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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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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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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Abbreviations

AMH:

Anti-müllerian hormone

BMI:

Body mass index

CI:

Confidence interval

CV:

Coefficient of variability

DBP:

Diastolic blood pressure

DHEA-S:

Dehydroepiandrosterone sulfate

FAI:

Free androgen index

FBG:

Fasting blood glucose

FG:

Ferriman-Gallwey

HDL-C:

High density lipoprotein cholesterol

HOMA-IR:

Homeostasis model assessment of insulin resistance

hs-CRP:

High sensitivity C-reactive protein

LDL-C:

Low density lipoprotein cholesterol

OR:

Odds ratio

PCOS:

Polycystic ovary syndrome

ROC:

Receiver Operator Characteristic

SFRP4:

Secreted frizzled-related protein 4

SBP:

Systolic blood pressure

T2DM:

Type 2 diabetes mellitus

VIF:

Variance inflation factor

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Funding

This study has not been funded by any organizations.

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Authors and Affiliations

Authors

Contributions

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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The subjects gave their oral and written informed consent before their inclusion in the study.

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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). https://doi.org/10.1007/s40618-019-01108-4

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  • DOI: https://doi.org/10.1007/s40618-019-01108-4

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