasing hormone agonist challenge in functional ovarian hyperandrogenism. J Clin Endocrinol Metab 1994; 79: 1686–1692.

    Article  PubMed  CAS  Google Scholar 

  30. Luppa P, Muller B, Jacob K, Kimmig R, Strowitzki T, Hoss C, Weber MM, Engelhardt D, Lobo RA. Variations of steroid hormone metabolites in serum and urine in polycystic ovary syndrome after nafarelin stimulation: evidence for an altered corticoid excretion. J Clin Endocrinol Metab 1995; 80: 280–288.

    Article  PubMed  CAS  Google Scholar 

  31. White D, Leigh A, Wilson C, Donaldson A, Franks S. Gonadotrophin and gonadal steroid response to a single dose of a long-acting agonist of gonadotrophin-releasing hormone in ovulatory and anovulatory women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1995; 42: 475–481.

    Article  CAS  Google Scholar 

  32. Ibanez L, Potau N, Zampolli M, Prat N, Gussinye M, Saenger P, Vicens-Calvet E, Carrascosa A. Source localization of androgen excess in adolescent girls. J Clin Endocrinol Metab 1994; 79: 1778–1784.

    Article  PubMed  CAS  Google Scholar 

  33. Grulet H, Hecart AC, Delemer B, Gross A, Sulmont V, Leutenegger M, Caron J. Roles of LH and insulin resistance in lean and obese polycystic ovary syndrome. Clin Endocrinol (Oxf) 1993; 38: 621–626.

    Article  CAS  Google Scholar 

  34. Holte J, Bergh T, Gennarelli G, Wide L. The independent effects of polycystic ovary syndrome and obesity on serum concentrations of gonadotrophins and sex steroids in premenopausal women. Clin Endocrinol (Oxf) 1994; 41: 473–481.

    Article  CAS  Google Scholar 

  35. Dale PO, Tanbo T, Vaaler S, Abyholm T. Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations. Fertil Steril 1992; 58: 487–491.

    PubMed  CAS  Google Scholar 

  36. Jacobs HS. Polycystic ovary syndrome: aetiology and management. Curr Opin Obstet Gynecol 1995; 7: 203–208.

    Article  PubMed  CAS  Google Scholar 

  37. Morales AJ, Laughlin GA, Butzow T, Maheshwari H, Bauman G, Yen SSC, Baumann G, Yen SS. Insulin, somatotropic, and luteinizing hormone axes in lean and obese women with polycystic ovary syndrome: common and distinct features. J Clin Endocrinol Metab 1996; 81: 2854–2864.

    Article  PubMed  CAS  Google Scholar 

  38. Barnes RB, Rosenfield RL. Pituitary-ovarian responses to nafarelin testing in the polycystic ovary syndrome. N Engl J Med 1989; 320: 559–565.

    Article  PubMed  CAS  Google Scholar 

  39. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17a activity and serum free testosterone after reduction in insulin secretion in women with polycystic ovary syndrome. N Engl J Med 1996; 335: 617–623.

    Article  PubMed  CAS  Google Scholar 

  40. Jakubowicz DJ, Nestler JE. 17a-Hydroxyprogesterone response 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.

    Article  PubMed  CAS  Google Scholar 

  41. Velazquez 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: 647–654.

    Article  PubMed  CAS  Google Scholar 

  42. Velazquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol 1997; 90: 392–395.

    Article  PubMed  CAS  Google Scholar 

  43. Velazquez EM, Mendoza SG, Wang P, Glueck CJ. Metformin therapy is associated with a decrease in plasma plasminogen activator inhibitor-1, lipoprotein(a), and immunoreactive insulin levels in patients with the polycystic ovary syndrome. Metabolism 1997; 46: 454–457.

    Article  PubMed  CAS  Google Scholar 

  44. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab 1996; 81: 3299–3306.

    Article  PubMed  CAS  Google Scholar 

  45. Everett RB, Porter JC, MacDonald PC, Gant NF. Relationship of maternal placental blood flow to the placental clearance of maternal plasma dehydroepiandrosterone sulfate through placental estradiol formation. Am J Obstet Gynecol 1980; 136: 435–439.

    PubMed  CAS  Google Scholar 

  46. Poretsky L. On the paradox of insulin-induced hyperandrogenism in insulin-resistant states. Endocr Rev 1991; 12: 3–13.

    Article  PubMed  CAS  Google Scholar 

  47. Buyalos RP. Insulin-like growth factor binding proteins in disorders of androgen excess. Sem Reprod Endocrinol 1994; 12: 21–25.

    Article  Google Scholar 

  48. Saltiel AR. Second messengers of insulin action. Diabetes Care 1990; 13: 244–256.

    Article  PubMed  CAS  Google Scholar 

  49. Lamer J. Insulin-signaling mechanisms: lessons from the old testament of glycogen metabolism and the new testament of molecular biology. Diabetes 1988; 37: 262–275.

    Google Scholar 

  50. Lamer J. Mediators of postreceptor action of insulin. Am J Med 1983; 74: 38–51.

    Article  Google Scholar 

  51. Nestler JE, Romero G, Huang LC, Zhang C, Lamer J. Insulin mediators are the signal transduction system responsible for insulin’s actions on human placental steroidogenesis. Endocrinology 1991; 129: 2951–2956.

    Article  PubMed  CAS  Google Scholar 

  52. Romero G, Garmey JC, Veldhuis JD. The involvement of inositol phosphoglycan mediators in the modulation of steroidogenesis by insulin and insulin-like growth factor-I. Endocrinology 1993; 132: 1561–1568.

    Article  PubMed  CAS  Google Scholar 

  53. Burger CW, Korsen T, van Kessel H, van Dop PA, Caron FJM, Schoemaker J. Pulsatile luteinizing hormone patterns in the follicular phase of the menstrual cycle, polycystic ovarian disease (PCOD) and non-PCOD secondary amenorrhea. J Clin Endocrinol Metab 1985; 61: 1126–1132.

    Article  PubMed  CAS  Google Scholar 

  54. Waldstreicher J, Santoro NF, Hall JE, Filicori M, Crowley WF Jr. Hyperfunction of the hypothalamic-pituitary axis in women with polycystic ovarian disease: indirect evidence for partial gonadotroph desensitization. J Clin Endocrinol Metab 1988; 66: 165–172.

    Article  PubMed  CAS  Google Scholar 

  55. Imse V, Holzapfel G, Hinney B, Kuhn W, Wuttke W. Comparison of luteinizing hormone pulsatility in the serum of women suffering from polycystic ovarian disease using a bioassay and five different immunoassays. J Clin Endocrinol Metab 1992; 74: 1053–1061.

    Article  PubMed  CAS  Google Scholar 

  56. Berga SL, Guzick DS, Winters SJ. Increased luteinizing hormone and a-subunit secretion in women with hyperandrogenic anovulation. J Clin Endocrinol Metab 1993; 77: 895–901.

    Article  PubMed  CAS  Google Scholar 

  57. Couzinet B, Brailly S, Thomas G, Schaison G, Thalabard JC. Effects of a pure antiandrogen on gonadotropin secretion in normal women and in polycystic ovarian disease. Fertil Steril 1989; 52: 42–50.

    PubMed  CAS  Google Scholar 

  58. Kazer RR, Kessel B, Yen SSC. Circulating luteinizing hormone pulse frequency in women with poly-cystic ovary syndrome. J Clin Endocrinol Metab 1987; 65: 233–236.

    Article  PubMed  CAS  Google Scholar 

  59. Dunaif A, Mandeli J, Fluhr H, Dobrjansky A. The impact of obesity and chronic hyperinsulinemia on gonadotropin release and gonadal steroid secretion in the polycystic ovary syndrome. J Clin Endocrinol Metab 1988; 66: 131–139.

    Article  PubMed  CAS  Google Scholar 

  60. Nestler JE. Role of obesity and insulin in the development of anovulation. In: Filicori M, Flamigni C, eds. Ovulation Induction: Basic Science and Clinical Advances. Elsevier, Amsterdam, 1994, pp. 103–114.

    Google Scholar 

  61. Adashi EY, Hsueh AJW, Yen SSC. Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinology 1981; 108: 1441–1449.

    Article  PubMed  CAS  Google Scholar 

  62. Yen SS, Laughlin GA, Morales AJ. Interface between extra-and intraovarian factors in polycystic ovarian syndrome. Ann NY Acad Sci 1993; 687: 98–111.

    Article  PubMed  CAS  Google Scholar 

  63. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17a activity and serum androgens. J Clin Endocrinol Metab 1997; 82: 4075–4079.

    Article  PubMed  CAS  Google Scholar 

  64. Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL, Polonsky KS. Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82: 2108–2116.

    Article  PubMed  CAS  Google Scholar 

  65. Guzick DS, Wing R, Smith D, Berga SL, Winters SJ. Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril 1994; 61: 598–604.

    PubMed  CAS  Google Scholar 

  66. Nestler JE, Powers LP, Matt DW, Steingold KA, Plymate SR, Rittmaster RS, Clore JN, Blackard WG. A direct effect of hyperinsulinemia on serum sex hormone-binding globulin levels in obese women with the polycystic ovary syndrome. J Clin Endocrinol Metab 1991; 72: 83–89.

    Article  PubMed  CAS  Google Scholar 

  67. Nestler JE. Editorial: Sex hormone-binding globulin: a marker for hyperinsulinemia and/or insulin resistance? J Clin Endocrinol Metab 1993; 76: 273–274.

    Article  PubMed  CAS  Google Scholar 

  68. Lindstedt G, Lundberg P-A, Lapidus L, Lundgren H, Bengtsson C, Bjorntorp P. Low sex hormone-binding globulin concentration as independent risk factor for development of NIDDM. 12-yr follow-up of population study of women in Gothenburg, Sweden. Diabetes 1991; 40: 123–128.

    Article  PubMed  CAS  Google Scholar 

  69. Haffner SM, Valdez RA, Morales PA, Hazuda HP, Stern MP. Decreased sex hormone-binding globulinpredicts non-insulin-dependent diabetes mellitus in women but not in men. J Clin Endocrinol Metab 1993; 77: 56–60.

    Article  PubMed  CAS  Google Scholar 

  70. Giudice LC. Insulin-like growth factors and ovarian follicular development. Endocr Rev 1992; 13: 641–669.

    PubMed  CAS  Google Scholar 

  71. Poretsky L, Glover B, Laumas V, Kahn M, Dunaif A 1988 The effects of experimental hyperinsulinemia on steroid secretion, ovarian [125I]insulin binding, and ovarian [’25I)insulin-like growth factor I binding in the rat. Endocrinology. 122: 581–585.

    Article  PubMed  CAS  Google Scholar 

  72. Nobels F, Dewailly D. Puberty and polycystic ovarian syndrome: the insulin/insulin-like growth factor I hypothesis. Fertil Steril 1992; 58: 655–666.

    PubMed  CAS  Google Scholar 

  73. Filicori M, Flamigni C, Cognigni G, Dellai P, Michelacci L, Arnone R. Increased insulin secretion in patients with multifollicular and polycystic ovaries and its impact on ovulation induction. Fertil Steril 1994; 62: 279–285.

    PubMed  CAS  Google Scholar 

  74. Dahlgren E, Janson PO, Johansson S, Mattson L-À, Lindstedt G, Crona N, Knutsson F, Lundberg P-A, Oden A. 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: 505–513.

    PubMed  CAS  Google Scholar 

  75. Wild RA, Alaupovic P, Parker IJ. Lipid and apolipoprotein abnormalities in hirsute women. I. The association with insulin resistance. Am J Obstet Gynecol 1992; 166: 1191–1196.

    Article  PubMed  CAS  Google Scholar 

  76. Wild RA. Obesity, lipids, cardiovascular risk, and androgen excess. Am J Med 1995; 98: 275–325.

    Article  Google Scholar 

  77. Rebuffe-Scrive M, Cullberg G, Lundberg P-A, Lindstedt G, Bjorntorp P. Anthropometric variables and metabolism in polycystic ovarian disease. Horm Metab Res 1989; 21: 391–397.

    Article  PubMed  CAS  Google Scholar 

  78. Bjorntorp P. 1996 The android woman-a risky condition. J Intern Med. 239: 105–110.

    Article  PubMed  CAS  Google Scholar 

  79. Dahlgren E, Janson PO, Johansson S, Lapidus L, Oden A. Polycystic ovary syndrome and risk for myocardial infarction. Evaluated from a risk factor model based on a prospective population study of women. Acta Obstet Gynecol Scand 1992; 71: 599–604.

    Article  PubMed  CAS  Google Scholar 

  80. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988; 37: 1595–1607.

    Google Scholar 

  81. Nestler JE. Assessment of insulin resistance. Sci Med 1994; 1: 58–67.

    CAS  Google Scholar 

  82. Kiddy DS, Hamilton Fairley D, Seppala M, Koistinen R, James VH, Reed MJ, Franks S. Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I. Clin Endocrinol (Oxf) 1989; 31: 757–763.

    Article  CAS  Google Scholar 

  83. Kiddy DS, Hamilton Fairley D, Bush A, Short F, Anyaoku V, Reed MJ, Franks S. Improvement in endocrine and ovarian function during dietary treatment of obese women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 1992; 36: 105–111.

    Article  CAS  Google Scholar 

  84. 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.

    Article  PubMed  CAS  Google Scholar 

  85. Zarday Z, ViktoraJ, Wolff FW. The effect of diazoxide on catecholamines. Metabolism 1966; 15: 257–261.

    Article  PubMed  CAS  Google Scholar 

  86. Belisle S, Osathanondh R, Tulchinsky D. The effect of constant infusion of unlabeled dehydroepiandrosterone sulfate on maternal plasma androgens and estrogens. J Clin Endocrinol Metab 1977; 45: 544–550.

    Article  PubMed  CAS  Google Scholar 

  87. 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: 900–903.

    Article  PubMed  CAS  Google Scholar 

  88. Fulghesu AM, Lanzone A, Andreani CL, Pierro E, Caruso A, Mancuso S. Effectiveness of a somatostatin analogue in lowering luteinizing hormone and insulin-stimulated secretion in hyperinsulinemic women with polycystic ovary disease. Fertil Steril 1995; 64: 703–708.

    PubMed  CAS  Google Scholar 

  89. Nagi DK, Yudkin JS. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in NIDDM subjects: A study of two ethnic groups. Diabetes Care 1993; 16: 621–629.

    Article  PubMed  CAS  Google Scholar 

  90. DeFronzo RA, Barzilai N, Simonson DC. Mechanism of metformin action in obese and lean noninsulindependent diabetic subjects. J Clin Endocrinol Metab 1991; 73: 1294–1301.

    Article  PubMed  CAS  Google Scholar 

  91. Nestler JE, Beer NA, Jakubowicz DJ, Beer RM. Effects of a reduction in circulating insulin by metformin on serum dehydroepiandrosterone sulfate in nondiabetic men. J Clin Endocrinol Metab 1994; 78: 549–554.

    Article  PubMed  CAS  Google Scholar 

  92. Ehrmann DA, Cavaghan MK, Imperial J, Sturis J, Rosenfield RL, Polonsky KS. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab 1997; 82: 524–530.

    Article  PubMed  CAS  Google Scholar 

  93. Bringer J, Lefebvre P, Boulet F, Grigorescu F, Renard E, Hedon B, Orsetti A, Jaffiol C. Body composition and regional fat distribution in polycystic ovarian syndrome. Relationship to hormonal and metabolic profiles. Ann NY Acad Sci 1993; 687: 115–123.

    Article  PubMed  CAS  Google Scholar 

  94. Nolan JJ, Ludvik B, Beerdsen P, Joyce M, Olefsky J. Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. N Engl J Med 1994; 331: 1188–1193.

    Article  PubMed  CAS  Google Scholar 

  95. Burghen GA, Givens JR, Kitabchi AE. 1980 Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab 1980; 50: 113–116.

    Article  Google Scholar 

Download references

Authors
  1. John E. Nestler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Shaman Pharmaceuticals, Inc., South San Francisco, CA, USA

    Gerald M. Reaven MD

  2. Stanford University School of Medicine, Stanford, CA, USA

    Gerald M. Reaven MD

  3. Stanford University School of Medicine, Stanford, CA, USA

    Ami Laws MD

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer Science+Business Media New York

About this chapter

Cite this chapter

Nestler, J.E. (1999). Insulin Resistance Effects on Sex Hormones and Ovulation in the Polycystic Ovary Syndrome. In: Reaven, G.M., Laws, A. (eds) Insulin Resistance. Contemporary Endocrinology, vol 12. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-716-1_19

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-716-1_19

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-086-1

  • Online ISBN: 978-1-59259-716-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation