Systemic inflammation and insulin resistance in the pathogenesis of polycystic ovary syndrome


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of ch ildbearing age, which affects 5-7% of the population and is associated with a broad spectrum of diseases: hypertension, dyslipidemia (DL), atherosclerosis, type 2 diabetes mellitus (T2DM), and gestational diabetes, increased risk of myocardial infarction, stroke, and higher cardiovascular and overall mortality rates. Inflammation, insulin resistance (IR), and hyperinsulinemia are permanent components of the pathogenesis of PCOS in obese women and in the majority of normal weight women due to the presence of a multitude of factors initiating systemic inflammation (SI) and IR. Metformin (MF) and pioglitasone (PG) are the only drugs that reduce SI and IR in different ways, which themselves used alone or in combination with hormonal agents make it possible to restore ovulation, fertility, and pregnancy carrying in 90% of the women, by minimizing the need for surgical intervention, as well as to prevent, stop, and ensure the regression of T2DM, dyslipidemia, non-alcoholic fatty liver disease, atherosclerosis, and hypertension. The administration of MF is completely safe and limited only by an individual’s intolerance that is mainly associated with gastrointestinal disorders. PG treatment requires monitoring the state of the bladder, eyeground, and bone mineral density due to rare changes in these organs and tissues.

Full Text

Restricted Access

About the authors

Mikhail S. Rasin

Internal Medicine Department № 3

MD, professor

Vladislav P. Zhitnik

Poltava City Maternity Hospital

doctor of the highest category, an obstetrician-gynecologist

References

  1. Сухих Г.Т., Краснопольский В.И., Рунихина Н.К., Ткачева О.Н., Ходжаева З.С., Петрухин В.А., Шестакова М.В., Бурумкулова Ф.Ф., Есаян Р.М., Колегаева О.И., Шарашкина Н.В., Кирсанова Т.В., Кошель Л.В. Переход на новый уровень ведения гипертензивных и метаболических осложнений при беременности: современные критерии диагностики гестационного сахарного диабета. Акушерство и гинекология. 2013; 3: 4-9. [Sukhikh G.T., Krasnopolsky V.I., Runikhina N.K., Tkacheva O.N., Khodzhaeva Z.S., Petrukhin V.A., Shestakova M.V., Burumkulova F.F., Esayan R.M., Kolegaeva O.I., Sharashkina N.V., Kirsanova T.V., Koshel L.V. Transition to a new level of management of hypertensive and metabolic complications in pregnancy: Current diagnostic criteria for gestational diabetes mellitus. Akusherstvo i ginekologiya/Obstetrics and gynecology. 2013; 3: 4-9. (in Russian)]
  2. Sathyapalan T., Atkin S.L. Mediators of inflammation in polycystic ovary syndrome in relation to adiposity. Mediators Inflamm. 2010; 2010: 758656.
  3. Azziz R., Woods K.S., Reyna R., Key T.J., Knochenhauer E.S., Yildiz B.O. The prevalence and features of the polycystic ovary syndrome in an unselected population. J. Clin. Endocrinol. Metab. 2004; 89(6): 2745-9.
  4. Lo J.C., Feigenbaum S.L., Yang J., Pressman A.R., Selby J.V., Go A.S. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2006; 91(4): 1357-63.
  5. Кайдашев І.П. Активація NF-kB при метаболічному синдромі. Фізіологічний журнал. 2012; 58: 93-101.
  6. Barber T.M., McCarthy M.I., Wass J.A., Franks S. Obesity and polycystic ovary syndrome. Clin. Endocrinol. (Oxford). 2006; 65(2): 137-45.
  7. Cosar E., Uçok K., Akgün L., Köken G., Sahin F.K., Arioz D.T., Bas O. Body fat composition and distribution in women with polycystic ovary syndrome. Gynecol. Endocrinol. 2008; 24(8): 428-32.
  8. Kirchengast S., Huber J. Body composition characteristics and body fat distribution in lean women with polycystic ovary syndrome. Hum. Reprod. 2001; 16(6): 1255-60.
  9. Charrière G., Cousin B., Arnaud E., André M., Bacou F., Penicaud L., Casteilla L. Preadipocyte conversion to macrophage: evidence of plasticity. J. Biol. Chem. 2003; 278(11): 9850-5.
  10. Wu H., Ghosh S., Perrard X.D., Feng L., Garcia G.E., Perrard J.L. et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 2007; 115(8): 1029-38.
  11. FestaA.,D’Agostino R.Jr., Williams K.,Karter A.J.,Mayer-Davis E.J., Tracy R.P., Haffner S.M. The relation of body fat mass and distribution to markers of chronic inflammation. Int. J. Obes. Relat. Metab. Disord. 2001; 25(10): 1407-15.
  12. Panidis D., Kourtis A., Farmakiotis D., Mouslech T., Rousso D., Koliakos G. Serum adiponectin levels in women with polycystic ovary syndrome. Hum. Reprod. 2000; 18(9): 1790-6.
  13. Kelly C.J., Lyall H., Petrie J.R., Gould G.W., Connell J.M., Rumley A. et al. A specific elevation in tissue plasminogen activator antigen in women with polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 2002; 87(7): 328790.
  14. Uncu G., Sözer M.C., Develioglu O., Cengiz C. The role of plasma renin activity in distinguishing patients with polycystic ovary syndrome (PCOS) from oligomenorrheic patients without PCOS. Gynecol. Endocrinol. 2002; 16(6): 447-52.
  15. Sayin N.C., Gücer F., Balkanli-Kaplan P., Yüce M.A., Ciftci S., Kücük M., Yardim T. Elevated serum TNF-alpha levels in normal-weight women with polycystic ovaries or the polycystic ovary syndrome. J. Reprod. Med. 2003; 48(3): 165-70.
  16. Carmina E., Orio F., Palomba S., Cascella T., Longo R.A., Colao A.M. et al. Evidence for altered adipocyte function in polycystic ovary syndrome. Eur. J. Endocrinol. 2005; 152(3): 389-94.
  17. Jaatinen T.A., Matinlauri I., Anttila L., Koskinen P., Erkkola R., Irjala K. Serum total renin is elevated in women with polycystic ovarian syndrome. Fertil. Steril. 1995; 63(5): 1000-4.
  18. Tian R., Hou G., Li D., Yuan T.F. A possible change process of inflammatory cytokines in the prolonged chronic stress and its ultimate implications for health. The Scientific World Journal. 2014; 2014: 780616.
  19. Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J. Leukoc. Biol. 2005; 78(4): 819-35.
  20. Calder P.C., Kew S. The immune system: a target for functional foods? Br. J. Nutr. 2002; 88(Suppl. 2): S165-77.
  21. Salmerón J., Manson J.E., Stampfer M.J., Colditz G.A., Wing A.L., Willett W.C. Dietary fiber, glycemic load, and risk of non-insulin-dependent diabetes mellitus in women. JAMA. 2007; 277(6): 472-7.
  22. Bastard J.P., Maachi M., Lagathu C., Kim M.J., Caron M., Vidal H. et al. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur. Cytokine Netw. 2006; 17(1): 4-12.
  23. Rohleder N. Stimulation of systemic low-grade inflammation by psychosocial stress. Psychosom. Med. 2014; 76(3):181-9.
  24. Romualdi D., Guido M., Ciampelli M., Giuliani M., Leoni F., Perri C., Lanzone A. Selective effects of pioglitazone on insulin and androgen abnormalities in normo- and hyperinsulinaemic obese patients with polycystic ovary syndrome. Hum. Reprod. 2003; 18(6): 1210-8.
  25. Guo S. Decoding insulin resistance and metabolic syndrome for promising therapeutic intervention. J. Endocrinol. 2014; 220(2): E1-3.
  26. Tsuchiya K., Tanaka J., Shuiqing Y., Welch C.L., DePinho R.A., Tabas I. et al. FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab. 2012; 15(3): 372-81.
  27. Diamanti-Kandarakis E., Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr. Rev. 2012; 33(6): 981-1030.
  28. Kim H.H., DiVall S.A., Deneau R.M., Wolfe A. Insulin regulation of GnRH gene expression through MAP kinase signaling pathways. Mol. Cell. Endocrinol. 2005; 242(1-2): 42-9.
  29. Gonzalez F. Inflammation in polycystic ovary syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids. 2012; 77(4): 300-5.
  30. Xiong Y.L., Liang X.Y., Yang X., Li Y., Wei L.N. Low-grade chronic inflammation in the peripheral blood and ovaries of women with polycystic ovarian syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2011; 159(1): 148-50.
  31. Spaczynski R. Z., Arici A., Duleba A.J. Tumor necrosis factor-α stimulates proliferation of rat ovarian theca-interstitial cells. Biol. Reprod. 1999; 61(4): 993-8.
  32. Rojas J., Châvez M., Olivar L., Rojas M., Morillo J., Mejias J. et al. Polycystic ovary syndrome, insulin resistance, and obesity: navigating the pathophysiologic labyrinth. Int. J. Reprod. Med. 2014; 2014: 719050.
  33. Inzucchi S.E., Bergenstal R.M., Buse J.B., Diamant M., Ferrannini E., Nauck M. et al. Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2012; 55(6): 1577-96.
  34. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998; 352(9131): 854-65.
  35. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N. Engl. J. Med. 2008; 359(15): 1577-89.
  36. Nestler J.E. Metformin for the treatment of the polycystic ovary syndrome. N. Engl. J. Med. 2008; 358(1): 47-54.
  37. Moghetti P., Castello R., Negri C., Tosi F., Perrone F., Caputo M. et al. Metformin effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. J. Clin. Endocrinol. Metab. 2000; 85(1): 139-46.
  38. Luque-Ramirez M., Mendieta-Azcona C., Alvarez-Blasco F., Escobar-Morreale H.F Effects of metformin versus ethinyl-estradiol plus cyproterone acetate on ambulatory blood pressure monitoring and carotid intima media thickness in women with the polycystic ovary syndrome. Fertil. Steril. 2009; 91(6): 2527-36.
  39. Gilbert C., Valois M., Koren G. Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil. Steril. 2006; 86(3): 658-63.
  40. Schernthaner G., Currie C.J., Schernthaner G.H. Do we still need pioglitazone for the treatment of type 2 diabetes? A risk-benefit critique in 2013. Diabetes Care. 2013; 36(Suppl.2): S155-61.
  41. Amato A.A., de Assis Rocha Neves F. Idealized PPAR7-based therapies: lessons from bench and bedside. PPAR Res. 2012; 2012: 978687.
  42. Aroda V.R., Ciaraldi T.P, Burke P., Mudaliar S., Clopton P., Phillips S. et al. Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial. J. Clin. Endocrinol. Metab. 2008; 94(2): 469-76.
  43. Govindarajan R., Ratnasinghe L., Simmons D.L., Siegel E.R., Midathada M.V., Kim L. et al. Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes. J. Clin. Oncol. 2007; 25(12): 1476-81.
  44. Kazerooni T., Ghaffarpasand F., Kazerooni Y., Kazerooni M., Setoodeh S. Short-term metformin treatment for clomiphene citrate-resistant women with polycystic ovary syndrome. Int. J. Gynaecol. Obstet. 2009; 107(1): 50-3.
  45. Aigner E., Bachofner N., Klein K., De Geyter C., Hohla F., Patsch W., Datz C. Retinol-binding protein 4 in polycystic ovary syndrome-association with steroid hormones and response to pioglitazone treatment. J. Clin. Endocrinol. Metab. 2009; 94(4): 1229-35.
  46. Aubuchon M., Lieman H., Stein D., Cohen H.W., Isaac B., Adel G. et al. Metformin does not improve the reproductive or metabolic profile in women with polycystic ovary syndrome (PCOS). Reprod. Sci. 2009; 16(10): 938-46.
  47. Valsamakis G., Lois K., Kumar S., Mastorakos G. Metabolic and other effects of pioglitazone as an add-on therapy to metformin in the treatment of polycystic ovary syndrome (PCOS). Hormones (Athens). 2013; 12(3): 363-78.
  48. Glintborg D., Hermann A.P., Andersen M., Hagen C., Beck-Nielsen H., Veldhuis J.D., Henriksen J.E. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome. Fertil. Steril. 2006; 86(2): 385-97.
  49. Brettenthaler N., De Geyter C., Huber P.R., Keller U. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2004; 89(8): 3835-40.
  50. Li X.J., Yu Y.X., Liu C.Q., Zhang W, Zhang H.J., Yan B. et al. Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta-analysis. Clin. Endocrinol. (Oxford). 2011; 74(3): 332-9.
  51. Ortega-Gonzâlez C., Luna S., Hernândez L., Crespo G., Aguayo P., Arteaga-Troncoso G., Parra A. Responses of serum androgen and insulin resistance to metformin and pioglitazone in obese, insulin-resistant women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 2005; 90(3): 1360-5.
  52. Naka K.K., Kalantaridou S.N., Kravariti M., Bechlioulis A., Kazakos N., Calis K.A. et al. Effect of the insulin sensitizers metformin and pioglitazone on endothelial function in young women with polycystic ovary syndrome: a prospective randomized study. Fertil. Steril. 2011; 95(1): 203-9.
  53. Ibanez L., Löpez-Bermejo A., del Rio L., Enriquez G., Valls C., de Zegher F. Combined low-dose pioglitazone, flutamide, and metformin for women with androgen excess. J. Clin. Endocrinol. Metab. 2007; 92(5): 1710-4.
  54. Thessaloniki ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Consensus on infertility treatment related to polycystic ovary syndrome. Fertil. Steril. 2008; 89(3): 505-22.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2015 Bionika Media

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies