The Brain and Gender Dysphoria

Sarah J. Lewis (Volunteer Researcher) sarah@transcience-project.org





Do trans-women have female brains? What about trans-men?. Reality is a little more complicated than the question suggests. There have been many studies in the last two decades which provide us with insights into how our brains work. This paper presents what we know so far about the role the brain plays in gender dysphoria.

Brain Stem

The first study of its kind was conducted by Zhou et al (1995)[1]. The study found sex a-typical differences in the stria terminalis of the brain stem when studying transgender subjects.

A follow up study by Kruijver et al (2000)[2] confirmed the findings and provided greater insight.

The central subdivision of the bed nucleus of the stria terminalis (BSTc) is sexually dimorphic. On average, the BSTc is twice as large in men as in women and contains twice the number of somatostatin neurons. These numbers do not appear to be influenced by sexual orientation or hormone replacement therapy - and both were controlled for by Zhou and Kruijver.

A paper by Chung et al (2000)[3] studied how the volume of the BSTc varied with age in both male and female subjects. They found that the dimorphism was only prevalent in adulthood. Suggesting that the differences found by Zhou and Kruijver are not a cause of gender dysphoria but rather a result.

Dissection of brain-stem. Lateral view. (Stria terminalis labelled at upper right.)

Putamen

In Luders et al. (2009)[4], 24 trans-women who hadn't started hormone-replacement therapy were studied via MRI. While regional grey matter concentrations were more similar to men than women, there was a significantly larger volume of grey matter in the right Putamen compared to men. As with many earlier studies, they concluded that gender dysphoria is associated with a distinct cerebral pattern.

In contrast, Savic et al (2011)[10] did not find any sex a-typical differences in the Putaman, or other investigated areas of the brain. They did however find differences between their trans-women group and both the male and female controls.

Coronal section of brain through anterior commissure. (Putamen labelled at center right.)

Superior Longitudinal Fasciculus

Two studies by Rametti et al (2011)[5][6] looked at white matter differences in both trans-men and trans-women.

In their study of trans-men they found that control males have significantly higher fractional anisotropy values (FA is a measure often used in diffusion imaging where it is thought to reflect fiber density, axonal diameter, and myelination in white matter) than control females "in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract".

Compared to control females in the study, trans-men "showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, trans-men showed only lower FA values in the corticospinal tract."

The study concluded that there was evidence for an inherent difference in the brain structure of trans-men.

In their study of trans-women they found that trans-women "differed from both male and female controls bilaterally in the superior longitudinal fasciculus, the right anterior cingulum, the right forceps minor, and the right corticospinal tract." The nature of these differences suggests that some fasciculi do not complete the masculinization process in trans-women during brain development.

Lateral surface of left cerebral hemisphere. Some of major association tracts are depicted. Superior longitudinal fasciculus is at center, in red.

The Hypothalamus

Berglund et al (2008)[7] demonstrated that brain activation in trans-women was similar to female controls (and dis-similar to male controls). The researchers' conclusion was, that in terms of pheromone activation, trans-women occupy an intermediate position with predominantly female features. The paper further speculates that the cause for the observed differences may lie in the structure of the hypothalamus.

Garcia-Falgueras and Swaab (2008)[8] investigated the hypothalamic uncinate nucleus, which is composed of two subnuclei, namely interstitial nucleus of the anterior hypothalamus (INAH) 3 and 4. They showed for the first time that INAH3 volume and number of neurons of trans-women is similar to that of control females. The study also included analysis of a single trans-man who also had a INAH3 volume and number of neurons within the male control range.

Median sagittal section of brain. Hypothalamus labelled bottom left.

Parietal-temporal-occipital

An interesting study by Schöning et al (2010)[9] found that male controls exhibited significantly greater activation of the left parietal cortex when performing mental rotation tasks, in addition they found that trans-women (both those who has started hormone replacement therapy and those who had not), exhibited strong activation in the temporo-occipital regions in comparison to controls males.

Finally

Like in many areas of science, it is difficult to unravel cause and effect. It is important to iterate that none of the studies presented provide us with a definite cause for gender dysphoria. It is also likely that gender dysphoria, and the social experiences it confers, also shape the brain.

Additionally, many of these studies hint at different mechanisms affecting trans-men compared to trans-women. It could very well turn out that gender dysphoria has completely different root causes affecting trans-men and trans-women.

It will take many more years of research and many more studies before we understand what is really going on inside the brains of transgender people. As new research becomes available we will work to summarize and update this article accordingly.

Citations

[1] Zhou, Jiang-Ning, Michel A. Hofman, Louis J. G. Gooren, and Dick F. Swaab. "A Sex Difference in the Human Brain and Its Relation to Transsexuality." Nature 378.6552 (1995): 68-70.



[2] Kruijver, F. P. M. "Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus." Journal of Clinical Endocrinology & Metabolism 85.5 (2000): 2034-041.



[3] Chung, W. C., G. J. Vries, and D. F. Swaab. "Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood." Brain Research (2001).



[4] Rametti, Giuseppina, Beatriz Carrillo, Esther Gómez-Gil, Carme Junque, Leire Zubiarre-Elorza, Santiago Segovia, Ángel Gomez, and Antonio Guillamon. "The Microstructure of White Matter in Male to Female Transsexuals before Cross-sex Hormonal Treatment. A DTI Study." Journal of Psychiatric Research 45.7 (2011): 949-54.



[5] Rametti, Giuseppina, Beatriz Carrillo, Esther Gómez-Gil, Carme Junque, Santiago Segovia, Ángel Gomez, and Antonio Guillamon. "White Matter Microstructure in Female to Male Transsexuals before Cross-sex Hormonal Treatment. A Diffusion Tensor Imaging Study." Journal of Psychiatric Research 45.2 (2011): 199-204.



[6] Luders, Eileen, Francisco J. Sánchez, Christian Gaser, Arthur W. Toga, Katherine L. Narr, Liberty S. Hamilton, and Eric Vilain. "Regional Gray Matter Variation in Male-to-female Transsexualism." NeuroImage 46.4 (2009): 904-07.



[7] Berglund, H., P. Lindstrom, C. Dhejne-Helmy, and I. Savic. "Male-to-Female Transsexuals Show Sex-Atypical Hypothalamus Activation When Smelling Odorous Steroids." Cerebral Cortex 18.8 (2008): 1900-908.



[8] Garcia-Falgueras, A., and D. F. Swaab. "A Sex Difference in the Hypothalamic Uncinate Nucleus: Relationship to Gender Identity." Brain 131.12 (2008): 3132-146.



[9] Schöning, Sonja, Almut Engelien, Christine Bauer, Harald Kugel, Anette Kersting, Cornelia Roestel, Pienie Zwitserlood, Martin Pyka, Udo Dannlowski, Wolfgang Lehmann, Walter Heindel, Volker Arolt, and Carsten Konrad. "Neuroimaging Differences in Spatial Cognition between Men and Male-to-Female Transsexuals Before and During Hormone Therapy." Journal of Sexual Medicine 7.5 (2010): 1858-867.



[10] Savic, I., and S. Arver. "Sex Dimorphism of the Brain in Male-to-Female Transsexuals." Cerebral Cortex 21.11 (2011): 2525-533.



Zhou, Jiang-Ning, Michel A. Hofman, Louis J. G. Gooren, and Dick F. Swaab. "A Sex Difference in the Human Brain and Its Relation to Transsexuality." Nature 378.6552 (1995): 68-70. (Paperdex)Kruijver, F. P. M. "Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus." Journal of Clinical Endocrinology & Metabolism 85.5 (2000): 2034-041. (Paperdex)Chung, W. C., G. J. Vries, and D. F. Swaab. "Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood." Brain Research (2001). (Paperdex)Rametti, Giuseppina, Beatriz Carrillo, Esther Gómez-Gil, Carme Junque, Leire Zubiarre-Elorza, Santiago Segovia, Ángel Gomez, and Antonio Guillamon. "The Microstructure of White Matter in Male to Female Transsexuals before Cross-sex Hormonal Treatment. A DTI Study." Journal of Psychiatric Research 45.7 (2011): 949-54. (Paperdex)Rametti, Giuseppina, Beatriz Carrillo, Esther Gómez-Gil, Carme Junque, Santiago Segovia, Ángel Gomez, and Antonio Guillamon. "White Matter Microstructure in Female to Male Transsexuals before Cross-sex Hormonal Treatment. A Diffusion Tensor Imaging Study." Journal of Psychiatric Research 45.2 (2011): 199-204. (Paperdex)Luders, Eileen, Francisco J. Sánchez, Christian Gaser, Arthur W. Toga, Katherine L. Narr, Liberty S. Hamilton, and Eric Vilain. "Regional Gray Matter Variation in Male-to-female Transsexualism." NeuroImage 46.4 (2009): 904-07. (Paperdex)Berglund, H., P. Lindstrom, C. Dhejne-Helmy, and I. Savic. "Male-to-Female Transsexuals Show Sex-Atypical Hypothalamus Activation When Smelling Odorous Steroids." Cerebral Cortex 18.8 (2008): 1900-908. (Paperdex)Garcia-Falgueras, A., and D. F. Swaab. "A Sex Difference in the Hypothalamic Uncinate Nucleus: Relationship to Gender Identity." Brain 131.12 (2008): 3132-146. (Paperdex)Schöning, Sonja, Almut Engelien, Christine Bauer, Harald Kugel, Anette Kersting, Cornelia Roestel, Pienie Zwitserlood, Martin Pyka, Udo Dannlowski, Wolfgang Lehmann, Walter Heindel, Volker Arolt, and Carsten Konrad. "Neuroimaging Differences in Spatial Cognition between Men and Male-to-Female Transsexuals Before and During Hormone Therapy." Journal of Sexual Medicine 7.5 (2010): 1858-867. (Paperdex)Savic, I., and S. Arver. "Sex Dimorphism of the Brain in Male-to-Female Transsexuals." Cerebral Cortex 21.11 (2011): 2525-533. (Paperdex)