Sex and Gender: The Biochemistry and Neuroscience of the Transgender Phenomenon

gender identity and gendery equality

Possibly the most important part of the mental model humans construct is their mental model of themselves. This is what we call our identity. It takes all the beliefs we have about ourselves and attempts to put them together into an internally coherent whole. Some of our most cherished political, religious, racial, and gender thoughts about ourselves tells us who we are and how we ought to interact with the world.

These beliefs about ourselves are not just thoughts, either. They are deeply held emotional states. They are how we relate to the world. We can have multiple sub-identities – my being a metal fan, a hip-hop fan, an atheist, an intellectual, a man, a brother, a son, etc. – but they all come together to form a single identity that we call the I. This is the fabric that holds together our mental model of the world into a single whole. I am a metal fan. I am a hip-hop fan. I am an atheist, and so on.

These emotional states are not purely mental models we even choose to create, either. They can be shaped and formed through our thoughts and self-talk, as is proposed in cognitive behavioral theory, but much of it comes from our biology as well.

For instance, political affiliation has been associated with differential brain structure. An MRI study showed that political conservatives, contrasted with political liberals (in the American sense of the word), had more gray matter in the right amygdala. Another fMRI study of risk-taking behavior showed political conservatives have more activity in the right amygdala. The amygdala is important in processing emotions such as fear and threat. These results seem to suggest that there is a biological component in conservative resistance to change, seeing progress as a threat to the status quo.

Another instance of identity that has become important in our times is gender identity. There is strong evidence of a biological component to this as well. There is research showing that pre-hormone treatment transgender people have brain biochemistry and anatomy more similar to the gender they identify as than they do their so-called assigned gender.

The 2000 paper by Frank Kruijver et al1 and the 2008 paper by Garcia-Falgueras and Swaab2 both show that the number of neurons, as well as the receptor BSTc (bed nucleus of the stria terminalis) in the male brain is the same as that in FtM transgender people, and vice versa for MtF transgender people (theirs is the same as cisgender females). This is regardless of whether they had begun hormone replacement therapy.


BSTc numbers for a MtF transgender woman are the same as that for a cisgender woman as opposed to a cisgender male.

The 2008 paper by Ramachandran and Mcgeoch3 discussed cisgender men who have had their penis amputated for various reasons report the sensation of a “phantom penis” while MtF transgender people who have had sex reassignment surgery report the sensation of a phantom penis significantly less often; FtM transgender people report the sensation of a phantom penis. Phantom limbs are known to occur because the feeling of your body does not happen in your body, but in the brain – the parietal region of the brain has our body “mapped” and all sensations actually occur there. The reduction in phantom penis reports in MtF transgender people, as well as the reporting of a phantom penis in FtM transgender people, suggests that the brains of these individuals has mapped their body in a way that corresponds to their gender identity as opposed to their birth sex.

The 2009 paper by Luders et al4 and a 2016 review article by Kreukels and Guillamon5 both show that, independent of hormone replacement therapy, the neuroanatomy of transgender people matches more closely to the sex with which they identify in some key ways while also displaying morphology similar to the sex to which they were born – in other words, the brain structures of both MtF and FtM transgender people lie somewhere in between male and female, with some regions appearing more like the gender with which they identify and others appear more like the sex to which they were born.

2019-11-09 10_55_35-References - Word

Rametti et al (2010)

A 2013 paper by Milton Diamond6 show that monozygotic (identical) twins show a 33% concordance in transgenderism amongst FtM transgender people and 28% amongst MtF transgender people, as opposed to 4.76% and 0.34% for dizygotic (fraternal) twins respectively. In other words, if one person in a set of twins is transgender, there is a significant chance the other one will be as well, whereas in fraternal twins, the correlation is significantly decreased, indicating a biological cause.

What is sex besides biochemistry? Besides chromosomes? Biology is dictated by chemicals and those chemicals can be administered exogenously. Anatomy can be surgically altered. With gene editing systems like CRISPR/Cas9, it is even theoretically possible to alter someone at the genetic level. Do these people still contain some essence of their former sex? None of this is to say how transgenderism ought to be treated medically/therapeutically, but there is compelling evidence that it is a real phenomenon and that it is largely a biological/neurological phenomenon.


  1. Frank P. M. Kruijver, Ji Neng Zhou, Chris W. Pool, Michel A. Hofman, Louis J Gooren, Dick F. Swaab, Male-to-female transsexuals have female neuron numbers in a limbic nucleus, Journal of Clinical Endocrinology & Metabolism, 2000.
  2. Garcia-Falgueras A, Swaab DF, A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity, Brain, 2008.
  3. Vilayanur S. Ramachandran and Paul D. Mcgeoch, Phantom penises in transsexuals: Evidence of an innate gender-specific body image in the brain, Journal of Consciousness Studies, 2008.
  4. Luders E, Sánchez FJ, Gaser C, Toga AW, Narr KL, Hamilton LS, Vilain E, Regional gray matter variation in male-to-female transsexualism, Neuroimage, 2009.
  5. Baudewijntje P.C. Kreukels & Antonio Guillamon, Neuroimaging studies in people with gender incongruence, International Review of Psychiatry, 2016.
  6. Milton Diamond, Transsexuality Among Twins: Identity Concordance, Transition, Rearing, and Orientation, International Journal of Transgenderism, 2013.

Further Reading

Luders et al (2012): Increased Cortical Thickness in Male-to-Female Transsexualism

Simon et al (2013): Regional Grey Matter Structure Differences between Transsexuals and Healthy Controls—A Voxel Based Morphometry Study

Rametti et al (2010): White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study