Brain structure
In the first of its kind, Zhou et al (1995) found that in a region of the brain called the bed nucleus of the stria terminalis (BSTc), a region known for sex and anxiety responses, MTF transsexuals have a female-normal size while FTM transsexuals have a male-normal size. While the transsexuals studied had taken hormones, this was accounted for by including non-transsexual male and female controls which, for a variety of medical reasons, had experienced hormone reversal. The controls still retained sizes typical for their gender. No relationship to sexual orientation was found.[20]
In a followup study, Kruijver et al (2000) looked at the number of neurons in BSTc instead of volumes. They found the same results as Zhou et al (1995), but with even more dramatic differences. One MTF subject who had never gone on hormones was also included, and who matched up with the female neuron counts nonetheless.[21]
In 2002, a followup study by Chung, De Vries, and Swaab found that significant sexual dimorphism (variation between sexes) in BSTc did not become established until adulthood. Chung et al theorized that either changes in fetal hormone levels produce changes in BSTc synaptic density, neuronal activity, or neurochemical content which later lead to size and neuron count changes in BSTc, or that the size of BSTc is affected by the failure to generate a gender identity consistent with one's anatomic sex.[22]
In a review of the evidence in 2006, Gooren confirms the earlier research as supporting the concept that transsexualism is a sexual differentiation disorder of the sex dimorphic brain.[23] Swaab (2004) concurs.[24]
In 2008, a new region with properties similar to that of BSTc in regards to transsexualism was found by Garcia-Falgueras and Swaab: the interstitial nucleus of the anterior hypothalamus (INAH3), part of the hypothalamic uncinate nucleus. The same method of controlling for hormone usage was used as in Zhou et al (1995) and Kruijver et al (2000). The differences were even more pronounced than with BSTc; control males averaged 1.9 times the volume and 2.3 times the neurons as control females, yet once again, regardless of hormone exposure, MTF transsexuals lay within the female range and the FTM transsexual within the male range.[25]
While MRI images cannot resolve as fine details as structures such as BSTc and INAH3, they can much more easily allow the study of larger brain structures. In Luders et al (2009), 24 MTF transsexuals not-yet treated with cross-sex hormones were studied via MRI. While regional gray matter concentrations were more similar to men than women, there was a significantly larger volume of gray matter in the right putamen compared to men. As with many earlier studies, they concluded that transsexualism is associated with a distinct cerebral pattern.[26]
An additional feature was studied in a group of FTM transsexuals who had not yet received cross-sex hormones: fractional anisotropy values for white matter in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Rametti et al (2010) discovered that, "Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract."[27]
A cautionary note is sounded in Hulshoff Pol et al (2006), which studied the changes in transsexual brains on hormone administration over four months via MRI. They discovered that whole brain volume for subjects, as well as hypothalamic volume for androgen treatment, and potentially more sexually dimorphic structures in that region, change significantly toward the size of the opposite gender during hormone treatment. The study does not criticize the controls used to account for this in the BSTc or INAH3 studies.[28] The study additionally concluded that before hormonal treatment, total brain volumes of the subjects were equivalent according to birth sex.