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Introduction Untreated transsexuals have a brain cortical phenotype. Cross-sex hormone treatments are used to masculinize or feminize the bodies of female-to-male (FtMs) or male-to-female (MtFs) transsexuals, respectively. Aim A longitudinal design was conducted to investigate the effects of treatments on brain cortical thickness (CTh) of FtMs and MtFs. Methods This study investigated 15 female-to-male (FtMs) and 14 male-to-female (MtFs) transsexuals prior and during at least six months of cross-sex hormone therapy treatment. Brain MRI imaging was performed in a 3-Tesla TIM-TRIO Siemens scanner. T1-weighted images were analyzed with FreeSurfer software to obtain CTh as well as subcortical volumetric values. Main Outcome Measures Changes in brain CTh thickness and volumetry associated to changes in hormonal levels due to cross-sex hormone therapy. Results After testosterone treatment, FtMs showed increases of CTh bilaterally in the postcentral gyrus and unilaterally in the inferior parietal, lingual, pericalcarine, and supramarginal areas of the left hemisphere and the rostral middle frontal and the cuneus region of the right hemisphere. There was a significant positive correlation between the serum testosterone and free testosterone index changes and CTh changes in parieto-temporo-occipital regions. In contrast, MtFs, after estrogens and antiandrogens treatment, showed a general decrease in CTh and subcortical volumetric measures and an increase in the volume of the ventricles. Conclusions Testosterone therapy increases CTh in FtMs. Thickening in cortical regions is associated to changes in testosterone levels. Estrogens and antiandrogens therapy in MtFs is associated to a decrease in the CTh that consequently induces an enlargement of the ventricular system.

Sex differences in cortical thickness (CTh) have been extensively investigated but as yet there are no reports on CTh in transsexuals. Our aim was to determine whether the CTh pattern in transsexuals before hormonal treatment follows their biological sex or their gender identity. We performed brain magnetic resonance imaging on 94 subjects: 24 untreated female-to-male transsexuals (FtMs), 18 untreated male-to-female transsexuals (MtFs), and 29 male and 23 female controls in a 3-T TIM-TRIO Siemens scanner. T1-weighted images were analyzed to obtain CTh and volumetric subcortical measurements with FreeSurfer software. CTh maps showed control females have thicker cortex than control males in the frontal and parietal regions. In contrast, males have greater right putamen volume. FtMs had a similar CTh to control females and greater CTh than males in the parietal and temporal cortices. FtMs had larger right putamen than females but did not differ from males. MtFs did not differ in CTh from female controls but had greater CTh than control males in the orbitofrontal, insular, and medial occipital regions. In conclusion, FtMs showed evidence of subcortical gray matter masculinization, while MtFs showed evidence of CTh feminization. In both types of transsexuals, the differences with respect to their biological sex are located in the right hemisphere.

Cross-sex hormonal treatment, family support, and working or studying are linked to a better self-reported QoL in transsexuals. Healthcare providers should consider these factors when planning interventions to promote the health-related QoL of transsexuals.