Serum Bile Acid Dysregulation in Polycystic Ovary Syndrome: Quantitative Insights from Mass Spectrometry-Based Profiling

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with substantial metabolic comorbidities, including obesity, insulin resistance, and dyslipidaemia. Beyond their classical digestive role, bile acids (BAs) function as metabolic signalling molecules that regulate glucose and lipid homeostasis and inflammation through receptors such as the farnesoid X receptor (FXR) and Takeda G-protein receptor 5 (TGR5). However, bile acid dysregulation in PCOS remains inadequately characterised. MethodsTargeted serum bile acid profiling was performed in PCOS (n = 86) and healthy controls (n = 60) using a validated LC-MS/MS method. Individual bile acids were quantified and classified into primary, secondary, and conjugated forms. Multivariate analyses were applied to identify group-level metabolic patterns. Functional bile acid indices reflecting hepatic conjugation and microbial transformation were calculated. Correlation analyses assessed between bile acids and clinical variables. ResultsPCOS women exhibited significantly higher serum levels of cholic acid and conjugated bile acids. Multivariate analyses revealed distinct bile acid signatures differentiating PCOS from controls, with deoxycholic acid, taurocholic acid, and cholic acid contributing most strongly to group separation. Pathway-based indices demonstrated an expanded conjugated bile acid pool, an increased conjugated-to-unconjugated bile acid ratio, and altered secondary-to-primary bile acid balance in PCOS. Several bile acids showed significant associations with androgen levels and gonadotropin ratios. ConclusionPCOS is characterised by coordinated alterations in bile acid metabolism, including hepatic synthesis, conjugation, and gut microbial transformation, highlighting bile acids as integrative metabolic signals linking endocrine and metabolic dysfunction in PCOS.