A Review on the Assessment of the Efficacy of Common Treatments in Polycystic Ovarian Syndrome on Prevention of Diabetes Mellitus
AbstractObjective: Polycystic ovarian syndrome (PCOS) is a common condition amongst women of reproductive age that can result in increased mortality and morbidity in women due to increased risk of diabetes mellitus and cardiovascular diseases. The aim of this systematic review was to assess the effectiveness of common treatments of PCOS on the predictors of diabetes in non-diabetic PCOS women.Materials and methods: An extensive search was performed on the publications in three medical databases including pubmed, scopus and google scholar from 1995 till 2017. The articles were screened based on their quality and included in this systematic review. A total of 25 articles including cohort, randomised controlled trial, review and meta-analysis were included in the review.Results: This systematic review revealed that the effect of lifestyle modification might be low in PCOS subjects due to high drop-out rate while the benefits of this intervention including weight and fat reduction may not be achieved by medical interventions. Metformin treatment may result in improvements in insulin sensitivity while its weight reduction effect is still not documented in PCOS subjects. Thiazolidendiones might be tolerated by the PCOS subjects and may result in similar effects as metformin but this effect should be documented by further studies.Conclusion: Combination of lifestyle modification with metformin or thiazolidinedions might improve the outcome of the prevention strategies. On the other hand this study revealed a different response to treatments in non-obese compared with obese PCOS subjects.
Macklon NS. Polycystic ovary syndrome. BMJ 2011; 343:d6407.
Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Human Reproduction Update 2010;16:347-63.
Teede H, Deeks A, Moran L. Polycystic ovary syndrome: a complex condition with psychological, reproductive and metabolic manifestations that impacts on health across the lifespan. BMC medicine 2010;8:41.
Salley KES, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Position statement: glucose intolerance in polycystic ovary syndrome—a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007 ;92:4546-56.
Teede HJ, Hutchison S, Zoungas S, Meyer C. Insulin resistance, the metabolic syndrome, diabetes, and cardiovascular disease risk in women with PCOS. Endocrine. 2006;30:45-53.
Sharma ST, Nestler JE. Prevention of diabetes and cardiovascular disease in women with PCOS: treatment with insulin sensitizers. Best Pract Res Clin Endocrinol Metab 2006;20:245-60.
Gambineri A, Patton L, Altieri P, Pagotto U, Pizzi C, Manzoli L, et al. Polycystic ovary syndrome is a risk factor for type 2 diabetes: results from a long-term prospective study. Diabetes 2012;61 :2369-74.
Hudecova M, Holte J, Olovsson M, Larsson A, Berne C, Poromaa IS. Diabetes and impaired glucose tolerance in patients with polycystic ovary syndrome--a long term follow-up. Hum Reprod 2011;26:1462-8.
da Costa BR, Cevallos M, Altman DG, Rutjes AWS, Egger M. Uses and misuses of the STROBE statement: bibliographic study. BMJ Open 2011;1:e000048.
Hoeger K, Davidson K, Kochman L, Cherry T, Kopin L, Guzick DS. The impact of metformin, oral contraceptives, and lifestyle modification on polycystic ovary syndrome in obese adolescent women in two randomized, placebo-controlled clinical trials. J Clin Endocrinol Metab 2008;93:4299-306.
Palomba S, Giallauria F, Falbo A, Russo T, Oppedisano R, Tolino A, et al. Structured exercise training programme versus hypocaloric hyperproteic diet in obese polycystic ovary syndrome patients with anovulatory infertility: a 24-week pilot study. Hum Reprod 2008;23:642-50.
Stamets K, Taylor DS, Kunselman A, Demers LM, Pelkman CL, Legro RS. 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 2004;81:630-7.
Douglas CC, Gower BA, Darnell BE, Ovalle F, Oster RA, Azziz R. Role of diet in the treatment of polycystic
ovary syndrome. Fertil Steril 2006;85:679-88.
Kasim-Karakas SE, Almario RU, Cunningham W. Effects of protein versus simple sugar intake on weight loss in polycystic ovary syndrome (according to the National Institutes of Health criteria). Fertil Steril 2009; 92:262-70.
Lord JM, Flight IHK, Norman RJ. Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ 2003;327:951-3.
Diamanti-Kandarakis E, Christakou CD, Kandaraki E, Economou FN. Metformin: an old medication of new fashion: evolving new molecular mechanisms and clinical implications in polycystic ovary syndrome. Eur J Endocrinol 2010;162:193-212.
Kumar N, Dey CS. Metformin enhances insulin signalling in insulin-dependent and-independent pathways in insulin resistant muscle cells. Br J Pharmacol. 2002;137:329-36
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;361:1894-901.
Lord J, Thomas R, Fox B, Acharya U, Wilkin T. 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 2006;113:817-24.
Harborne LR, Sattar N, Norman JE, Fleming R. Metformin and weight loss in obese women with polycystic ovary syndrome: comparison of doses. J Clin Endocrinol Metab 2005;90:4593-8.
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;85:139-46.
Kahn CR, Chen L, Cohen SE. Unraveling the mechanism of action of thiazolidinediones. J Clin Invest 2000;106:1305-7.
Chojkier M. Troglitazone and liver injury: in search of answers. Hepatology 2005;41:237-46.
Gale EA. Troglitazone: the lesson that nobody learned? Diabetologia 2006;49:1-6.
Grillier-Vuissoz I, Mazerbourg S, Boisbrun M, Kuntz S, Chapleur Y, Flament S. PPARγ-independent activity of thiazolidinediones: a promising mechanism of action for new anticancer drugs? Journal of Carcinogenesis & Mutagenesis 2012: S8: 002.
Lewis JD, Ferrara A, Peng T, Hedderson M, Bilker WB, Quesenberry CP, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011;34:916-22.
Cho LW, Kilpatrick ES, Keevil BG, Coady AM, Atkin SL. Effect of metformin, orlistat and pioglitazone treatment on mean insulin resistance and its biological variability in polycystic ovary syndrome. Clin Endocrinol (Oxf) 2009;70:233-7.
Baillargeon J-P, Jakubowicz DJ, Iuorno MJ, Jakubowicz S, Nestler JE. 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.
Brettenthaler N, De Geyter C, Huber PR, Keller U. Effect of the insulin sensitizer pioglitazone on insulin resistance, hyperandrogenism, and ovulatory dysfunction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004;89:3835-40.
Meyer C, McGrath BP, Teede HJ. Effects of medical therapy on insulin resistance and the cardiovascular system in polycystic ovary syndrome. Diabetes Care 2007;30:471-8.
Hoeger KM. Role of lifestyle modification in the management of polycystic ovary syndrome. Best Pract Res Clin Endocrinol Metab 2006;20:293-310.
Kocak M, Caliskan E, Simsir C, Haberal A. Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome. Fertil Steril 2002;77:101-6.
Legro RS, Barnhart HX, Schlaff WD, Carr BR, Diamond MP, Carson SA, et al. Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome. N Engl J Med 2007;356:551-66.
Jayagopal V, Kilpatrick ES, Holding S, Jennings PE, Atkin SL. Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome. J Clin Endocrinol Metab 2005;90:729-33.
Glueck CJ, Goldenberg N, Sieve L, Wang P. An observational study of reduction of insulin resistance and prevention of development of type 2 diabetes mellitus in women with polycystic ovary syndrome treated with metformin and diet. Metabolism 2008;57:954-60.
Glueck CJ, Papanna R, Wang P, Goldenberg N, Sieve-Smith L. Incidence andtreatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism 2003;52:908-15.
Hoeger KM, Kochman L, Wixom N, Craig K, Miller RK, Guzick DS. 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. Fertil Steril 2004;82:421-9.
Graff SK, Mario FM, Ziegelmann P, Spritzer PM. Effects of orlistat vs. metformin on weight loss-related clinical variables in women with PCOS: systematic review and meta-analysis. Int J Clin Pract 2016;70:450-61.
Trolle B, Flyvbjerg A, Kesmodel U, Lauszus FF. Efficacy of metformin in obese and non-obese women with polycystic ovary syndrome: a randomized, double-blinded, placebo-controlled cross-over trial. Hum Reprod 2007;22:2967-73.
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 trial. J Clin Endocrinol Metab2002;87:569-74.
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;85:2767-74.
Yarali H, Yildiz BO, Demirol A, Zeyneloğlu HB, Yiğit N, Bükülmez O, et al. Co-administration of metformin during rFSH treatment in patients with clomiphene citrate-resistant polycystic ovarian syndrome: a prospective randomized trial. Hum Reprod 2002;17:289-94.
Morin-Papunen L, Rautio K, Ruokonen A, Hedberg P, Puukka M, Tapanainen JS. Metformin reduces serum C-reactive protein levels in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003;88:4649-54.
Dereli D, Dereli T, Bayraktar F, Ozgen AG, Yilmaz C. Endocrine and metabolic effects of rosiglitazone in non-obese women with polycystic ovary disease. Endocr J 2005; 52: 299-308.
Panidis D, Farmakiotis D, Rousso D, Kourtis A, Katsikis I, Krassas G. 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 Steril2008;89:899-906.
Salas-Salvadó J, Martinez-Gonzalez M, Bullo M, Ros E. The role of diet in the prevention of type 2 diabetes. Nutr Metab Cardiovasc Dis 2011; 21 Suppl 2:B32-48.
Dashti S, Esfehani AJ, Joseph HJL. The preventive effect of physical activity on weight maintenance in overweight and obese women. Clin Ter 2014;165:155-61.
Dashti S, Su TT, Esfehani AJ, Esfehani RJ. Effect of Physical Activity Level on Emotional Status of Iranian Women. World Applied Sciences Journal 2014;30:852-7.
Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450c17α activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. N Engl J Med 1996;335:617-23.