Abstract
OBJECTIVE: Bile acids are indispensable modulators in the development of polycystic ovary syndrome (PCOS). Our previous study identified that metformin and canagliflozin have similar efficacy in patients with PCOS combined with insulin resistance (IR). However, the effect of metformin or canagliflozin on bile acid metabolism in patients with PCOS has not been elucidated. The objective of this study was to use targeted metabolomics technology to compare alterations of circulating bile acid metabolites in patients with PCOS before and after treatment with metformin or canagliflozin. DESIGN AND PATIENTS: This study was a subanalysis of a previous randomized open-label study, in which patients with PCOS combined with IR were enrolled and treated with either metformin (n = 35) or canagliflozin (n = 33) for 12 weeks. MEASUREMENTS: The serum bile acid profile was measured using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The differences in serum bile acid metabolites in patients with PCOS before and after treatment were analyzed. In addition, the correlation between bile acid metabolites and PCOS-related clinical characteristics was evaluated. RESULTS: There were no significant differences in serum bile acid metabolites in patients with PCOS before and after canagliflozin treatment. Metformin treatment substantially decreased serum total bile acid levels in patients with PCOS, especially primary conjugated bile acids. The levels of taurochenodeoxycholic acid (TCDCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) showed significant differences from baseline in the serum of patients with PCOS after treatment with metformin. Correlation analysis showed that alterations of GCA, TCDCA, and GCDCA were associated with changes in multiple clinical parameters of patients with PCOS treated with metformin. CONCLUSION: The effects of metformin and canagliflozin on bile acids metabolism in patients with PCOS are different. The beneficial effects of metformin on PCOS may be related to the changes in bile acid metabolites. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04700839.