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.1PubMed Central. Early androgen exposure and human gender development 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.2Frontiers in Neuroendocrinology. Sexual differentiation of the human brain: Relation to gender identity, sexual orientation and neuropsychiatric disorders
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.3PubMed Central. Neurobiology of gender identity and sexual orientation 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.4PubMed. A sex difference in the human brain and its relation to transsexuality 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.5PubMed Central. Increased Cortical Thickness in Male-to-Female Transsexualism 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.6Hormones and Behavior. Neurobiological characteristics associated with gender identity: Findings from neuroimaging studies in the Amsterdam cohort of children and adolescents experiencing gender incongruence 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.7PubMed Central. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging
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.8Scientific Reports. Structural connections in the brain in relation to gender identity and sexual orientation 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.9Cerebral Cortex. Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex 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.9Cerebral Cortex. Neural Systems for Own-body Processing Align with Gender Identity Rather Than Birth-assigned Sex 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.10PubMed Central. Intrinsic network connectivity and own body perception in gender dysphoria 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.11NeuroImage. Brain network interactions in transgender individuals with gender incongruence
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.12Neurophysiologie Clinique. Brain sexual differentiation and effects of cross-sex hormone therapy in transpeople: A resting-state functional magnetic resonance study 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.13Psychoneuroendocrinology. Subcortical gray matter changes in transgender subjects after long-term cross-sex hormone administration 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.14NeuroImage. Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects
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.15Psychoneuroendocrinology. The influence of sex steroid treatment on insular connectivity in gender dysphoria 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.16Psychoneuroendocrinology. Gender-affirming hormone treatment and cognitive function in transgender young adults: a systematic review and meta-analysis 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.17ESPE Abstracts. Spatial navigation and memory in transgender male adolescents treated with gender affirming hormones
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.18The Journal of Sexual Medicine. Long-Term Gender-Affirming Hormone Therapy and Cognitive Functioning in Older Transgender Women Compared With Cisgender Women and Men
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.19PubMed. The impact of suppressing puberty on neuropsychological function: A review 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.20PubMed Central. Androgen Receptor Repeat Length Polymorphism Associated with Male-to-Female Transsexualism A later meta-analysis confirmed this pattern, finding a statistically significant but small difference in repeat length between transgender women and cisgender men.21PubMed. Polymorphic Cytosine-Adenine-Guanine Repeat Length of Androgen Receptor Gene and Gender Incongruence in Trans Women: A Systematic Review and Meta-Analysis of Case-Control Studies 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.22The Journal of Clinical Endocrinology & Metabolism. Genetic Link Between Gender Dysphoria and Sex Hormone Signaling
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.23PubMed Central. Epigenetics Is Implicated in the Basis of Gender Incongruence: An Epigenome-Wide Association Analysis 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.24Scientific Reports. CBLL1 is hypomethylated and correlates with cortical thickness in transgender men before gender affirming hormone treatment 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.25PubMed Central. Sex beyond the genitalia: The human brain mosaic 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.26PubMed. Beyond sex differences and a male-female continuum: Mosaic brains in a multidimensional space
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.27History and Philosophy of the Life Sciences. After the trans brain: a critique of the neurobiological accounts of embodied trans* identities 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.28PubMed. Psychological outcomes and gender-related development in complete androgen insensitivity syndrome 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.29PubMed. Male gender identity in complete androgen insensitivity syndrome
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.30PubMed Central. Sex differences in brain developing in the presence or absence of gonads 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.31PubMed Central. Neural, not gonadal, origin of brain sex differences in a gynandromorphic finch 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.32Nature Communications. Elevated rates of autism, other neurodevelopmental and psychiatric diagnoses, and autistic traits in transgender and gender-diverse individuals 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.33PubMed Central. Gender Incongruence and Autistic Traits: Cerebral and Behavioral Underpinnings 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.34Cerebral Cortex. The autism spectrum among transgender youth: default mode functional connectivity
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.35Frontiers in Sociology. Social exclusion and psychopathology in LGBTQ+ communities: a neuropsychosocial review
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.36PubMed. Gender minority stress and diurnal cortisol profiles among transgender and gender diverse people in the United States 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 2011.37Frontiers in Human Neuroscience. A brief historic overview of sexual and gender diversity in neuroscience: past, present, and future 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.6Hormones and Behavior. Neurobiological characteristics associated with gender identity: Findings from neuroimaging studies in the Amsterdam cohort of children and adolescents experiencing gender incongruence
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.