Research Article| Volume 159, ISSUE 1, P127-131, November 2011

Download started.


Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome



      To evaluate the clinical, endocrine and metabolic effects of metformin and N-acetyl-cysteine (NAC) in patients with polycystic ovary syndrome (PCOS).

      Study design

      In this prospective trial, 100 women with PCOS were randomly divided to receive metformin (500 mg p.o. three times daily) or NAC (600 mg p.o. three times daily) for 24 weeks. Hyperandrogenism, lipid profiles, hirsutism scores, menstrual irregularity, insulin sensitivity and tumour necrosis factor-α (TNF-α) levels were measured at baseline and after the treatment period.


      Both treatments resulted in a significant decrease in body mass index, hirsutism score, fasting insulin, HOMA index, free testosterone and menstrual irregularity compared with baseline values, and both treatments had equal efficacy. NAC led to a significant decrease in both total cholesterol and low-density lipoprotein levels, whereas metformin only led to a decrease in total cholesterol level. Although TNF-α levels increased following treatment for both groups, the difference from baseline was not significant.


      Metformin and NAC appear to have comparable effects on hyperandrogenism, hyperinsulinaemia and menstrual irregularity in women with PCOS. The effects of metformin and NAC on insulin sensitivity are not associated with TNF-α.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


        • Knochenhauer E.S.
        • Key T.J.
        • Kahsar-Miller M.
        • Waggoner W.
        • Boots L.R.
        • 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
        • Ciampelli M.
        • Lanzone A.
        Insulin and polycystic ovary syndrome: a new look at an old subject.
        Gynecol Endocrinol. 1998; 12: 277-292
        • Legro R.S.
        • Kunselman A.R.
        • Dodson W.C.
        • Dunaif A.
        Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women.
        J Clin Endocrinol Metab. 1999; 84: 165-169
        • Olszanecka-Glinianowicz M.
        • Banaś M.
        • Zahorska-Markiewicz B.
        • et al.
        Is the polycystic ovary syndrome associated with chronic inflammation per se?.
        Eur J Obstet Gynecol Reprod Biol. 2007; 133: 197-202
        • Iuorno M.J.
        • Nestler J.E.
        The polycystic ovary syndrome: treatment with insulin sensitizing agents.
        Diabetes Obes Metab. 1999; 1: 127-136
        • González F.
        • Minium J.
        • Rote N.S.
        • Kirwan J.P.
        Hyperglycemia alters tumor necrosis factor-alpha release from mononuclear cells in women with polycystic ovary syndrome.
        J Clin Endocrinol Metab. 2005; 90: 5336-5342
        • Stein I.F.
        • Leventhal M.L.
        Amenorrhea associated with bilateral polycystic ovaries.
        Am J Obstet Gynecol. 1935; 29: 181-191
        • Nestler J.E.
        • Jakubowicz D.J.
        • Evans W.S.
        • Pasquali R.
        Effects of metformin on spontaneous and clomiphene-induced ovulation in the polycystic ovary syndrome.
        N Engl J Med. 1998; 338: 1876-1880
        • Velazquez E.M.
        • Mendoza S.
        • Hamer T.
        • Sosa F.
        • Glueck C.J.
        Metformin therapy in polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating normal menses and pregnancy.
        Metabolism. 1994; 43: 647-654
        • Velázquez E.
        • Acosta A.
        • Mendoza S.G.
        Menstrual cyclicity after metformin therapy in polycystic ovary syndrome.
        Obstet Gynecol. 1997; 90: 392-395
        • Kolodziejczyk B.
        • Duleba A.J.
        • Spaczynski R.Z.
        • Pawelczyk L.
        Metformin therapy decreases hyperandrogenism and hyperinsulinemia in women with polycystic ovary syndrome.
        Fertil Steril. 2000; 73: 1149-1154
        • Lord J.M.
        • Flight I.H.
        • Norman R.J.
        Metformin in polycystic ovary syndrome: systematic review and meta-analysis.
        BMJ. 2003; 327: 951-953
        • Costello M.F.
        • Shrestha B.
        • Eden J.
        • Johnson N.P.
        • Sjoblom P.
        Metformin versus oral contraceptive pill in polycystic ovary syndrome: a Cochrane review.
        Hum Reprod. 2007; 22: 1200-1209
        • Fulghesu A.M.
        • Ciampelli M.
        • Muzj G.
        • Belosi C.
        • Selvaggi L.
        • Ayala G.F.
        • Lanzone A.
        N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome.
        Fertil Steril. 2002; 77: 1128-1135
        • Kilic-Okman T.
        • Kucuk M.
        N-acetyl-cysteine treatment for polycystic ovary syndrome.
        Int J Gynaecol Obstet. 2004; 85: 296-297
        • Rizk A.Y.
        • Bedaiwy M.A.
        • Al-Inany H.G.
        N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome.
        Fertil Steril. 2005; 83: 367-370
        • Pieper G.M.
        • Siebeneich W.
        Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction.
        J Cardiovasc Pharmacol. 1998; 32: 101-105
        • Elnashar A.
        • Fahmy M.
        • Mansour A.
        • Ibrahim K.
        N-acetyl cysteine vs. metformin in treatment of clomiphene citrate-resistant polycystic ovary syndrome: a prospective randomized controlled study.
        Fertil Steril. 2007; 88: 406-409
      1. 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 2004;81:19-25.

        • Balen A.H.
        • Laven J.S.
        • Tan S.L.
        • Dewailly D.
        Ultrasound assessment of the polycystic ovary: international consensus definitions.
        Hum Reprod Update. 2003; 9: 505-514
        • Harborne L.
        • Fleming R.
        • Lyall H.
        • Sattar N.
        • Norman J.
        Metformin or antiandrogen in the treatment of hirsutism in polycystic ovary syndrome.
        J Clin Endocrinol Metab. 2003; 88: 4116-4123
        • Hatch R.
        • Rosenfield R.L.
        • Kim M.H.
        • Tredway D.
        Hirsutism: implications, etiology, and management.
        Am J Obstet Gynecol. 1981; 140: 815-830
      2. ACOG Committee on Practice Bulletins – Gynecology. ACOG Practice Bulletin No. 108: Polycystic ovary syndrome. Obstet Gynecol 2009;114:936-49.

        • Kazerooni T.
        • Dehghan-Kooshkghazi M.
        Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome.
        Gynecol Endocrinol. 2003; 17: 51-56
        • Cheang K.I.
        • Huszar J.M.
        • Best A.M.
        • Sharma S.
        • Essah P.A.
        • Nestler J.E.
        Long-term effect of metformin on metabolic parameters in the polycystic ovary syndrome.
        Diab Vasc Dis Res. 2009; 6: 110-119
        • Moghetti P.
        • Castello R.
        • Negri C.
        • 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
        • Tang T.
        • Glanville J.
        • Hayden C.J.
        • White D.
        • Barth J.H.
        • Balen A.H.
        Combined lifestyle modification and metformin in obese patients with polycystic ovary syndrome. A randomized, placebo-controlled, double-blind multicentre study.
        Hum Reprod. 2006; 21: 80-89
        • Hoeger K.
        • Davidson K.
        • Kochman L.
        • Cherry T.
        • Kopin L.
        • Guzick D.S.
        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: 4299-4306
        • Nestler J.E.
        • Stovall D.
        • Akhter N.
        • Iuorno M.J.
        • Jakubowicz D.J.
        Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome.
        Fertil Steril. 2002; 77: 209-215
        • Costello M.F.
        • Eden J.A.
        A systematic review of the reproductive system effects of metformin in patients with polycystic ovary syndrome.
        Fertil Steril. 2003; 79: 1-13
        • Kashyap S.
        • Wells G.A.
        • Rosenwaks Z.
        Insulin-sensitizing agents as primary therapy for patients with polycystic ovarian syndrome.
        Hum Reprod. 2004; 19: 2474-2483
        • Hotamisligil G.S.
        • Murray D.L.
        • Choy L.N.
        • Spiegelman B.M.
        Tumor necrosis factor alpha inhibits signaling from the insulin receptor.
        Proc Natl Acad Sci USA. 1994; 91: 4854-4858
        • Gonzalez F.
        • Thusu K.
        • Abdel-Rahman E.
        • Prabhala A.
        • Tomani M.
        • Dandona P.
        Elevated serum levels of tumor necrosis factor alpha in normal-weight women with polycystic ovary syndrome.
        Metabolism. 1999; 48: 437-441
        • Ren T.
        • He J.
        • Jiang H.
        • et al.
        Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-alpha or isoproterenol.
        J Mol Endocrinol. 2006; 37: 175-183
        • Lim S.S.
        • Clifton P.M.
        • Noakes M.
        • Norman R.J.
        Obesity management in women with polycystic ovary syndrome.
        Womens Health (Lond Engl). 2007; 3: 73-86