University of Oulu

Wang et al. BMC Medicine (2018) 16:17, DOI 10.1186/s12916-018-1008-8

Metabolic characterization of menopause : cross-sectional and longitudinal evidence

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Author: Wang, Qin1; Ferreira, Diana L. Santos1; Nelson, Scott M.2;
Organizations: 1Computational Medicine, Faculty of Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
2School of Medicine, University of Glasgow, Glasgow, UK
3Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
4MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK
5Population Health Science, Bristol Medical School, University of Bristol, Bristol, UK
6NMR Metabolomics Laboratory, School of Pharmacy, University of Eastern Finland, Kuopio, Finland
7Systems Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Australia
8Department of Epidemiology and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, School of Public Health and Preventive Medicine, The Alfred Hospital, Monash University, Melbourne, Australia
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2018-03-15


Background: Women who experience menopause are at higher cardiometabolic risk and often display adverse changes in metabolic biomarkers compared with pre-menopausal women. It remains elusive whether the changes in cardiometabolic biomarkers during the menopausal transition are due to ovarian aging or chronological aging. Well-conducted longitudinal studies are required to determine this. The aim of this study was to explore the crosssectional and longitudinal associations of reproductive status, defined according to the 2012 Stages of Reproductive Aging Workshop criteria, with 74 metabolic biomarkers, and establish whether any associations are independent of age-related changes.

Methods: We determined cross-sectional associations of reproductive status with metabolic profiling in 3,312 UK midlife women. In a subgroup of 1,492 women who had repeat assessments after 2.5 years, we assessed how the change in reproductive status was associated with the changes in metabolic biomarkers. Metabolic profiles were measured by high-throughput quantitative nuclear magnetic resonance metabolomics. In longitudinal analyses, we compared the change in metabolic biomarkers for each reproductive-status category change to that of the reference of being pre-menopausal at both time points. As all women aged by a similar amount during follow-up, these analyses contribute to distinguishing age-related changes from those related to change in reproductive status.

Results: Consistent cross-sectional and longitudinal associations of menopause with a wide range of metabolic biomarkers were observed, suggesting the transition to menopause induces multiple metabolic changes independent of chronological aging. The metabolic changes included increased concentrations of very small very low-density lipoproteins, intermediate-density lipoproteins, low-density lipoproteins (LDLs), remnant, and LDL cholesterol, and reduced LDL particle size, all toward an atherogenic lipoprotein profile. Increased inflammation was suggested via an inflammatory biomarker, glycoprotein acetyls, but not via C-reactive protein. Also, levels of glutamine and albumin increased during the transition. Most of these metabolic changes seen at the time of becoming post-menopausal remained or became slightly stronger during the post-menopausal years.

Conclusions: The transition to post-menopause has effects on multiple circulating metabolic biomarkers, over and above the underlying age trajectory. The adverse changes in multiple apolipoprotein-B-containing lipoprotein subclasses and increased inflammation may underlie women’s increased cardiometabolic risk in their post-menopausal years.

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Series: BMC medicine
ISSN: 1741-7015
ISSN-E: 1741-7015
ISSN-L: 1741-7015
Volume: 16
Article number: 17
DOI: 10.1186/s12916-018-1008-8
Type of Publication: A1 Journal article – refereed
Field of Science: 3141 Health care science
Funding: This study is funded by the British Heart Foundation (SP/07/008/24066), Wellcome (WT092830M;, and the UK Medical Research Council (G1001357). ALSPAC receives core funding from the University of Bristol, Wellcome, and the UK Medical Research Council (102215/2/13/2). MAK receives funding from the Sigrid Juselius Foundation, Finland. DLSF, MAK, and DAL work in a unit that receives funds from the University of Bristol and the UK Medical Research Council (MC_UU_12013/1 and MC_UU_12013/5). DAL is a senior investigator for the National Institute for Health Research (NF-SI-0611–10196).
Copyright information: © The Author(s). 2018. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.