Longitudinal study of plasma metabolites during menopause and their associations with later onset of metabolic syndrome #MMPMID41389027
Miyake A; Iida M; Harada S; Sugiyama D; Matsumoto M; Miyagawa N; Toki R; Edagawa S; Hirata A; Kuwabara K; Okamura T; Sato A; Amano K; Hirayama A; Sugimoto M; Soga T; Tomita M; Arakawa K; Kisu I; Yamagami W; Takebayashi T
J Clin Endocrinol Metab 2025[Dec]; ? (?): ? PMID41389027show ga
CONTEXT: Previous metabolomics studies suggest potential associations between menopausal changes in lipids and an increased risk of metabolic syndrome (MetS). However, longitudinal data on other key metabolites, such as branched-chain amino acids and homocysteine, remain limited, and most studies lack long-term follow-up across the menopause transition. OBJECTIVE: This study aimed to investigate longitudinal changes in circulating metabolites during menopause over a mean follow-up of 5 years and assess their associations with subsequent MetS development. METHODS: Premenopausal women from the Tsuruoka Metabolomics Cohort Study who participated in at least one follow-up survey were included. Menopausal status, data on MetS, and plasma metabolites profiled using capillary electrophoresis mass spectrometry were assessed at each visit. Thirty-one metabolites were examined for associations with menopausal status using mixed-effects models. The association of these menopause-related metabolites with MetS development was examined via logistic regression analysis adjusted for follow-up duration. RESULTS: Among 953 women (43.8 +/- 5.4 years old), 316 (33.2%) reached menopause during follow-up (5.0 +/- 1.1 years). Eighteen metabolites changed significantly with menopause, particularly those related to BCAA metabolism, urea cycle, and homocysteine metabolism. Of 695 women without MetS at baseline, 65 (9.4%) developed MetS. Glutamate (odds ratio [95% confidence interval]: 1.95 [1.49-2.57]) was associated with higher MetS risk. Higher levels of glutamate, valine, leucine, and cystine were significantly associated with the development of hyperglycemia. CONCLUSIONS: Longitudinal changes in charged metabolites occur across the menopausal transition, with specific metabolites such as glutamate possibly contributing to the metabolic alterations underlying increased MetS risk.
J+Clin+Endocrinol+Metab 2025 ; ? (?): ?
