Skip to main content
SpringerLink
Log in

Effect of ethinyl estradiol–cyproterone acetate treatment on asymmetric dimethyl-arginine levels in women with polycystic ovary syndrome

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Our study was undertaken to evaluate the levels of asymmetric dimethyl-arginine (ADMA) in a group of patients affected with polycystic ovary syndrome (PCOS)—under ethinyl estradiol–cyproterone acetate treatment or not—as compared with a group of healthy controls.

Methods

Fifty-eight women with PCOS and 45 patients as control group were included in the study. The 58 women with PCOS were separated into two groups: Group A (n = 29) were treated with an oral contraceptive pill containing 0.035 mg of ethinyl estradiol (EE) and 2 mg of cyproterone acetate (CA) (Diane-35) for 6 months. Group B (n = 29) did not take any drug. Group C (n = 45) was healthy women as control group. Serum levels of ADMA, lipid and glucose metabolism parameters, hormone profile were measured on the sixth month of treatment.

Results

ADMA levels were similar in women with PCOS and controls, whereas ADMA levels significantly decreased after a period of 6 months treatment with EE + CA in women with PCOS. ADMA levels and insulin resistance were decreased with treatment. However, patients with PCOS had significantly higher total cholesterol and Low-density lipoprotein cholesterol (LDL-C) compared to controls, treatment with EE + CA did not provide any improvement on lipid parameters.

Conclusion

Serum ADMA levels and insulin resistance were lower in PCOS group treated with EE + CA than control group.

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

Fig. 1

Similar content being viewed by others

References

  1. Hwang JL, Seow KM, Lin YH, Huang LW, Hsieh BC, Tsai YL, Wu GJ, Huang SC, Chen CY, Chen PH, Tzeng CR (2004) Ovarian stimulation by concomitant administration of cetrorelix acetate and HMG following Diane-35 pre-treatment for patients with polycystic ovary syndrome: a prospective randomized study. Hum Reprod 19:1993–2000

    Article  CAS  PubMed  Google Scholar 

  2. Azziz R, Marin C, Hoq L, Badamgarav E, Song P (2005) Healthcare-related economic burden of the polycystic ovary syndrome (PCOS) during the reproductive lifespan. J Clin Endocrinol Metab 90:4650–4658

    Article  CAS  PubMed  Google Scholar 

  3. Cibula D, Cifkova R, Fanta M, Polende R, Zivny J, Skibova J (2000) Increased risk of noninsulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of polycystic ovary syndrome. Hum Reprod 15:785–789

    Article  CAS  PubMed  Google Scholar 

  4. Lambrinoudaki I (2011) Cardiovascular risk in postmenopausal women with the polycystic ovary syndrome. Maturitas 68:13–16. doi:10.1016/j.maturitas.2010.09.005

    Article  PubMed  Google Scholar 

  5. Vallance P, Leone A, Calver A, Collier J, Moncada S (1992) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575

    Article  CAS  PubMed  Google Scholar 

  6. Siroka R, Cibulka R, Rajkl D, Racek J (2006) Asymmetric dimethylarginine—a novel cardiovascular risk factor. Vnitr Lek 52:249–255

    CAS  PubMed  Google Scholar 

  7. Zoccali C (2006) Asymmetric dimethylarginine (ADMA): a cardiovascular and renal risk factor on the move. J Hypertens 24:611–619

    Article  CAS  PubMed  Google Scholar 

  8. Zsuga Judit, Gesztelyi Rudolf, Török Janos, Keki Sandor, Bereczki Daniel (2005) Asymmetric dimethylarginine: a molecule responsible for the coexistence of insulin resistance and atherosclerosis via dual nitric oxide synthase inhibition. Med Hypotheses 65:1091–1098

    Article  CAS  PubMed  Google Scholar 

  9. Prelevic GM, Wurzburger MI, Balint-Peric L, Puzigaca Z (1989) Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome. Gynecol Endocrinol 3:269–280

    Article  CAS  PubMed  Google Scholar 

  10. Demirel F, Bideci A, Cinaz P, Camurdan MO, Biberoglu G, Yesilkaya E, Hasanoglu A (2007) Serum leptin, oxidized low density lipoprotein and plasma asymmetric dimethylarginine levels and their relationship with dyslipidaemia in adolescent girls with polycystic ovary syndrome. Clin Endocrinol 67:129–134

    Article  CAS  Google Scholar 

  11. Charitidou C, Farmakiotis D, Zournatzi V, Pidonia I, Pegiou T, Karamanis N, Hatzistilianou M, Katsikis I, Panidis D (2008) The administration of estrogens, combined with anti-androgens, has beneficial effects on the hormonal features and asymmetric dimethyl-arginine levels, in women with the polycystic ovary syndrome. Atherosclerosis 196:958–965

    Article  CAS  PubMed  Google Scholar 

  12. Macut D, Micic D, Cvijovic G, Sumarac M, Kendereski A, Zoric S, Pejkovic D (2001) Cardiovascular risk in adolescent and young adult obese females with PCOS. J Pediatr Endocrinol Metab 14:1353–1359

    PubMed  Google Scholar 

  13. Tarkun I, Arslan BC, Cantürk Z, Türemen E, Sahin T, Duman C (2004) Endothelial dysfunction in young women with polycystic ovary syndrome: relationship between insulin resistance and low-grade chronic inflammation. J Cin Endocrinol Metab 89:5592–5596

    Article  CAS  Google Scholar 

  14. Kelly CJ, Speirs A, Gould GW, Petrie JR, Lyall H, Connell JM (2002) Altered vascular function in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 87:742–746

    Article  CAS  PubMed  Google Scholar 

  15. Diamanti-Kandarakis E, Spina G, Kouli C, Migdalis I (2001) Increased endothelin-I levels in women with polycystic ovary syndrome and the beneficial effect of metformin therapy. J Clin Endocrinol Metab 86:4666–4673

    Article  CAS  PubMed  Google Scholar 

  16. Böger RH, Bode-Böger SF, Tsao PS, Lin PS, Chan JR, Cooke JP (2000) An endogenous inhibitor of nitric oxide synthase regulates endothelial adhesiveness for monocytes. J Am Coll Cardiol 36:2287–2295

    Article  PubMed  Google Scholar 

  17. Rubanyi GM (1993) The role of the endothelium in cardiovascular homeostasis and disease. J Cardiovasc Pharmacol 22:1–14

    Article  Google Scholar 

  18. Holden DP, Cartwright JE, Nussey SS, Whitley GS (2003) Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine. Circulation 108:1575–1580

    Article  CAS  PubMed  Google Scholar 

  19. Stuhlinger MC, Abbasi F, Chu JW, Lamendola C, McLaughlin TL, Cooke JP, Reaven GM, Tsao PS (2002) Relationship between insulin resistance and an endogenous nitric oxide synthase inhibitor. JAMA 287:1420–1426

    Article  PubMed  Google Scholar 

  20. Miyazaki H, Matsuoka H, Cooke JP, Usui M, Ueda S, Okuda S, Imaizumi T (1999) Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis. Circulation 99:1141–1146

    Article  CAS  PubMed  Google Scholar 

  21. Sydow K, Mondon CE, Cooke JP (2005) Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. Vasc Med 10:135–143

    Article  Google Scholar 

  22. Vrbíková J, Stanická S, Dvoráková K, Hill M, Vondra K, Bendlová B, Stárka L (2004) Metabolic and endocrine effects of treatment with peroral or transdermal oestrogens in conjunction with peroral cyproterone acetate in women with polycystic ovary syndrome. Eur J Endocrinol 150:215–223

    Article  PubMed  Google Scholar 

  23. Mastorakos G, Koliopoulos C, Deligeoroglou E, Diamanti-Kandarakis E, Creatsas G (2006) Effects of two forms of combined oral contraceptives on carbohydrate metabolism in adolescents with polycystic ovary syndrome. Fertil Steril 85:420–427

    Article  CAS  PubMed  Google Scholar 

  24. Gambineri A, Pelusi C, Vicennati V, Pagotto U, Pasquali R (2002) Obesity and the polycystic ovary syndrome. İnt J Obes Relat Metab Disord 26:883–896

    Article  CAS  PubMed  Google Scholar 

  25. Mittermayer F, Mayer BX, Meyer A, Winzer C, Pacini G, Wagner OF, Wolzt M, Kautzky-Willer A (2002) Circulating concentrations of asymmetrical dimethyl-L-arginine are increased in women with previous gestational diabetes. Diabetologia 45:1372–1378

    Article  CAS  PubMed  Google Scholar 

  26. Fard A, Tuck CH, Donis JA, Sciacca R, Di Tullio MR, Wu HD, Bryant TA, Chen NT, Torres-Tamayo M, Ramasamy R, Berglund L, Ginsberg HN, Homma S, Cannon PJ (2000) Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 20:2039–2044

    Article  CAS  PubMed  Google Scholar 

  27. Paiva H, Laakso J, Lehtimaki T, Isomustajarvi M, Ruokonen I, Laaksonen R (2003) Effect of high-dose statin treatment on plasma concentrations of endogenous nitric oxide synthase inhibitors. J Cardiovasc Pharmacol 41:219–222

    Article  PubMed  Google Scholar 

  28. Eid HM, Eritsland J, Larsen J, Amesen H, Seljeflot I (2003) Increased levels of asymmetric dimethylarginine in populations at risk for atherosclerotic disease. Effects of pravastatin. Atheroscler 166:279–284

    Article  CAS  Google Scholar 

  29. Amador N, Espinoza G, Guizar JM, Gonzalez M, Alpizar M (2001) Comparison between HOMA IR and Minmod for insulin sensitivity measurement in polycystic ovary syndrome. La Revista de Investigacion Clinica 53:407–412

    CAS  Google Scholar 

Download references

Acknowledgments

We thank biochemistry laboratory personnel and our local ethic committee for their contribution.

Conflict of interest

No conflict of interest is present for each author and no financial support is obtained.

Author information

Authors and Affiliations

  1. Department of Endocrinology, Faculty of Medical School, Turgut Ozal University, Ankara, Turkey

    Feridun Karakurt

  2. Department of Endocrinology, Regional Training and Research Hospital, Erzurum, Turkey

    Ayse Carlioglu

  3. Department of Obstetrics and Gynecology, Faculty of Medical School, Turgut Ozal University, Ciftlik Cad. No:57, Emek, 06510, Ankara, Turkey

    Ikbal Kaygusuz & Ilknur Inegöl Gumus

  4. Department of Internal Medicine, Faculty of Medical School, Turgut Ozal University, Ankara, Turkey

    Burak Uz & Derya Akdeniz

Authors
  1. Feridun Karakurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ayse Carlioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ikbal Kaygusuz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ilknur Inegöl Gumus
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Burak Uz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Derya Akdeniz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ikbal Kaygusuz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karakurt, F., Carlioglu, A., Kaygusuz, I. et al. Effect of ethinyl estradiol–cyproterone acetate treatment on asymmetric dimethyl-arginine levels in women with polycystic ovary syndrome. Arch Gynecol Obstet 289, 135–140 (2014). https://doi.org/10.1007/s00404-013-2960-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-013-2960-3

Keywords

Search

Navigation