Archives of Gynecology and Obstetrics

, Volume 291, Issue 5, pp 1075–1080 | Cite as

No relationship between osteoprotegerin concentrations and endothelial dysfunction in non-obese women with and without polycystic ovary syndrome

  • Remzi Abali
  • Nicel Tasdemir
  • Seref Alpsoy
  • Ufuk Göker Tasdemir
  • Savas Guzel
  • Mehmet Aytac Yuksel
  • Ilkbal Temel Yuksel
  • Murat Yilmaz
General Gynecology



To investigate the relationships of osteoprotegerin (OPG) concentrations to brachial artery flow-mediated vasodilation (FMD) and the carotid artery intima media thickness (CIMT) in polycystic ovary syndrome (PCOS).


Thirty-seven women with PCOS and 41 controls matched for body mass index (BMI) and age were included in study. The serum OPG concentrations, hormonal and metabolic profiles were measured in women with PCOS and in control group. The CIMT and brachial artery FMD were evaluated in both groups.


The mean serum concentrations of all hormones were comparable, except LH, which was higher in women with PCOS. Lipid parameters were similar between groups. There were no differences between groups with respect to fasting glucose, 2-h glucose, fasting insulin, HbA1c and HOMA-IR. The mean osteoprotogerin concentrations were higher in PCOS group (11.39 ± 2.29 vs. 10.22 ± 2.25 pmol/L, P = 0.026). The mean CIMT was higher in PCOS group than control group (0.52 ± 0.058 vs. 0.45 ± 0.059 mm, P < 0.01). The mean brachial artery FMD was lower in PCOS group (0.068 ± 0.022 vs. 0.055 ± 0.029, P = 0.017).


We found high osteoprotogerin concentrations, increased CIMT and decreased FMD, in women with PCOS. However, there was no correlation between osteoprotegerin and cardiovascular risk markers.


Polycystic Ovary syndrome Osteoprotegerin Carotid intima-media thickness FLOW-mediated dilatation Cardiovascular disease 


Conflict of interest

The authors have no conflicts of interest.


  1. 1.
    Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO (2004) The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab 89(6):2745–2749. doi: 10.1210/jc.2003-032046 CrossRefPubMedGoogle Scholar
  2. 2.
    Karaer A, Cavkaytar S, Mert I, Buyukkagnici U, Batioglu S (2010) Cardiovascular risk factors in polycystic ovary syndrome. J Obstet Gynaecol 30(4):387–392. doi: 10.3109/01443611003763408 CrossRefPubMedGoogle Scholar
  3. 3.
    Legro RS (2003) Polycystic ovary syndrome and cardiovascular disease: a premature association? Endocr Rev 24(3):302–312CrossRefPubMedGoogle Scholar
  4. 4.
    Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M (2007) Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation 115(4):459–467. doi: 10.1161/CIRCULATIONAHA.106.628875 CrossRefPubMedGoogle Scholar
  5. 5.
    Gokce N, Keaney JF Jr, Hunter LM, Watkins MT, Menzoian JO, Vita JA (2002) Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation 105(13):1567–1572CrossRefPubMedGoogle Scholar
  6. 6.
    Liang YL, Teede H, Kotsopoulos D, Shiel L, Cameron JD, Dart AM, McGrath BP (1998) Non-invasive measurements of arterial structure and function: repeatability, interrelationships and trial sample size. Clin Sci (Lond) 95(6):669–679CrossRefGoogle Scholar
  7. 7.
    Folkow B, Svanborg A (1993) Physiology of cardiovascular aging. Physiol Rev 73(4):725–764PubMedGoogle Scholar
  8. 8.
    Collin-Osdoby P, Rothe L, Anderson F, Nelson M, Maloney W, Osdoby P (2001) Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J Biol Chem 276(23):20659–20672. doi: 10.1074/jbc.M010153200 CrossRefPubMedGoogle Scholar
  9. 9.
    Dhore CR, Cleutjens JP, Lutgens E, Cleutjens KB, Geusens PP, Kitslaar PJ, Tordoir JH, Spronk HM, Vermeer C, Daemen MJ (2001) Differential expression of bone matrix regulatory proteins in human atherosclerotic plaques. Arterioscler Thromb Vasc Biol 21(12):1998–2003CrossRefPubMedGoogle Scholar
  10. 10.
    Yano K, Tsuda E, Washida N, Kobayashi F, Goto M, Harada A, Ikeda K, Higashio K, Yamada Y (1999) Immunological characterization of circulating osteoprotegerin/osteoclastogenesis inhibitory factor: increased serum concentrations in postmenopausal women with osteoporosis. J Bone Miner Res 14(4):518–527. doi: 10.1359/jbmr.1999.14.4.518 CrossRefPubMedGoogle Scholar
  11. 11.
    Browner WS, Lui LY, Cummings SR (2001) Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J Clin Endocrinol Metab 86(2):631–637. doi: 10.1210/jcem.86.2.7192 PubMedGoogle Scholar
  12. 12.
    Shargorodsky M, Boaz M, Luckish A, Matas Z, Gavish D, Mashavi M (2009) Osteoprotegerin as an independent marker of subclinical atherosclerosis in osteoporotic postmenopausal women. Atherosclerosis 204(2):608–611. doi: 10.1016/j.atherosclerosis.2008.10.024 CrossRefPubMedGoogle Scholar
  13. 13.
    Mangan SH, Van Campenhout A, Rush C, Golledge J (2007) Osteoprotegerin upregulates endothelial cell adhesion molecule response to tumor necrosis factor-alpha associated with induction of angiopoietin-2. Cardiovasc Res 76(3):494–505. doi: 10.1016/j.cardiores.2007.07.017 CrossRefPubMedCentralPubMedGoogle Scholar
  14. 14.
    Candido R, Toffoli B, Corallini F, Bernardi S, Zella D, Voltan R, Grill V, Celeghini C, Fabris B (2010) Human full-length osteoprotegerin induces the proliferation of rodent vascular smooth muscle cells both in vitro and in vivo. J Vasc Res 47(3):252–261. doi: 10.1159/000257339 CrossRefPubMedGoogle Scholar
  15. 15.
    ESHRE/ASRM R (2004) Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 19(1):41–47CrossRefGoogle Scholar
  16. 16.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419CrossRefPubMedGoogle Scholar
  17. 17.
    de Groot PC, Dekkers OM, Romijn JA, Dieben SW, Helmerhorst FM (2011) PCOS, coronary heart disease, stroke and the influence of obesity: a systematic review and meta-analysis. Hum Reprod Update 17(4):495–500. doi: 10.1093/humupd/dmr001 CrossRefPubMedGoogle Scholar
  18. 18.
    Cibula D, Cifkova R, Fanta M, Poledne R, Zivny J, Skibova J (2000) Increased risk of non-insulin dependent diabetes mellitus, arterial hypertension and coronary artery disease in perimenopausal women with a history of the polycystic ovary syndrome. Hum Reprod 15(4):785–789CrossRefPubMedGoogle Scholar
  19. 19.
    Lakhani K, Hardiman P, Seifalian AM (2004) Intima-media thickness of elastic and muscular arteries of young women with polycystic ovaries. Atherosclerosis 175(2):353–359. doi: 10.1016/j.atherosclerosis.2004.04.007 CrossRefPubMedGoogle Scholar
  20. 20.
    ESHRE, ASRM. R (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 27(1):14–24. doi: 10.1093/humrep/der396 CrossRefGoogle Scholar
  21. 21.
    Paradisi G, Steinberg HO, Hempfling A, Cronin J, Hook G, Shepard MK, Baron AD (2001) Polycystic ovary syndrome is associated with endothelial dysfunction. Circulation 103(10):1410–1415CrossRefPubMedGoogle Scholar
  22. 22.
    Tarkun I, Arslan BC, Canturk Z, Turemen E, Sahin T, Duman C (2004) Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. J Clin Endocrinol Metab 89(11):5592–5596. doi: 10.1210/jc.2004-0751 CrossRefPubMedGoogle Scholar
  23. 23.
    Sorensen MB, Franks S, Robertson C, Pennell DJ, Collins P (2006) Severe endothelial dysfunction in young women with polycystic ovary syndrome is only partially explained by known cardiovascular risk factors. Clin Endocrinol 65(5):655–659. doi: 10.1111/j.1365-2265.2006.02645.x CrossRefGoogle Scholar
  24. 24.
    Talbott EO, Zborowski JV, Boudreaux MY, McHugh-Pemu KP, Sutton-Tyrrell K, Guzick DS (2004) The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome. J Clin Endocrinol Metab 89(12):6061–6067. doi: 10.1210/jc.2003-032110 CrossRefPubMedGoogle Scholar
  25. 25.
    Talbott EO, Guzick DS, Sutton-Tyrrell K, McHugh-Pemu KP, Zborowski JV, Remsberg KE, Kuller LH (2000) Evidence for association between polycystic ovary syndrome and premature carotid atherosclerosis in middle-aged women. Arterioscler Thromb Vasc Biol 20(11):2414–2421CrossRefPubMedGoogle Scholar
  26. 26.
    Meyer ML, Malek AM, Wild RA, Korytkowski MT, Talbott EO (2012) Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update 18(2):112–126. doi: 10.1093/humupd/dmr046 CrossRefPubMedCentralPubMedGoogle Scholar
  27. 27.
    Mutlu B, Tigen K, Gurel E, Ozben B, Karaahmet T, Basaran Y (2011) The predictive value of flow-mediated dilation and carotid artery intima-media thickness for occult coronary artery disease. Echocardiography 28(10):1141–1147. doi: 10.1111/j.1540-8175.2011.01492.x CrossRefPubMedGoogle Scholar
  28. 28.
    Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang IK, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W Jr, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT (2003) From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation 108(15):1772–1778. doi: 10.1161/01.CIR.0000087481.55887.C9 CrossRefPubMedGoogle Scholar
  29. 29.
    Sprung VS, Atkinson G, Cuthbertson DJ, Pugh CJ, Aziz N, Green DJ, Cable NT, Jones H (2012) Endothelial function measured using flow mediated dilation in polycystic ovarian syndrome: a meta-analysis of the observational studies. Clin Endocrinol. doi: 10.1111/j.1365-2265.2012.04490.x Google Scholar
  30. 30.
    Jono S, Ikari Y, Shioi A, Mori K, Miki T, Hara K, Nishizawa Y (2002) Serum osteoprotegerin levels are associated with the presence and severity of coronary artery disease. Circulation 106(10):1192–1194CrossRefPubMedGoogle Scholar
  31. 31.
    Zauli G, Corallini F, Bossi F, Fischetti F, Durigutto P, Celeghini C, Tedesco F, Secchiero P (2007) Osteoprotegerin increases leukocyte adhesion to endothelial cells both in vitro and in vivo. Blood 110(2):536–543. doi: 10.1182/blood-2007-01-068395 CrossRefGoogle Scholar
  32. 32.
    Pepene CE, Ilie IR, Marian I, Duncea I (2011) Circulating osteoprotegerin and soluble receptor activator of nuclear factor kappaB ligand in polycystic ovary syndrome: relationships to insulin resistance and endothelial dysfunction. Eur J Endocrinol 164(1):61–68. doi: 10.1530/EJE-10-0720 CrossRefPubMedGoogle Scholar
  33. 33.
    Escobar-Morreale HF, Botella-Carretero JI, Martinez-Garcia MA, Luque-Ramirez M, Alvarez-Blasco F, San Millan JL (2008) Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome. Eur J Endocrinol 159(3):225–232. doi: 10.1530/EJE-08-0107 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Remzi Abali
    • 1
  • Nicel Tasdemir
    • 1
  • Seref Alpsoy
    • 2
  • Ufuk Göker Tasdemir
    • 3
  • Savas Guzel
    • 4
  • Mehmet Aytac Yuksel
    • 5
  • Ilkbal Temel Yuksel
    • 6
  • Murat Yilmaz
    • 7
  1. 1.Department of Gynecology and Obstetrics, Faculty of MedicineNamik Kemal UniversityTekirdagTurkey
  2. 2.Department of Cardiology, Faculty of MedicineNamik Kemal UniversityTekirdagTurkey
  3. 3.Department of Gynecology and ObstetricsTekirdag Hayrabolu State HospitalTekirdagTurkey
  4. 4.Department of Biochemistry, Faculty of MedicineNamik Kemal UniversityTekirdagTurkey
  5. 5.Department of Gynecology and Obstetrics, Cerrahpasa Faculty of Medicineİstanbul UniversityIstanbulTurkey
  6. 6.Department of Obstetrics and GynecologyIstanbul Okmeydani Research and Training HospitalIstanbulTurkey
  7. 7.Department of Endocrinology, Faculty of MedicineNamik Kemal UniversityTekirdagTurkey

Personalised recommendations