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Sammy Profile picture
@NeuroSGS
Jul 19, 2022 • 23 tweets • 6 min read • Read on X
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Do transgender persons show sex atypical brains?

Many people suggest that trans people have brains more inline with their desired gender, and this causes feelings of gender incongruence.

However, if we take a closer look, we see some important underlying issues.
In a famous study, the authors compared prepubertal and adolescent children, then suggest sex atypical cerebral differentiation occurs within these individuals.
pubmed.ncbi.nlm.nih.gov/28972892/
The authors found sex atypical differences in the adolescent cohort (when the majority of the cohort is homosexual)

Homosexuality = 23% of trans boys + 44% of trans girls (prepubertal children; left)

Homosexuality = 100% of trans boys + 78% of trans girls (adolescent; right) ImageImage
The only non-sex typical finding which was specific to gender dysphoria (GD) was in visual network-1 (VN-1; via fMRI)

It was suggested that alterations in this network may disrupt body perception in GD individuals.
In another study by some of the same authors, they tested whether transgender people (with GD) would have sex atypical hypothalamic activation to androstenedione (a steroid hormone in human sweat that causes sex-specific olfactory responses).
ncbi.nlm.nih.gov/pmc/articles/P…
But similar to the previous study, sexual orientation was not accounted for. Image
Why is this important?

Well, the same sex atypical hypothalamic response is observed in homosexual men:
pubmed.ncbi.nlm.nih.gov/15883379/
And in homosexual women:

pubmed.ncbi.nlm.nih.gov/16705035/
It’s becoming increasingly clear that the only people with any sort of sex atypical cerebral differentiation occurs in homosexual individuals (on average).
This is further supported by functional connectivity studies sex atypical amygdala co-variance
ncbi.nlm.nih.gov/pmc/articles/P…
You can see this here:

Notice the high similarity in amygdala activity (at rest) between heterosexual females and homosexual males (and vice versa) Image
Interestingly, in an effort to bring all of this together, Savic et al., 2011 examined the brains of heterosexual transgender people in order to control for sexual orientation.
pubmed.ncbi.nlm.nih.gov/21467211/
The authors found sexual dimorphism in various gray matter parameters in control male and females. However, these findings were NOT found in the heterosexual transgender population. Image
So rather than sex atypical brain structure/function, what is specific to GD itself?
It’s been shown that individuals with GD show weaker structural & functional connectivity within the default mode network (DMN) of the brain, which is vital for body perception/image and self referential processing
nature.com/articles/s4159…
Findings which have been replicated here:
pubmed.ncbi.nlm.nih.gov/32057995/
And here:

pubmed.ncbi.nlm.nih.gov/27444730/
The DMN consists of cerebral midline structures, including the medial prefrontal cortex (mPFC) and the posterior cingulate cortex (PCC) Image
Interestingly, it’s been shown that trans individuals (with GD) show a stronger activation pattern within these DMN structures when viewing pictures of their body morphed to the opposite sex
pubmed.ncbi.nlm.nih.gov/31813993/
You can see the results here: Image
It’s important to note that correlation is NOT causation. Just because we observe a different pattern in GD subjects compared to neuro-typical controls, doesn’t not suggest it’s innate (born with) or a product of post natal experience. We simply don’t know.
Also, transgender people tend to have lots of co-morbidities from depression, anxiety, anorexia, autism, and a homosexual orientation. All of this needs to be considered when looking at neuroscience studies on this population.
For an overview on molecular hypothalamic differences in relation to homosexuality and gender dysphoria, see thread here:

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More from @NeuroSGS

Sammy Profile picture
May 29
The claim that trans women “have female brains” is not supported by the evidence. One of the most persistent problems in this literature is the failure to disentangle “gender identity” from sexual orientation. Several findings interpreted as evidence of a “female-typical” neuroanatomy in trans women closely resemble patterns previously reported in homosexual males. This is precisely why Savic & Arver (2011) restricted their sample to gynephilic trans women (natal males attracted to women), despite the expectation of feminisation, they actually found that major sexually dimorphic neuroanatomical characteristics remained male-typical and explicitly rejected a simple feminisation account.

The sexual-orientation confound is particularly important because some of the most widely cited “sex-atypical” findings in trans women are not unique to trans populations. Berglund et al. (2006) reported that homosexual women exhibited hypothalamic responses to putative pheromonal compounds that resembled those observed in heterosexual men, while Savic & Lindström (2005) found that homosexual men displayed female-typical patterns of hypothalamic activation. Similar findings have subsequently been cited as evidence of feminised neurobiology in trans women (Burke et al., 2014), despite the fact that the study cohort were predominantly homosexual relative to natal sex. Any interpretation that attributes these neural characteristics specifically to “gender identity” must therefore explain why comparable effects are observed in homosexual individuals who do not experience gender dysphoria.

Cross-sex hormone exposure introduces an equally serious interpretive problem. Estradiol and anti-androgen treatment have been shown to alter cortical thickness, grey matter volume, white matter microstructure, hypothalamic morphology, and patterns of functional connectivity within months of treatment initiation. Hulshoff Pol et al. (2006), for example, observed measurable structural brain changes following hormone treatment, promoting a “sex-atypical” phenotype. Consequently, studies examining participants after years of hormone therapy cannot reliably distinguish pre-existing developmental characteristics from treatment effects. Yet many highly cited papers either include hormonally treated participants or compare treated and untreated individuals in ways that make causal inference difficult.

These issues are compounded by small sample sizes, inadequate control for developmental stage, and the fact that male and female brains are not discrete categories but highly overlapping distributions. The most defensible conclusion from the current evidence is that *some* neural features MAY be associated with gender dysphoria, but causality cannot be implied. The much stronger claim that trans women simply “have female brains” remains unproven and is not the consensus finding of contemporary neuroscience.
pubmed.ncbi.nlm.nih.gov/21467211/
pnas.org/doi/10.1073/pn…
Read 5 tweets
Sammy Profile picture
Aug 28, 2025
It's often been stated that a particular white matter tract in the human brain, the inferior fronto-occipital fasciculus (IFOF; see below), is altered in gender dysphoria (GD) and may even be the neurological location/substrate for "gender identity".

But what does the data say? Image
The first report of an altered IFOF in GD comes from this 2017 paper (), in which they found reduced white matter structural integrity (FA values) in transgender women (not trans men), and appeared independent of sexual orientation. pmc.ncbi.nlm.nih.gov/articles/PMC57…Image
Later in 2022, this was "replicated" () in adolescent trans girls (mean age = 15.4). However, no sex-reversal was seen in dysphoric pre-pubescent children (mean age = 10.4).

Importantly, this sample overlapped with the study cited above. pmc.ncbi.nlm.nih.gov/articles/PMC10…Image
Read 14 tweets
Sammy Profile picture
Mar 21, 2025
A thread of mis-information here…
You make the claim that the hypothalamic nuclei (the BSTc in the cited Zhou et al., 1995 study), in transwomen is similar to that of natal women. However, you fail to mention that the BSTc doesn’t become dimorphic until 30-35 years of age and instead assume causality.
You then go onto talk about a few papers (vaguely) that include functional brain activity, neuroimaging (looking at cortical thickness), and various responses.

You fail to mention the impact that homosexuality may have on the results and make the assumption of causality (again)
Read 8 tweets
Sammy Profile picture
Aug 23, 2024
This paper suggests that untreated male-to-female transsexuals (MtF; n = 18) and FtMs (n = 24) show signs of feminisation and masculinisation, respectively, in relation to cortical thickness (CTh).

Let’s take a look: Image
In their whole-brain comparison on CTh in relation to sexual dimorphism, the authors found that FtMs did not differ from female controls (thus having a CTh pattern congruent with their biological sex). Similarly, MtFs also did not differ to female controls (thus having a CTh pattern reflective of the opposite sex).
However, both sets of transsexual subjects did show some differences in relation to both male and female controls (see figure below): Image
Read 8 tweets
Sammy Profile picture
Dec 7, 2023
Brain activation patterns (those involved in self-referential/own body-perception processing) in trans men (n=14) & women (n=16) are similar to those of male (n=15) & female (n=15) controls, except when viewing their bodies morphed to the opposite sex:
pubmed.ncbi.nlm.nih.gov/31813993/
Image
Participants wore a skin-tight suit which was virtually morphed to appear more masculine or feminine, representing images that are associated with either their natal sex or the opposite sex.

They then view these images in different increments in an fMRI scanner: Image
As expected, trans participants subjectively rated their bodies morphed toward the opposite sex as being more like "me", whereas male and female controls rated their natal sexed body images as being more like "me": Image
Read 9 tweets
Sammy Profile picture
Dec 5, 2023
NEW STUDY: This is the first attempt to assess the translational potential for utilizing mice as a model for investigating human sex differences in the brain, focusing on regional grey matter volume (GMV).

Let's take a look 👀
Using a large cohort from the Human Connectome Project (597 females & 496 males) and mice (213 females & 216 males), total tissue volume (TTV; i.e., brain size) was assessed.

Human males showed a 13.5% larger TTV, whereas mice showed no such sex difference: Image
After TTV correction + multiple comparisons, 65.8% of the human brain showed statistically significant sex differences, of which 63.8% were female-bias & 36.3% were male-bias.

In mice, 58.6% of all regions were sexually dimorphic, with 53% being female-bias & 47% male-bias.
Read 12 tweets

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