Journal of Endocrinological Investigation

, Volume 32, Issue 11, pp 870–872 | Cite as

Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycistic ovary syndrome

  • A. Masha
  • C. Manieri
  • S. Dinatale
  • G. A. Bruno
  • E. Ghigo
  • V. Martina
Rapid Communication


Nitric oxide (NO) plays a wide spectrum of biological actions including a positive role in oocyte maturation and ovulation. Free radicals levels have been shown elevated in polycistic ovary syndrome (PCOS) and therefore would be responsible for quenching NO that, in turn, would play a role in determining oligo- or amenorrhea connoting PCOS. Eight patients with PCOS displaying oligo-amenorrhea from at least 1 yr underwent a combined treatment with N-acetylcysteine (NAC) (1200 mg/die) plus L-arginine (ARG) (1600 mg/die) for 6 months. Menstrual function, glucose and insulin levels, and, in turn, homeostasis model assessment (HOMA) index were monitored. Menstrual function was at some extent restored as indicated by the number of uterine bleedings under treatment (3.00, 0.18–5.83 vs 0.00, 0.00–0.83; p<0.02). Also, a well-defined biphasic pattern in the basal body temperature suggested ovulatory cycles. The HOMA index decreased under treatment (2.12, 1.46–4.42 vs 3.48, 1.62–5.95; p<0.05). In conclusion, this preliminary, open study suggests that prolonged treatment with NAC+ARG might restore gonadal function in PCOS. This effect seems associated to an improvement in insulin sensitivity.


L-arginine N-acetylcysteine PCOS 


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  1. 1.
    Franks S. Polycystic ovarian syndrome. N Engl J Med 1995, 333: 853–61.PubMedCrossRefGoogle Scholar
  2. 2.
    Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001, 103: 1410–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997, 18: 774–800.PubMedGoogle Scholar
  4. 4.
    Nácul AP, Andrade CD, Schwarz P, de Bittencourt PI Jr, Spritzer PM. Nitric oxide and fibrinogen in polycystic ovary syndrome: associations with insulin resistance and obesity. Eur J Obstet Gynecol Reprod Biol 2007, 133: 191–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Goud PT, Goud AP, Diamond MP, Gonik B, Abu-Soud HM. Nitric oxide extends the oocyte temporal window for optimal fertilization. Free Radic Biol Med 2008, 45: 453–9.PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Jablonka-Shariff A, Olson LM. The role of nitric oxide in oocyte meiotic maturation and ovulation: meiotic abnormalities of endothelial nitric oxide synthase knock-out mouse oocytes. Endocrinology 1998, 136: 2944–54.Google Scholar
  7. 7.
    Friebe A, Koesling D. Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 2003, 93: 96–105.PubMedCrossRefGoogle Scholar
  8. 8.
    Ignarro LJ, Edwards JC, Gruetter DY, Barry BK, Gruetter CA. Possible involvement of S-nitrosothiols in the activation of guanylate cyclase by nitroso compounds. FEBS Lett 1980: 110: 275–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Martina V, Bruno GA, Trucco F, et al. Platelet cNOS activity is reduced in patients with IDDM and NIDDM. Thromb Haemost 1998, 79: 520–2.PubMedGoogle Scholar
  10. 10.
    Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414: 813–20.PubMedCrossRefGoogle Scholar
  11. 11.
    González F, Rote NS, Minium J, Kirwan JP. Reactive oxygen species-induced oxidative stress in the development of insulin resistance and hyperandrogenism in polycystic ovary syndrome. J Clin Endocrinol Metab 2006, 91: 336–40.PubMedCrossRefGoogle Scholar
  12. 12.
    Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003, 80: 123–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Martina V, Masha A, Gigliardi VR, et al. Long-term N-acetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 2008, 31: 940–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Azziz R, Carmina E, Dewailly D, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006, 91: 4237–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Rizk AY, Bedaiwy MA, Al-Inany HG. N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil Steril 2005, 83: 367–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Kilic-Okman T, Kucuk M. N-acetyl-cysteine treatment for polycystic ovary syndrome. Int J Gynaecol Obstet 2004, 85: 296–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Fulghesu AM, Ciampelli M, Muzj G, Belosi C, et al. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril 2002, 77: 1128–35.PubMedCrossRefGoogle Scholar
  18. 18.
    Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation 2006, 113: 1888–904.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2009

Authors and Affiliations

  • A. Masha
    • 1
  • C. Manieri
    • 1
  • S. Dinatale
    • 1
  • G. A. Bruno
    • 1
  • E. Ghigo
    • 1
  • V. Martina
    • 1
  1. 1.Division of Endocrinology, Department of Internal MedicineUniversity of TurinTurinItaly

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