Diffusion tensor imaging (DTI) can sensitively detect white matter sex differences and the effects of pharmacological treatments. Before cross-sex hormone treatment, the white matter microstructure of several brain bundles in female-to-male transsexuals (FtMs) differs from those in females but not from that in males. The purpose of this study was to investigate whether cross-sex hormone treatment (androgenization) affects the brain white matter microstructure. Using a Siemens 3 T Trio Tim Magneton, DTI was performed twice, before and during cross-sex hormonal treatment with testosterone in 15 FtMs scanned. Fractional anisotropy (FA) was analyzed on white matter of the whole brain, and the latter was spatially analyzed using Tract-Based Spatial Statistics. Before each scan the subjects were assessed for serum testosterone, sex hormone binding globulin level (SHBG), and their free testosterone index. After at least seven months of cross-gender hormonal treatment, FA values increased in the right superior longitudinal fasciculus (SLF) and the right corticospinal tract (CST) in FtMs compared to their pre-treatment values. Hierarchical regression analyses showed that the increments in the FA values in the SLF and CST are predicted by the free testosterone index before hormonal treatment. All these observations suggest that testosterone treatment changes white matter microstructure in FtMs.
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