Definition: The neurobiological processes that create a person’s internal sense of being male, female, both, neither, or somewhere along a spectrum. This aspect of human development begins before birth as the brain develops and is influenced by genetics, prenatal hormones, and brain organization. For most people, neurobiological sex aligns with biological sex, but for some it does not.
Key Insight: Gender identity is a naturally occurring aspect of human neurodevelopment. It develops independently from the physical characteristics of the body, although the two usually are in alignment.
Continuum
Typical Female Identity <–> Nonbinary Variations <–> Typical Male Identity
Why It Matters
Understanding neurobiological sex explains why a person’s internal sense of self may differ from their physical sex characteristics. This provides the scientific foundation for understanding transgender identities while recognizing that gender identity is a naturally developing aspect of the human brain rather than a personal choice.
These studies are not presented to prove that God does or does not exist, nor to argue for or against evolution or any other belief system. They are included because they investigate one specific question, whether gender identity has measurable neurodevelopmental and biological components. You are free to disagree with the conclusions, but I hope that you’ll at least see why I (and many people who are Transsexual or Transgender) believe our experience was not simply a choice.
Scientific Foundations
Brain Structure
BSTc Studies
Zhou Jiang-Ning et al. (1995) — A Sex Difference in the human Brain and its Relation to Transsexuality
Demonstrated that the central subdivision of the bed nucleus of the stria terminalis (BSTc), a brain region involved in sexual differentiation, more closely resembled a person’s experienced gender than their sex assigned at birth, providing early evidence that gender identity has a neurobiological basis.
F.P.M. Kruijver et al. (2000) — Male-to-Female Transsexuals Have Female Neuron Numbers in a Limbic Nucleus
Demonstrated that male-to-female transgender individuals had female-typical numbers of neurons in the BSTc, reinforcing earlier findings that gender identity is associated with sexually differentiated brain structures rather than being explained by adult hormone treatment or sexual orientation
INAH3 studies
Garcia-Falgueras & Swabb (2008) — A Sex Difference in the Hypothalamic Uncinate Nucleus: Relationship to Gender Identity
Found that the sexually differentiated uncinate nucleus (NAH3 region) in transgender individuals more closely resembled their experienced gender than their sex assigned at birth, providing additional evidence that gender identity has a neurobiological basis.
Dick F. Swaab (2009) — Sexual Differentiation of the Human Brain in Relation to Gender Identity and Sexual Orientation
Reviewed evidence that sexual differentiation of the human brain occurs during prenatal development and summarized findings from BSTc, INAH3, hormonal, and genetic research supporting a neurobiological basis for gender identity.
Cortical thickness
Eileen Luders et al. (2012) —Increased Cortical Thickness in Male-to-Female Transsexualism
Found that untreated transgender women exhibited increased cortical thickness in multiple brain regions compared with cisgender men, with cortical patterns shifted toward those typically observed in cisgender women. These findings provided additional evidence that brain anatomy is associated with gender identity.
Laura Zubiaurre-Elorza et al. (2013) —Cortical Thickness in Untreated Transsexuals
Reported that untreated transgender participants showed cortical thickness patterns that differed from their sex assigned at birth in several brain regions supporting a neurodevelopmental basis for gender identity.
White matter connectivity
Rametti et al., (2011) — Female-to-Male White Matter Microstructure in Female-to-Male Transsexuals Before Cross-Sex Hormonal treatment. A Diffusion Tensor Imaging Study
Used diffusion tensor imaging (DTI) to show that untreated transgender men had white matter microstructure patterns shifted toward cisgender men before hormone treatment, supporting a neurodevelopmental basis for gender identity.
Rametti et al., (2011) —Male-to-Female The Microstructure of White Matter in Male-to-Female Transsexuals before Cross-Sex Hormonal Treatment. A DTI Study
Used diffusion tensor imaging (DTI) to show that untreated transgender women had white matter microstructure patterns shifted toward cisgender women before hormone treatment, supporting a neurodevelopmental basis for gender identity.
Genetics and Epigenetics
Sex Differentiation Genes
Theisen et al., (2019) — Variants in sex differentiation genes
Identified variants in genes involved in sex differentiation that were associated with transgender identity, supporting the idea that gender identity is influenced by multiple genetic factors rather than a single “transgender gene.”
Epigenetics
Parodi et al., (2021) — Epigenetic DNA methylation differences
Found differences in DNA methylation patterns associated with gender identity, suggesting that epigenetic regulation may contribute to the neurodevelopmental processes underlying gender identity.
EEG
Flor-Henry, P., et al. (2010) — EEG Analysis of Male-to-Female Transsexuals: Discriminant Function and Source Analysis. Clinical EEG and Neuroscience, 41(4), 219-222
EEG analysis identified brain activity patterns in untreated transgender women that differed from cisgender men and showed characteristics more consistent with their experienced gender identity, providing early neurophysiological evidence that gender identity has measurable brain correlates.
Recent Evidence (2020-2024)
Kurth et al., (2022) — Brain sex in trans women shifted toward gender identity
Used a multivariate MRI classifier in transgender women before hormone therapy and found that brain anatomy was shifted away from sex assigned at birth and toward gender identity. Rather than fitting a simple male/female binary, the study supported a continuum of neurobiological variation and reinforced earlier findings from structural neuroimaging.
Majid et al., (2021) — Neural systems for own-body perception align with identity rather than Birth-assigned Sex
Used functional MRI to study how transgender and cisgender participants processed images of their own bodies. The researchers found that both groups activated similar self- and body-processing brain networks when viewing bodies that aligned with their gender identity, rather than their birth-assigned sex. These findings suggest that the brain’s representation of the body is organized around gender identity rather than assigned sex.
Mueller et al., (2021) — The Neuroanatomy of Transgender Identity: Mega-Analytic Findings From the ENIGMA Transgender Persons Working Group
This is the largest structural MRI analysis in transgender people to date and comes from the ENIGMA consortium. It examined 803 transgender participants and concluded that transgender people show a distinctive neuroanatomical phenotype rather than simply having brains that are shifted completely toward one sex or the other
Kim et al., (2023) — Genetic association indicates identity is polygenic.
Analyzed genetic variation across the genome and found that gender identity is influenced by many genes acting together rather than a single “gender identity gene”. The findings support the view that gender identity is a complex, polygenic neurodevelopmental trait.
Xerxa et al., (2023) — Gender diversity & brain morphology in adolescents
Examined more than 2000 adolescents from the general population and found that while overall brain size did not differ, gender diversity was associated with specific regional brain morphology, supporting a biological contribution to gender diversity without implying a single “transgender brain.”
Julie Bakker (2024) — Neurobiological Characteristics associated with gender identity
Reviewed structural and functional MRI studies of transgender children and adolescents, finding evidence that aspects of brain development align with gender identity before hormone treatment. The review also identified distinctive transgender neural characteristics, suggesting neurodevelopmental patterns that extend beyond a simple male-female binary.
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