Decreased SFRP5 correlated with excessive metabolic inflammation in polycystic ovary syndrome could be reversed by metformin: implication of its role in dysregulated metabolism

Yi Zhang,Lihong Geng,Jun Hu,Lingna Kong,Hongbo Qi,Hongying Zhang,Hua Huang,Yuxin Ran,Ying Chen

doi:10.1186/s13048-021-00847-4

Abstract

BackgroundPolycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature. Secreted frizzled-related protein (SFRP) 5 is an anti-inflammatory adipokine implicated in metabolic homeostasis. We aimed to confirm the correlation between SFRP5, metabolic inflammation and PCOS, investigate the predictive value of SFRP5 for PCOS and the involvement of SFRP5 in metformin treated PCOS.MethodsThis retrospective case–control study included 140 PCOS and 33 control women. Sixty seven PCOS women were included for detecting serum SFRP5 level and its correlation with metabolic inflammation. Predictive value of SFRP5 for PCOS was evaluated by logistic regression and receiver operating characteristic (ROC) analyses. Seventy three PCOS women complicated with impaired glucose tolerance (IGT)/insulin resistance (IR) were included for investigating the effects of metformin (37 with metformin vs. 36 without metformin) on SFRP5, pro-inflammatory cytokines, ovulation and pregnancy rate.ResultsPlasma SFRP5 levels were decreased in PCOS (odds ratio: 0.78, 95% confidence interval (CI):0.703–0.866, P < 0.001) independent of obesity. SFRP5 was negatively associated with IL-6, TNFα, FAI and HOMA-IR. The cut-off point of SFRP5 < 46.13 ng/ml was optimal to identify PCOS with a higher specificity of 96.87% and a relatively lower sensitivity compared to AMH. SFRP5 increased specificity of AMH for predicting PCOS, especially which with relatively decreased AMH (< 4.7 ng/ml). Metformin promoted SFRP5 and decreased leptin, IL-6 and TNFα secretion in PCOS women with metabolic abnormality in a time dependent manner and with improved ovulation rate and pregnancy rate.ConclusionDecreased SFRP5 was associated with metabolic inflammation in PCOS and has a potential role for the supplement of AMH in predicting PCOS. The reverse of serum SFRP5 by metformin indicated that SFRP5 participated in the improvment of follicular development by metformin. Further prospective investigations are needed to confirm these preliminary data.

Highlights

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature
No obvious difference of SFRP5 level was found between normal weight (BMI < 25) and overweight / obese (BMI ≥ 25) Polycystic ovary syndrome (PCOS) patients, body mass index (BMI), waist hip ratio (WHR), HOMA-insulin resistance (IR) and fasting insulin (FINS) levels were significantly higher in the latter
Consistent with the findings of Hu, we found serum SFRP5 levels were decreased in PCOS in Chinese population [22], which was opposite to the findings of Almario in American population [21]

Summary

Introduction

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder of heterogeneous nature. Polycystic ovary syndrome (PCOS) is a complex endocrine disorder characterized by oligo-anovulation (OA), polycystic ovarian morphology (PCOM), hyperandrogenism (HA) and accompanied by metabolic aberrations (adverse lipid profile, impaired glucose tolerance (IGT), insulin resistance (IR) and type 2 diabetes mellitus (T2DM)). About 30 to 50% of lean PCOS women still have an increased risk of metabolic abnormalities [4, 5]. There are a portion of PCOS women without abnormal glycolipid metabolism exhibiting HA and ovarian dysfunction. Biomarkers such as anti-Müllerian hormone (AMH) have been suggested for diagnosis of PCOS, none of them could be used independently [6].

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