Exp Clin Endocrinol Diabetes 2008; 116(4): 231-235
DOI: 10.1055/s-2007-992154
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Oxidative Stress Markers in Young Patients with Polycystic Ovary Syndrome, The Relationship between Insulin Resistances

M. Karadeniz 1 , M. Erdoğan 1 , S. Tamsel 3 , A. Zengi 1 , G. E. Alper 2 , O. Çağlayan 4 , F. Saygılı 1 , C. Yılmaz 1
  • 1Department of Endocrinolgy, Ege University Hospital, Izmir, Turkey
  • 2Department of Biochemistry, Ege University Hospital, Izmir, Turkey
  • 3Department of Radiology, Ege University Hospital, Izmir, Turkey
  • 4Department of Biochemistry, Kırıkkale University Hospital, Izmir, Turkey
Further Information

Publication History

received 16.04.2007 first decision 23.08.2007

accepted 11.10.2007

Publication Date:
07 April 2008 (online)

Abstract

Objective: Polycystic ovary syndrome is a syndrome of ovarian dysfunction. Oxidative stress, inflammation and endothelial cell activation are thought to play concomitant roles in the pathogenesis of the above diseases particularly in the development of atherosclerotic lesions.

Research Design and Methods: We studied 58 polycystic ovary syndrome patients and age-matched 25 healthy controls consisting of women that have regular, ovulatory cycles and normal androgen levels. Homeostasis Model Assessment-Insulin Resistance for this study was taken as 1.75 that is the upper level of confidence interval of %95 of the mean of the healthy group. PCOS patients were divided into two groups as for below the cut-off level (<1.75) and above the cut-off level (≥1.75). hs-CRP, fibrinogen, malondialdehyde, nitric oxide and disulfide level results were compared both in PCOS and control groups.

Results: In this study, sensitive CRP was found to be statical significantly higher in polycystic ovary syndrome groups whose Homeostasis Model Assessment-Insulin Resistance were ≥1.75 and <1.75 when compared to the control group. But, no significantly correlation was determined between malondialdehyde, nitric oxide and disulfide levels and CRP elevation.

Conclusions: In our study, because those participants were young and non- obese patients with PCOS, malondialdehyde, nitric oxide and disulfide levels and Carotid Artery Intima-Media Thickness measurements as a pre-indicator of cardiovascular disease were not found to be different from those of the controls.

References

  • 1 Franks S. Diagnosis of the polycystic ovary syndrome: in defence of the Rotterdam criteria.  J Clin Endocrinol Metab. 2006;  91 786-789
  • 2 Broekmans FJ, Knauff EA, Valkenburg O, Laven JS, Eijkemans MJ, Fauser BC. PCOS according to the Rotterdam consensus criteria: Change in prevalence among WHO-II anovulation and association with metabolic factors.  BJOG. 2006;  113 ((10)) 1210-1217
  • 3 Landmesser U, Harrison DG, Drexler H. Oxidant stress-a major cause of reduced endothelial nitric oxide availability in cardiovascular disease.  Eur J Clin Pharmacol. 2006;  62 13-19
  • 4 Li H, Junk P, Huwiler A, Burkhardt C, Wallerath T, Pfeilschifter J, Forstermann U. Dual effect of ceramide on human endothelial cells: induction of oxidative stress and transcriptional upregulation of endothelial nitric oxide synthase.  Circulation. 2002; 22;  106 ((17)) 2250-2256
  • 5 Halcox JPJ, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA, Nour KRA, Quyyumi AA. Prognostic value of coronary vascular endothelial dysfunction.  Circulation. 2002;  106 653-658
  • 6 Konukoglu D, Serin O, Turhan MS. Plasma total homocysteine concentrations in obese and non-obese female patients with type 2 diabetes mellitus; its relations with plasma oxidative stress and nitric oxide levels.  Clin Hemorheol Microcirc. 2005;  33 ((1)) 41-46
  • 7 Keaney JF, Larson MG, Vasan RS, Wılson PWF, Lıpınska I, Corey D, Massaro JM, Sutherland P, Vıta JA, Benjamın EJ. Obesity and systemic oxidative stress - clinical correlates of oxidative stress in the Framingham Study.  Arterioscl Thromb Vasc Biol. 2003;  23 434-439 , 14.
  • 8 Ruiz MC, Medina A, Moreno JM, Gomez I, Ruiz N, Bueno P, Asensio C, Osuna A. Relationship between oxidative stress parameters and atherosclerotic signs in the carotid artery of stable renal transplant patients.  Transplant Proc. 2005;  37 ((9)) 3796-3799
  • 9 Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibova J. Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of polycystic ovary syndrome.  Hum Reprod. 2000;  15 785-789
  • 10 Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB. Lipoprotein lipid concentration and cardiovascular risk in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 1985;  61 946-951
  • 11 Graf MJ, Richards CJ, Brown V, Meissner L, Dunaif A. The independent effects of hyperandrogenemia, hyperinsulinemia and obesity on lipid and lipoprotein profiles in women.  Clin Endocrin Metabol. 1990;  33 119-131
  • 12 Boulman N, Levy Y, Leiba R. et al . Increased C-reactive protein levels in the polycystic ovary syndrome (a marker of cardiovascular disease).  J Clin Endocrinol Metab. 2004;  89 2160-2165
  • 13 Orio F, Palomba S, Biase S Di. et al . Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2003;  88 673-679
  • 14 Diamanti-Kandarakis E, Spina G, Kouli C, Migdalis I. Increased endothelin-1 levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy.  J Clin Endocrinol Metab. 2001;  86 4666-4673
  • 15 Kotur-Stevuljevic J, Memon L, Stefanovic A, Spasic S, Spasojevic-Kalimanovska V, Bogavac-Stanojevic N, Kalimanovska-Ostric D, Jelic-Ivanovic Z, Zunic G. Correlation of oxidative stress parameters and inflammatory markers in coronary artery disease patients.  Clin Biochem. 2006;  30 , [Epub ahead of print]
  • 16 Paradisi G, Steinberg HO, Hempfling A. et al . Polycystic ovary syndrome is associated with endothelial dysfunction.  Circulation. 2001;  103 1410-1415
  • 17 Talbott EO, Zborowski JV, Rager JR, Boudreaux MY, Edmundowicz DA, Guzick DS. Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic syndrome.  J Clin Endocrinol Metab. 2004;  89 5454-5461
  • 18 Lakhani K, Hardiman P, Seifalian AM. Intima-media thickness of elastic and muscular arteries of young women with polycystic ovaries.  Atherosclerosis. 2004;  175 353-359
  • 19 The Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group . Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS).  Hum Reprod. 2004;  19 ((1)) 41-47
  • 20 Yagi K. Lipid peroxides in hepatic, gastrointestinal and pancreatic diseases. In: D Armstrong (ed): Free radicals in Diagnostic Medicine. New York, NY, Plenum Press 1994: 165-169
  • 21 Miranda KM, Espey MG, Wink DA. A rapid, simple spectrophometric method for simultaneous detection of nitrate and nitrite.  Nitric Oxide. 2001;  5 62-71
  • 22 Sedlak J, Lindsay RH. Estimation of total, protein-bound and nonprotein sulfhydryl groups in tissue with Ellman's reagent.  Anal Biochem. 1968;  25 192-205
  • 23 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: Insulin resistance and beta cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 24 Yarali H, Yildirir A, Aybar F, Kabakci G, Bukulmez O, Akgul E, Oto A. Diastolic dysfunction and increased serum homocysteine concentrations may contribute to increased cardiovascular risk in patients with polycystic ovary syndrome.  Fertil Steril. 2001;  76 ((3)) 511-516
  • 25 Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD. Polycystic ovary syndrome is associated with endothelial dysfunction.  Circulation. 2001; 13;  103 ((10)) 1410-1415
  • 26 Kelly CJ, Speirs A, Gould GW, Petrie JR, Lyall H, Connell JM. vascular function in young women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2002;  87 ((2)) 742-746
  • 27 Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. grade chronic inflammation in women with polycystic ovarian syndrome.  J Clin Endocrinol Metab. 2001;  86 ((6)) 2453-2455
  • 28 Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome.  Gynecol Obstet Invest. 2002;  53 ((3)) 157-162
  • 29 Muneyyirci-Delale O, Nacharaju VL, Dalloul M, Jalou S, Rahman M, Altura BM, Altura BT. Divalent cations in women with PCOS: implications for cardiovascular disease.  Gynecol Endocrinol. 2001;  15 ((3)) 198-201
  • 30 Glueck CJ, Sieve L, Zhu B, Wang P. Plasminogen activator inhibitor activity, 4G5G polymorphism of the plasminogen activator inhibitor 1 gene, and first-trimester miscarriage in women with polycystic ovary syndrome.  Metabolism. 2006;  55 ((3)) 345-352
  • 31 Sies H. Oxidative stress: introductory remarks. In: Oxidative Stress. edited by Sies H. New York: Academic 1985: 1-8
  • 32 Sies H. Oxidative Stress: Oxidants and Antioxidants. London: Academic 1991
  • 33 Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association, and the German Diabetes Society.  Diabetes Metab Res Rev. 2001;  17 189-212
  • 34 Zquierdo-Vega JA, Soto CA, Sanchez-Pena LC, Vizcaya-Ruiz A De, Del Razo LM. Diabetogenic effects and pancreatic oxidative damage in rats subchronically exposed to arsenite.  Toxicol Lett. 2006 5;  160 ((2)) 135-142
  • 35 Habib MP, Dickerson FD, Mooradian AD. Effect of diabetes, insulin and glucose load on lipid peroxidation in the rat.  Metabolism. 1994;  43 1442-1445
  • 36 Urakawa H, Katsuki A, Sumida Y, Gabazza EC, Murashima S, Morioka K. et al . Oxidative stress is associated with adiposity and insulin resistance in men.  J Clin Endocrinol Metab. 2003;  88 4673-4676
  • 37 Fleming R. The use of insulin sensitising agents in ovulation induction in women with polycystic ovary syndrome.  Hormones (Athens). 2006;  5 ((3)) 171-178 , Review.
  • 38 Pasquali R, Gambineri A, Pagotto U. The impact of obesity on reproduction in women with polycystic ovary.  syndrome BJOG. 2006;  113 ((10)) 1148-1159 , Epub 2006 Jul 7. Review.
  • 39 Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms.  Circulation. 2006; 18;  113 ((15)) 1888-1904
  • 40 Jobgen WS, Fried SK, Fu WJ, Meininger CJ, Wu G. Regulatory role for the arginine-nitric oxide pathway in metabolism of energy substrates.  J Nutr Biochem. 2006;  17 ((9)) 571-588
  • 41 Chen NG, Azhar S, Abbasi F, Carantoni M, Reaven GM. The relationship between plasma glucose and insulin response to oral glucose, LDL oxidation, and soluble intercellular adhesion molecule-1 in healthy volunteers.  Atherosclerosis. 2000;  152 203-208
  • 42 Nourooz-Zadeh J, Tajaddini-Sarmadi J, MacCarthy S, Betteridge J, Wolff SP. Elevated levels of authentic plasma hydroperoxides in NIDDM.  Diabetes. 1995;  44 1054-1058
  • 43 Levitt NS, Stansberry KB, Wynchank S, Vinik AI. The natural progression of autonomic neuropathy and autonomic function tests in a cohort of people with IDDM.  Diabetes Care. 1996;  19 751-754
  • 44 Douglas W, Zochodne MD. FRPC: peripheral nerve disease, in Evidence-Based Diabetes Care. Editors: Hertzel C. Gerstein and R. Brion Haynes. BC Decker Inc. Hamilton, London 2001: 466-479
  • 45 Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease.  Fertil Steril. 2003;  80 ((1)) 123-127
  • 46 Tsimikas S, Brilakis ES, Lennon RJ, Miller ER, Witztum JL, MacConnell JP, Kornman KS, Berger PB. Relationship of IgM and IgG autoantibodies to oxidized low density lipoprotein and apolipoprotein B100-immune complexes with angiographically determined coronary artery disease and cardiovascular events.  J Lipid Res. 2006;  8 , [Epub ahead of print]
  • 47 Lee KU. Oxidative stress markers in Korean subjects with insulin resistance syndrome.  Diabetes Res Clin Pract. 2001;  54 ((Suppl 2)) S29-33
  • 48 Kokic AN, Stevic Z, Stojanovic S, Blagojevic DP, Jones DR, Pavlovic S, Niketic V, Apostolski S, Spasic MB. Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients.  Redox Rep. 2005;  10 ((5)) 265-270
  • 49 Kenyon NJ, Last MS, Eiserich JP, Morrissey BM, Temple LM, Last JA. Differentiation of the roles of NO from airway epithelium and inflammatory cells in ozone-induced lung inflammation.  Toxicol Appl Pharmacol. 2006; 15;  215 ((3)) 250-259
  • 50 Alexandraki K, Protogerou AD, Papaioannou TG, Piperi C, Mastorakos G, Lekakis J, Panidis D, Diamanti-Kandarakis E. Microvascular and macrovascular dysfunction is not accompanied by structural arterial injury in polycystic ovary syndrome.  Hormones (Athens). 2006;  5 ((2)) 126-136
  • 51 Orio F, Palomba S, Cascella T, Simone B De, Biase S Di, Russo T, Labella D, Zullo F, Lombardi G, Colao A. Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2004;  89 4588-4593
  • 52 Vural B, Caliskan E, Turkoz E, Kilic T, Demirci A. Evaluation of metabolic syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome Hum.  Reprod 1. 2005;  20 ((9)) 2409-2413
  • 53 Talbott E, Guzick D, Sutton-Tyrrell K, MacHugh-Pemu K, Zborowski J, Remsberg K, Kuller L. Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.  Arterioscler Thromb Vasc Biol. 2000;  20 2414-2421
  • 54 Talbott EO, Zborowski JV, Rager GR. et al . Evidence for an association between metabolic cardiovascular syndrome and coronary and aortic calcification among women with polycystic ovary syndrome.  Journal of Clinical Endocrinology and Metabolism. 2004;  89 , pp. 5454-5461
  • 55 Talbott EO, Guzick DS, Sutton-Tyrrell K. et al . Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women.  Arteriosclerosis Thrombosis and Vascular Biology. 2000;  20 ((11)) 2414-2421
  • 56 Solomon CG, Hu FB, Dunaif A. et al . Menstrual cycle irregularity and risk for future cardiovascular disease.  Journal of Clinical Endocrinology and Metabolism. 2002;  87 ((5)) 2013-2017

Correspondence

M. ErdoğanMD 

Department of Endocrinology and Metabolism Disease

Ege University Medical School

35100 Izmir

Turkey

Phone: +90/232/347 30 85

Fax: +90/232/373 77 01

Email: drmerdogan@yahoo.com

    >