High Variability in Traditional Polycystic Ovary Syndrome Biomarkers: Embracing the Need for Biomarkers Derived Through Integrative Approaches

Abstract

Polycystic Ovary Syndrome (PCOS) is a complex reproductive disorder characterized by irregular menstrual cycles, polycystic ovaries, and hyperandrogenism. Diagnosis is often complicated by phenotype variability and inconsistent biomarker use. This metaanalysis, conducted according to PRISMA 2020 guidelines and based on studies published between 2010 and May 2023, investigates the heterogeneity in key PCOS biomarkers, testosterone and LH/FSH ratio, using a random-effects model. Thirteen studies were included in the meta-analysis. Biomarker-specific analyses were conducted using R to evaluate variations in testosterone and LH/FSH ratios. Sample sizes consisted of 500 PCOS cases and 592 controls for testosterone, and 1184 PCOS cases and 1410 controls for the LH/FSH ratio. Heterogeneity and subgroup variability were assessed independently for each biomarker. Marked heterogeneity was observed across studies, with I² values of 95% for testosterone and 99% for the LH/FSH ratio. Contributing factors included variability in population demographics, diagnostic criteria, and assay methodologies. Traditional assays often fail to sensitively detect testosterone in women, while visual scoring methods are vulnerable to observer bias The observed heterogeneity underscores the limitations of conventional biomarkers in diagnosing PCOS. A move toward standardised, sensitive, and phenotype-specific diagnostic tools is crucial. Multi-steroid panels and integrative omics-based approaches can address variability and enhance diagnostic accuracy. Integrating novel biomarkers such as DAPK2, S100A9, Bacteroides vulgatus, and microRNA-6767-5p holds promise for improved diagnosis of PCOS subtypes. AGP may help identify normoandrogenic presentations. Embracing immune-metabolic insights supports the development of diverse, accessible, and validated diagnostics aligned with the goals of precision medicine and improved women's reproductive health.