XY karyotype men have about twice the volume and twice the number of neurons as XX karyotype women in two regions of the brain, called the BSTc and INAH3 regions. (Bao, Kruijver) An early study of cadaver brains found that transwomen have roughly the same numbers of neurons in these areas as XX women (Zhou), and this has been backed up by further non-invasive imaging studies. (Bao, Kruijver) A single transman who was tested was found to have an XY male number of neurons.(Bao, Kruijver) However, it should be noted that in the imaging study, the differences from person to person were somewhat wide-ranging, and the sample sizes were very small.
MRI data from 24 transwomen who had not started hormone treatment revealed that while their overall grey matter appeared similar to that of XY karyotype males, they possessed a significantly larger amount of grey matter in the right putamen. In fact, the grey matter structure of the transwomen was much closer to those seen in XX karyotype female subjects. In short, while the brains of the transwomen resembled XY male brains in terms of grey matter, in one specific region their brains appeared to be “feminized.” (Luders)
A study of the white matter in the brains of 18 transmen, 24 XY karyotype males, and 19 XX karyotype females using diffusion tensor imaging (DTI) showed that the white matter structure of transmen was much closer to that of XY males than XX females. In fact, the white matter of their brain differed from the XY males only in a single region of the brain, whereas they differed from the XX women in three regions of the brain. None of the transmen had received hormone treatment at the time of the study. (Rametti, 2011) A follow-up study by the same researchers found that after the transmen had received hormone treatment, significant changes occurred in their brains, making them appear even more masculinized in certain regions which are associated with XY males. (Rametti, 2012)
A positron emission tomography (PET) study showed that smelling androgens (male pheromones) caused transwomen to respond in the hypothalamus region of their brain in a manner similar to XX karyotype women. However, smelling estrogen-based pheromones also caused them to respond in the hypothalamus region in a manner similar to XY karyotype men. This combination of results suggests that transwomen occupy an “intermediate position with predominantly female features” in the way the hypothalamus reacted. (Berglund)
An MRI study of 22 transwomen and 28 transmen examined the shape of the corpus callosum in the brain at a specific cross-sectional plane, and compared this shape with that observed in 211 XY karyotype males and 211 XX karyotype females. Their results demonstrated that not only could the sex of the patient be determined with 74% accuracy from the MRI picture, but the shapes of the brains in the transsexuals strongly reflected their gender, and not their biological sex. (Yokota)
A recent study examined cortical thickness in the brain between 29 XY karyotype males, 23 XX karyotype females, 24 transmen, and 18 transwomen. None of the transsexual subjects had received any hormone treatment prior to the study. Using an MRI, the researchers found that the transwomen had more cortical thickness than the XY males in three regions of the brain. The transmen showed evidence of masculinization of their grey matter. In all transsexuals studied, the key differences from their biological sex were found in the right hemisphere. (Zubiaurre)
Testing of a chemical produced in our bodies called “brain-derived neurotropic factor” (BDNF) in 45 transwomen found that when they were compared with 66 XY karyotype male control subjects, the transwomen had significantly lower levels of BDNF. However, this could be a result of higher stress levels and higher emotional trauma levels in the transsexual sampling. It should also be noted that no women control subjects were compared in this study. (Fontanari)
Genetic testing of 112 transwomen and 258 XY karyotype male control subjects found that the transwomen had significant differences in androgen receptor genes. The result of this difference could lead to less effective testosterone signaling, meaning that there would be significantly less “masculinization” of the brain in the womb. This would result in a brain which was much more feminized, leading to a female gender identity. (Hare)
An admittedly small study of 9 post-operative transwomen showed their brain activation was similar to women when viewing pictures showing erotic male images. (Oh) However, this study doesn’t so much address the root cause of the transsexuality as it shows that their sexual attraction towards men led to the same brain reaction as seen in heterosexual women.