Transgender Neuroscience: The Brain and Gender Identity

Neuroscience research over the past three decades has found that transgender individuals’ brains often show structural and functional patterns that differ from those of cisgender people who share their birth-assigned sex, sometimes shifting toward patterns more typical of their experienced gender. But these findings resist the tidy narrative of “a female brain trapped in a male body” or vice versa. The reality involves prenatal hormones, genetics, epigenetics, connectivity patterns, and how the brain processes its own body, all layered on top of a growing recognition that no brain is purely “male” or “female” in the first place.

Prenatal Hormones and the Foundation of Gender Identity

The leading biological framework for understanding gender identity starts before birth. During fetal development, testosterone and other androgens shape the developing brain in ways that appear to influence later gender-related behavior and identity. Research on people exposed to atypical hormone levels in the womb, whether from genetic conditions or medications taken during pregnancy, has consistently found shifts in childhood play behavior, sexual orientation, and gender identity itself.¹ The basic model holds that the fetal brain develops in a male-typical direction when exposed to testosterone and in a female-typical direction in its absence.²

Evidence supporting this model draws from animal research, measurements of biological markers linked to androgen exposure, and clinical studies of people with differences of sex development.³ The idea is that gender identity gets “programmed” during a critical window of brain development that may not align perfectly with genital development, since the two happen at different stages of fetal life. When the hormonal signals during those windows diverge, the result could be a person whose brain-based sense of gender does not match the body that developed under different hormonal timing. This remains a working hypothesis rather than a proven mechanism, but it is the framework most neuroscientists in the field operate within.

Structural Brain Differences

The study that launched this field into public awareness came in 1995, when researchers examined post-mortem brains and found that a tiny structure called the bed nucleus of the stria terminalis (BSTc), a region involved in sexual behavior, was smaller in transgender women than in cisgender men and closer in volume to what is seen in cisgender women.⁴ That finding was striking but came from a handful of brains. In the years since, brain imaging in living people has expanded the picture considerably.

MRI studies have found that transgender women who have not yet started hormone therapy tend to have cortical thickness patterns that differ from cisgender men. One study found significantly thicker cortex in transgender women across multiple brain regions, including parts of the frontal, parietal, and temporal lobes, with no regions where cisgender men had thicker cortex than transgender women.⁵ These differences existed before any hormone treatment, which matters because it rules out the possibility that the differences are simply a result of taking estrogen.

That said, the structural findings are not uniform across studies. Sample sizes in neuroimaging research on transgender populations remain modest, and this limits how confidently any single finding can be generalized.⁶ A brain scan study with 20 or 30 participants can detect group-level patterns, but it cannot tell you whether a given individual’s scan “looks transgender.” That distinction between group averages and individual prediction is important, and researchers in the field emphasize it frequently.

White Matter and How Brain Regions Connect

Beyond the gray matter on the brain’s surface, researchers have looked at white matter, the cabling that connects different brain regions. These studies use a technique called diffusion tensor imaging to measure how water moves along nerve fibers, which reveals how tightly organized those connections are. The results here are genuinely mixed. One study found no significant differences in white matter organization between transgender and cisgender groups.⁷

A larger study, however, did find differences. Transgender women showed lower white matter organization than cisgender heterosexual men in several major fiber bundles, including connections running front to back through the brain and the pathways linking movement-related areas. Interestingly, transgender women’s white matter patterns did not differ from those of cisgender women, meaning the values were shifted away from their birth-assigned sex group and toward their experienced gender group. For transgender men, the picture was less clear-cut: their white matter differed from cisgender men’s but not as dramatically, and the affected tracts were somewhat different.⁸ This asymmetry, where the findings for transgender women are often more pronounced or easier to detect than those for transgender men, appears across multiple types of brain studies and is not yet well explained.

How the Brain Processes Its Own Body

Some of the most intriguing research concerns how transgender people’s brains respond when they see images of bodies. When transgender and cisgender people were shown digitally morphed body images, both groups activated similar brain systems when viewing bodies that aligned with their gender identity, even when those bodies were physically opposite to birth-assigned sex for the transgender participants.⁹ In other words, the brain’s self-recognition and body-processing networks responded to gender identity, not to the sex listed on a birth certificate.

Transgender participants also showed greater activation in prefrontal brain areas involved in self-referential processing when viewing bodies that were ambiguous or morphed toward their gender identity.⁹ A separate study looking at resting-state brain connectivity found that transgender men showed weaker connections within brain networks involved in body perception and sense of self compared to cisgender controls, and that stronger connectivity in these networks was linked to identifying more strongly with bodies matching their gender identity.¹⁰ These body-processing findings are hard to dismiss as artifacts because they show a functional alignment between brain activity and experienced identity, not just a structural measurement that could mean many things.

Functional Brain Networks at Rest

When the brain is not performing a specific task, it settles into organized patterns of activity known as resting-state networks. Researchers have compared these network patterns in transgender and cisgender groups. One study found that transgender men, transgender women, and cisgender women all showed decreased connectivity compared with cisgender men in regions linked to attention, decision-making, and awareness of bodily states. Transgender men additionally showed weaker connections between networks handling salience, self-reflection, motor control, and executive function.¹¹

Other studies have been less dramatic. One found that within several major brain networks, including the default mode network and the salience network, connectivity patterns were largely similar across transgender and cisgender groups.¹² This inconsistency is a recurring feature of the literature. Studies differ in sample size, scanning protocols, and statistical methods, and results do not always replicate cleanly from one lab to the next.

What Hormone Therapy Does to the Brain

Gender-affirming hormone therapy changes the body in well-documented ways. It also changes the brain. In transgender women receiving estrogen and anti-androgen treatment, researchers have observed decreases in hippocampal volume and increases in ventricle size.¹³ A more recent study documented hormone-driven changes in gray matter density and microstructure across multiple regions, including the insula, cingulate cortex, and fusiform gyrus, along with effects on an enzyme involved in neurotransmitter metabolism.¹⁴

Hormone therapy also shifts functional connectivity. One study found that transgender women showed increased connectivity between the insula and regions involved in emotional regulation and attention after starting treatment, a pattern not seen in cisgender male controls over the same time period.¹⁵ These changes are real and measurable, but their meaning for everyday experience is less clear. Whether shifting gray matter density in the fusiform gyrus by a measurable fraction translates into a felt change in how someone perceives faces or processes emotions remains an open question. What the research does establish is that sex hormones actively sculpt brain structure throughout life, not only during fetal development.

Cognitive Effects of Hormone Therapy

A common concern about hormone therapy is whether it affects thinking or memory. A systematic review and meta-analysis found no evidence that gender-affirming hormones impair cognitive function in either direction of transition. Transgender men receiving testosterone showed enhanced visuospatial ability, and transgender women on estrogen showed slightly better verbal working memory compared to pre-treatment baselines.¹⁶ One study of transgender male adolescents on testosterone found their spatial navigation and memory performance was comparable to cisgender males and better than cisgender females.¹⁷

Over the long term, the picture is reassuring but nuanced. A study of older transgender women who had been on hormone therapy for an average of 24 years found their overall cognitive screening scores were slightly higher than those of both cisgender women and cisgender men, though they scored somewhat lower on verbal memory tasks compared to cisgender women. The differences were small, and the researchers characterized the long-term cognitive effects as minimal.¹⁸

Puberty blockers in adolescents are a separate and more uncertain issue. A review of the available evidence found that in animal studies, the cognitive effects of suppressing puberty are complex and often depend on sex, and there is no evidence that these effects fully reverse after stopping treatment. No human studies have systematically tracked cognitive function from before puberty suppression through follow-up with adequate controls.¹⁹ This is one of the areas where the evidence genuinely has not caught up with clinical practice.

Genetics, Receptors, and Epigenetics

If prenatal hormones are one part of the puzzle, genetics may be another. One line of research has focused on the androgen receptor gene, which determines how sensitive the body’s cells are to testosterone. A study found that transgender women had slightly longer repeat sequences in this gene compared to cisgender men, a variation associated with weaker testosterone signaling.²⁰ A later meta-analysis confirmed this pattern, finding a statistically significant but small difference in repeat length between transgender women and cisgender men.²¹ A broader genetic study also identified associations between gender dysphoria and variants in genes involved in estrogen receptors and steroid metabolism, with several gene combinations overrepresented in transgender women that would be expected to reduce masculinization.²²

Beyond the genetic code itself, how genes are switched on and off matters. Epigenetic research has found that transgender and cisgender people have different patterns of DNA methylation, the chemical markers that regulate gene activity, even before starting hormone therapy.²³ One study drilled into specific genes and found that a gene called CBLL1, involved in nerve fiber insulation in the brain, showed unusually low methylation in transgender men compared to both cisgender men and cisgender women. This methylation pattern correlated with cortical thickness in certain brain regions.²⁴ The implication is that the biological basis of gender identity may involve not just which genes you carry but how actively those genes are read, potentially set up by conditions in the womb.

The Brain Mosaic Problem

All of this research operates against a backdrop of an inconvenient truth: human brains do not come in “male” and “female” versions in any clean sense. A landmark analysis of over 1,400 brain scans found extensive overlap between men and women on every gray matter, white matter, and connectivity measure examined. Brains that were internally consistent, with all features falling on the “male” or “female” end, were rare. Most brains were unique mosaics, with some features more common in women, others more common in men, and many common in both.²⁵ This mosaic view has been reinforced by subsequent work arguing that brains exist in a multidimensional space rather than along a single male-to-female spectrum.²⁶

This creates a conceptual tension for transgender neuroscience. If there is no single “male brain” pattern to detect, then saying a transgender woman has a “female brain” oversimplifies what the data actually show. Critics have argued that some neurobiological accounts of trans identity inadvertently reinforce a binary view of brain sex that the broader neuroscience literature has moved away from.²⁷ The more careful interpretation is that transgender people’s brains show specific atypical patterns in particular circuits and regions, especially those involved in body perception and hormonal sensitivity, without the whole brain being categorically “cross-sex.”

Lessons from Intersex Conditions and Animal Models

Some of the clearest evidence that biology shapes gender identity comes from people with differences of sex development. Individuals with complete androgen insensitivity syndrome (CAIS) have XY chromosomes and produce testosterone, but their cells cannot respond to it. Nearly all develop a female gender identity and show psychological outcomes indistinguishable from those of other women, which underscores how central androgen signaling is to masculine-typical development.²⁸ Yet at least one case report documents a CAIS individual who developed a male gender identity, complicating any purely hormonal explanation and suggesting other factors can override the expected outcome.²⁹

Animal research adds another dimension. In mice genetically engineered to lack functional gonads, several brain regions still developed sex differences, pointing to direct genetic influences on brain sexual differentiation independent of hormones.³⁰ A remarkable natural experiment in zebra finches made the case even more strikingly: a rare bird whose brain was genetically male on one side and female on the other showed masculine brain features on the male side, even though both halves were bathed in the same hormonal environment. The genetic sex of the brain cells themselves contributed to how they developed.³¹ These findings do not translate directly to humans, but they demonstrate that brain sex differentiation is not purely about hormones. Genes expressed within brain cells play a role too.

The Overlap with Autism

One of the most replicated findings in this area is that transgender and gender-diverse individuals are diagnosed with autism at substantially higher rates than cisgender people. A large study found the odds of an autism diagnosis were roughly four to six times higher among transgender and gender-diverse individuals compared to cisgender people, even after accounting for age and education level.³² Nobody knows exactly why this co-occurrence exists. Some researchers have proposed that autistic individuals may be less influenced by social norms around gender and therefore more likely to recognize and report gender incongruence. Others suspect shared neurodevelopmental pathways.

Brain imaging studies are beginning to explore the overlap. In one study, people with higher autistic traits showed stronger identification with bodies morphed opposite to their birth-assigned sex, and autistic traits correlated with thinner cortex in temporal regions.³³ When researchers specifically looked at transgender youth with and without autism using gold-standard diagnostic procedures, the brain connectivity patterns associated with autism in transgender youth resembled those seen in autistic cisgender youth, suggesting the autism-related neural features are genuine and not an artifact of being transgender.³⁴

Minority Stress and Its Neural Footprint

The brain does not develop and function in a social vacuum. Transgender people face disproportionate discrimination, rejection, and violence, and this chronic stress leaves measurable marks on the nervous system. Research on minority stress suggests it disrupts the circuits connecting the brain’s emotional centers with its regulation centers, alters stress hormone cycling, and increases the overall wear on the body’s stress-response systems.³⁵

A study measuring cortisol, the body’s primary stress hormone, across the day in transgender and gender-diverse Americans found that those experiencing the highest levels of enacted stigma had a blunted morning cortisol spike and a sluggish decline through the day, ending up with elevated cortisol at bedtime. That flattened daily pattern is associated with chronic stress exposure and health risks. On the other hand, feeling connected to a supportive community was associated with a healthier, more dynamic cortisol rhythm.³⁶ This finding is a reminder that when studying the brains of transgender people, it can be difficult to disentangle what is intrinsic neurobiology from what is the brain’s response to living in a hostile environment. The two are not neatly separable.

A Field Still Taking Shape

Transgender neuroscience as a recognizable research area is surprisingly young. A historical review noted that trans-specific and gender-diversity-related research only became a significant presence in the neuroscience literature after 2000, with affirmative approaches gaining traction only in the decade starting around 2011.³⁷ The field’s relative youth explains some of its limitations: small samples, inconsistent methods across labs, and a bias toward studying transgender women over transgender men. Researchers themselves acknowledge that sample sizes remain modest and limit generalizability.⁶

What the evidence does and does not support is worth being honest about. It supports the idea that gender identity has a biological component, shaped by prenatal hormones, genetics, and epigenetics, and reflected in measurable brain features. It does not support the idea that a brain scan can diagnose someone as transgender, that there is a single “transgender brain type,” or that any individual’s gender identity can be reduced to a neuroimaging finding. The science is real, and it matters, but it describes group-level tendencies across many dimensions, not a binary switch that flips in one direction or another.