Sex-steroid hormones such as testosterone and estradiol play a key role in sexual differentiation during gestation but exert also strong effects on the body and the brain during puberty or even in adulthood. In addition, influences on cognition and emotional processing are frequently reported. The investigations of transgender people undergoing cross-sex hormone therapy provide a unique model for studying those effects on gray and white matter brain structure in vivo by using the technique of structural magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). The investigation of white matter brain structure using DWI in 29 female-to-male (FtM) and 15 male-to-female (MtF) before treatment and after one and 4 months of continuous hormonal administration led to alterations in several white matter tracts. In FtMs, decreases in mean diffusivity (MD) and increases in fractional anisotropy (FA) values were detected, while in MtFs the opposite results were found (Kranz et al., 2017). As the hypothalamus is thought to be crucially involved in hormonal regulation, changes were assessed in this specific brain region, again after those two time points in comparison to baseline. The analysis in 25 FtM participants showed unilateral MD reductions after 1 month and bilateral decreases after 4 months of treatment (Kranz et al., 2018). Those results suggest androgenization-related effects in FtM and feminization-related changes in MtF. The assessment of gray matter changes due to hormonal administration after 4 months revealed widespread decreases in subcortical areas, most pronounced in the hippocampus for 14 MtF subjects, who received estradiol and anti-androgens (Seiger et al., 2016). In addition, decreases in 18 FtMs were found in Broca's and Wernicke's areas with higher levels of bioavailable testosterone after one month explicitly in those areas related to speech and language processing. Simultaneously, a strengthening of the fiber tract connecting those two brain regions was observed (Hahn et al., 2016).
References: Kranz GS, Seiger R, Kaufmann U, et al. Effects of sex hormone treatment on white matter microstructure in individuals with gender dysphoria. Neuroimage. 2017;150:60-67.
Kranz GS, Hahn A, Kaufmann U, et al. Effects of testosterone treatment on hypothalamic neuroplasticity in female-to-male transgender individuals. Brain Struct Funct. 2018;223(1):321-328.
Seiger R, Hahn A, Hummer A, et al. Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration. Psychoneuroendocrinology. 2016;74:371-379.
Hahn A, Kranz GS, Sladky R, et al. Testosterone affects language areas of the adult human brain. Hum Brain Mapp. 2016;37(5):1738-48.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology