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

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.