A hypothesis article published in Journal of Neuroendocrinology by the group of Guillamón, Fernández and Pásaro (UNED and University of A Coruña) proposes an integrative framework for how feminizing hormone therapy —estrogens combined with antiandrogens— modifies the brain structure of transgender women.
Feminizing gender-affirming hormone therapy (GAHT) produces widely documented somatic changes, but its effects on the central nervous system remain a matter of debate. This work proposes that estrogens exert a modulatory role on cortical and subcortical regions involved in body perception and identity, in line with studies showing increases in cortical thickness or changes in connectivity after treatment.
The authors articulate their hypothesis from three lines of evidence: previous neuroimaging studies in transgender people, the literature on sex steroid-mediated brain plasticity in animal models and humans, and the group’s own data on estrogen and androgen receptors. They argue that the brain is not a statically dimorphic organ but rather retains plasticity throughout adult life, susceptible to modulation by the hormonal environment.
The text underscores the need for longitudinal studies with a controlled design that allow separating the hormonal effects from the changes associated with the very experience of identity. It also points out important limitations of the current literature, such as the heterogeneity of therapeutic regimens, small sample sizes and the absence of long-term follow-up.
This is a theoretical-oriented work that, without contributing new data, organizes and systematizes the available evidence and proposes testable hypotheses for future research on hormone-induced brain plasticity in the context of gender dysphoria.
Bibliographic reference
Zubiaurre-Elorza L, Uribe C, Marcos A, et al. The effects of feminization hormone therapy on the brain of transgender women: A hypothesis. J Neuroendocrinol. 2025;37(7):e70026.
DOI: https://doi.org/10.1111/jne.70026
PMID: 40145530
Publication consultation: the original reference can be consulted in open access or through the DOI indicated.
