Comparison of metformin and N-acetylcysteine on metabolic parameters in women with polycystic ovarian syndrome

Hina Ali, Gita Radhakrishnan, Alpana Singh


Background: Polycystic ovary syndrome (PCOS) is a common disease that affects up to 10% of women of reproductive age, in which hyperandrogenism (HA), enlarged cystic ovaries, and chronic anovulation often co-exist with obesity, dyslipidemia and insulin resistance (IR). There is a need for an alternative to metformin with minimal side effects to improve insulin sensitivity and correct dyslipidemia in PCOS patients.

Methods: It was a prospective, Randomized controlled clinical trial. 116 PCOS patients, 58 each in two groups received either Metformin 500 mg TDS or N-acetylcysteine (NAC) 600 mg TDS for 3 months. Clinical and biochemical parameters contributing to metabolic syndrome (MS) and insulin resistance (fasting blood sugar (FBS), fasting insulin (FI), FBS:FI, HOMA-IR and QUICKI) were assessed at the start and end of the study. Results were compared between the two groups.

Results: Both treatment modalities resulted in a significant reduction in number of cases with IR (p=0.001) and MS. Fasting hyperinsulinemia improved in 15 % (p=0.12) and 30% (p=0.001) of patients while 12% (p=0.23) and 18% (p=0.049) improvement was seen in FBS:FI in MET and NAC group respectively. Similarly, improvement in HOMA-IR was 12% (p=0.30) and 32% (p=0.001) in MET and NAC group which is significant with NAC. QUICKI and impaired glucose tolerance showed significant improvement in both the groups with a p-value of 0.04 and 0.006, 0.035 and 0.046 respectively. Significant reduction was seen in triglycerides (p=0.048) in NAC group.

Conclusions: NAC is equally efficacious as metformin in improving parameters of insulin resistance and metabolic syndrome with minimal occasional side effects ensuring better compliance for a long-term therapy.


Metformin, Metabolic syndrome, N-acetylcysteine

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Ciampelli M, Lanzone A. Insulin and polycystic ovary syndrome: a new look at an old subject. Gynecol Endocrinol. 1998;12(4):277-92.

Diamanti-Kandarakis E. Polycystic ovarian syndrome: pathophysiology, molecular aspects and clinical implications. Expert Rev Mol Med. 2008;10(2).

Schuring AN, Schulte N, Sonntag B, Kiesel L. Androgens and insulin-two key players in polycystic ovary syndrome. Recent concepts in the pathophysiology and genetics of polycystic ovary syndrome. Gynakol Geburtshilfliche Rundsch 2008;48(1): 9-15.

Frank S. Polycystic ovary syndrome: a changing perspective. Clin Endocrinol. 1989;31:87-120.

Lanzone A, Fulghesu AM, Andreani CL, Apa R, Fortini A, Caruso A, et al. Insulin secretion in polycystic ovarian disease: effect of ovarian suppression by GnRH agonist. Hum Reprod. 1990;5(2):143-9.

Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002;77(6):1128-35.

Randeva HS, Lewandowski KC, Drzewoski J, Brooke-Wavell K, O'Callaghan C, Czupryniak L, et al. Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2002;87(10):4496-501.

Ketel IJ, Stehouwer CD, Serné EH, Korsen TJ, Hompes PG, Smulders YM, et al. Obese but not normal weight women with polycystic ovary syndrome are characterized by metabolic and microvascular insulin resistance. J Clin Endocrinol Metab. 2008;93(9):3365-72.

Weidmann P, de Courten M, Bohlen L. Insulin resistance, hyperinsulinemia and hypertension. J Hypertens. 1993;Suppl 11(5):S27-38.

Orio F, Vuolo L, Palomba S, Lombardi G, Colao A. Metabolic and cardiovascular consequences of polycystic ovary syndrome. Minerva Ginecol 2008;60(1):39-51.

Yilmaz M, Biri A, Bukan N, Karakoç A, Sancak B, Törüner F, et al. Levels of lipoprotein and homocysteine in non-obese and obese patients with polycystic ovary syndrome. Gynecol Endocrinol. 2005;20(5):258-63.

Robinson S, Henderson AD, Gelding SV. Dyslipidaemia is associated with insulin resistance in women with polycystic ovary syndrome. Clin Endocrinol. 1996;44:277-84.

Dunaif A, Segal KR, Futterweit W. Profound peripheral insulin resistance, independent Dobr Jansky A of obesity, in polycystic ovary syndrome. Diabetes. 1989;38:1165-74.

Poretsky L. Commentary: Polycystic ovary syndrome-increased or preserved insulin sensitivity to insulin? J Clin Endo Metabol. 2006;91:2859-60.

Ek I, Arner P, Bergqvist A, Carlström K, Wahrenberg H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab. 1997;82:1147-53.

Dhindsa G, Bhatia R, Dhindsa M, Bhatia V. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome. J Postgrad Med. 2004;50(2):140-4.

Moll E, Bossuyt PM, Korevaar JC, Lambalk CB, van der Veen F. Effect of clomifene citrate plus metformin and clomifene citrate plus placebo on induction of ovulation in women with newly diagnosed polycystic ovary syndrome: randomised double blind clinical trial. BMJ. 2006;332(7556):1485.

Gilling-Smith C, Willis DS, Beard RW, Franks S. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J Clin Endocrinol Metab. 1994;79(4):1158-65.

Hillier SG, Tetsuka M. Role of androgens in follicle maturation and atresia. Baillieres Clin Obstet Gynaecol. 1997;11(2)249-60.

Hardiman P, Pillay OC, Atiomo W. Polycystic ovary syndrome and endometrial carcinoma. Lancet. 2003;361(9371):1810-2.

The Practice Committee of the American Society for Reproductive Medicine. Use of insulin sensitizing agents in the treatment of polycystic ovary syndrome. Fertil Steril. 2004;82:S181-3.

De Leo V, la Marca A, Petraglia F. Insulin-lowering agents in the management of polycystic ovary syndrome. Endocr Rev. 2003;24(5):633-67.

Nestler JE. Obesity, insulin, sex steroids and ovulation. Int J Obes Relat Metab Disord. 2000;24(2):S71-S73.

Velazquez EM, Mendoza S, Hamer T, Sosa F, Glueck CK. Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy. Metabolism. 1994;43:647-54.

Velázquez E, Acosta A, Mendoza SG. Menstrual cyclicity after metformin therapy in polycystic ovary syndrome. Obstet Gynecol. 1997;90:392-95.

Kilicdag EB, Bagis T, Zeyneloglu HB, Tarim E, Aslan E, Haydardedeoglu B, et al. Homocysteine levels in women with polycystic ovary syndrome treated with metformin versus rosiglitazone: a randomized study. Hum Reprod. 2005;20(4):895-9.

Soltan-Sharifi MS, Mojtahedzadeh M, Najafi A. Improvement by N-acetylcysteine of acute respiratory distress syndrome through increasing intracellular glutathione and extracellular thiol molecules and anti-oxidant power: evidence for underlying toxicological mechanisms. Hum Exp Toxocol. 2007;26(9):697-703.

Ammon HP, Muller PH, Eggstrein M, Wintermantel C, Aigner B, Safayhi H. Increase in glucose consumption by acetylcysteine during hyper-glycemic clamp: A study with healthy volunteers. Arzneimittelforschung. 1992;42(5):642-5.

Ventura P, Panini R, Pasini MC, Scarpetta G, Salvioli G. N-Acetyl-cysteine reduces homocysteine plasma levels after single intravenous administration by increasing thiols urinary excretion. Pharmacol Res. 1999;40:345-50.

Fox R. Prevalence of a positive family history of type 2 diabetes in women with polycystic ovarian disease. Gynecol Endocrinol. 1999; 13(6): 390-3.

Davies MJ, Marino JL, Willson KJ, March WA, Moore VM. Intergenerational associations of chronic disease and polycystic ovary syndrome. PLoS One. 2011;6(10):e25947.

Glueck CJ, Papanna R, Wang P. Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovary syndrome. Metabolism. 2003;52:908-15.

Dokras A, Bochner M, Hollinrake E, Markham S, Vanvoorhis B, Jagasia DH. Screening women with polycystic ovary syndrome for metabolic syndrome. Obstet Gynecol. 2005;106:131-7.

Ehrmann DA, Liljenquist DR, Kasza K, Azziz R, Legro RS, Ghazzi MN. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2006;91(1):48-53.

Majumdar A and Singh TA. Comparison of clinical features and health manifestations in lean vs. obese Indian women with polycystic ovarian syndrome. J Hum Reprod Sci. 2009;2(1):12-7.

Peppard HR, Marfori J, Iuorno MJ, Nestler JE. Prevalence of polycystic ovary syndrome among premenopausal women with type 2 diabetes. Diabetes Care 2001; 24(6): 1050-2.

Kauffman RP, Baker VM, Dimarino P. Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: A comparison of two distinct populations. Am J Obstet Gynecol. 2002;187:1362-9.

Nawrocka-Rutkowska J, Ciećwież S, Marciniak A, Brodowska A, Wiśniewska B, Kotlęga D et al. Insulin resistance assessment in patients with polycystic ovary syndrome using different diagnostic criteria- Impact of metformin treatment. Ann Agric Environ Med. 2013;20(3):528-32.

Gayatri K, Kumar JS, Kumar BB. Metformin and N-acetyl cysteine in polycystic ovarian syndrome- a comparative study. Indian J Clin Med. 2010;1:7-13.

Salehpour S, Tohidi M, Mohammad RA, Amirzargar N. N-acetyl cysteine, a novel remedy for polycystic ovarian syndrome. Int J Fertil Steril. 2009;3(2):66-73.

Elnashar A, Fahmy M, Mansour A, Ibrahim K. N-acetylcysteine vs metformin in treatment of clomifene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study. Fertil Steril. 2007;88(2):406-9.

Oner G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):127-31.