• The following is a talk given at the Evangelical Theological Society in San Diego, California on November 22, 2024.

What is transgenderism?

What is “transgenderism”? This term is more loaded than you might think. The suffix “ism” can describe a disease condition like autism or hypothyroidism. It can also describe a habit or predilection, such as altruism or racism. Finally, it can represent an ideology like capitalism or Marxism. Some activists object to use of the word “transgenderism” because it might sound like it’s just an ideology. But a quick search turns up over 28,000 scholarly papers that use the term, so I’m going to go with it. In the following discussion, “transgenderism” simply means the state of being transgender, whatever that means.

The Gender Dilemma

So, what does it mean? Most commonly, it describes an individual who identifies with a gender that does not correspond to their sex. Beyond that, we run quite suddenly into a series of contradictions and conundrums. What is gender? Nobody can agree on that. As reported this summer, a 5-year project funded by the EU was unable to agree on a definition despite over 4 million dollars in funding:^[1]

“With teams from a variety of backgrounds, it was important to explore definitions of sex and gender in our discussions. What clearly emerged from the study pre-presentations and ensuing discussions was that ‘sex’ and ‘gender’ often interacted and were difficult to tease apart. Defining and documenting gender was found to be complex, challenging, and was approached in diverse ways in the funded studies.”

Various claims are made by those in the category of advocates, who call themselves “gender-affirming.” One is that sex and gender are independent of one another or only loosely linked. But if sex and gender are different, then what is gender? There’s no diagnostic test for that. It comes down to whatever the person claims for him or herself. Is it ontologically possible to have a body of one sex but the mind of another? Aren’t you still defining gender in terms of sex?

And how would one know they feel like the opposite sex, having never been there? Not being a woman, I could never know how it felt to have the mind of a woman. So in practice, this reduces to filtering one’s personality and preferences through highly stereotypical views of masculinity and femininity.

 The implication is that gender is a personal trait, like extroversion or left-handedness: that is innate, immutable, and independent of sex – except those things can be observed by another party. If it’s not sex, from what part of the mind or body does gender originate? Nobody can say. It’s almost Aristotelian, as if there were transcendental forms of male, female, and other in the realm of being that constitute the substance of a person, even if the accident is of the opposite sex—kind of like how transubstantiation works in the Catholic Eucharist.

 But if gender exists only in the mind of the perceiver, it is unfalsifiable. To believe is to see. Or is it? Maybe we can test that theory.

Not only can we not define gender, but there is no consensus, even within our various tribes, regarding how to frame it.

Competing interpretations of transgenderism

Within the population that might be described as “trans-affirming,” there are at least three popular interpretations that are mostly contradictory:

1. Transgenderism is biologically based but dysfunctional. “DSM” stands for Diagnostic and Statistical Manual, and it serves as a reference for the categorization and diagnosis of mental illness. We’re now in the fifth edition, which came out in 2013. This position – that it’s a mental illness – would have been the consensus of almost the entire scientific community before the DSM-5, and it was called “gender identity disorder.” The manual changed in 2013, but that doesn’t mean everybody’s on board. The ones who still think of it as a mental illness may or may not support gender affirmation in young people.
   
2. Transgenderism is biologically based but merely a normal variant. The DSM-5 depathologized cross-sex gender identification, meaning it’s no longer considered a disorder of any sort. For many who accept this framework, people really are the gender they identify as, whether they actually transition or not. This group would totally support gender affirmation.
   
3. Biology has little or nothing to do with it. It is socially constructed, pure and simple, and that’s OK. This point of view is reflected more among philosophers like Michel Foucault and Judith Butler. The ones in this camp also generally support gender affirmation.
   

Among the “gender-critical group,” we also see competing interpretations:

1. It is a mental illness in the classic sense. Again, this was the mainstream position until 2013. Except some in this group tend not to support the so-called “gender affirmation.”
   
2. It is a delusion, just another example of someone passionately believing in something that doesn’t correspond to reality, like flat-earthers. But they’re not mentally ill.
   
3. It is a social contagion where young people imitate those they admire in an effort to gain acceptance or look cool. Perhaps it is a manifestation of mimetic desire, as described Rene Girard.
   
4. It’s a self-selected identity, a consequence of expressive individualism (per Charles Taylor). Carl Trueman did a masterful job in explaining how this viewpoint emerged as a reigning paradigm, but it’s not necessarily all-encompassing.
   

These explanations are not mutually exclusive, by the way. Most of these could be true in some cases, although the normal variant viewpoint doesn’t meld very well with other positions. On the other hand, it’s worth noting that the last three gender-critical explanations are perfectly consistent with it being a social construct, differing from Butler only in the sense of it being a negative thing.

With so many different viewpoints, you can see why there might so much heat and so little light. It’s difficult either to prove or disprove something when nobody can agree on what it is. It’s like nailing jello to the wall.

Why bring in neuroscience?

So how does neuroscience factor into this discussion? In several ways. First, those in the affirming community regularly trumpet the latest study claiming to prove that gender is both innate and independent of sex. (This puts them at odds with the “social construct” contingent. They continue to deny that there are any sex-related differences in the brain and see gender as just the second verse of the same song).

Second, these different hypotheses regarding transgenderism enable us to make predictions that can be tested. Third, an accumulated body of neuroscience was already in place well before transgenderism captured global attention, and this earlier understanding can and should inform our thinking. Advocates may say that social and medical transitioning merely brings the body into line with the mind, but what if it goes the other way? What if the cart is pulling the horse, meaning gender affirmation changes the brain?

I’m going to structure this in the form of four essential questions.

1. What is neuroscience?
   
2. What does it have to do with transgenderism?
   
3. What does the research show?
   
4. How should neuroscience inform our understanding of transgenderism?
   
   

What is neuroscience?

In July of 1989, President George Bush signed a proclamation declaring the 1990s as the “Decade of the Brain.” What emerged over the ensuing decade and continues to this day was an explosion of research into the human brain: how it forms, how it works, and how things go wrong. Neuroscience is a broad field that includes anatomy, biology, chemistry, psychology, sociology, and multiple medical specialties including my own specialty of neuroradiology.

Very new to the research scene

In the case of transgenderism, however, hardly any research had been done prior to the mid-2000s, mostly because it was rare. This chart indicates the number of neuroimaging studies that included transgender participants, rising from 1 in 1991 to 83 in 2024.^[2]

Different ways to study the brain

We have many different methods to study the brain. These include:

1. Behavioral study and psychological testing
   
2. Chemical analysis of hormones and neurotransmitters, like testosterone, estrogen, and dopamine
   
3. Examination of brain structure by MRI in living people. This is what we call gross anatomy, which means you can see it without a microscope.
   
4. Functional imaging, particularly MRI. Brain regions that are active use more oxygen and demand more blood flow, so we can use MRI to look at changes in blood flow at rest or during particular brain tasks.
   
5. Postmortem analysis and brain dissection. For obvious reasons, this is less help in humans.
   
6. The use of animal models using all of those techniques and more.
   

How does it relate to transgenderism?

In the case of transgenderism, neuroscience can and has been used to:

1. Elucidate differences in the brain in an attempt to explain it.
   
2. Test hypotheses concerning its cause.
   
3. Predict the outcome of interventions.
   

Many things are consistent with reproducible findings in the brain

I’d say at the outset that even if research finds that transgender brains differ in certain respects, that doesn’t narrow the range of possible explanations as much as you might think. Finding changes in the brain wouldn’t necessarily prove whether it was biologically based, a normal variant, or a mental illness.

Hypotheses regarding transgenderism

Leaving all the complexities aside, a popular version in public use boils down to the claim that one can have a male brain in a female body, or a female brain with a male body. If there were a way to tell male brains from female brains, we could then look at the brains of transgender people and see if their brain matches their sex or their gender identity. So can we? As a matter of fact, the very idea that male and female brains might possibly be different was a matter of hot contention for quite some time. But over time, the evidence continued to pile up.

Reasons to suppose sex differences exist

Little boys and little girls differ in many ways. Almost every parent and teacher knows that. So, there was always a good reason to think male and female brains were different. That would be the best explanation for consistent and reproducible differences in personality and behavior evidenced not only in human children but many higher primates. Many psychiatric and neurological disorders show a strong sex predilection, whether it be autism (males) or Alzheimer’s (females). Then, the obvious realization that men and women differ in their genetic makeup and experience different hormonal influences during critical periods of development.^[3]

Looking for sex differences

If there are differences between male and female brains, these could show up in different ways. Differences in visible structure could be explored in living subjects using high resolution MRI. Differences in microstructure would require more precise microscopic analysis, meaning either postmortem examinations or animal studies. Differences in the chemical environment, via such modulators as hormones and neurotransmitters, are less amenable to study by imaging. Differences in brain function can be explored using specialized MRI techniques that look at blood flow and brain activation, using what we call functional MRI.

What does neuroscience reveal?

Sex differences: findings

Simply looking at brain structure with MRI, subtle differences emerge that are detectable by computer analysis but imperceptible to the human eye. Brain size corresponds to body size, and because men are, on average, larger, male brains average about 9% larger than female brains. But female brains make up the difference with a higher density of neurons in the same volume of gray matter. Also, in women, the gray matter is a little thicker, whereas males have a higher percentage of white matter. Male brains show more interconnection within the hemispheres, whereas female brains show more connection between the hemispheres.

With functional MRI, that looks at active communication between various brain networks, researchers are now reporting extraordinary accuracy in distinguishing male from female brains and identifying which brain regions differ most greatly.^[4] The differences were bimodal, meaning two distinct peaks with a valley in the middle.

The fat in the back of this Bactrian camel is bimodally distributed.

Bimodal is really quite different from a “spectrum” or “continuum.” And brain differences begin to develop in utero in response to circulating sex hormones.

By the middle of the last decade, most neuroscientists considered the matter as settled. The entire January 2017 issue of the Journal of Neuroscience Research was dedicated to evidence for sex-based brain differences. In his introduction, journal editor Larry Cahill wrote, “The notion that sex matters fundamentally, powerfully, and pervasively for all of neuroscience (not just for reproduction) is an idea whose time indeed has come.”

This has been effectively settled, but that doesn’t mean there aren’t still a lot of diehards who refuse to bow to the evidence. Almost all of them are in the Judith Butler camp.

Where does this leave us?

Since it’s reasonably possible to tell whether a brain is more male or female based on sophisticated imaging techniques, it is possible to study transgender subjects and determine whether their brain corresponds closer to their sex or their gender identity. In the next section, I’m going to walk through a few studies from the last four years. The results are mixed, although the most recent studies indicate that transgender brains are much closer to their own sex than the opposite sex.

Neuroimaging studies of the transgender brain

Flint et al

This study reported in 2020 used a machine algorithm to try and differentiate male and female brains based on structure, and then applied the rules to 26 transwomen.^[5] In the trans subjects, the discriminator was less accurate in predicting a male brain. In other words, the brains of transwomen deviated a little from the average male brain and were a little more likely to be misclassified as female.

They concluded it was somewhat of a wash: not your average male brain, but not female either:

“Our results support the hypothesis that brain structure in TW differs from brain structure of their biological sex (male) as well as their perceived gender (female).”

Clemens et al

That same year another group used functional MRI on a group of 92 subjects equally divided between men, women, transmen, and transwomen, 26 in each group.^[6] This method basically looks at which regions of the brain are talking with each other. They applied a machine learning technique to try and separate the four groups, then retrospectively applied that technique to the same group of subjects, claiming the ability to predict better than mere chance. There are several flaws with this study. The accuracy rate, though higher than pure chance, remained rather low (25% would have been random). But what’s worse is that they applied their tool to the same set of patients used to develop the tool. That’s the research equivalent of arguing in a circle. They should have applied the rule to a set of unknown patients to result in anything meaningful.

Mueller et al

Another report one year later looked just at structural MRI with a subject group of 214 transmen, 172 transwomen, 196 women, and 221 men.^[7] They claimed significant differences between cisgender and transgender subjects in the volumes of some regions of the brain.

“Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype.”

What did they NOT find? They didn’t find that the transmen brains looked more male, or the transwomen brains looked more female.

Figerio et al

That same year another group published a review of 39 studies reporting brain imaging in transgender subjects.^[8] They noted that these 39 projects were extremely heterogeneous both in terms of their patient profiles and the techniques that were used. The authors acknowledged that almost all studies found some difference between transgender and cisgender subjects, but they still remained closer to their sex than their gender identity.

“Our results suggest that some…features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex.”

Xerxa et al

A newer and much larger study came from the Netherlands in 2023, using structural imaging in adolescents between ages 13 and 15.^[9]

“In this cross-sectional study of 2165 [ages 13-15] adolescents from the Netherlands general population, no significant differences in total brain volumetric measures were observed between youths who reported gender diversity and youths who did not.”

The results did point to one possible area of difference, but only in those born boys:

“However, these findings further suggest that gender diversity in the general population correlates with specific brain morphologic features in the inferior temporal gyrus among youths who are assigned male at birth.”

Wiersch et al

Some of these earlier studies didn’t take head size into account, which would throw the findings off one way or another, since that’s one of the most consistent differences between male and female brains. This 2023 report using structural imaging found that after taking the total intracranial volume into account, that the model was equally accurate in determining sex in both cis and trans subjects.^[10] In other words, their brains matched their sex, not their gender identity.

Maniaci et al

Bringing us now into 2024, this study reported the results of functional MRI in 19 transmen (FtM).^[11] Because it’s functional imaging, it has implications for cognition and behavior. The researchers reported that:

“Contrary to the assumption that cognitive function in trans individuals aligns more closely with their gender identity counterpart, our findings suggest a similar cognitive profile between trans men and cisgender women.”

Dhamala et al

This last paper appeared in mid 2024 and made a small splash. The researchers examined a dataset of thousands of children age 9 to 20 and used functional MRI first to look for correlations with their sex, and then to look for correlations with gender identity. Of course, there’s no test for gender identity, so they asked the children a few questions and asked their parents about play behavior. They claimed that the research supported the idea that sex and gender correlate with different brain regions and thus could be different things.

This is what they found: 

• Certain brain regions were correlated with sex, but “gender” was more distributed through the cerebral cortex.
  
• Sex and gender were strongly correlated(!), so predicting gender was simple if you just used sex as a criterion.
  
• However, their ability to predict gender apart from sex was far less accurate.

My critique of this would be that the deck was stacked the moment they defined gender. If you define gender in terms unrelated to biological sex, that is the likely result.

Finally, a major shortcoming of all these studies is that they don’t attempt to distinguish between early and late-onset cases, and some were entirely done on adults. They may not even be relevant to adolescent-onset cases, which many of us believe should be in a category of their own. Since there’s no diagnostic test for transgender, we really can’t know if all of the transgender subjects were trans, nor whether all the control subjects were not. It’s really hard to study something that you can’t define and can’t objectively determine.

Summing up these reports, we can conclude that in some respects, a transgender brain could be less masculinized in a male or less feminized in a female, but this is true of many who are not trans. Male and female brains differ, and the differences are in a bimodal distribution with some overlap. We’ve known for decades that the differences between boys and girls are on the average, and don’t apply to every single child. Some girls are tomboys, and some little boys are bookish. That can be called gender atypia or gender nonconformity. It’s totally normal, and we see evidence of it reflected in those studies showing male and female brain patterns spread out along those curves.

Identity formation

One thing on which almost everyone agrees is that gender is a matter of personal identification. Well, identity formation is also something that has been closely studied. Research has found that issues of personal identity are linked to an area of the brain called the medial prefrontal cortex, which is itself a part of the default mode network.^[12] This network is the one engaged in self-awareness, self-reflection, and daydreaming.

So if being transgender is a matter of identity, of course it wouldn’t be related to sex-different regions. It’s exactly what anyone should predict.

Regions of brain that differ between sex are NOT related to regions of the brain associated with identity formation. Therefore, it is completely plausible that gender identity can conflict with sex. Furthermore, identity formation is heavily influenced by social factors. This can be why Lisa Littman and Abigail Schrier found that many adolescent and pre-adolescent girls were being shaped by social media.

How should neuroscience inform our understanding?

So in conclusion, what does transgenderism look like through the lens of neuroscience?

First, there is so far no evidence that a person of one sex can have a brain of the opposite sex. Even the studies that found a difference, found a very small one, and the subjects remained closer to their sex than their preferred gender.

Second, be skeptical of all claims that imaging studies ”prove” there is a transgender brain. Many earlier studies have been undermined by later research. Until somebody can actually define gender, I don’t see how it could ever be proved.

Third, identity and sex involve different regions of the brain, so it’s possible them to diverge. That doesn’t prove it’s healthy or normal.

Lastly, be wary that “gender-affirming” care is really “gender-confirming” care. What do I mean by that?

Brain plasticity

The adult human brain is determined by a lot of factors beyond our genes, The brain is adaptable, a child’s brain much more so, and its growth is modulated by genetics, the hormonal environment, and social factors.

Puberty is a critical window in brain development dependent upon sex hormones. This is not something one should be messing with.

So far, there is little data on the long-term effects of puberty blockers in children, but what has been reported so far gives us cause for concern, like measurable declines in IQ. We can prove in the lab that puberty blockers cause permanent and irreversible changes in brain development in animal models.^[13] To assume it wouldn’t happen in humans is dangerously naïve.

Practice makes permanent

It is well-established that the majority of children with gender dysphoria literally grow out of it (“desist”), turning into adults at peace with their sexed bodies.^[14] But in the Tavistock series from the UK, the desistence rate after puberty blockers dropped from around 85% to a shocking 2%.^[15] Why is this bad? Among many reasons, it can lead to permanent sterility, sexual dysfunction, and a lifetime on medication. But according to everything we know about child development, even social transitioning is self-reinforcing. Those seemingly harmless things like changing names and pronouns have a direct influence on the developing brain.

Concluding comments

• The evidence so far confirms that the brains of trans individuals remain much more similar to their sex than their gender identity.
  
• The mind may shape treatment, but treatment shapes the mind.
  
• To be gender atypical is a feature of our created diversity, not a disease.
  
• Be suspicious: many extravagant claims will be made.
  
• Be humble. Denigrating science or scientists reflects poorly upon us.
  
• Don’t be defensive: a Christian position does not exclude the possibility of brain alterations.
  
• Any brain findings related to transgenderism cannot establish whether it is “good,” “normal,” or “healthy” (Hume’s Law)
  

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2. Kennis, Mathilde, Robin Staicu, Marieke Dewitte, Guy T’Sjoen, Alexander T. Sack, and Felix Duecker. “Heed Lessons from Past Studies Involving Transgender People: First, Do No Harm.” Nature 629, no. 8014 (May 2024): 998–1000. https://doi.org/10.1038/d41586-024-01521-7. ↑
   

   
   

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5. Flint, Claas, Katharina Förster, Sophie A. Koser, Carsten Konrad, Pienie Zwitserlood, Klaus Berger, Marco Hermesdorf et al. “Biological sex classification with structural MRI data shows increased misclassification in transgender women.” Neuropsychopharmacology 45, no. 10 (2020): 1758-1765. ↑
   

   
   

6. Benjamin Clemens, Birgit Derntl, Elke Smith, Jessica Junger, Josef Neulen, Gianluca Mingoia, Frank Schneider, Ted Abel, Danilo Bzdok, Ute Habel, Predictive Pattern Classification Can Distinguish Gender Identity Subtypes from Behavior and Brain Imaging, Cerebral Cortex, Volume 30, Issue 5, May 2020, Pages 2755–2765, https://doi.org/10.1093/cercor/bhz272 ↑
   

   
   

7. Mueller SC, Guillamon A, Zubiaurre-Elorza L, Junque C, Gomez-Gil E, Uribe C, Khorashad BS, Khazai B, Talaei A, Habel U, Votinov M, Derntl B, Lanzenberger R, Seiger R, Kranz GS, Kreukels BPC, Kettenis PTC, Burke SM, Lambalk NB, Veltman DJ, Kennis M, Sánchez FJ, Vilain E, Fisher AD, Mascalchi M, Gavazzi G, Orsolini S, Ristori J, Dannlowski U, Grotegerd D, Konrad C, Schneider MA, T’Sjoen G, Luders E. The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group. J Sex Med. 2021 Jun;18(6):1122-1129. doi: 10.1016/j.jsxm.2021.03.079. Epub 2021 May 22. PMID: 34030966. https://pubmed.ncbi.nlm.nih.gov/34030966/ ↑
   

   
   

8. Frigerio, Alberto, Lucia Ballerini, and Maria Valdes Hernandez. “Structural, functional, and metabolic brain differences as a function of gender identity or sexual orientation: a systematic review of the human neuroimaging literature.” Archives of sexual behavior 50, no. 8 (2021): 3329-3352. ↑
   

   
   

9. Xerxa, Yllza, Tonya White, Samantha Busa, Leonardo Trasande, Manon HJ Hillegers, Vincent W. Jaddoe, Francisco Xavier Castellanos, and Akhgar Ghassabian. “Gender diversity and brain morphology among adolescents.” JAMA Network Open 6, no. 5 (2023): e2313139-e2313139. ↑
   

   
   

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11. Maniaci, Giuseppe, Giorgio Collura, Caterina La Cascia, Tommaso Piccoli, Eleonora Bongiorno, Ilaria Barresi, Maurizio Marrale et al. “Beyond the Gender Binarism: Neural Correlates of Trans Men in a Functional Connectivity–Resting-State fMRI Pilot Study.” Journal of Clinical Medicine 13, no. 19 (2024): 5856. https://www.mdpi.com/2077-0383/13/19/5856 ↑
    

    
    

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