Archives of Gynecology and Obstetrics

, Volume 300, Issue 6, pp 1785–1790 | Cite as

Serum zonulin level is not elevated in patients with polycystic ovary syndrome without metabolic syndrome

  • Zeynep CetinEmail author
  • Arzu Kosem
  • Bulent Can
  • Ozden Baser
  • Merve Catak
  • Turan Turhan
  • Dilek Berker
Gynecologic Endocrinology and Reproductive Medicine



Polycystic ovary syndrome (PCOS) is a complex disorder with gynecological, metabolic and carcinogenic effects. Increased intestinal permeability is related with obesity, insulin resistance, type 1 and 2 diabetes mellitus. The existence of such a relationship between PCOS and intestinal permeability has come to an end. Zonulin can change intestinal permeability, and this effect is reversible. We studied the relation between zonulin and the hormonal and metabolic parameters of PCOS.


A total of 45 women with PCOS and 17 healthy women were included in the study. Histories were taken from all the participants, body mass indexes were calculated, and biochemical tests and suprapubic over ultrasonography were made. Zonulin was studied with enzyme-linked immunosorbent assay.


Serum zonulin levels were similar between PCOS and control groups (p = 0.893). In all participants, there were negative correlations between zonulin and the total cholesterol, LDL-cholesterol, triglycerides and non-HDL-cholesterol (respectively, p = 0.00, 0.018, 0.004, 0.002), there were boundary correlations with age and total cholesterol/HDL-cholesterol (respectively, p = 0.052 and 0.058). No statistically significant was detected in the PCOS group except negative correlation between zonulin and age (p = 0.046), boundary correlation between zonulin and total cholesterol/HDL-cholesterol (p = 0.064).


PCOS patients did not have metabolic syndrome. Zonulin was not higher in PCOS then controls, and it had only negative relation with age. The negative relation between zonulin and some metabolic parameters in all participants was not detected in PCOS group. So zonulin is not a useful molecule for the diagnosis of PCOS without metabolic syndrome.


Polycystic ovary syndrome Zonulin Metabolic syndrome 


Author contributions

ZC contributed to project development, data management, manuscript writing, and data analysis. AK was involved in project development, data collection, and kit (zonulin) running. BC, OB, and MC collected the data. TT was involved in data collection and kit running. DB contributed to project development and manuscript editing.


The funding support was applied from Ankara Numune Education and Research Hospital Scientific Research Support Fund.

Compliance with ethical standards

Conflict of interest

Zeynep Cetin, Arzu Kosem, Bulent Can, Ozden Baser, Merve Catak, Turan Turhan and Dilek Berker declare that they have no conflict of interest.

Ethical approval

The local ethics committee of University of Health Sciences Ankara Numune Education and Research Hospital approved this study with ID: 1190/2017. All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study does not contain any study animals. This is a sectional study.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Knochenhauer ES, Key TJ, Kahsar-Miller M, Waggoner W, Boots LR, Azziz R (1998) Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study. J Clin Endocrinol Metab 83:3078–3082PubMedGoogle Scholar
  2. 2.
    Zawadzki JK, Dunaif A (1992) Diagnostic criteria for polycystic ovary syndrome: towards a rational aproach. In: Dunaif A, Givens JR, Hasltine F et al (eds) polycystic ovary syndrome. Blackwell Scientific, Cambridge, pp 377–384Google Scholar
  3. 3.
    Zhang D, Zhang L, Yue F, Zheng Y, Russell R (2015) Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation. Eur J Endocrinol 172:29–36CrossRefGoogle Scholar
  4. 4.
    Wang W, Uzzau S, Goldblum SE, Fasano A (2000) Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci 113:4435–4440PubMedGoogle Scholar
  5. 5.
    Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Carteni M, Generoso M et al (2006) Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes 55:1443–1449CrossRefGoogle Scholar
  6. 6.
    Jayashree B, Bibin YS, Prabhu D, Shanthirani CS, Gokulakrishnan K, Lakshmi BS, Mohan V, Balasubramanyam M (2014) Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 388:203–210. CrossRefGoogle Scholar
  7. 7.
    Fasano A (2011) Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity and cancer. Physiol Rev 91:151–175CrossRefGoogle Scholar
  8. 8.
    Fasano A (2001) Pathological and therapeutical implications of macromolecule passage through the tight junction. In: Cereijido M, Anderson J (eds) Tight junctions. CRC, Boca Raton, pp 697–722Google Scholar
  9. 9.
    El Asmar R, Panigrahi P, Bamford P, Berti I, Not T, Coppa GV, Catassi C, Fasano A (2002) Host-dependent activation of the zonulin system is involved in the impairment of the gut barrier function following bacterial colonization. Gastroenterology 123:1607–1615CrossRefGoogle Scholar
  10. 10.
    Moreno-Navarrete JM, Sabater M, Ortega F et al (2012) Circulating zonulin, a marker of intestinal permeability, is increased in association with obesity-associated insulin resistance. PLoS ONE 7:e37160CrossRefGoogle Scholar
  11. 11.
    Tripathi A, Lammers KM, Goldblum S, Shea-Donohue T, Netzel-Arnett S et al (2009) Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci USA 106:16799–16804CrossRefGoogle Scholar
  12. 12.
    Brock M, Trenkmann M, Gay RE, Gay S, Speich R et al (2011) MicroRNA-18a enhances the interleukin-6-mediated production of the acute-phase proteins fibrinogen and haptoglobin in human hepatocytes. J Biol Chem 286:40142–40150CrossRefGoogle Scholar
  13. 13.
    Tremellen K, Pearce K (2012) Dysbiosis of gut microbiota (DOGMA)—a novel theory for the development of polycystic ovarian syndrome. Med Hypotheses 79:104–112. CrossRefPubMedGoogle Scholar
  14. 14.
    Moghetti P, Tosi F, Bonin C, Di Sarra D, Fiers T, Kaufman JM, Giagulli VA, Signori C, Zambotti F, Dall’Alda M et al (2013) Divergences in insulin resistance between the different phenotypes of the polycystic ovary syndrome. J Clin Endocrinol Metab 98:628–637. CrossRefGoogle Scholar
  15. 15.
    Goodarzi MO, Korenman SG (2003) The importance of insulin resistance in polycystic ovary syndrome. Fertil Steril 80:255–258. CrossRefPubMedGoogle Scholar
  16. 16.
    Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Investig 116:1793–1801. CrossRefPubMedGoogle Scholar
  17. 17.
    Li MF, Zhou XM, Li XL (2018) The effect of berberine on polycystic ovary syndrome patients with insulin resistance (PCOS-IR): a meta-analysis and systematic review. Evid Based Complement Alternat Med 2018:2532935PubMedPubMedCentralGoogle Scholar
  18. 18.
    Łagowska K, Bajerska J, Jamka M (2018) The role of vitamin D oral supplementation in insulin resistance in women with polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Nutrients 10(11):1637. CrossRefPubMedCentralGoogle Scholar
  19. 19.
    Hackbart KS, Cunha PM, Meye RK, Wiltbank MC (2013) Effect of glucocorticoid-induced insulin resistance on follicle development and ovulation. Biol Reprod 88:88–153. CrossRefGoogle Scholar
  20. 20.
    Song DK, Hong YS, Sung YA, Lee H (2017) Insulin resistance according to β-cell function in women with polycystic ovary syndrome and normalglucosetolerance. PLoS ONE 12:e0178120. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Endocrinology and Metabolism DepartmentAmasya University Sabuncuğlu Serefeddin Education and Research HospitalAmasyaTurkey
  2. 2.Biochemistry DepartmentAnkara City HospitalAnkaraTurkey
  3. 3.Endocrinology and Metabolism DepartmentIstanbul Civilization UniversityIstanbulTurkey
  4. 4.Endocrinology and Metabolism DepartmentYozgat City HospitalYozgatTurkey
  5. 5.Endocrinology and Metabolism DepartmentTokat Public HospitalTokatTurkey
  6. 6.Endocrinology and Metabolism DepartmentUniversity of Medical Sciences Ankara City HospitalAnkaraTurkey

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