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 Jul;37(7):e70026.
doi: 10.1111/jne.70026. Epub 2025 Mar 27.

The effects of feminization hormone therapy on the brain of transgender women: A hypothesis

Leire Zubiaurre-Elorza  1 , Carme Uribe  2 , Alberto Marcos  3 , Rosa Fernández  4 , Eduardo Pásaro  4 , Mª Cruz Rodríguez Del Cerro  3 , Sarah M Burke  5 , Antonio Guillamon  3
Affiliations
Review

The effects of feminization hormone therapy on the brain of transgender women: A hypothesis

Leire Zubiaurre-Elorza et al. J Neuroendocrinol. 2025 Jul.

Abstract

Gender-affirming hormone therapy (GAHT) is a medical treatment used to help transgender individuals align their physical appearance with their gender identity. GAHT in transgender women (TW) has been found to lead to a reduction in brain tissue with an expansion of the ventricles. We discuss an animal model studying the effects of GAHT that suggests dehydration of brain tissue and an alteration in the relative concentration of brain metabolites. We hypothesize that estradiol, acting on astrocytes, alters cerebral blood flow, water metabolism, and metabolite concentration and argue that these changes could explain the higher risk of stroke observed in GAHT-treated TW compared to untreated cisgender men. Future studies should clarify the mechanisms underlying the brain tissue changes induced by GAHT.

Keywords: MRI; astrocytes; estradiol; fractional anisotropy; transgender women.

PubMed Disclaimer

References

REFERENCES

    1. Osterlund MK, Grandien K, Keller E, Hurd YL. The human brain has distinct regional expression patterns of estrogen receptor alpha mRNA isoforms derived from alternative promoters. J Neurochem. 2000;75(4):1390‐1397.
    1. Osterlund MK, Gustafsson JA, Keller E, Hurd YL. Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: distinct distribution pattern to ERalpha mRNA. J Clin Endocrinol Metab. 2000;85(10):3840‐3846.
    1. González M, Cabrera‐Socorro A, Pérez‐García CG, et al. Distribution patterns of estrogen receptor alpha and beta in the human cortex and hippocampus during development and adulthood. J Comp Neurol. 2007;503(6):790‐802.
    1. Biegon A. In vivo visualization of aromatase in animals and humans. Front Neuroendocrinol. 2016;40:42‐51.
    1. Krause DN, Duckles SP, Gonzales RJ. Local oestrogenic/androgenic balance in the cerebral vasculature. Acta Physiol (Oxf). 2011;203(1):181‐186.

LinkOut - more resources