A1 Journal article (refereed)
Menopause modulates the circulating metabolome : evidence from a prospective cohort study (2022)

Karppinen, J. E., Törmäkangas, T., Kujala, U. M., Sipilä, S., Laukkanen, J., Aukee, P., Kovanen, V., & Laakkonen, E. K. (2022). Menopause modulates the circulating metabolome : evidence from a prospective cohort study. European Journal of Preventive Cardiology, 29(10), 1448-1459. https://doi.org/10.1093/eurjpc/zwac060

JYU authors or editors

Publication details

All authors or editorsKarppinen, Jari E.; Törmäkangas, Timo; Kujala, Urho M.; Sipilä, Sarianna; Laukkanen, Jari; Aukee, Pauliina; Kovanen, Vuokko; Laakkonen, Eija K.

Journal or seriesEuropean Journal of Preventive Cardiology



Publication year2022

Publication date12/05/2022


Issue number10

Pages range1448-1459

PublisherOxford University Press (OUP)

Publication countryUnited Kingdom

Publication languageEnglish


Persistent website addresshttps://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwac060/6580397

Publication open accessOpenly available

Publication channel open accessPartially open access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/82724


We studied the changes in the circulating metabolome and their relation to the menopausal hormonal shift in 17β-oestradiol and follicle-stimulating hormone levels among women transitioning from perimenopause to early postmenopause.

Methods and results
We analysed longitudinal data from 218 Finnish women, 35 of whom started menopausal hormone therapy during the study. The menopausal transition was monitored with menstrual diaries and serum hormone measurements. The median follow-up was 14 months (interquartile range: 8–20). Serum metabolites were quantified with targeted nuclear magnetic resonance metabolomics. The model results were adjusted for age, follow-up duration, education, lifestyle, and multiple comparisons. Menopause was associated with 85 metabolite measures. The concentration of apoB (0.17 standard deviation [SD], 99.5% confidence interval [CI] 0.03–0.31), very-low-density lipoprotein triglycerides (0.25 SD, CI 0.05–0.45) and particles (0.21 SD, CI 0.05–0.36), low-density lipoprotein (LDL) cholesterol (0.17 SD, CI 0.01–0.34) and particles (0.17 SD, CI 0.03–0.31), high-density lipoprotein (HDL) triglycerides (0.24 SD, CI 0.02–0.46), glycerol (0.32 SD, CI 0.07–0.58) and leucine increased (0.25 SD, CI 0.02–0.49). Citrate (−0.36 SD, CI −0.57 to −0.14) and 3-hydroxybutyrate concentrations decreased (−0.46 SD, CI −0.75 to −0.17). Most metabolite changes were associated with the menopausal hormonal shift. This explained 11% and 9% of the LDL cholesterol and particle concentration increase, respectively. Menopausal hormone therapy was associated with increased medium-to-large HDL particle count and decreased small-to-medium LDL particle and glycine concentration.

Menopause is associated with proatherogenic circulating metabolome alterations. Female sex hormones levels are connected to the alterations, highlighting their impact on women’s cardiovascular health.

Keywordsmetabolismmetabolic disordersmetabolic productscardiovascular diseaseshormonal factorsmenopausehormone therapyestradiolcohort study

Free keywordsmenopause; hormone replacement therapy; cardiovascular diseases; metabolomics; oestradiol

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Ministry reportingYes

Reporting Year2022

JUFO rating1

Last updated on 2024-15-06 at 00:26