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
. 2025 Apr;21(4):214-229.
doi: 10.1038/s41574-024-01061-0. Epub 2024 Nov 25.

Leveraging research into sex differences and steroid hormones to improve brain health

Affiliations
Review

Leveraging research into sex differences and steroid hormones to improve brain health

Bonnie H Lee et al. Nat Rev Endocrinol. 2025 Apr.

Abstract

Sex differences, driven in part by steroid hormones, shape the structure and function of the brain throughout the lifespan and manifest across brain health and disease. The influence of steroid hormones on neuroplasticity, particularly in the adult hippocampus, differs between the sexes, which has important implications for disorders and diseases that compromise hippocampus integrity, such as depression and Alzheimer disease. This Review outlines the intricate relationship between steroid hormones and hippocampal neuroplasticity across the adult lifespan and explores how the unique physiology of male and female individuals can affect health and disease. Despite calls to include sex and gender in research, only 5% of neuroscience studies published in 2019 directly investigated the influence of sex. Drawing on insights from depression, Alzheimer disease and relevant hippocampal plasticity, this Review underscores the importance of considering sex and steroid hormones to achieve a comprehensive understanding of disease susceptibility and mechanisms. Such consideration will enable the discovery of personalized treatments, ultimately leading to improved health outcomes for all.

PubMed Disclaimer

Conflict of interest statement

Competing interests: The authors declare no competing interests.

References

    1. Mauvais-Jarvis, F. et al. Sex and gender: modifiers of health, disease, and medicine. Lancet 396, 565–582 (2020). - PubMed - PMC
    1. Heise, L. et al. Gender inequality and restrictive gender norms: framing the challenges to health. Lancet 393, 2440–2454 (2019). - PubMed
    1. Wierenga, L. M. et al. Recommendations for a better understanding of sex and gender in the neuroscience of mental health. Biol. Psychiatry Glob. Open Sci. 4, 100283 (2024). - PubMed
    1. Poganik, J. R. et al. Biological age is increased by stress and restored upon recovery. Cell Metab. 35, 807–820.e5 (2023). - PubMed - PMC
    1. Mehta, D. et al. Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proc. Natl Acad. Sci. USA 110, 8302–8307 (2013). - PubMed - PMC

Substances

LinkOut - more resources