A Systematic Review of Structural and Functional Brain Differences between Transgender and Cisgender Individuals: Findings from Neuroimaging Studies

Introduction: Gender dysphoria (GD) in transgender individuals is often treated with gender-affirming hormone therapy (GAHT), which may induce structural and functional brain changes. While sex hormones significantly influence brain morphology, the neurobiological effects of GAHT remain insufficiently understood. Recent imaging studies suggest alterations in brain regions linked to body perception and self-awareness. Method A comprehensive search of PubMed, Scopus, and Web of Science was conducted to identify neuroimaging studies on brain alterations in transgender individuals before and/or after hormone therapy. Eligible studies included adult transgender participants, cisgender controls, and used imaging modalities such as MRI, fMRI, DTI, VBM, or PET. Data extraction and quality assessment were independently performed using the Newcastle-Ottawa Scale. Results Across 22 neuroimaging studies, transgender individuals showed consistent structural and functional brain differences compared with cisgender controls. Pre-hormone therapy findings indicated distinct gray- and white-matter patterns and altered connectivity within the default mode and body-perception networks. Following gender-affirming hormone therapy, region-specific, hormone-dependent changes were observed in cortical and subcortical structures, accompanied by network-level reorganization. Discussion Transgender individuals exhibit distinct structural and functional brain characteristics compared with cisgender controls. Before GAHT, differences in gray and white matter and altered connectivity within self-referential networks indicate unique neurodevelopmental patterns. Following hormone therapy, region-specific, hormone-dependent neuroplasticity emerges, particularly within the insula, prefrontal, and limbic regions. These findings suggest that both early neurodevelopmental processes and endocrine modulation contribute to the neural diversity underlying gender identity.