Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Aug 22;396(10250):565-582.
doi: 10.1016/S0140-6736(20)31561-0.

Sex and gender: modifiers of health, disease, and medicine

Franck Mauvais-Jarvis  1 , Noel Bairey Merz  2 , Peter J Barnes  3 , Roberta D Brinton  4 , Juan-Jesus Carrero  5 , Dawn L DeMeo  6 , Geert J De Vries  7 , C Neill Epperson  8 , Ramaswamy Govindan  9 , Sabra L Klein  10 , Amedeo Lonardo  11 , Pauline M Maki  12 , Louise D McCullough  13 , Vera Regitz-Zagrosek  14 , Judith G Regensteiner  15 , Joshua B Rubin  16 , Kathryn Sandberg  17 , Ayako Suzuki  18
Affiliations
Review

Sex and gender: modifiers of health, disease, and medicine

Franck Mauvais-Jarvis et al. Lancet. .

Erratum in

  • Department of Error.
    [No authors listed] [No authors listed] Lancet. 2020 Sep 5;396(10252):668. doi: 10.1016/S0140-6736(20)31827-4. Lancet. 2020. PMID: 32891210 Free PMC article. No abstract available.

Abstract

Clinicians can encounter sex and gender disparities in diagnostic and therapeutic responses. These disparities are noted in epidemiology, pathophysiology, clinical manifestations, disease progression, and response to treatment. This Review discusses the fundamental influences of sex and gender as modifiers of the major causes of death and morbidity. We articulate how the genetic, epigenetic, and hormonal influences of biological sex influence physiology and disease, and how the social constructs of gender affect the behaviour of the community, clinicians, and patients in the health-care system and interact with pathobiology. We aim to guide clinicians and researchers to consider sex and gender in their approach to diagnosis, prevention, and treatment of diseases as a necessary and fundamental step towards precision medicine, which will benefit men's and women's health.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Genetic causes of sex differences (A) Genetic sex differences start with cells carrying either XX or XY chromosome complement (eg, genes outside the testis-determining SRY gene), which generates ubiquitous sex differences in the molecular makeup of all male and female cells. (B) Random inactivation of one X chromosome in female cells causes another level of sex differences in gene expression. Some X-linked genes escape inactivation in female individuals and have a higher expression in female than male individuals. (C) The Y chromosomal SRY gene directs the development of a testis in male individuals, which produces a surge of testicular testosterone at the end of pregnancy. The testosterone surge programmes cellular gene expression and tissue structure in multiple organs of male individuals via epigenetic remodelling. The combination of these genetic and developmental events programmes sex differences in physiology and susceptibility to diseases that will manifest in adulthood.
Figure 2
Figure 2
Inter-relation between sex and gender in health, diseases, and medicine Biological sex causes sex differences through genetic and hormonal influences in disease pathophysiology, clinical manifestations, and response to treatment. Sex also influences behaviours (towards more aggressive or caring phenotypes). On the other hand, gender-related behaviours (eg, smoking, lifestyle, perceived stress, and nutritional habits) produce epigenetic modifications that modulate the expression of biological sex. Gender constructs determine patients' perception of disease, help-seeking behaviour, and individual use of health care. Gender constructs also influence decision making and trigger different therapeutic responses from providers, biased by gender.
Figure 3
Figure 3
Percent distribution of the ten leading causes of death, by sex: USA, 2017 Adapted from Heron. CPD=chronic pulmonary disease.
Figure 4
Figure 4
Disabling disorders with high sex influence on prevalence For each disease, bars represent the prevalence (%) in male individuals and female individuals.
Figure 5
Figure 5
Summary of recommendations to promote sex and gender equity in the biomedical enterprise
See this image and copyright information in PMC

References

    1. Clayton JA. Studying both sexes: a guiding principle for biomedicine. FASEB J. 2016;30:519–524. - PMC - PubMed
    1. Schiebinger L, Leopold SS, Miller VM. Editorial policies for sex and gender analysis. Lancet. 2016;388:2841–2842. - PubMed
    1. Geller SE, Koch AR, Roesch P, Filut A, Hallgren E, Carnes M. The more things change, the more they stay the same: a study to evaluate compliance with inclusion and assessment of women and minorities in randomized controlled trials. Acad Med. 2018;93:630–635. - PMC - PubMed
    1. Klein SL, Schiebinger L, Stefanick ML, et al. Opinion: sex inclusion in basic research drives discovery. Proc Natl Acad Sci USA. 2015;112:5257–5258. - PMC - PubMed
    1. Danska JS. Sex matters for mechanism. Sci Transl Med. 2014;6 - PubMed

Publication types