Exp Clin Endocrinol Diabetes 2010; 118(3): 161-166
DOI: 10.1055/s-0029-1220770
Article

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

Comparison Of The Effects Of Atorvastatin And Simvastatin In Women With Polycystic Ovary Syndrome: A Prospective, Randomized Study

C. Kaya1 , R. Pabuccu1 , S. D. Cengiz2 , I. Dünder2
  • 1Ufuk University, Faculty of Medicine, Department of Obstetrics and Gynecology
  • 2Ankara University, Faculty of Medicine, Department of Obstetrics and Gynecology
Further Information

Publication History

received 28.10.2008 first decision 22.01.2009

accepted 20.04.2009

Publication Date:
09 February 2010 (online)

Abstract

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, insulin resistance (IR), and chronic inflammation. Simvastatin improves endocrine/clinical aspects of PCOS and decreases systemic inflammation in PCOS. There have been no comparative studies carried out regarding the effects of different statin treatment in PCOS. We aimed to assess the effects of two different statin treatments on various metabolic, endocrine, oxidative and inflammatory factors in PCOS.

Design: Prospective, randomized clinical trial

Methods: Sixty-four (64) women with PCOS were included in the study. Group 1 had (atorvastatin, 20lmg daily; n=32) or group 2 had (simvastatin, 20l mg daily n=32). The metabolic, endocrine, inflammatory and oxidative profiles were evaluated.

Results: Group 1 resulted in a significant reduction in the HOMA index and fasting insulin (−26.9±9.6%, −26.2±10.8%, P<0.01, respectively).CRP levels decreased by 63.6±15.9% in group 1 (P<0.01), whereas in the group 2 it decreased by 34.6±10.7% (P<0.05). Serum levels of LH declined by 19.1±4.5% (P<0.05) in the group 1 and by 39.3±11.9% (P<0.01) in the group 2. FAI decreased by −20±9.9% in group 1 (P<0.05) and it decreased by −38.7±13.8% in the group 2 (P<0.01). MDA levels decreased by 32.6±9.6% in group 1 (P<0.05), whereas in the group 2 it decreased by 30.3±10.9% (P<0.01). HOMA index and fasting insulin showed a reduction but not reached statistically significance in the group 2 (8.3±1.9%, 3.0±0.8%, P>0.05, respectively).

Conclusion: Both the statins are effective in reducing inflammation, hyperandrogenemia, oxidative stress and metabolic parameters. While atorvastatin has more noticeable effects on fasting insulin and insulin sensitivity, simvastatin has a dominant effect on total T in PCOS women.

References

  • 1 Ashwell M, Chinn S, Stalley S, Garrow JS. Female fat distribution-a simple classification based on two circumference measurements.  Int J Obes. 1982;  6 143-152
  • 2 Balen AH, Laven JS, Tan SL, Dewailly D. Ultrasound assessment of the polycystic ovary: international consensus definitions.  Hum Reprod Update. 2003;  9 505-514
  • 3 Belli SH, Graffigna MN, Oneta A, Otero P, Schurman L, Levalle OA. Effect of rosiglitazone on insulin resistance, growth factors, and reproductive disturbances in women with polycystic ovary syndrome.  Fertil Steril. 2004;  81 624-629
  • 4 Chen MJ, Yang WS, Yang JH, Chen CL, Ho HN, Yang YS. Relationship between androgen levels and blood pressure in young women with polycystic ovary syndrome.  Hypertension. 2007;  49 1442-1447
  • 5 Banaszewska BL, Spaczynski RZ, Dziura J, Duleba AJ. Effects of simvastatin and oral contraceptive agent on polycystic ovary syndrome: prospective, randomized, crossover trial.  J Clin Endocrinol Metab. 2007;  92 456-461
  • 6 Boulman N, levy Y, Leiba R, Schachar S, Linn R, Zinder O, Blumenfeld Z. Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease.  J Clin Endocrinol Metab. 2004;  89 2160-2165
  • 7 Dale PO, Tanbo T, Vaaler S. et al . Body weight, hyperinsulinemia, and gonadotrophin levels in the polycystic ovarian syndrome: evidence of two distinct populations.  Fertil Steril. 1992;  58 487-491
  • 8 Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG. et al . A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile.  J Clin Endocrinol Metab. 1999;  84 4006-4011
  • 9 Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GP. Pathophysiology and types of dyslipidemia in PCOS.  Endocrinol and Metabol. 2007;  18 281-285
  • 10 Duleba AJ, Foyouzi N, Karaca H, Pehlivena T, Kwintkiewicz J, Behrman HR. Proliferation of ovarian theca-interstitial cells is modulated by antioxidants and oxidative stres.  Hum reprod. 2004;  19 1519-1524
  • 11 Duleba AJ, Banaszewska B, Spacynski RZ, Pawelcyzyk L. Simvastatin improves biochemical parameters in women with polycystic ovary syndrome: results of a prospective, randomized trial.  Fertil Steril. 2006;  85 996-1001
  • 12 Expert Committee on the Diagnosis and Classification . Follow-up Report on the Diagnosis of Diabetes Mellitus Diabetes Care.  2003;  26 3160-3167
  • 13 Ferriman D, Gallway JD. Clinical assessment of body hair growth in women.  J Clin Endocrinol Metab. 1961;  21 1440-1447
  • 14 Güçlü F, Ozmen B, Hekimsoy Z, Kirmaz C. Effects of statin group drug, pravastatin, on the insulin resistance in patients with metabolic syndrome.  Biomed Pharmakother. 2004;  58 614-618
  • 15 Huptas S, Geiss HC, Otto C, Parhofer G. Effect of Atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome.  Am J Cardiol. 2006;  98 66-69
  • 16 Izquierdo D, Foyoyouzi N, Kwintkiewicz J, Duleba AJ. Mevastatin inhibits ovarian theca-interstitial cell proliferation and steroidogenesis.  Fertil Steril. 2004;  82 ((Suppl 3)) 1193-1197
  • 17 Jialal I, Stein D, Balis D, Grundy SM, Adams-Huet B, Devaraj S. Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor Therapy on High Sensitive C-Reactive Protein Levels.  Circulation. 2001;  103 1933-1935
  • 18 Kaya C, Cengiz SD, Berker B, Demirta° S, Cesur M, Erdoğan G. Comparative effects of atorvastatin and simvastatin on the plasma total homocysteine levels in women with polycystic ovary syndrome: a prospective randomized study.  Fertil Steril. 2008 Aug 8;  [Epub ahead of print]
  • 19 Kelly CC, Lyall H, Petrie JR, Gould GW, Connell JM, Sattar N. Low grade chronic inflammation in women with polycystic ovary syndrome.  J Clin Endocrinol Metab. 2001;  86 2453-2455
  • 20 Kwintkiewicz J, Foyouzi N, Piotrowski P, Rzepczynska I, Duleba AJ. Mevastatin inhibits proliferation of rat ovarian theca-interstitial cells by blocking the mitogen-activated protein kinase patway.  Fertil steril. 2006;  86 ((Supp 3)) 1053-1058
  • 21 McFarlane SI, Banerji M, Sowers JR. Insulin resistance and cardiovascular disease.  J Clin Endocrinol Metab. 2001;  86 713-718
  • 22 Shaw LJ, Bairey MNC, Aziz R, Stanczyk FZ, Sopko G, Braunstein GD. et al . Postmenopausal women with a history of irregular menses and elevated androgen measurements at high risk for worsening cardiovascular event-free survival: results from the national institutes of health—national heart, lung, and blood institute sponsored women's ischemia syndrome evaluation.  J Clin Endocrinol Metab. 2008;  93 1276-1284
  • 23 Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Tracher DF, Turner RI. Homeostasis model assessment: insulin resistance and β cell function from fasting plasma glucose and insulin concentrations in man.  Diabetologia. 1985;  28 412-419
  • 24 McFarlane SI, Muniyappa R, Francisco R, Sowers JR. Pleiotropic effects of statins: lipid production and beyond.  J Clin Endocrinol Metab. 2002;  887 1451-1458
  • 25 Nelson VL, Legro RS, Staruss JF, McAllister JM. Augmented androgen production is a stable steroidogenic phenotype of propagated theca cells from polycystic ovaries.  Mol Endocrinol. 1999;  13 946-957
  • 26 Okon MA, Laird SM, Tuckerman EM, Li TCS. Androgens levels in women who have recurrent miscarriage and their correlation with markers of endometrial function.  Fertil Steril. 1998;  69 ((4)) 682-690
  • 27 Pasceri V, Willerson JT, Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells.  Circulation. 2000;  102 2165-2168
  • 28 Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon III RO, Criqui M. et al . Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Center for Disease Control and Prevention and the American Heart Association.  Circulation. 2003;  107 499-511
  • 29 Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome.  Fertil Steril. 2004;  82 ((Suppl 3)) 1193-1197
  • 30 Sabuncu T, Vural H, Harma M, Harma M. Oxidative stress in polycystic ovary syndrome and its contribution to the risk of cardiovascular disease.  Clin Biochemistry. 2001;  34 407
  • 31 Sakara M, Tasaka K, Kurachi H. et al . Changes of bioactive luteinising hormone after laparoscopic ovarian cautery in patients with polycystic ovarian syndrome.  Fertil Steril. 1990;  53 611-613
  • 32 Sing U, Devaraj S, Jialal I, Siegel D. Effect of Atorvastatin (10 versus 80 mg) on Biomarkers of Inflammation and Oxidative Stress in Subjects With Metabolic Syndrome.  Am J Cardiol. 2008;  102 321-325
  • 33 Spagnoli LG, Bonanno E, Sangiorgi G, Mauriello A. Role of Inflammation in atherosclerosis.  J Nucl Med. 2007;  48 1800-1815
  • 34 Talbott E, Guzick D, Clerici A, Berga S, Detre K, Weimer K. et al . Coronary heart disease risk factors in women with polycystic ovary syndrome.  Arterioscler Thromb Vasc Biol. 1995;  95 (15) 821-826
  • 35 Travia D, Tosi F, Negri C, Faccini G, Moghetti P, Muggeo M. Sustained therapy with 3-hydroxy-3-methylglutaryl-coenzyme-A reductase inhibitors does not impair steroidegenesis by adrenals and gonads.  J Clin Endocrinol Metab. 1995;  80 836-840
  • 36 Verma S, Wang CH, Li SH, Dumont AS, Fedak PW. et al . A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis.  Circulation. 2002;  106 913-919

Correspondence

MD C. Kaya

Faculty of Medicine

Department of Obstetrics and Gynecology and Infertility

Ufuk University

Email: kayacemil000@yahoo.com

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