Advertisement

Hormones

, Volume 13, Issue 4, pp 488–497 | Cite as

The bencfit-to-risk ratio of common treatments in PCOS: effect of oral contraceptives versus metformin on atherogenic markers

  • Charikleia Christakou
  • Anastasios Kollias
  • Christina Piperi
  • Ilias Katsikis
  • Dimitrios Panidis
  • Evanthia Diamanti-Kandarakis
Research paper

Abstract

OBJECTIVE

To compare the effects of oral contraceptives (OCPs) and metformin on atherogenic markers, including serum levels of advanced glycated end products (AGEs) and C-reactive protein (CRP), in lean women (Body Mass Index below 25 kg/m2) with polycystic ovary syndrome (PCOS), defined by NIH criteria.

DESIGN

Prospective open-label study

RESULTS

One hundred and twenty women with PCOS were treated for 6 months with one of the following treatments: ethinylestradiol plus cyproterone acetate (OCP 1, n=40) or ethinylestradiol plus drospirenone (OCP2, n = 40) or metformin (MET, n=40). The three groups were age and BMI-matched (mean age: 22 ± 0.56 yrs in group OCP1; 23.24 ± 0.64 yrs in group OCP2; 21.50 ± 0.53 yrs in group MET; mean BMI 21.80 ± 0.35 kg/m2 in group OCP1; 22.37 ± 0.48 kg/m2 in group OCP2; 23.03 ± 0.67 kg/m2 in group MET). At 6 months serum AGEs were decreased in group OCP1 (P=0.005) and group MET (P=0.001), whereas these were marginally decreased in group OCP2 (P=0.069). Treatment with metformin was associated with a greater percent decrease of AGEs. CRP was decreased with metformin (P < 0.001), but was increased with OCPs (P<0.001).

CONCLUSIONS

This study evaluates common therapeutic options in women with PCOS by reconsidering and prioritizing the goals of treatment. OCPs and metformin appear to have differential effects on atherogenic molecules in lean PCOS patients, but metformin was superior in reducing serum AGEs and CRP. Clinicians should individualize the benefit-to-risk ratio of pharmaceutical intervention in women with PCOS in order to choose the formulation with the greatest overall efficacy as well as safety in terms of cardiovascular risk.

Key Words

Atherogenic markers Metformin Oral contraceptives Polycystic ovary syndrome 

References

  1. 1.
    Diamanti-Kandarakis E, Dunaif A, 2012 Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 33: 981–1030.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Diamanti-Kandarakis E, Katsikis I, Piperi C, et al, 2008 Increased serum advanced glycation end-products is a distinct finding in lean women with polycystic ovary syndrome (PCOS). Clin Endocrinol (Oxf) 69: 634–641.CrossRefGoogle Scholar
  3. 3.
    Vlassara H, 2005 Advanced glycation in health and disease: role of the modern environment. Ann N Y Acad Sci 1043: 452–460.CrossRefGoogle Scholar
  4. 4.
    Diamanti-Kandarakis E, Piperi C, Patsouris E, et al, 2007 Immunohistochemical localization of advanced glycation end-products (AGEs) and their receptor (RAGE) in polycystic and normal ovaries. Histochem Cell Biol 127: 581–589.CrossRefGoogle Scholar
  5. 5.
    Baillargeon JP, McClish DK, Essah PA, Nestler JE, 2005 Association between the current use of low-dose oral contraceptives and cardiovascular arterial disease: a metaanalysis. J Clin Endocrinol Metab 90: 3863–3870.CrossRefGoogle Scholar
  6. 6.
    Merz CN, Johnson BD, Berga S, Braunstein G, Reis SE, Bittner V, WISE Study Group, 2006 Past oral contraceptive use and angiographic coronary artery disease in postmenopausal women: data from the National Heart, Lung, and Blood Institute-sponsored Women’s Ischemia Syndrome Evaluation. Fertil Steril 85: 1425–1431.CrossRefGoogle Scholar
  7. 7.
    Diamanti-Kandarakis E, Paterakis T, Alexandraki K, et al, 2006 Indices of low-grade chronic inflammation in polycystic ovary syndrome and the beneficial effect of metformin. Hum Reprod 21: 1426–1431.CrossRefGoogle Scholar
  8. 8.
    Diamanti-Kandarakis E, Alexandraki K, Piperi C, et al, 2007 Effect of metformin administration on plasma advanced glycation end product levels in women with polycystic ovary syndrome. Metabolism 56: 129–134.CrossRefGoogle Scholar
  9. 9.
    Zawadski JK, Dunaif A 1992 Diagnostic criteria for polycystic ovary syndrome: Towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GE (eds) Polycystic Ovary Syndrome (Current Issues in Endocrinology and Metabolism), Blackwell Scientific Inc, Boston; p, 377.Google Scholar
  10. 10.
    Diamanti-Kandarakis E, Piperi C, Kalofoutis A, Creatsas G, 2005 Increased levels of serum advanced glycation end-products in women with polycystic ovary syndrome. Clin Endocrinol (Oxf) 62: 37–43.CrossRefGoogle Scholar
  11. 11.
    Morin-Papunen LC, Vauhkonen I, Koivunen RM, Ruokonen A, Martikainen HK, Tapanainen JS, 2003 Metformin versus ethinyl estradiol-cyproterone acetate in the treatment of nonobese women with polycystic ovary syndrome: a randomized study. J Clin Endocrinol Metab 88: 148–156.CrossRefGoogle Scholar
  12. 12.
    Nader S, Diamanti-Kandarakis E, 2007 Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis. Hum Reprod 22: 317–322.CrossRefGoogle Scholar
  13. 13.
    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.CrossRefGoogle Scholar
  14. 14.
    Teede HJ, Meyer C, Hutchison SK, Zoungas S, McGrath BP, Moran LJ, 2010 Endothelial function and insulin resistance in polycystic ovary syndrome: the effects of medical therapy. Fertil Steril 93: 184–191.CrossRefGoogle Scholar
  15. 15.
    González F, 2012 Inflammation in Polycystic Ovary Syndrome: underpinning of insulin resistance and ovarian dysfunction. Steroids 77: 300–305.CrossRefGoogle Scholar
  16. 16.
    Christakou C, Diamanti-Kandarakis E, 2013 Structural, biochemical and non-traditional cardiovascular risk markers in PCOS. Curr Pharm Des 19: 5764–5774.CrossRefGoogle Scholar
  17. 17.
    Jabbour HN, Sales KJ, Catalano RD, Norman JE, 2009 Inflammatory pathways in female reproductive health and disease. Reproduction 138: 903–919.CrossRefGoogle Scholar
  18. 18.
    Corrado E, Rizzo M, Coppola G, et al, 2010 An update on the role of markers of inflammation in atherosclerosis. J Atheroscler Thromb 17: 1–11.CrossRefGoogle Scholar
  19. 19.
    Rusa R, Alkayed N, Crain B, et al, 1999 17beta-estradiol reduces stroke injury in estrogen-deficient female animals. Stroke 30: 1665–1670.CrossRefGoogle Scholar
  20. 20.
    Mukherjee TK, Reynolds PR, Hoidal JR, 2005 Differential effect of estrogen receptor alpha and beta agonists on the receptor for advanced glycation end product expression in human microvascular endothelial cells. Biochim Biophys Acta 1745: 300–309.CrossRefGoogle Scholar
  21. 21.
    Mukhopadhyay S, Mukherjee TK, 2005 Bridging advanced glycation end product, receptor for advanced glycation end product and nitric oxide with hormonal replacement/estrogen therapy in healthy versus diabetic postmenopausal women: a perspective. Biochim Biophys Acta 1745: 145–155.CrossRefGoogle Scholar
  22. 22.
    Kislinger T, Tanji N, Wendt T, et al, 2001 Receptor for advanced glycation end products mediates inflammation and enhanced expression of tissue factor in vasculature of diabetic apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 21: 905–910.CrossRefGoogle Scholar
  23. 23.
    Schmidt AM, Yan SD, Wautier JL, Stern D, 1999 Activation of receptor for advanced glycation end products: a mechanism for chronic vascular dysfunction in diabetic vasculopathy and atherosclerosis. Circ Res 84: 489–497.CrossRefGoogle Scholar
  24. 24.
    Vongpatanasin W, Tuncel M, Wang Z, Arbique D, Mehrad B, Jialal I, 2003 Differential effects of oral versus transdermal estrogen replacement therapy on C-reactive protein in postmenopausal women. J Am Coll Cardiol 41: 1358–1363.CrossRefGoogle Scholar
  25. 25.
    Palacios S, Foidart JM, Genazzani A, 2006 Advances in hormone replacement therapy with drospirenone, a unique progestogen with aldosterone receptor antagonism. Maturitas 55: 297–307.CrossRefGoogle Scholar
  26. 26.
    Ridker PM, Rifai N, Rose L, Buring JE, Cook NR, 2002 Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347: 1557–1565.CrossRefGoogle Scholar
  27. 27.
    Packard R, Libby P, 2008 Inflammation in Atherosclerosis: From Vascular Biology to Biomarker Discovery and Risk Prediction. Clin Chem 54: 24–38.CrossRefGoogle Scholar
  28. 28.
    Beisswenger PJ, Ruggiero-Lopez D, 2003 Metformin inhibition of glycation processes. Diabetes Metab 29 (4 Pt 2): 6S95–103.CrossRefGoogle Scholar
  29. 29.
    Tanaka Y, Iwamoto H, Onuma T, Kawamori R, 1997 Inhibitory effect of metformin on formation of advanced glycation end products. Curr Ther Res 58: 693–697.CrossRefGoogle Scholar
  30. 30.
    Tanaka Y, Uchino H, Shimizu T, et al, 1999 Effect of metformin on advanced glycation end product formation and peripheral nerve function in streptozotocin-induced diabetic rats. Eur J Pharmacol 376: 17–22.CrossRefGoogle Scholar
  31. 31.
    Bhattacharya SM, Jha A, 2012 Comparative study of the therapeutic effects of oral contraceptive pills containing desogestrel, cyproterone acetate, and drospirenone in patients with polycystic ovary syndrome. Fertil Steril 98: 1053–1059.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2014

Authors and Affiliations

  • Charikleia Christakou
    • 1
  • Anastasios Kollias
    • 1
  • Christina Piperi
    • 2
  • Ilias Katsikis
    • 3
  • Dimitrios Panidis
    • 3
  • Evanthia Diamanti-Kandarakis
    • 1
  1. 1.Endocrine Unit, Third Department of Internal Medicine‘Sotiria’ HospitalAthensGreece
  2. 2.Department of Biological Chemistry, Medical SchoolUniversity of AthensAthensGreece
  3. 3.Division of Endocrinology and Human Reproduction, Second Department of Obstetrics and Gynecology, Medical SchoolAristotle University of ThessalonikiThessalonikiGreece

Personalised recommendations