Metformin and Lifestyle Intervention in Women With Polycystic Ovary Syndrome

Summary

Polycystic ovary syndrome is a frequent cause of abnormal menses and infertility. It has also been related to cardiovascular disease. The objective of this trial is to evaluate the clinical and metabolic efficacy of metformin plus life style modifications in women with polycystic ovary syndrome compared with life style modifications and placebo

Timeline

Start

2003-01

Primary completion

2005-09

Completion

2005-12

Publications

• Background Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.
• Background Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab. 2000 Jul;85(7):2434-8. doi: 10.1210/jcem.85.7.6682.
• Background Diamanti-Kandarakis E, Kouli CR, Bergiele AT, Filandra FA, Tsianateli TC, Spina GG, Zapanti ED, Bartzis MI. A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. J Clin Endocrinol Metab. 1999 Nov;84(11):4006-11. doi: 10.1210/jcem.84.11.6148.
• Background Ehrmann DA. Polycystic ovary syndrome. N Engl J Med. 2005 Mar 24;352(12):1223-36. doi: 10.1056/NEJMra041536. No abstract available.
• Background Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997 Dec;18(6):774-800. doi: 10.1210/edrv.18.6.0318.
• Background Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989 Sep;38(9):1165-74. doi: 10.2337/diab.38.9.1165.
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• Background Alberti KG, Zimmet P, Shaw J; IDF Epidemiology Task Force Consensus Group. The metabolic syndrome--a new worldwide definition. Lancet. 2005 Sep 24-30;366(9491):1059-62. doi: 10.1016/S0140-6736(05)67402-8. No abstract available.
• Background Legro RS, Kunselman AR, Dodson WC, Dunaif A. Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. J Clin Endocrinol Metab. 1999 Jan;84(1):165-9. doi: 10.1210/jcem.84.1.5393.
• Background Christian RC, Dumesic DA, Behrenbeck T, Oberg AL, Sheedy PF 2nd, Fitzpatrick LA. Prevalence and predictors of coronary artery calcification in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003 Jun;88(6):2562-8. doi: 10.1210/jc.2003-030334.
• Background Wild RA. Long-term health consequences of PCOS. Hum Reprod Update. 2002 May-Jun;8(3):231-41. doi: 10.1093/humupd/8.3.231.
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• Background Talbott E, Clerici A, Berga SL, Kuller L, Guzick D, Detre K, Daniels T, Engberg RA. Adverse lipid and coronary heart disease risk profiles in young women with polycystic ovary syndrome: results of a case-control study. J Clin Epidemiol. 1998 May;51(5):415-22. doi: 10.1016/s0895-4356(98)00010-9.
• Background Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation. 2001 Mar 13;103(10):1410-5. doi: 10.1161/01.cir.103.10.1410.
• Background Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003 Oct;14(8):365-70. doi: 10.1016/j.tem.2003.08.002.
• Background Matthaei S, Stumvoll M, Kellerer M, Haring HU. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev. 2000 Dec;21(6):585-618. doi: 10.1210/edrv.21.6.0413.
• Background Harborne L, Fleming R, Lyall H, Norman J, Sattar N. Descriptive review of the evidence for the use of metformin in polycystic ovary syndrome. Lancet. 2003 May 31;361(9372):1894-901. doi: 10.1016/S0140-6736(03)13493-9.
• Background Norman RJ, Homan G, Moran L, Noakes M. Lifestyle choices, diet, and insulin sensitizers in polycystic ovary syndrome. Endocrine. 2006 Aug;30(1):35-43. doi: 10.1385/ENDO:30:1:35.
• Background Azziz R, Ehrmann D, Legro RS, Whitcomb RW, Hanley R, Fereshetian AG, O'Keefe M, Ghazzi MN; PCOS/Troglitazone Study Group. Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter, double blind, placebo-controlled trial. J Clin Endocrinol Metab. 2001 Apr;86(4):1626-32. doi: 10.1210/jcem.86.4.7375.
• Background Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CJ. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. 1994 May;43(5):647-54. doi: 10.1016/0026-0495(94)90209-7.
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• Background Escobar-Morreale HF, Serrano-Gotarredona J, Avila S, Villar-Palasi J, Varela C, Sancho J. The increased circulating prostate-specific antigen concentrations in women with hirsutism do not respond to acute changes in adrenal or ovarian function. J Clin Endocrinol Metab. 1998 Jul;83(7):2580-4. doi: 10.1210/jcem.83.7.4960.
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• Background Morin-Papunen L, Vauhkonen I, Koivunen R, Ruokonen A, Martikainen H, Tapanainen JS. Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab. 2003 Jan;88(1):148-56. doi: 10.1210/jc.2002-020997.
• Background Lord JM, Flight IH, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25;327(7421):951-3. doi: 10.1136/bmj.327.7421.951.
• Background Lord JM, Flight IH, Norman RJ. Insulin-sensitising drugs (metformin, troglitazone, rosiglitazone, pioglitazone, D-chiro-inositol) for polycystic ovary syndrome. Cochrane Database Syst Rev. 2003;(3):CD003053. doi: 10.1002/14651858.CD003053.
• Background Guzelmeric K, Seker N, Unal O, Turan C. High serum prostate-specific antigen concentrations in hirsute women do not decrease with treatment by the combination of spironolactone and the contraceptive pill. Gynecol Endocrinol. 2004 Oct;19(4):190-5. doi: 10.1080/09513590400012069.
• Background Escobar-Morreale HF, Avila S, Sancho J. Serum prostate-specific antigen concentrations are not useful for monitoring the treatment of hirsutism with oral contraceptive pills. J Clin Endocrinol Metab. 2000 Jul;85(7):2488-92. doi: 10.1210/jcem.85.7.6664.
• Background Bahceci M, Bilge M, Tuzcu A, Tuzcu S, Bahceci S. Serum prostate specific antigen levels in women with polycystic ovary syndrome and the effect of flutamide+desogestrel/ethinyl estradiol combination. J Endocrinol Invest. 2004 Apr;27(4):353-6. doi: 10.1007/BF03351061.
• Background Negri C, Tosi F, Dorizzi R, Fortunato A, Spiazzi GG, Muggeo M, Castello R, Moghetti P. Antiandrogen drugs lower serum prostate-specific antigen (PSA) levels in hirsute subjects: evidence that serum PSA is a marker of androgen action in women. J Clin Endocrinol Metab. 2000 Jan;85(1):81-4. doi: 10.1210/jcem.85.1.6230.
• Background Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007 Feb;92(2):405-13. doi: 10.1210/jc.2006-1864. Epub 2006 Nov 7.
• Background Gullu S, Emral R, Asik M, Cesur M, Tonyukuk V. Diagnostic value of prostatic specific antigen in hirsute women. J Endocrinol Invest. 2003 Dec;26(12):1198-202. doi: 10.1007/BF03349157.
• Background 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 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.
• Fux Otta C, Wior M, Iraci GS, Kaplan R, Torres D, Gaido MI, Wyse EP. Clinical, metabolic, and endocrine parameters in response to metformin and lifestyle intervention in women with polycystic ovary syndrome: a randomized, double-blind, and placebo control trial. Gynecol Endocrinol. 2010 Mar;26(3):173-8. doi: 10.3109/09513590903215581.

Drugs

Indications