Review Article | Published:

The effects of oestrogens and their receptors on cardiometabolic health

Nature Reviews Endocrinology volume 13, pages 352364 (2017) | Download Citation


Cardiovascular disease (CVD) is one of the leading causes of mortality in developed countries. The incidence of CVD is sexually dimorphic, and research has focused on the contribution of sex steroids to the development and progression of the cardiometabolic syndrome, which is defined as a clustering of interrelated risk factors that promote the development of atherosclerosis (which can lead to CVD) and type 2 diabetes mellitus. Data are inconclusive as to how sex steroids and their respective receptors increase or suppress the risk of developing the cardiometabolic syndrome and thus CVD. In this Review, we discuss the potential role, or roles, of sex hormones in cardiometabolic health by first focusing on the influence of oestrogens and their receptors on the risk of developing cardiometabolic syndrome and CVD. We also highlight what is known about testosterone and its potential role in protecting against the development of the cardiometabolic syndrome and CVD. Given the inconclusive nature of the data regarding the direct effects of each sex hormone, we advocate and highlight the importance of studying the relative levels and the ratio of sex hormones to each other, as well as the use of cross sex hormone therapy and its effect on cardiometabolic health.

Key points

  • Cardiometabolic syndrome is a cluster of diseases (including type 2 diabetes mellitus (T2DM) and atherosclerosis) that can result in cardiovascular disease (CVD), a leading cause of mortality in developed countries

  • The incidence of CVD differs between men and women, but the reason for this dimorphism remains elusive because most basic and clinical research has been conducted predominantly in men

  • Premenopausal women have a reduced risk of CVD compared with age-matched men, and mortality as a result of CVD is higher in premenopausal women than in age-matched men; however, questions remain about the protective role of oestrogens

  • Physiological concentrations of oestrogens in men seem to protect against the development of T2DM and might mediate reductions in the risk of CVD

  • Oestrogens act in target tissues through oestrogen receptors and G protein-coupled oestrogen receptor 1 to reduce the risk of CVD

  • Sex hormones and their contribution to the risk of CVD should be evaluated by looking at the relative ratios of oestrogens to androgens rather than to their specific effects in isolation

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E.M. is supported by the Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) grant 1160820. R.S.S. is supported by Fundação de Amparo à Pesquisa do Estado de São Paulo-FAPESP grants 2012/50430-9 and 2013/07607-8. A.C. is supported by the FONDECYT grant 1140908 and by Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP) Advanced Center for Chronic Diseases (ACCDiS) grant 15130011.

Author information


  1. Department of Physiology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile.

    • Eugenia Morselli
  2. Obesity and Comorbidities Research Center, Institute of Biology, State University of Campinas, Campinas 1, 3083–864, Brazil.

    • Roberta S. Santos
  3. Cedars-Sinai Diabetes and Obesity Research Institute, Department of Biomedical Research, Los Angeles, California 90048, USA.

    • Roberta S. Santos
    •  & Deborah J. Clegg
  4. Advanced Center for Chronic Diseases (ACCDiS) and Center for Molecular Studies of the Cell (CEMC), Santiago 8380000, Chile.

    • Alfredo Criollo
  5. Instituto de Investigación en Ciencias Odontológicas (ICOD), Facultad de Odontología, Universidad de Chile, Santiago 8380492, Chile.

    • Alfredo Criollo
  6. Applied Physiology and Advanced Imaging Laboratory, Department of Kinesiology, University of Texas at Arlington, Texas 76019, USA.

    • Michael D. Nelson
  7. Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.

    • Biff F. Palmer


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E.M., R.S.S. and D.J.C. researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the article before submission. A.C., M.D.N. and B.F.P. contributed to discussion of the content.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Deborah J. Clegg.


Oestrogenic effects

Oestrogen is the primary female sex hormone. It is responsible for the development and regulation of the female reproductive system and secondary sex characteristics.


The covalent attachment of fatty acids, such as palmitic acid, to cysteine and less frequently to serine and threonine residues of proteins, which are typically membrane proteins.


A special type of lipid raft, they are small (50–100 nanometres) invaginations of the plasma membrane in many vertebrate cell types, especially in endothelial cells and adipocytes.

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