Long-Term Plasma Metabolite Changes During Menopause and Metabolic Syndrome Risk
Overview
This longitudinal study of 953 women over approximately 5 years identified significant changes in 18 plasma metabolites during menopause, particularly involving branched-chain amino acids (BCAAs), urea cycle, and homocysteine metabolism. Elevated glutamate and other metabolites were linked to an increased risk of developing metabolic syndrome (MetS) and hyperglycemia post-menopause.
Background
Menopause induces substantial metabolic alterations that increase the risk of metabolic syndrome (MetS), a cluster of conditions including hyperglycemia, dyslipidemia, hypertension, and abdominal obesity. MetS prevalence is notably higher in postmenopausal women, contributing to increased cardiovascular disease and stroke risk. While lipid changes have been studied, the role of amino acids such as BCAAs and homocysteine in MetS development during menopause remains less understood. Long-term metabolomic data are needed to clarify these associations.
Data Highlights
Metabolite
Change with Menopause
Association with MetS Risk (Odds Ratio [95% CI])
Glutamate
Increased
1.95 [1.49-2.57]
Valine
Increased
Significantly associated with hyperglycemia development
Leucine
Increased
Significantly associated with hyperglycemia development
Cystine
Increased
Significantly associated with hyperglycemia development
Key Findings
Eighteen plasma metabolites changed significantly during menopause, especially those related to BCAA metabolism, urea cycle, and homocysteine metabolism.
Among 695 women without MetS at baseline, 9.4% developed MetS over follow-up.
Higher glutamate levels were strongly associated with increased risk of MetS (OR 1.95).
Elevated glutamate, valine, leucine, and cystine levels were linked to the development of hyperglycemia.
Longitudinal metabolomic profiling revealed that charged metabolites undergo significant alterations during the menopausal transition.
Clinical Implications
Monitoring plasma metabolites such as glutamate and BCAAs during and after menopause may help identify women at higher risk for developing metabolic syndrome and hyperglycemia. Early detection of these metabolic changes could inform timely interventions to mitigate cardiovascular and metabolic disease risk in postmenopausal women.
Conclusion
Menopause is associated with significant long-term changes in plasma metabolites that contribute to increased metabolic syndrome risk. Targeting these metabolic alterations may improve prevention strategies for metabolic disorders in aging women.
References
Tsuruoka Metabolomics Cohort Study/2024 -- Long-Term Analysis of Plasma Metabolite Changes During Menopause and Their Links to Subsequent Development of Metabolic Syndrome
