Plasma Metabolic Profiles in Women are Menopause Dependent

Abstract

Menopause is an endocrinological transition that greatly affects health and disease susceptibility in middle-aged and elderly women. To gain new insights into the metabolic process of menopause, plasma metabolic profiles in 115 pre- and post-menopausal women were systematically analyzed by ultra-performance liquid chromatography/mass spectrometry in conjunction with univariate and multivariate statistical analysis. Metabolic signatures revealed considerable differences between pre- and post-menopausal women, and clear separations were observed between the groups in partial least-squares discriminant analysis score plots. In total, 28 metabolites were identified as potential metabolite markers for menopause, including up-regulated acylcarnitines, fatty acids, lysophosphatidylcholines, lysophosphatidylethanolamines, and down-regulated pregnanediol-3-glucuronide, dehydroepiandrosterone sulfate, p-hydroxyphenylacetic acid and dihydrolipoic acid. These differences highlight that significant alterations occur in fatty acid β-oxidation, phospholipid metabolism, hormone metabolism and amino acid metabolism in post-menopausal women. In conclusion, our plasma metabolomics study provides novel understanding of the metabolic profiles related to menopause, and will be useful for investigating menopause-related diseases and assessing metabolomic confounding factors.

Fig 1. PLS-DA three-dimensional scores plots and validation plots.

(A) PLS-DA three-dimensional scores plot for pre-menopausal women versus post-menopausal women in ESI+ mode (three latent variables, R2X = 0.208, R2Y = 0.701, Q2 = 0.306). (B) Validation plot for pre-menopausal women versus post-menopausal women in ESI+ mode. (C) PLS-DA three-dimensional scores plot for pre-menopausal women versus post-menopausal women in ESI- mode (three latent variables, R2X = 0.278, R2Y = 0.713, Q2 = 0.450). (D) Validation plot for pre-menopausal women versus post-menopausal women in ESI- mode.

Fig 2. Heat map demonstrating 28 menopause-related metabolites in 115 pre-menopausal and post-menopausal women.