Endocrine

, Volume 44, Issue 3, pp 583–590

Lifestyle intervention and anti-obesity therapies in the polycystic ovary syndrome: impact on metabolism and fertility

  • Dimitrios Panidis
  • Konstantinos Tziomalos
  • Efstathios Papadakis
  • Christos Vosnakis
  • Panagiotis Chatzis
  • Ilias Katsikis
Review

Abstract

Obesity is frequently present in patients with polycystic ovary syndrome (PCOS) and plays an important role in the pathogenesis of the metabolic, endocrine, and reproductive abnormalities associated with this syndrome. We aimed to summarize the effects of lifestyle changes and anti-obesity pharmacotherapy in patients with PCOS. We reviewed the literature regarding the effects of lifestyle changes and anti-obesity agents on the metabolic and endocrine abnormalities of PCOS. Lifestyle changes, including diet, exercise, and behavioral modification, appear to improve the metabolic and reproductive abnormalities of overweight and obese patients with PCOS. Therefore, lifestyle changes appear to represent the first-line management for all overweight and obese patients with PCOS. However, the optimal composition of diet and the optimal type of exercise in these patients are unknown. Anti-obesity agents that have been studied in PCOS include orlistat, sibutramine, and rimonabant. However, the latter two agents have been withdrawn from the market because of side effects. Long-term studies with orlistat in overweight and obese diabetic patients showed greater weight loss and metabolic and cardiovascular benefits than those achieved with lifestyle changes alone. However, there are limited data on the efficacy of orlistat in women with PCOS. In conclusion, lifestyle changes (diet, exercise and behavioral modification), particularly when combined with anti-obesity agents, exert beneficial effects on the endocrine abnormalities of obese patients with PCOS and improve metabolic parameters.

Keywords

Diet Exercise Orlistat Sibutramine Polycystic ovary syndrome Insulin resistance 

References

  1. 1.
    J.E. Nestler, Metformin for the treatment of the polycystic ovary syndrome. N. Engl. J. Med. 358, 47–54 (2008)PubMedCrossRefGoogle Scholar
  2. 2.
    D. Panidis, K. Tziomalos, E. Papadakis, I. Katsikis, Infertility treatment in PCOS: lifestyle interventions, medications and surgery, in Polycystic Ovary Syndrome: Novel Insights into Causes and Therapy, ed. by D. Macut, M. Pfeifer, B. Yildiz, E. Diamanti-Kandarakis (Karger, Basel, 2012)Google Scholar
  3. 3.
    B.C. Fauser, B.C. Tarlatzis, R.W. Rebar, R.S. Legro, A.H. Balen, R. Lobo, E. Carmina, J. Chang, B.O. Yildiz, J.S. Laven, J. Boivin, F. Petraglia, C.N. Wijeyeratne, R.J. Norman, A. Dunaif, S. Franks, R.A. Wild, D. Dumesic, K. Barnhart, Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM-sponsored 3rd PCOS consensus workshop group. Fertil. Steril. 97, 28–38.e25 (2012)PubMedCrossRefGoogle Scholar
  4. 4.
    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. 81, 19–25 (2004)Google Scholar
  5. 5.
    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. 19, 41–47 (2004)Google Scholar
  6. 6.
    S. Franks, Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: in defense of the Rotterdam criteria. J. Clin. Endocrinol. Metab. 91, 786–789 (2006)PubMedCrossRefGoogle Scholar
  7. 7.
    R. Azziz, Controversy in clinical endocrinology: diagnosis of polycystic ovarian syndrome: the Rotterdam criteria are premature. J. Clin. Endocrinol. Metab. 91, 781–785 (2006)PubMedCrossRefGoogle Scholar
  8. 8.
    J.K. Zawadski, A. Dunaif, in Polycystic Ovary Syndrome, ed. by A. Dunaif, J.R. Givens, F.P. Haseltine, G.E. Merriam; in Current Issues in Endocrinology and Metabolism ed. by S.M. Hershman (Blackwell, Boston 1992) pp. 377–384Google Scholar
  9. 9.
    R. Azziz, E. Carmina, D. Dewailly, E. Diamanti-Kandarakis, H.F. Escobar-Morreale, W. Futterweit, O.E. Janssen, R.S. Legro, R.J. Norman, A.E. Taylor, S.F. Witchel, Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society: the Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil. Steril. 91, 456–488 (2009)PubMedCrossRefGoogle Scholar
  10. 10.
    F.J. Broekmans, E.A. Knauff, O. Valkenburg, J.S. Laven, M.J. Eijkemans, B.C. Fauser, PCOS according to the Rotterdam consensus criteria: change in prevalence among WHO-II anovulation and association with metabolic factors. BJOG 113, 1210–1217 (2006)PubMedCrossRefGoogle Scholar
  11. 11.
    C.K. Welt, J.A. Gudmundsson, G. Arason, J. Adams, H. Palsdottir, G. Gudlaugsdottir, G. Ingadottir, W.F. Crowley, Characterizing discrete subsets of polycystic ovary syndrome as defined by the Rotterdam criteria: the impact of weight on phenotype and metabolic features. J. Clin. Endocrinol. Metab. 91, 4842–4848 (2006)PubMedCrossRefGoogle Scholar
  12. 12.
    D. Panidis, K. Tziomalos, G. Misichronis, E. Papadakis, G. Betsas, I. Katsikis, D. Macut, Insulin resistance and endocrine characteristics of the different phenotypes of polycystic ovary syndrome: a prospective study. Hum. Reprod. 27, 541–549 (2012)PubMedCrossRefGoogle Scholar
  13. 13.
    R.S. Legro, D. Driscoll, J.F. Strauss 3rd, J. Fox, A. Dunaif, Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc. Natl. Acad. Sci. U.S.A. 95, 14956–14960 (1998)PubMedCrossRefGoogle Scholar
  14. 14.
    M.D. Kahsar-Miller, C. Nixon, L.R. Boots, R.C. Go, R. Azziz, Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil. Steril. 75, 53–58 (2001)PubMedCrossRefGoogle Scholar
  15. 15.
    S. Franks, M.I. McCarthy, K. Hardy, Development of polycystic ovary syndrome: involvement of genetic and environmental factors. Int. J. Androl. 29, 278–285; discussion 286–290 (2006)Google Scholar
  16. 16.
    R.J. Norman, D. Dewailly, R.S. Legro, T.E. Hickey, Polycystic ovary syndrome. Lancet 370, 685–697 (2007)PubMedCrossRefGoogle Scholar
  17. 17.
    S.F. Witchel, S.E. Recabarren, F. González, E. Diamanti-Kandarakis, K.I. Cheang, A.J. Duleba, R.S. Legro, R. Homburg, R. Pasquali, R.A. Lobo, C.C. Zouboulis, F. Kelestimur, F. Fruzzetti, W. Futterweit, R.J. Norman, D.H. Abbott, Emerging concepts about prenatal genesis, aberrant metabolism and treatment paradigms in polycystic ovary syndrome. Endocrine 42, 526–534 (2012)PubMedCrossRefGoogle Scholar
  18. 18.
    N.A. Georgopoulos, E. Kandaraki, D. Panidis, Hyperandrogenism in PCOS. in Diagnosis and Management of Polycystic Ovary Syndrome, ed. by N.R. Farid, E. Diamanti-Kandarakis (Springer, New York, 2009), pp. 105–110Google Scholar
  19. 19.
    F. González, C.L. Sia, F.Z. Stanczyk, H.E. Blair, M.E. Krupa, Hyperandrogenism exerts an anti-inflammatory effect in obese women with polycystic ovary syndrome. Endocrine 42, 726–735 (2012)PubMedCrossRefGoogle Scholar
  20. 20.
    T. Tsilchorozidou, C. Overton, G.S. Conway, The pathophysiology of polycystic ovary syndrome. Clin. Endocrinol. (Oxf.) 60, 1–17 (2004)CrossRefGoogle Scholar
  21. 21.
    E. Diamanti-Kandarakis, A.G. Papavassiliou, Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol. Med. 12, 324–332 (2006)PubMedCrossRefGoogle Scholar
  22. 22.
    R. Deniz, B. Gurates, S. Aydin, H. Celik, I. Sahin, Y. Baykus, Z. Catak, A. Aksoy, C. Citil, S. Gungor, Nesfatin-1 and other hormone alterations in polycystic ovary syndrome. Endocrine 42, 694–699 (2012)PubMedCrossRefGoogle Scholar
  23. 23.
    K. Farrell, M.H. Antoni, Insulin resistance, obesity, inflammation, and depression in polycystic ovary syndrome: biobehavioral mechanisms and interventions. Fertil. Steril. 94, 1565–1574 (2010)PubMedCrossRefGoogle Scholar
  24. 24.
    L.J. Moran, S.K. Hutchison, R.J. Norman, H.J. Teede, Lifestyle changes in women with polycystic ovary syndrome. Cochrane Database Syst. Rev. 7, CD007506 (2011)Google Scholar
  25. 25.
    M.E. Sastre, M.O. Prat, M.A. Checa, R.C. Carreras, Current trends in the treatment of polycystic ovary syndrome with desire for children. Ther. Clin. Risk Manag. 5, 353–360 (2009)PubMedGoogle Scholar
  26. 26.
    A. Badawy, A. Elnashar, Treatment options for polycystic ovary syndrome. Int. J. Womens Health 3, 25–35 (2011)PubMedCrossRefGoogle Scholar
  27. 27.
    L.J. Moran, M.L. Misso, R.A. Wild, R.J. Norman, Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum. Reprod. Update 16, 347–363 (2010)PubMedCrossRefGoogle Scholar
  28. 28.
    A.M. Clark, W. Ledger, C. Galletly, L. Tomlinson, F. Blaney, X. Wang, R.J. Norman, Weight loss results in significant improvement in pregnancy and ovulation rates in anovulatory obese women. Hum. Reprod. 10, 2705–2712 (1995)PubMedCrossRefGoogle Scholar
  29. 29.
    A.M. Clark, B. Thornley, L. Tomlinson, C. Galletley, R.J. Norman, Weight loss in obese infertile women results in improvement in reproductive outcome for all forms of fertility treatment. Hum. Reprod. 13, 1502–1505 (1998)PubMedCrossRefGoogle Scholar
  30. 30.
    M.M. Huber-Buchholz, D.G. Carey, R.J. Norman, Restoration of reproductive potential by lifestyle modification in obese polycystic ovary syndrome: role of insulin sensitivity and luteinizing hormone. J. Clin. Endocrinol. Metab. 84, 1470–1474 (1999)PubMedCrossRefGoogle Scholar
  31. 31.
    R.L. Thomson, J.D. Buckley, M. Noakes, P.M. Clifton, R.J. Norman, G.D. Brinkworth, The effect of a hypocaloric diet with and without exercise training on body composition, cardiometabolic risk profile, and reproductive function in overweight and obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 93, 3373–3380 (2008)PubMedCrossRefGoogle Scholar
  32. 32.
    R.L. Thomson, J.D. Buckley, G.D. Brinkworth, Exercise for the treatment and management of overweight women with polycystic ovary syndrome: a review of the literature. Obes. Rev. 12, e202–e210 (2011)PubMedCrossRefGoogle Scholar
  33. 33.
    R.L. Thomson, J.D. Buckley, S.S. Lim, M. Noakes, P.M. Clifton, R.J. Norman, G.D. Brinkworth, Lifestyle management improves quality of life and depression in overweight and obese women with polycystic ovary syndrome. Fertil. Steril. 94, 1812–1816 (2010)PubMedCrossRefGoogle Scholar
  34. 34.
    K. Marsh, J. Brand-Miller, The optimal diet for women with polycystic ovary syndrome? Br. J. Nutr. 94, 154–165 (2005)PubMedCrossRefGoogle Scholar
  35. 35.
    H. Farshchi, A. Rane, A. Love, R.L. Kennedy, Diet and nutrition in polycystic ovary syndrome (PCOS): pointers for nutritional management. J. Obstet. Gynaecol. 27, 762–773 (2007)PubMedCrossRefGoogle Scholar
  36. 36.
    G.U. Liepa, A. Sengupta, D. Karsies, Polycystic ovary syndrome (PCOS) and other androgen excess-related conditions: can changes in dietary intake make a difference? Nutr. Clin. Pract. 23, 63–71 (2008)PubMedCrossRefGoogle Scholar
  37. 37.
    L.J. Moran, M. Noakes, P.M. Clifton, L. Tomlinson, C. Galletly, R.J. Norman, Dietary composition in restoring reproductive and metabolic physiology in overweight women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 88, 812–819 (2003)PubMedCrossRefGoogle Scholar
  38. 38.
    K. Stamets, D.S. Taylor, A. Kunselman, L.M. Demers, C.L. Pelkman, R.S. Legro, A randomized trial of the effects of two types of short-term hypocaloric diets on weight loss in women with polycystic ovary syndrome. Fertil. Steril. 81, 630–637 (2004)PubMedCrossRefGoogle Scholar
  39. 39.
    K.A. Marsh, K.S. Steinbeck, F.S. Atkinson, P. Petocz, J.C. Brand-Miller, Effect of a low glycemic index compared with a conventional healthy diet on polycystic ovary syndrome. Am. J. Clin. Nutr. 92, 83–92 (2010)PubMedCrossRefGoogle Scholar
  40. 40.
    H.H. Mehrabani, S. Salehpour, Z. Amiri, S.J. Farahani, B.J. Meyer, F. Tahbaz, Beneficial effects of a high-protein, low-glycemic-load hypocaloric diet in overweight and obese women with polycystic ovary syndrome: a randomized controlled intervention study. J. Am. Coll. Nutr. 31, 117–125 (2012)PubMedCrossRefGoogle Scholar
  41. 41.
    S.E. Kasim-Karakas, R.U. Almario, L. Gregory, R. Wong, H. Todd, B.L. Lasley, Metabolic and endocrine effects of a polyunsaturated fatty acid-rich diet in polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 89, 615–620 (2004)PubMedCrossRefGoogle Scholar
  42. 42.
    C.C. Douglas, B.A. Gower, B.E. Darnell, F. Ovalle, R.A. Oster, R. Azziz, Role of diet in the treatment of polycystic ovary syndrome. Fertil. Steril. 85, 679–688 (2006)PubMedCrossRefGoogle Scholar
  43. 43.
    L.J. Moran, R. Pasquali, H.J. Teede, K.M. Hoeger, R.J. Norman, Treatment of obesity in polycystic ovary syndrome: a position statement of the Androgen Excess and Polycystic Ovary Syndrome Society. Fertil. Steril. 92, 1966–1982 (2009)PubMedCrossRefGoogle Scholar
  44. 44.
    A. Tolino, V. Gambardella, C. Caccavale, A. D’Ettore, F. Giannotti, V. D’Antò, C.L. De Falco, Evaluation of ovarian functionality after a dietary treatment in obese women with polycystic ovary syndrome. Eur. J. Obstet. Gynecol. Reprod. Biol. 119, 87–93 (2005)PubMedCrossRefGoogle Scholar
  45. 45.
    J. Holte, T. Bergh, C. Berne, L. Wide, H. Lithell, Restored insulin sensitivity but persistently increased early insulin secretion after weight loss in obese women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 80, 2586–2593 (1995)PubMedCrossRefGoogle Scholar
  46. 46.
    T.L. Bützow, M. Lehtovirta, R. Siegberg, O. Hovatta, R. Koistinen, M. Seppäla, D. Apter, The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women. J. Clin. Endocrinol. Metab. 85, 3271–3275 (2000)PubMedCrossRefGoogle Scholar
  47. 47.
    P. Andersen, I. Seljeflot, M. Abdelnoor, H. Arnesen, P.O. Dale, A. Løvik, K. Birkeland, Increased insulin sensitivity and fibrinolytic capacity after dietary intervention in obese women with polycystic ovary syndrome. Metabolism 44, 611–616 (1995)PubMedCrossRefGoogle Scholar
  48. 48.
    H.S. Randeva, K.C. Lewandowski, J. Drzewoski, K. Brooke-Wavell, C. O’Callaghan, L. Czupryniak, E.W. Hillhouse, G.M. Prelevic, Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 87, 4496–4501 (2002)PubMedCrossRefGoogle Scholar
  49. 49.
    B. Bruner, K. Chad, D. Chizen, Effects of exercise and nutritional counseling in women with polycystic ovary syndrome. Appl. Physiol. Nutr. Metab. 31, 384–391 (2006)PubMedCrossRefGoogle Scholar
  50. 50.
    C. Vigorito, F. Giallauria, S. Palomba, T. Cascella, F. Manguso, R. Lucci, A. De Lorenzo, D. Tafuri, G. Lombardi, A. Colao, F. Orio, Beneficial effects of a three-month structured exercise training program on cardiopulmonary functional capacity in young women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 92, 1379–1384 (2007)PubMedCrossRefGoogle Scholar
  51. 51.
    S. Palomba, F. Giallauria, A. Falbo, T. Russo, R. Oppedisano, A. Tolino, A. Colao, C. Vigorito, F. Zullo, F. Orio, Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum. Reprod. 23, 642–650 (2008)PubMedCrossRefGoogle Scholar
  52. 52.
    J.A. Hawley, Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance. Diabetes Metab. Res. Rev. 20, 383–393 (2004)PubMedCrossRefGoogle Scholar
  53. 53.
    C.L. Harrison, C.B. Lombard, L.J. Moran, H.J. Teede, Exercise therapy in polycystic ovary syndrome: a systematic review. Hum. Reprod. Update. 17, 171–183 (2011)PubMedCrossRefGoogle Scholar
  54. 54.
    F. Giallauria, S. Palomba, L. Maresca, L. Vuolo, D. Tafuri, G. Lombardi, A. Colao, C. Vigorito, O. Francesco, Exercise training improves autonomic function and inflammatory pattern in women with polycystic ovary syndrome (PCOS). Clin. Endocrinol. (Oxf.) 69, 792–798 (2008)CrossRefGoogle Scholar
  55. 55.
    D.S. Guzick, R. Wing, D. Smith, S.L. Berga, S.J. Winters, Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil. Steril. 61, 598–604 (1994)PubMedGoogle Scholar
  56. 56.
    G.A. Bray, Medical therapy for obesity: current status and future hopes. Med. Clin. North Am. 91, 1225–1253, xi (2007)Google Scholar
  57. 57.
    D. Panidis, D. Farmakiotis, D. Rousso, A. Kourtis, I. Katsikis, G. Krassas, Obesity, weight loss, and the polycystic ovary syndrome: effect of treatment with diet and orlistat for 24 weeks on insulin resistance and androgen levels. Fertil. Steril. 89, 899–906 (2008)PubMedCrossRefGoogle Scholar
  58. 58.
    M.A. Rubio, M. Gargallo, Isabel Millán, A., Moreno, B.: drugs in the treatment of obesity: sibutramine, orlistat and rimonabant. Public Health Nutr. 10, 1200–1205 (2007)PubMedCrossRefGoogle Scholar
  59. 59.
    E. Diamanti-Kandarakis, I. Katsikis, C. Piperi, K. Alexandraki, D. Panidis, Effect of long-term orlistat treatment on serum levels of advanced glycation end-products in women with polycystic ovary syndrome. Clin. Endocrinol. (Oxf.) 66, 103–109 (2007)Google Scholar
  60. 60.
    V. Jayagopal, E.S. Kilpatrick, S. Holding, P.E. Jennings, S.L. Atkin, Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J. Clin. Endocrinol. Metab. 90, 729–733 (2005)PubMedCrossRefGoogle Scholar
  61. 61.
    A.E. Nieuwenhuis-Ruifrok, W.K. Kuchenbecker, A. Hoek, P. Middleton, R.J. Norman, Insulin sensitizing drugs for weight loss in women of reproductive age who are overweight or obese: systematic review and meta-analysis. Hum. Reprod. Update 15, 57–68 (2009)PubMedCrossRefGoogle Scholar
  62. 62.
    B. Trolle, A. Flyvbjerg, U. Kesmodel, 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. Hum. Reprod. 22, 2967–2973 (2007)PubMedCrossRefGoogle Scholar
  63. 63.
    R. Pasquali, A. Gambineri, D. Biscotti, V. Vicennati, L. Gagliardi, D. Colitta, S. Fiorini, G.E. Cognigni, M. Filicori, A.M. Morselli-Labate, 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. 85, 2767–2774 (2000)PubMedCrossRefGoogle Scholar
  64. 64.
    P. Moghetti, R. Castello, C. Negri, F. Tosi, F. Perrone, M. Caputo, E. Zanolin, M. Muggeo, 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. 85, 139–146 (2000)PubMedCrossRefGoogle Scholar
  65. 65.
    J. Lord, R. Thomas, B. Fox, U. Acharya, T. Wilkin, The effect of metformin on fat distribution and the metabolic syndrome in women with polycystic ovary syndrome–a randomised, double-blind, placebo-controlled trial. BJOG 113, 817–824 (2006)PubMedCrossRefGoogle Scholar
  66. 66.
    G. Ladson, W.C. Dodson, S.D. Sweet, A.E. Archibong, A.R. Kunselman, L.M. Demers, N.I. Williams, P. Coney, R.S. Legro, The effects of metformin with lifestyle therapy in polycystic ovary syndrome: a randomized double-blind study. Fertil. Steril. 95, 1059–1066.e1-7 (2011)Google Scholar
  67. 67.
    N. Agarwal, S.P. Rice, H. Bolusani, S.D. Luzio, G. Dunseath, M. Ludgate, D.A. Rees, Metformin reduces arterial stiffness and improves endothelial function in young women with polycystic ovary syndrome: a randomized, placebo-controlled, crossover trial. J. Clin. Endocrinol. Metab. 95, 722–730 (2010)PubMedCrossRefGoogle Scholar
  68. 68.
    J.P. Baillargeon, D.J. Jakubowicz, M.J. Iuorno, S. Jakubowicz, J.E. Nestler, Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. Fertil. Steril. 82, 893–902 (2004)PubMedCrossRefGoogle Scholar
  69. 69.
    T. Tang, J.M. Lord, R.J. Norman, E. Yasmin, A.H. Balen, Insulin-sensitising drugs (metformin, rosiglitazone, pioglitazone, d-chiro-inositol) for women with polycystic ovary syndrome, oligo amenorrhoea and subfertility. Cochrane Database Syst. Rev. 5, CD003053 (2012)Google Scholar
  70. 70.
    S. Palomba, F. Orio Jr, A. Falbo, F. Manguso, T. Russo, T. Cascella, A. Tolino, E. Carmina, A. Colao, F. Zullo, Prospective parallel randomized, double-blind, double-dummy controlled clinical trial comparing clomiphene citrate and metformin as the first-line treatment for ovulation induction in nonobese anovulatory women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab. 90, 4068–4074 (2005)PubMedCrossRefGoogle Scholar
  71. 71.
    M.T. Sheehan, Polycystic ovarian syndrome: diagnosis and management. Clin. Med. Res. 2, 13–27 (2004)PubMedCrossRefGoogle Scholar
  72. 72.
    A.M. Herriot, S. Whitcroft, Y. Jeanes, A retrospective audit of patients with polycystic ovary syndrome: the effects of a reduced glycaemic load diet. J. Hum. Nutr. Diet. 21, 337–345 (2008)PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Dimitrios Panidis
    • 1
  • Konstantinos Tziomalos
    • 2
  • Efstathios Papadakis
    • 1
  • Christos Vosnakis
    • 1
  • Panagiotis Chatzis
    • 1
  • Ilias Katsikis
    • 1
  1. 1.Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and GynecologyAristotle University of Thessaloniki, Hippokration HospitalThessalonikiGreece
  2. 2.First Propedeutic Department of Internal MedicineAHEPA Hospital, Aristotle University of ThessalonikiThessalonikiGreece

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