Mass spectrometry-based untargeted metabolomics study of polycystic ovary syndrome

Abstract Background Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder, and its diagnosis remains controversial due to heterogeneous phenotypes and varying diagnostic criteria. Insulin resistance and its metabolic consequences are central features of PCOS management. Metabolomics has increasingly been applied to elucidate the pathophysiology of complex disorders. In this study, we sought to determine which serum metabolites and metabolic pathways are differentially altered in women with PCOS compared with healthy controls, thereby addressing whether metabolomic profiling can reveal candidate biomarkers for early diagnosis and potential therapeutic targets. Methods Fifty patients diagnosed with PCOS and 50 healthy controls matched for age and body mass index (BMI) were included in the study. Blood samples were collected for metabolomic analysis and routine biochemical parameters. Metabolomic analysis was performed by UPLC-HRMS and data were processed using MZmine, TidyMass and MetaboAnalyst. Metabolite annotation was performed using databases such as HMDB, MassBank and MoNA. Results Metabolomic analysis revealed 49 compounds in the serum of PCOS patients, 39 of which were upregulated and 10 of which were downregulated. Compounds such as di(2-ethylhexyl) phthalate (DEHP), promethazine N-oxide, tetrahydromagnolol, 5-methyl-5-phenylhydantoin, valerenic acid, butylparaben, erucamide, DDAO, d-erythro-sphinganin-1-phosphate and 1-arachidoyl-2-hydroxy-sn-glycero-3-phosphocholine were significantly higher in the PCOS group. Compounds such as L-methyladenosine, cystine, glu-gln and 2,2’-methylene-bis(6-tert-butyl-4-methylphenol) were significantly lower. In the pathway analysis performed using KEGG database, sphygolipid metabolism, sphygolipid signaling pathway, neuroactive ligand-receptor interaction and phenylalanine metabolism were found to be the most affected pathways. Conclusion This study demonstrates distinct alterations in lipid and amino acid metabolism in PCOS and highlights the accumulation of exogenous molecules, including endocrine disruptors, in patient serum. By integrating metabolomic profiling with clinical phenotyping, our findings provide novel insights into PCOS pathophysiology and suggest potential serum biomarkers that may support early diagnosis and personalized therapeutic approaches.