Preliminary lipidomics and transcriptomics reveals stage-specific dynamic metabolic patterns from menopause transition to postmenopause

Objective: This study aimed to systematically analyze the clinical indicators, lipid metabolism, and leukocyte transcriptomic profiles of premenopausal, menopause transition, and postmenopausal women. It sought to explore stage-specific characteristics of lipid metabolism and gene expression and their potential associations with key clinical indicators. Methods: Clinical indicators were collected, and untargeted lipidomics and leukocyte transcriptomic sequencing were performed. Multivariate statistical analyses were used to assess intergroup differences. Significant patterns in lipid and gene expression changes were identified through trend clustering, volcano plots, and Venn diagram analyses. GO and KEGG enrichment analyses were conducted to investigate the biological functions and pathway enrichment of differentially expressed genes. Results: With advancing menopausal stages, E2 levels were lower, while FSH and LH levels were higher. BMI was higher during the menopause transition and subsequently declined, whereas CHOL and LDLC levels were higher in both the menopause transition and postmenopause stages.Specific lipid classes showed partial return to baseline or further regulation in postmenopause. Transcriptomic analysis identified stage-specific differentially expressed genes enriched in inflammation- and lipid metabolism-related pathways. E2 was positively correlated with lipid molecules and marker genes, but negatively correlated with CHOL. Conclusion: This preliminary study indicates that menopausal stages are associated with significant stage-specific differences in lipid metabolism and gene expression, with the menopause transition identified as a critical phase of lipid metabolic reorganization. Certain lipids and genes may serve as potential biomarkers for menopause-associated metabolic differences. These findings provide important insights for early warning and intervention strategies targeting menopause-related health issues.