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  • Review article
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Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes

Nature Reviews Cardiology volume 20, pages 236–247 (2023)Cite this article

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Abstract

Despite a growing body of evidence, the distinct contributions of biological sex and the sociocultural dimension of gender to the manifestations and outcomes of ischaemic heart disease and heart failure remain unknown. The intertwining of sex-based differences in genetic and hormonal mechanisms with the complex dimension of gender and its different components and determinants that result in different disease phenotypes in women and men needs to be elucidated. The relative contribution of purely biological factors, such as genes and hormones, to cardiovascular phenotypes and outcomes is not yet fully understood. Increasing awareness of the effects of gender has led to efforts to measure gender in retrospective and prospective clinical studies and the development of gender scores. However, the synergistic or opposing effects of sex and gender on cardiovascular traits and on ischaemic heart disease and heart failure mechanisms have not yet been systematically described. Furthermore, specific considerations of sex-related and gender-related factors in gender dysphoria or in heart–brain interactions and their association with cardiovascular disease are still lacking. In this Review, we summarize contemporary evidence on the distinct effects of sex and gender as well as of their interactions on cardiovascular disease and how they favourably or unfavourably influence the pathogenesis, clinical manifestations and treatment responses in patients with ischaemic heart disease or heart failure.

Key points

  • Sex-related and gender-related factors often have opposite effects on the clinical manifestations and outcomes of cardiovascular disease.

  • Some sex-related differences in the human cardiovascular system already exist at birth and are due to purely biological mechanisms, that is, genes and sex hormones.

  • Gender-related variables or scores allow for the characterization of individuals beyond their biological sex, and the effects of gender might even oppose the effects of biological sex on clinical outcomes.

  • The predominantly male leadership and workforce in clinical cardiology is a disadvantage for women as patients.

  • Cardiovascular disease risk factors related to female biological sex or feminine gender include, among others, pregnancy complications, breast cancer therapy, autoimmune and rheumatic diseases, depression, and household-related stress.

  • Despite a more favourable biology, gender-related factors impair outcomes in women with coronary artery disease or heart failure compared with those in men.

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Fig. 1: Concepts of sex and gender in medicine.
Fig. 2: Interactions between sex and gender in health and disease throughout the life cycle.
Fig. 3: Gender score distribution in females and males in an aged German population.
Fig. 4: Sex-related and gender-related disparities in CVD risk and outcomes.

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Acknowledgements

The authors thank Susan Bengs (University Hospital Zurich, Zurich, Switzerland) for preparing the illustrations for initial submission and Nicola Lott (University Hospital Zurich, Zurich, Switzerland) for proofreading. V.R.-Z. has received research funding from GE Academy H2020-SwafS-2018-2020/EU: 824585; Gendage (01GL1716A), Bundesministerium für Bildung und Forschung (BMBF), Germany; and Gender/Sex in Multiple Sclerosis (ZMV I 1 - 25 20 FSB 431), Bundesministerium für Gesundheit (BMG), Germany. C.G. has received research funding from the Swiss National Science Foundation (SNSF); the Olga Mayenfisch Foundation, Switzerland; the OPO Foundation, Switzerland; the Novartis Foundation, Switzerland; the Swiss Heart Foundation; the Olten Heart Foundation, Switzerland, the Helmut Horten Foundation, Switzerland; the EMDO Foundation, Switzerland; the Iten-Kohaut Foundation, Switzerland, the University Zurich (UZH) Foundation, Switzerland; the University Hospital Zurich (USZ) Foundation, Switzerland; and the LOOP Zurich, Switzerland.

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Authors and Affiliations

  1. Institute for Gender in Medicine, Charité University Medicine Berlin, Berlin, Germany

    Vera Regitz-Zagrosek

  2. Faculty of Medicine, University of Zurich, Zurich, Switzerland

    Vera Regitz-Zagrosek

  3. Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland

    Catherine Gebhard

  4. Department of Cardiology, Inselspital Bern University Hospital, Bern, Switzerland

    Catherine Gebhard

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  1. Vera Regitz-Zagrosek
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V.R.-Z. researched data for the article. Both authors wrote the article and reviewed and/or edited the manuscript before submission.

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Gendered Innovations: https://genderedinnovations.stanford.edu

International Society for Gender Medicine: http://www.isogem.eu/

Organization for the Study of Sex Differences: https://www.ossdweb.org/

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Regitz-Zagrosek, V., Gebhard, C. Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes. Nat Rev Cardiol 20, 236–247 (2023). https://doi.org/10.1038/s41569-022-00797-4

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