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Effects of Thiazolidinediones on Polycystic Ovary Syndrome: a Meta-analysis of Randomized Placebo-Controlled Trials

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Abstract

Introduction

Thiazolidinedione (TZD) is one of the therapy options for polycystic ovary syndrome (PCOS) patients; however, the effectiveness of TZD in the treatment of PCOS remains controversial. The aim of this metaanalysis was to clarify the role that TZDs play in the treatment of PCOS.

Methods

The authors searched the following databases for any date up to June 2012 for randomized controlled trials on PCOS treatment in which interventions for the experimental and control groups were TZDs and placebo, respectively: Medline, Embase, and the Cochrane library.

Results

The search strategy identified 173 potential publications, eight of which were included. In the treatment of PCOS, the insulin-lowering effects of TZDs were superior to placebo (95% CI −1.50 to −0.12; P = 0.021), and the lowering of fasting blood glucose was superior to placebo (95% CI −1.06 to −0.05; P = 0.031). There was no difference in reduction of the Ferriman-Gallwey scores or the androgen levels between TZDs and placebo (95% CI −0.57 to 0.10; P = 0.169 and 95% CI −0.64 to 0.09; P = 0.141, respectively). The effects of TZDs on body weight reduction were inferior to placebo (95% CI 0.13 to 0.66; P = 0.003). Significant between-study heterogeneity was detected for several variables assessed.

Conclusion

This is the first meta-analysis to evaluate the role that TZDs plays in the treatment of PCOS compared with placebo. The currently available data showed that TZDs can effectively reduce insulin and fasting blood glucose levels in patients with PCOS, but TZDs may not effectively reduce the Ferriman-Gallwey score or androgen levels and may increase body weight.

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References

  1. Gangale MF, Miele L, Lanzone A, et al. Longterm metformin treatment is able to reduce the prevalence of metabolic syndrome and its hepatic involvement in young hyperinsulinaemic overweight patients with polycystic ovarian syndrome. Clin Endocrinol (Oxf). 2011;75:520–527.

    Article  CAS  Google Scholar 

  2. Kim JJ, Choi YM, Cho YM, et al. Prevalence of elevated glycated hemoglobin in women with polycystic ovary syndrome. Hum Reprod. 2012;27:1439–1444.

    Article  PubMed  CAS  Google Scholar 

  3. Chang AY, Ayers C, Minhajuddin A, et al. Polycystic ovarian syndrome and subclinical atherosclerosis among women of reproductive age in the Dallas heart study. Clin Endocrinol (Oxf), 2011;75:89–96.

    Article  Google Scholar 

  4. Wild RA, Carmina E, Diamanti-Kandarakis E, et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab. 2010;95:2038–2049.

    Article  PubMed  CAS  Google Scholar 

  5. Phelan N, O’Connor A, Kyaw-Tun T, et al. Lipoprotein subclass patterns in women with polycystic ovary syndrome (PCOS) compared with equally insulin-resistant women without PCOS. J Clin Endocrinol Metab. 2010;95:3933–3939.

    Article  PubMed  CAS  Google Scholar 

  6. Fearnley EJ, Marquart L, Spurdle AB, et al. Polycystic ovary syndrome increases the risk of endometrial cancer in women aged less than 50 years: an Australian case-control study. Cancer Causes Control. 2010;21:2303–2308.

    Article  PubMed  Google Scholar 

  7. Atiomo W, Read A, Golding M, et al. Local recruitment experience in a study comparing the effectiveness of a low glycaemic index diet with a low calorie healthy eating approach at achieving weight loss and reducing the risk of endometrial cancer in women with polycystic ovary syndrome (PCOS). Contemp Clin Trials. 2009;30:451–456.

    Article  PubMed  Google Scholar 

  8. Vgontzas AN, Bixler EO, Chrousos GP. Metabolic disturbances in obesity versus sleep apnoea: the importance of visceral obesity and insulin resistance. J Intern Med. 2003;254:32–44.

    Article  PubMed  CAS  Google Scholar 

  9. Ahmed W, Ziouzenkova O, Brown J, et al. PPARs and their metabolic modulation: new mechanisms for transcriptional regulation? J Intern Med. 2007;262:184–198.

    Article  PubMed  CAS  Google Scholar 

  10. Koenen TB, Tack CJ, Kroese JM, et al. Pioglitazone treatment enlarges subcutaneous adipocytes in insulin-resistant patients. J Clin Endocrinol Metab. 2009;94:4453–4457.

    Article  PubMed  CAS  Google Scholar 

  11. Schoppee PD, Garmey JC, Veldhuis JD. Putative activation of the peroxisome proliferator-activated receptor γ impairs androgen and enhances progesterone biosynthesis in primary cultures of porcine theca cells. Biol Reprod. 2002;66:190–198.

    Article  PubMed  CAS  Google Scholar 

  12. Faich GA, Moseley RH. Troglitazone (Rezulin) and hepatic injury. Pharmacoepidemiol Drug Saf. 2001;10:537–547.

    Article  PubMed  CAS  Google Scholar 

  13. Bell DS, Ovalle F. Late-onset troglitazone-induced hepatic dysfunction. Diabetes Care. 2000;23:128–129.

    Article  PubMed  CAS  Google Scholar 

  14. Murphy EJ, Davern TJ, Shakil AO, et al. Troglitazone-induced fulminant hepatic failure. Acute Liver Failure Study Group. Dig Dis Sci. 2000;45:549–553.

    Article  PubMed  CAS  Google Scholar 

  15. Li XJ, Yu YX, Liu CQ, et al. Metformin vs thiazolidinediones for treatment of clinical, hormonal and metabolic characteristics of polycystic ovary syndrome: a meta-analysis. Clin Endocrinol (Oxf). 2011;74:332–339.

    Article  CAS  Google Scholar 

  16. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004;81:19–25.

    Google Scholar 

  17. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, ed. Polycystic Ovary Syndrome. Boston: Blackwell Scientific, 1995:377–384.

    Google Scholar 

  18. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;21:339.

    Google Scholar 

  19. DerSimonian R, Kacker, R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28:105–114.

    Article  PubMed  Google Scholar 

  20. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med. 2002;21:1539–1558.

    Article  PubMed  Google Scholar 

  21. Naka KK, Kalantaridou SN, Kravariti M, 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;95:203–209.

    Article  PubMed  CAS  Google Scholar 

  22. Aigner E, Bachofner N, Klein K, et al. Retinolbinding protein 4 in polycystic ovary syndrome—association with steroid hormones and response to pioglitazone treatment. J Clin Endocrinol Metab. 2009;94:1229–1235.

    Article  PubMed  CAS  Google Scholar 

  23. Aroda VR, Ciaraldi TP, Burke P, et al. Metabolic and hormonal changes induced by pioglitazone in polycystic ovary syndrome: a randomized, placebo-controlled clinical trial. J Clin Endocrinol Metab. 2009;94:469–476.

    Article  PubMed  CAS  Google Scholar 

  24. Glintborg D, Hermann AP, Andersen M, et al. Effect of pioglitazone on glucose metabolism and luteinizing hormone secretion in women with polycystic ovary syndrome. Fertil Steril. 2006;86:385–397.

    Article  PubMed  CAS  Google Scholar 

  25. Ma LK, Jin LN, Yu Q, Xu L. Effect of lifestyle adjustment, metformin and rosiglitazone in polycystic ovary syndrome. Zhonghua Fu Chan Ke Za Zhi. 2007;42:294–297.

    PubMed  Google Scholar 

  26. Rautio K, Tapanainen JS, Ruokonen A, Morin-Papunen LC. Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study. Hum Reprod. 2006;21:1400–1407.

    Article  PubMed  CAS  Google Scholar 

  27. Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil Steril. 2004;82:893–902.

    Article  PubMed  CAS  Google Scholar 

  28. Liao L, Tian YJ, Zhao JJ, et al. Metformin versus metformin plus rosiglitazone in women with polycystic ovary syndrome. Chin Med J (Engl). 2011;124:714–718.

    CAS  Google Scholar 

  29. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440–1447.

    Article  PubMed  CAS  Google Scholar 

  30. Chalmers TC, Celano P, Sacks HS, Smith H Jr. Bias in treatment assignment in controlled clinical trials. N Engl J Med. 1983;309:1359–1361.

    Google Scholar 

  31. Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias: dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA. 1995;273:408–412.

    Article  PubMed  CAS  Google Scholar 

  32. Cochrane Handbook for Systematic Reviews of Interventions. Available at: External link http://www.cochrane-handbook.org/. Accessed June 22 2012.

  33. Bloomgarden ZT. Type 2 diabetes: uses of thiazolidinediones and insulin. Diabetes Care. 2011;34:11–16.

    Article  Google Scholar 

  34. Stein LL, Dong MH, Loomba R. Insulin sensitizers in nonalcoholic fatty liver disease and steatohepatitis: current status. Adv Ther. 2009;26:893–907.

    Article  PubMed  CAS  Google Scholar 

  35. Quinn CE, Hamilton PK, Lockhart CJ, McVeigh GE. Thiazolidinediones: effects on insulin resistance and the cardiovascular system. Br J Pharmacol. 2008;153:636–645.

    Article  PubMed  CAS  Google Scholar 

  36. Ko GT, Tsang PC, Wai HP, et al. Rosiglitazone versus bedtime insulin in the treatment of patients with conventional oral antidiabetic drug failure: a 1-year randomized clinical trial. Adv Ther. 2006;23:799–808.

    Article  PubMed  CAS  Google Scholar 

  37. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;14:2457–2471.

    Article  Google Scholar 

  38. Rubenstrunk A, Hanf R, Hum DW, Fruchart JC, Staels B. Safety issues and prospects for future generations of PPAR modulators. Biochim Biophys Acta. 2007;1771:1065–1081.

    Article  PubMed  CAS  Google Scholar 

  39. Nissen SE, Wolski K. Rosiglitazone Revisited: An updated meta-analysis of risk in for myocardial infarction and cardiovascular mortality. Arch Intern Med. 2010;170:1191–1201.

    Article  PubMed  CAS  Google Scholar 

  40. Singh S, Loke Y.K, Furberg CD. Long-term risk of cardiovascular events with rosiglitazone: a metaanalysis. JAMA. 2007;298:1189–1195.

    Article  PubMed  CAS  Google Scholar 

  41. Bodmer M., Meier C, Kraenzlin ME, Meier CR. Risk of fractures with glitazones: a critical review of the evidence to date. Drug Saf. 2009;32:539–547.

    Article  PubMed  CAS  Google Scholar 

  42. Piccinni C, Motola D, Marchesini G, et al. Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting. Diabetes Care. 2011;34:1369–1371.

    Article  PubMed  Google Scholar 

  43. Lewis JD, Ferrara A, Peng T, Poluzzi E. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care. 2011;34:916–922.

    Article  PubMed  CAS  Google Scholar 

  44. Li W, Macdonald TM, Mackenzie IS. Pioglitazone and bladder cancer: a propensity score matched cohort study. Br J Clin Pharmacol. 2012. Epub ahead of print.

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Authors and Affiliations

  1. Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Qiang Du, Sheng Yang, Yan-Jun Wang & Bo Wu

  2. Library, Shengjing Hospital of China Medical University, Shenyang, China

    Yue-Yang Zhao

  3. Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China

    Bin Fan

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  1. Qiang Du
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Correspondence to Qiang Du.

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Du, Q., Yang, S., Wang, YJ. et al. Effects of Thiazolidinediones on Polycystic Ovary Syndrome: a Meta-analysis of Randomized Placebo-Controlled Trials. Adv Therapy 29, 763–774 (2012). https://doi.org/10.1007/s12325-012-0044-6

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