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Journal of Obesity
Volume 2011 (2011), Article ID 402052, 6 pages
http://dx.doi.org/10.1155/2011/402052
Review Article

Pharmacological Treatment of Obesity in Patients with Polycystic Ovary Syndrome

1Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU3 2RW, UK
2Michael White Diabetes Centre, 220-236 Analby Road, Hull Royal Infirmary, Hull HU3 2JZ, UK

Received 20 April 2010; Revised 13 July 2010; Accepted 4 November 2010

Academic Editor: S. B. Heymsfield

Copyright © 2011 Hassan Kahal et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. Azziz, K. S. Woods, R. Reyna, T. J. Key, E. S. Knochenhauer, and B. O. Yildiz, “The prevalence and features of the polycystic ovary syndrome in an unselected population,” Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 6, pp. 2745–2749, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  2. E. S. Knochenhauer, T. J. Key, M. Kahsar-Miller, W. Waggoner, L. R. Boots, and R. Azziz, “Prevalence of the polycystic ovary syndrome in unselected black and white women of the Southeastern United States: a prospective study,” Journal of Clinical Endocrinology and Metabolism, vol. 83, no. 9, pp. 3078–3082, 1998. View at Publisher · View at Google Scholar · View at Scopus
  3. E. Diamanti-Kandarakis, C. R. Kouli, A. T. Bergiele et al., “A survey of the polycystic ovary syndrome in the Greek Island of Lesbos: hormonal and metabolic profile,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 11, pp. 4006–4011, 1999. View at Scopus
  4. M. Asunción, R. M. Calvo, J. L. San Millá N, J. Sancho, S. Avila, and H. F. Escobar-Morreale, “A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 7, pp. 2434–2438, 2000. View at Publisher · View at Google Scholar · View at Scopus
  5. A. H. Balen, G. S. Conway, G. Kaltsas et al., “Polycystic ovary syndrome: the spectrum of the disorder in 1741 patients,” Human Reproduction, vol. 10, no. 8, pp. 2107–2111, 1995. View at Scopus
  6. C. J. Glueck, S. Dharashivkar, P. Wang et al., “Obesity and extreme obesity, manifest by ages 20-24 years, continuing through 32-41 years in women, should alert physicians to the diagnostic likelihood of polycystic ovary syndrome as a reversible underlying endocrinopathy,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 122, no. 2, pp. 206–212, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  7. B. C. J. M. Fauser, . Tarlatzis, . Fauser et al., “Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome,” Human Reproduction, vol. 19, no. 1, pp. 41–47, 2004. View at Publisher · View at Google Scholar · View at Scopus
  8. J. K. Zawadzki and A. Dunaif, “Diagnostic criteria for polycystic ovary syndrome: towards a rational approach,” in Polycystic Ovary Syndrome, A. Dunaif, J. R. Givens, F. P. Haseltine, and G. R. Merriam, Eds., pp. 59–69, Blackwell, Oxford, UK, 1992.
  9. S. Franks, “Diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria,” Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 3, pp. 786–789, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  10. A. Dunaif, K. R. Segal, W. Futterweit, and A. Dobrjansky, “Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome,” Diabetes, vol. 38, no. 9, pp. 1165–1174, 1989. View at Scopus
  11. P. E. Scherer, S. Williams, M. Fogliano, G. Baldini, and H. F. Lodish, “A novel serum protein similar to C1q, produced exclusively in adipocytes,” Journal of Biological Chemistry, vol. 270, no. 45, pp. 26746–26749, 1995. View at Publisher · View at Google Scholar · View at Scopus
  12. K. A. Toulis, D. G. Goulis, D. Farmakiotis et al., “Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis,” Human Reproduction Update, vol. 15, no. 3, pp. 297–307, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  13. A. O'Connor, N. Phelan, T. Kyaw Tun, G. Boran, J. Gibney, and H. M. Roche, “High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 3, pp. 1378–1385, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  14. C. Weyer, T. Funahashi, S. Tanaka et al., “Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 5, pp. 1930–1935, 2001. View at Publisher · View at Google Scholar · View at Scopus
  15. C. S. Mantzoros, “The role of leptin in human obesity and disease: a review of current evidence,” Annals of Internal Medicine, vol. 130, no. 8, pp. 671–680, 1999. View at Scopus
  16. E. Carmina, F. Orio, S. Palomba et al., “Evidence for altered adipocyte function in polycystic ovary syndrome,” European Journal of Endocrinology, vol. 152, no. 3, pp. 389–394, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  17. D. Glintborg, M. Andersen, C. Hagen et al., “Evaluation of metabolic risk markers in polycystic ovary syndrome (PCOS). Adiponectin, ghrelin, leptin and body composition in hirsute PCOS patients and controls,” European Journal of Endocrinology, vol. 155, no. 2, pp. 337–345, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  18. A. Atamar, B. Demir, G. Bayhan, Y. Atamer, N. Ilhan, and Z. Akkuş, “Serum levels of leptin and homocysteine in women with polycystic ovary syndrome and its relationship to endocrine, clinical and metabolic parameters,” Journal of International Medical Research, vol. 36, no. 1, pp. 96–105, 2008. View at Scopus
  19. M. G. Li, G. L. Ding, XI. J. Chen et al., “Association of serum and follicular fluid leptin concentrations with granulosa cell phosphorylated signal transducer and activator of transcription 3 expression in fertile patients with polycystic ovarian syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 92, no. 12, pp. 4771–4776, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  20. C. M. Steppan, S. T. Bailey, S. Bhat et al., “The hormone resistin links obesity to diabetes,” Nature, vol. 409, no. 6818, pp. 292–293, 2001.
  21. H. Mu, R. Ohashi, S. Yan et al., “Adipokine resistin promotes in vitro angiogenesis of human endothelial cells,” Cardiovascular Research, vol. 70, no. 1, pp. 146–157, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  22. S. Virtue and A. Vidal-Puig, “It's not how fat you are, it's what you do with it that counts,” PLoS Biology, vol. 6, no. 9, article e237, 2008. View at Publisher · View at Google Scholar · View at PubMed
  23. F. de Zegher, A. Lopez-Bermejo, and L. Ibáñez, “Adipose tissue expandability and the early origins of PCOS,” Trends in Endocrinology and Metabolism, vol. 20, no. 9, pp. 418–423, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  24. D. Meirow, O. Yossepowitch, A. Rosler et al., “Insulin resistant and non-resistant polycystic ovary syndrome represent two clinical and endocrinological subgroups,” Human Reproduction, vol. 10, no. 8, pp. 1951–1956, 1995. View at Scopus
  25. D. A. Ehrmann, M. K. Cavaghan, R. B. Barnes, J. Imperial, and R. L. Rosenfield, “Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome,” Diabetes Care, vol. 22, no. 1, pp. 141–146, 1999. View at Publisher · View at Google Scholar · View at Scopus
  26. E. Talbott, D. Guzick, A. Clerici et al., “Coronary heart disease risk factors in women with polycystic ovary syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 15, no. 7, pp. 821–826, 1995. View at Scopus
  27. E. Diamanti-Kandarakis, K. Alexandraki, A. Protogerou et al., “Metformin administration improves endothelial function in women with polycystic ovary syndrome,” European Journal of Endocrinology, vol. 152, no. 5, pp. 749–756, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  28. S. Rajendran, S. R. Willoughby, W. P. A. Chan et al., “Polycystic ovary syndrome is associated with severe platelet and endothelial dysfunction in both obese and lean subjects,” Atherosclerosis, vol. 204, no. 2, pp. 509–514, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  29. E. Dahlgren, P. O. Janson, S. Johansson, L. Lapidus, and A. Oden, “Polycystic ovary syndrome and risk for myocardial infarction: evaluated from a risk factor model based on a prospective population study of women,” Acta Obstetricia et Gynecologica Scandinavica, vol. 71, no. 8, pp. 599–604, 1992. View at Scopus
  30. S. Wild, T. Pierpoint, P. McKeigue, and H. Jacobs, “Cardiovascular disease in women with polycystic ovary syndrome at long- term follow-up: a retrospective cohort study,” Clinical Endocrinology, vol. 52, no. 5, pp. 595–600, 2000. View at Publisher · View at Google Scholar · View at Scopus
  31. L. J. Shaw, C. N. B. Merz, R. Azziz 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,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 4, pp. 1276–1284, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  32. T. Apridonidze, P. A. Essah, M. J. Iuorno, and J. E. Nestler, “Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 4, pp. 1929–1935, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  33. T. Douchi, H. Ijuin, S. Nakamura, T. Oki, S. Yamamoto, and Y. Nagata, “Body fat distribution in women with polycystic ovary syndrome,” Obstetrics and Gynecology, vol. 86, no. 4, part 1, pp. 516–519, 1995. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Acien, F. Quereda, P. Matallin, et al., “Insulin, androgens, and obesity in women with and without polycystic ovary syndrome: a heterogeneous group of disorders,” Fertility and Sterility, vol. 72, no. 1, pp. 32–40, 1999. View at Publisher · View at Google Scholar
  35. F. Álvarez-Blasco, J. I. Botella-Carretero, J. L. San Millán, and H. F. Escobar-Morreale, “Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women,” Archives of Internal Medicine, vol. 166, no. 19, pp. 2081–2086, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  36. B. O. Yildiz, E. S. Knochenhauer, and R. Azziz, “Impact of obesity on the risk for polycystic ovary syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 1, pp. 162–168, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  37. L. J. Moran, M. Noakes, P. M. Clifton, L. Tomlinson, C. Galletly, and R. J. Norman, “Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 2, pp. 812–819, 2004.
  38. M. M. Huber-Buchholz, D. G. P. Carey, and R. J. Norman, “Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone,” Journal of Clinical Endocrinology and Metabolism, vol. 84, no. 4, pp. 1470–1474, 1999. View at Scopus
  39. L. J. Moran, M. Noakes, P. M. Clifton, G. A. Wittert, G. Williams, and R. J. Norman, “Short-term meal replacements followed by dietary macronutrient restriction enhance weight loss in polycystic ovary syndrome,” American Journal of Clinical Nutrition, vol. 84, no. 1, pp. 77–87, 2006. View at Scopus
  40. J. Holte, T. Bergh, C. Berne, L. Wide, and H. Lithell, “Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 80, no. 9, pp. 2586–2593, 1995.
  41. T. Sabuncu, M. Harma, M. Harma, Y. Nazligul, and F. Kilic, “Sibutramine has a positive effect on clinical and metabolic parameters in obese patients with polycystic ovary syndrome,” Fertility and Sterility, vol. 80, no. 5, pp. 1199–1204, 2003. View at Publisher · View at Google Scholar · View at Scopus
  42. T. Sathyapalan, LI. W. Cho, E. S. Kilpatrick, A. M. Coady, and S. L. Atkin, “A comparison between rimonabant and metformin in reducing biochemical hyperandrogenaemia and insulin resistance in patients with polycystic ovary syndrome (PCOS): a randomized open-label parallel study,” Clinical Endocrinology, vol. 69, no. 6, pp. 931–935, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  43. R. Guerciolini, “Mode of action of orlistat,” International Journal of Obesity, vol. 21, supplement 3, pp. S12–S23, 1997.
  44. R. Padwal, S. K. Li, and D. C. W. Lau, “Long-term pharmacotherapy for overweight and obesity: a systematic review and meta-analysis of randomized controlled trials,” International Journal of Obesity, vol. 27, no. 12, pp. 1437–1446, 2003. View at Publisher · View at Google Scholar · View at PubMed
  45. J. S. Torgerson, J. Hauptman, M. N. Boldrin, and L. Sjöström, “XENical in the prevention of diabetes in obese subjects (XENDOS) study: a randomized study of orlistat as an adjunct to lifestyle changes for the prevention of type 2 diabetes in obese patients,” Diabetes Care, vol. 27, no. 1, pp. 155–161, 2004. View at Publisher · View at Google Scholar · View at Scopus
  46. V. Jayagopal, E. S. Kilpatrick, S. Holding, P. E. Jennings, and S. L. Atkin, “Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 2, pp. 729–733, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  47. L. W. Cho, E. S. Kilpatrick, B. G. Keevil, A. M. Coady, and S. L. Atkin, “Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome,” Clinical Endocrinology, vol. 70, no. 2, pp. 233–237, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  48. E. Diamanti-Kandarakis, I. Katsikis, C. Piperi, K. Alexandraki, and D. Panidis, “Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome,” Clinical Endocrinology, vol. 66, no. 1, pp. 103–109, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  49. E. Diamanti-Kandarakis, C. D. Christakou, E. Kandaraki, and F. N. Economou, “Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome,” European Journal of Endocrinology, vol. 162, no. 2, pp. 193–212, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  50. S. M. Setter, J. L. Iltz, J. Thams, and R. K. Campbell, “Metformin hydrochloride in the treatment of type 2 diabetes mellitus: a clinical review with a focus on dual therapy,” Clinical Therapeutics, vol. 25, no. 12, pp. 2991–3026, 2003. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Fleming, Z. E. Hopkinson, A. Michael Wallace, I. A. Greer, and N. Sattar, “Ovarian function and metabolic factors in women with oligomenorrhea treated with metformin in a randomized double blind placebo-controlled trial,” Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 2, pp. 569–574, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. P. Moghetti, R. Castello, C. Negri 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,” Journal of Clinical Endocrinology and Metabolism, vol. 85, no. 1, pp. 139–146, 2000. View at Publisher · View at Google Scholar · View at Scopus
  53. B. Trolle, A. Flyvbjerg, U. Kesmodel, and F. F. Lauszus, “Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial,” Human Reproduction, vol. 22, no. 11, pp. 2967–2973, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  54. J. M. Lord, I. H. K. Flight, and R. J. Norman, “Metformin in polycystic ovary syndrome: systematic review and meta-analysis,” British Medical Journal, vol. 327, no. 7421, pp. 951–955, 2003. View at Scopus
  55. G. A. R. Maciel, J. M. Soares, E. L. Alves Da Motta, M. A. Haidar, G. Rodrigues De Lima, and E. C. Baracat, “Nonobese women with polycystic ovary syndrome respond better than obese women to treatment with metformin,” Fertility and Sterility, vol. 81, no. 2, pp. 355–360, 2004. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  56. L. R. Harborne, N. Sattar, J. E. Norman, and R. Fleming, “Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 8, pp. 4593–4598, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  57. T. Sathyapalan, L. W. Cho, E. S. Kilpatrick, A. M. Coady, and S. L. Atkin, “Metformin maintains the weight loss and metabolic benefits following rimonabant treatment in obese women with polycystic ovary syndrome (PCOS),” Clinical Endocrinology, vol. 70, no. 1, pp. 124–128, 2009. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  58. H. C. S. Howlett and C. J. Bailey, “A risk-benefit assessment of metformin in type 2 diabetes mellitus,” Drug Safety, vol. 20, no. 6, pp. 489–503, 1999. View at Publisher · View at Google Scholar · View at Scopus
  59. P. L. Brubaker and Y. Anini, “Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2,” Canadian Journal of Physiology and Pharmacology, vol. 81, no. 11, pp. 1005–1012, 2003. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  60. D. J. Drucker, “The biology of incretin hormones,” Cell Metabolism, vol. 3, no. 3, pp. 153–165, 2006. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  61. A. Mari, K. Degn, B. Brock, J. Rungby, E. L. E. Ferrannini, and O. Schmitz, “Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on β-cell function in normal living conditions,” Diabetes Care, vol. 30, no. 8, pp. 2032–2033, 2007. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  62. B. Willms, J. Werner, J. J. Holst, C. Ørskov, W. Creutzfeldt, and M. A. Nauck, “Gastric emptying, glucose responses, and insulin secretion after a liquid test meal: effects of exogenous glucagon-like peptide-1 (GLP-1)-(7-36) amide in type 2 (noninsulin-dependent) diabetic patients,” Journal of Clinical Endocrinology and Metabolism, vol. 81, no. 1, pp. 327–332, 1996. View at Scopus
  63. A. Flint, A. Raben, A. K. Ersbøll, J. J. Holst, and A. Astrup, “The effect of physiological levels of glucagon-like peptide-1 on appetite, gastric emptying, energy and substrate metabolism in obesity,” International Journal of Obesity, vol. 25, no. 6, pp. 781–792, 2001.
  64. K. P. Kinzig, D. A. D'Alessio, and R. J. Seeley, “The diverse roles of specific GLP-1 receptors in the control of food intake and the response to visceral illness,” Journal of Neuroscience, vol. 22, no. 23, pp. 10470–10476, 2002. View at Scopus
  65. K. Elkind-Hirsch, O. Marrioneaux, M. Bhushan, D. Vernor, and R. Bhushan, “Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome,” Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 7, pp. 2670–2678, 2008. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  66. A. Astrup, S. Rössner, L. Van Gaal et al., “Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study,” The Lancet, vol. 374, no. 9701, pp. 1606–1616, 2009. View at Publisher · View at Google Scholar · View at Scopus
  67. J. B. Buse, J. Rosenstock, G. Sesti et al., “Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (LEAD-6),” The Lancet, vol. 374, no. 9683, pp. 39–47, 2009. View at Publisher · View at Google Scholar · View at Scopus
  68. M. Parks and C. Rosebraugh, “Weighing risks and benefits of liraglutide—the FDA's review of a new antidiabetic therapy,” New England Journal of Medicine, vol. 362, no. 9, pp. 774–777, 2010. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  69. G. M. Eid, D. R. Cottam, L. M. Velcu et al., “Effective treatment of polycystic ovarian syndrome with Roux-en-Y gastric bypass,” Surgery for Obesity and Related Diseases, vol. 1, no. 2, pp. 77–80, 2005. View at Publisher · View at Google Scholar · View at PubMed · View at Scopus
  70. H. F. Escobar-Morreale, J. I. Botella-Carretero, F. Álvarez-Blasco, J. Sancho, and J. L. San Millán, “The polycystic ovary syndrome associated with morbid obesity may resolve after weight loss induced by bariatric surgery,” Journal of Clinical Endocrinology and Metabolism, vol. 90, no. 12, pp. 6364–6369, 2005. View at Publisher · View at Google Scholar · View at PubMed