Detection of urine metabolites in polycystic ovary syndrome by UPLC triple-TOF-MS

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder whose pathogenesis remains unclear. There are also no effective biomarkers for this disease. We evaluated the metabolic changes in PCOS patients and to investigate potential metabolic biomarkers for PCOS. Methods: Twenty-two women with PCOS and 15 healthy controls were studied. Urine samples were assessed through ultra-performance liquid chromatography-mass spectrometry followed by principal component analysis and partial least squares discriminant analysis. Results: Using the presented methods, 59 urine metabolites were found at different concentrations in PCOS patients. Moreover, two novel potential biomarkers, testosterone-glucuronide and 11 alpha-hydroxyprogesterone, and four candidate biomarkers, benzofenap, methionyl-phenylalanine, MG(18:4(6Z,9Z,12Z,15Z)/0:0/0:0) and 2-(14,15-epoxyeicosatrienoyl) glycerol, were found to show significant differences through variance analysis (P<0.01) and were identified as target metabolites. The two potential biomarkers identified in this study highly correlate to the metabolites catalyzed by the ovarian cytochrome P450c17 alpha. Conclusions: Two novel potential urinary biomarkers, testosterone-glucuronide and 11 alpha-hydroxyprogesterone, and four candidate urinary biomarkers, benzofenap, methionyl-phenylalanine, MG(18:4(6Z,9Z,12Z,15Z)/0:0/0:0), and 2-(14,15-epoxyeicosatrienoyl) glycerol, were identified in PCOS patients by a metabolomic approach. Further study of the biomarkers using larger populations is needed to validate these biomarkers and thereby understand the pathogenesis of PCOS, potentially allowing for its diagnosis. (C) 2015 Elsevier B.V. All rights reserved.