Skip to main content
SpringerLink
Log in

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

  • Rapid Communication
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Franks S. Polycystic ovarian syndrome. N Engl J Med 1995, 333: 853–61.

    Article  PubMed  CAS  Google Scholar 

  2. Paradisi G, Steinberg HO, Hempfling A, et al. Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 2001, 103: 1410–5.

    Article  PubMed  CAS  Google Scholar 

  3. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997, 18: 774–800.

    PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  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. Friebe A, Koesling D. Regulation of nitric oxide-sensitive guanylyl cyclase. Circ Res 2003, 93: 96–105.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    PubMed  CAS  Google Scholar 

  10. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001, 414: 813–20.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  CAS  Google Scholar 

  16. Kilic-Okman T, Kucuk M. N-acetyl-cysteine treatment for polycystic ovary syndrome. Int J Gynaecol Obstet 2004, 85: 296–7.

    Article  PubMed  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Endocrinology, Department of Internal Medicine, University of Turin, Turin, Italy

    A. Masha, C. Manieri, S. Dinatale, G. A. Bruno, E. Ghigo & V. Martina MD

Authors
  1. A. Masha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Manieri
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Dinatale
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. A. Bruno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. E. Ghigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. Martina MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. Martina MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Masha, A., Manieri, C., Dinatale, S. et al. Prolonged treatment with N-acetylcysteine and L-arginine restores gonadal function in patients with polycistic ovary syndrome. J Endocrinol Invest 32, 870–872 (2009). https://doi.org/10.1007/BF03345763

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03345763

Keywords

Search

Navigation