Fertility and Sterility
Volume 82, Issue 2 , Pages 421-429 , August 2004

A randomized, 48-week, placebo-controlled trial of intensive lifestyle modification and/or metformin therapy in overweight women with polycystic ovary syndrome: A pilot study

Presented in part at the 58th Annual Meeting of the American Society for Reproductive Medicine, Seattle, Washington, October 12–17, 2002.

  • Kathleen M Hoeger, M.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
    • Corresponding Author InformationReprint requests: Kathleen M. Hoeger, M.D., University of Rochester School of Medicine and Dentistry, Department of Obstetrics and Gynecology, 601 Elmwood Avenue, Box 668, Rochester, New York 14642, USA (FAX: 585-746-4146).
  • ,
  • Lynda Kochman, R.N., C.C.R.C.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • ,
  • Nellie Wixom, R.D.

      Affiliations

    • University of Rochester School of Nursing, Rochester, New York, USA
  • ,
  • Kimberly Craig, B.S.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • ,
  • Richard K Miller, Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
  • ,
  • David S Guzick, M.D., Ph.D.

      Affiliations

    • Department of Obstetrics and Gynecology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA

Received 30 September 2003 ,Revised 4 February 2004 ,Accepted 4 February 2004.

References 

  1. Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R. Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States (a prospective study). J Clin Endocrinol Metab. 1998;83:3078–3082
  2. Zawadzki JK, Dunaif A. Diagnositic criteria for polycystic ovary syndrome: towards a rational approach. In:  Dunaif A,  Givens JR,  Haseltine FP,  Merriam GR editor. Polycystic ovary syndrome. Oxford, United Kingdom: Blackwell Scientific; 1992;p. 377–384
  3. Hoeger K. Obesity and weight loss in polycystic ovary syndrome. Obstet Gynecol Clin North Am. 2001;28:85–97
  4. Dunaif A, Segal KR, Futterweit W, Dobrjansky A. Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. Diabetes. 1989;38:1165–1174
  5. Franks S, Gilling-Smith C, Watson H, Willis D. Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am. 1999;28:361–378
  6. Dunaif A, Graf M, Mandeli J, Laumas V, Dobrjansky A. Characterization of groups of hyperandrogenic women with acanthosis nigricans, impaired glucose tolerance, and/or hyperinsulinemia. J Clin Endocrinol Metab. 1987;65:499–507
  7. Chang RJ, Nakamura RM, Judd HL, Kaplan SA. Insulin resistance in nonobese patients with polycystic ovarine disease. J Clin Endocrinol Metab. 1983;57:356–359
  8. Dunaif A. Insulin resistance and the polycystic ovary syndrome (mechanism and implications for pathogenesis). Endocr Rev. 1997;18:774–800
  9. Barbieri RL. Hyperandrogenism, insulin resistance and acanthosis nigricans. 10 years of progress. J Reprod Med. 1994;39:327–336
  10. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med. 1996;335:617–623
  11. Nestler JE, Jakubowicz DJ, Evans WS, Pasquali R. Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome. N Engl J Med. 1998;338:1876–1880
  12. Morin-Papunen LC, Koivunen RM, Ruokonen A, Martikainen HK. Metformin therapy improves the menstrual pattern with minimal endocrine and metabolic effects in women with polycystic ovary syndrome. Fertil Steril. 1998;69:691–696
  13. Fleming R, Hopkinson ZE, Wallace AM, Greer IA, Sattar N. Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind, placebo controlled fashion. J Clin Endocrinol Metab. 2002;87:569–574
  14. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996;81:3299–3306
  15. Ehrmann DA, Schneider DJ, Sobel BE, Cavaghan MK, Imperial J, Rosenfield RL, et al.  Troglitazone improves defects in insulin action, insulin secretion, ovarian steroidogenesis, and fibrinolysis in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82:2108–2116
  16. Azziz R, Ehrmann D, Legro RS, Whitcomb RW, Hanley R, Fershetian AG, et al.  Troglitazone improves ovulation and hirsutism in the polycystic ovary syndrome (a multicenter, double blind, placebo-controlled trial). J Clin Endocrinol Metab. 2001;86:1626–1632
  17. Ehrmann DA, Cavaghan MK, Imperial J, Sturis J, Rosenfield RL, Polonsky KS. Effects of metformin on insulin secretion, insulin action, and ovarian steroidogenesis in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82:524–530
  18. Pasquali R, Casimirri F, Venturoli S, Antonio M, Morselli L, Reho S, et al.  Body fat distribution has weight-independent effects on clinical, hormonal, and metabolic features of women with polycystic ovary syndrome. Metabolism. 1994;43:706–713
  19. Guzick DS, Wing R, Smith D, Berga SL, Winters SJ. Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril. 1994;61:598–604
  20. Saris WH. Very-low-calorie diets and sustained weight loss. Obes Res. 2001;9(Suppl 4):295S–301S
  21. Huber-Buchholz MM, Carey DG, Norman RJ. Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome (role of insulin sensitivity and luteinizing hormone). J Clin Endocrinol Metab. 1999;84:1470–1474
  22. Pasquali R, Gambineri A, Biscotti D, Vicennati V, Gagliardi L, Colitta D, et al.  Effect of long-term treatment with metformin added to hypocaloric diet on body composition, fat distribution, and androgen and insulin levels in abdominally obese women with and without the polycystic ovary syndrome. J Clin Endocrinol Metab. 2000;85:2767–2774
  23. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346:393–403
  24. Taylor RW, Keil D, Gold EJ, Williams SM, Goulding A. Body mass index, waist girth, and waist-to-hip ratio as indexes of total and regional adiposity in women (evaluation using receiver operating characteristic curves). Am J Clin Nutr. 1998;67:44–49
  25. Ferriman D, Gallwey JD. Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 1961;21:1440–1447
  26. Santoro N, Crawford SL, Allsworth JE, Gold EB, Greendale GA, Korenman S, et al.  Assessing menstrual cycles with urinary hormone assays. Am J Physiol Endocrinol Metab. 2003;284:E521–530
  27. Legro RS. Polycystic ovary syndrome. Long term sequelae and management. Minerva Ginecol. 2002;54:97–114
  28. Nestler JE, Jakubowicz DJ. Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens. J Clin Endocrinol Metab. 1997;82:4075–4079
  29. 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;85:139–146
  30. Pasquali R, Casimirri F, Colella P, Melchionda N. Body fat distribution and weight loss in obese women. Am J Clin Nutr. 1989;49:185–187
  31. Hamilton-Fairley D, Kiddy D, Anyaoku V, Koistinen R, Seppala M, Franks S. Response of sex hormone binding globulin and insulin-like growth factor binding protein-1 to an oral glucose tolerance test in obese women with polycystic ovary syndrome before and after calorie restriction. Clin Endocrinol (Oxf). 1993;39:363–367
  32. Appel LJ, Champagne CM, Harsha DW, Cooper LS, Obarzanek E, Elmer PJ, et al.  Effects of comprehensive lifestyle modification on blood pressure control (main results of the PREMIER clinical trial). JAMA. 2003;289:2083–2093
  33. Pasanisi F, Contaldo F, de Simone G, Mancini M. Benefits of sustained moderate weight loss in obesity. Nutr Metab Cardiovasc Dis. 2001;11:401–406
  34. Thompson PD, Buchner D, Pina IL, Balady GJ, Williams MA, Marcus BH, et al.  Exercise and physical activity in the prevention and treatment of atherosclerotic cardiovascular disease (a statement from the Council on Clinical Cardiology (Subcommittee on Exercise, Rehabilitation, and Prevention) and the Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity)). Circulation. 2003;107:3109–3116
  35. Moran LJ, Noakes M, Clifton PM, Tomlinson L, Norman RJ. Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2003;88:812–819
  36. Foster GD, Wyatt HR, Hill JO, McGuckin BG, Brill C, Mohammed BS, et al.  A randomized trial of a low-carbohydrate diet for obesity. N Engl J Med. 2003;348:2082–2090

 Supported by a Mae Stone Goode foundation grant (KMH); Women's Reproductive Health Research Career Center grant K12 HD01332-03 to the University of Rochester; and General Clinical Research Center grant 5 M01 RR00044, National Center for Research Resources, National Institutes of Health.

PII: S0015-0282(04)00731-9

doi: 10.1016/j.fertnstert.2004.02.104

Fertility and Sterility
Volume 82, Issue 2 , Pages 421-429 , August 2004