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Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome

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Secreted frizzled-related protein 4 (SFRP4) is an adipokine involving in apoptotic process during ovulation and energy metabolism. Polycystic ovary syndrome (PCOS) is a common reproductive and metabolic disorder associated with insulin resistance and impaired oocyte maturation as well as apoptotic dysfunctions through oocyte development. Our aim was to determine whether there was an alteration in levels of SFRP4 and if there was an association between metabolic or hormonal parameters and SFRP4 in women with PCOS.


We enrolled 80 subjects with PCOS and 80 age- and body mass index (BMI)-matched subjects with normal menstrual cycle into current case–control study. Metabolic and hormonal parameters of enrolled subjects were determined. Circulating SFRP4 levels were measured with ELISA method.


We found that circulating SFRP4 levels were elevated in women with PCOS with respect to controls (5.87 ± 1.91 vs. 3.72 ± 1.29 ng/ml, P < 0.001). We also found a positive association between SFRP4 and insulin resistance, androgens, ovarian follicular number or ovarian volume in women with PCOS. Binary logistic regression analysis revealed that subjects with the highest tertile of SFPR4 levels displayed increased possibility of having PCOS risk compared to those subjects with the lowest tertile of SFRP4 levels.


Increased SFRP4 levels were not only associated with higher possibility of having PCOS but also related to insulin resistance, hyperandrogenism, ovarian follicular number and ovarian volume, suggesting that SFPR4 could be a player in different pathophysiologic pathways of PCOS.

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Anti-müllerian hormone


Body mass index


Confidence interval


Coefficient of variability


Diastolic blood pressure


Dehydroepiandrosterone sulfate


Free androgen index


Fasting blood glucose




High density lipoprotein cholesterol


Homeostasis model assessment of insulin resistance


High sensitivity C-reactive protein


Low density lipoprotein cholesterol


Odds ratio


Polycystic ovary syndrome


Receiver Operator Characteristic


Secreted frizzled-related protein 4


Systolic blood pressure


Type 2 diabetes mellitus


Variance inflation factor


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Authors and Affiliations



M.B., M.C., I.D., A.G, and P.A. participated in study design and B.A. and M.C. performed ELISA. M.B., M.C., I.D., A.G, P.A. and B.A. participated in study design, analyzed the data, wrote, reviewed and edited the manuscript. M.C., I.D., A.G. and P.A. provided serum samples and contributed to discussions of data interpretation. All authors reviewed and edited the manuscript. M.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Correspondence to M. Calan.

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The study adhered strictly to the principles of the Declaration of Helsinki as revised in 2008.

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Bicer, M., Alarslan, P., Guler, A. et al. Elevated circulating levels of secreted frizzled-related protein 4 in relation to insulin resistance and androgens in women with polycystic ovary syndrome. J Endocrinol Invest 43, 305–313 (2020).

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