Insulin Resistance and Polycystic ovary Syndrome: A Review

  • Mudasir Maqbool Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India
  • Mohmad Amin Dar Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India
  • Imran Gani Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India
  • Mohammad Ishaq Geer Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common, yet complex, endocrine disorder affecting women in their reproductive years and is a leading cause of infertility. This disease appears to be multifactorial and polygenic in nature involving multisystem dysfunction, namely reproduction, endocrine and metabolic. Hyperandrogenism and insulin resistance appear to be central cause to the pathophysiology of the disease. The glucose and insulin metabolism pathways have been studied and debated to understand whether Insulin Resistance is due to a defect in insulin action or a primary defect in β-cell function or decreased hepatic clearance of insulin, or a combination of all these factors. Numerous studies have demonstrated that obese, normal weight and thin women with PCOS have a form of insulin resistance that is unique and intrinsic to the disorder. Moreover obese women with PCOS possess an additional burden of insulin resistance resulting from their excess adiposity. Hyperinsulinemia leads to increase in androgen production directly by acting as a co-gonadotropin, augmenting Luteinizing Hormone activity within the ovary, and indirectly by increasing serum LH pulse amplitude. Whereas Androgens may in turn contribute at least partially to the insulin resistance state linked with PCOS.  In this review, we will briefly study the role of insulin resistance in polycystic ovary syndrome.


Keywords: Polycystic ovary syndrome, insulin resistance, Hyperandrogenism.

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Author Biographies

Mudasir Maqbool, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Mohmad Amin Dar, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Imran Gani, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Mohammad Ishaq Geer, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal Srinagar-190006, Jammu and Kashmir, India

References

1. Goldenberg N, Gleck C. “Medical Therapy in women with polycystic ovarian syndrome before and during pregnancy and lactation “ Minerva Ginecol 2008; 60(1):63-75 .
2. Boosma CM, Fauser BC, Macklon NS, “Pregnancy Complications in Women with PCOS”. Semin Repord. Med 2008; 26(1):72-84.
3. The Rotterdam ESHRE / ASRAM – sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long term health risks related to PCOS. Hum Repord 2004: 19(1):41- 47.
4. Reaven GM Syndrome X: 6 years later. J Int Med Suppl 1994; 736:13-22.
5. Dorkas A, Bochner M, Hollinrake E, Markham S, Vanvoorhis B, Jagasia DH. Screening women with PCOS for metabolic syndrome. Obstet Gyneacol 2005; 106:131-137.
6. Gaducci A, Gargini A, Palla E, Fanucchi A, Genazzani AR. PCOS and gynecological cancers: is there a link? Gynecol Endocrinol 2005; 20:200-208.
7. Spritzer PM, Morsch DM, Wiltgen D. PCOS associated neoplasms. Arq bras endocrinol metabol 2005; 49:805-810.
8. Ehrmann DA, Barnes RB, Rosenfield RL. Polycystic ovary syndrome as a form of functional ovarian hyperandrogenism due to dysregulation of androgen secretion. Endocr Rev 1995; 16(3):322-353.
9. Cheatham B, Kahn CR. Insulin action and the insulin signaling network. Endocr Rev 1995; 16(2):117-142.
10. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; 18(6):774-800.
11. Robert Y, Dubrulle F, Gaillandre L, Ardaens Y, Thomas-Desrousseaux P, Lemaitre L, Dewailly D. Ultrasound assessement of ovarian stroma hypertrophy in hyperandrogenism and ovula-tion disorders: visual analysis versus computerized qualification. Fertil Steril 1995; 64(2):307-312.
12. Steil GM, Volund A, Kahn SE, Bergman RN. Reduced sample number for calculation of insulin sensitivity and glucose effectiveness from the minimal model. Suitability for use in population studies. Diabetes 1993; 42(2):250-256.
13. Holte J. Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome. Baill Clin Endocrinol Metab 1996; 10(2):221-247.
14. Corbould A, Kim YB, Youngren JF, et al. Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling. Am J Physiol Endocrinol Metab 2005; 288:E1047-E1054.
15. Gilling-Smith C, Story H, Rogers V & Franks S Evidence for a primary abnormality of thecal cell steroidogenesis in the polycystic ovary syndrome. Clin Endocrinol 1997; 47:93-99
16. Arlt W, Auchus RJ and Miller WL. Thiazolidinediones but not metformin directly inhibit the steroidogenic enzymes P450cl7 and 3beta-hydroxysteroid dehydrogenase. J Biol Chem 2001; 276:16767-16771.
17. Zachary T B. World Congress on the Insulin Resistance Syndrome. Insulin resistance mechanisms, the brain, and insulin resistance in youth and in the polycystic ovary syndrome. Diabetes Care 2009; 33:el24-el30.
18. Deugarte CM, Bartolucci AA, Azziz R. Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertil Steril 2005; 83:1454–60.
19. Nestler JE, Jakubowicz DJ, De Vergas 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; 83:2001-5
20. Pugeat M, Ducluzeau PH. Insulin resistance,polycystic ovary syndrome and metformin. Drugs 1999; 58(1):41–6.
21. Legro RS, Gnatuk CL, Kunselman AR, Dunaif A. Changes in glucose tolerance over time in women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 2005; 90(6):3236–42.
22. Song SH, Rhodes CJ, Veldhuis JD, Butler PC. Diazoxide attenuates glucose-induced defects in first-phase insulin release and pulsatile insulin secretion in human islets. Endocrinol 2003; 144:3399–405.
23. Panidis D, Skiadopoulos S, Rousso D, Ioannides D, Panidou E. Association of acanthosis nigricans with insulin resistance in polycystic ovary syndrome. Br J Dermatol 1995; 132:936–41.
24. Adashi EY, Hsueh AJ, Yen SS. Insulin enhancement of luteinizing hormone and follicle-stimulating hormone release by cultured pituitary cells. Endocrinol 1981; 108(4):1441-9.
25. Moghetti P, Castello R, Negri C, Tosi F, Spiazzi GG, Brun E et al. Insulin infusion amplifies 17 alpha-hydroxycorticosteroid intermediates response to adrenocorticotropin in hyperandrogenic women: apparent relative impairment of 17,20-lyase activity. J Clin Endocrinol Metab 1996; 81(3):881-6.
26. Remsberg KE, Talbott EO, Zborowski JV, Evans RW, McHugh-Pemu K. Evidence for competing effects of body mass, hyperinsulinemia, insulin resistance, and androgens on leptin levels among lean, overweight, and obese women with polycystic ovary syndrome. Fertil Steril 2002; 78:479–86.
27. Vandermolen DT, Ratts VS, Evans WS, Stovall DW, Kauma SW, Nestler JE. Metformin increases the ovulatory rate and pregnancy rate from clomiphene citrate in patients with polycystic syndrome who are resistent to clomiphene citrate alone. Fertil Steril 2001; 75:310–15.
28. Schroder AK, Tauchert S, Ortmann O, Diedrich K, Weiss JM. Insulin resistance in patients with polycystic ovarysyndrome. Ann Med 2004; 36:426–39.
29. Weiss JM, Polack S, Diedrich K, Ortmann O. Effects of insulin on luteinising hormone and prolactin secretion and calcium signalling in female rat pituitary cells. Arch Gynecol Obstet 2003; 269(1):45–50.
30. 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(2):323-31.
31. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R. Obesity and the polycystic ovary syndrome. Int J Obes Relat Metab Disord 2002; 26(7):883-96.
32. Murray RD, Davison RM, Russel RC, Conway GS. Clinical presentation of PCOS following development of an insulinoma: Case report. Hum Reprod 2000; 15(1):86-88.
33. Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Tapanainen JS. Insulin sensitivity, insulin secretion, and metabolic and hormonal parameters in healthy women and women with polycystic ovaries. Hum Reprod 2000; 15(6):1266-1274.
34. Butzow T, Lehtovirta M, Siegberg R, Hovatta O, Koistinen R, Seppala M, Apter D. The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. J Clin Endocrinol Metab 2000; 85(9):3271-3275.
35. Rincon J, Holmang A, Wahlstrom EO, Lonnroth P, Bjorntorp P, Zierath JR, Wallberg-Henriksson H. Mechanisms behind insulin resistance in rat skeletal muscle after oophorectomy and additional testosterone treatment. Diabetes 1996; 45(5):615-621.
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Maqbool M, Dar MA, Gani I, Geer MI. Insulin Resistance and Polycystic ovary Syndrome: A Review. JDDT [Internet]. 15Feb.2019 [cited 28Mar.2024];9(1-s):433-6. Available from: https://jddtonline.info/index.php/jddt/article/view/2275