Abstract
Chronic low-grade inflammation plays a crucial role in the pathophysiology of polycystic ovary syndrome (PCOS). This systematic review aims to synthesize the recent evidence on key inflammatory markers in PCOS and the role of IL-6. A comprehensive literature search was conducted using the PubMed, Web of Science, Cochrane Library, and Google Scholar databases. Studies published between 2014 and 2024 were screened based on predefined eligibility criteria. Both observational and interventional studies that reported levels of inflammatory markers in patients with polycystic ovary syndrome (PCOS) were included. Data were systematically extracted, and the quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS) for observational studies, the Cochrane Risk of Bias tool for randomized controlled trials (RCTs), and the ROBINS-1 tool for non-randomized controlled trials. A statistical synthesis of IL-6 levels was performed for the meta-analysis using a random-effects model in R. A total of 44 studies met the inclusion criteria for qualitative analysis and identified 94 biomarkers. The most commonly used biomarkers across the majority of studies, listed in descending order, are as follows: high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), CRP, adiponectin, IL-18, vascular endothelial growth factor (VEGF), IL-8, IL-1β, sex hormone binding globulin (SHBG), leptin, and vascular cell adhesion protein 1 (VCAM-1). Additionally, four case-control studies conducted in four countries (Taiwan, Russia, Spain, and Turkey) were included in the quantitative analysis, which involved 689 participants (PCOS group: n = 365; Control group: n = 324). The pooled mean difference (MD), calculated using the random-effects model, was 0.72 (0.47; 0.98) (p < 0.0001), indicating a significant increase in IL-6 levels among PCOS patients compared to the control group. The funnel plot exhibited slight asymmetry, suggesting publication bias, where smaller studies with negative or neutral results may be absent. The adjusted effect size after trim and fill analysis remained significant, indicating that publication bias is unlikely to affect the conclusions substantially. Chronic low-grade inflammation plays a crucial role in PCOS, and IL-6 levels in women with PCOS were elevated. Potential markers that can be investigated to assess inflammatory status in PCOS include hs-CRP, TNFα, CRP, adiponectin, IL-18, VEGF, IL-8, iIL-1β, SHBG, leptin, and VCAM-1.