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Gender incongruence Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The term replaced the previous diagnostic label of gender ide ...
is the state of having a
gender identity Gender identity is the personal sense of one's own gender. Gender identity can correlate with a person's assigned sex or can differ from it. In most individuals, the various biological determinants of sex are congruent and consistent with the in ...
that does not correspond to one's
sex assigned at birth Sex assignment (also known as gender assignment) is the discernment of an infant's sex, typically made at birth based on an examination of the baby's external genitalia by a healthcare provider such as a midwife, nurse, or physician. In the ...
. This is experienced by people who identify as
transgender A transgender (often shortened to trans) person has a gender identity different from that typically associated with the sex they were sex assignment, assigned at birth. The opposite of ''transgender'' is ''cisgender'', which describes perso ...
or
transsexual A transsexual person is someone who experiences a gender identity that is inconsistent with their assigned sex, and desires to permanently transition to the sex or gender with which they identify, usually seeking medical assistance (incl ...
, and often results in
gender dysphoria Gender dysphoria (GD) is the distress a person experiences due to inconsistency between their gender identitytheir personal sense of their own genderand their sex assigned at birth. The term replaced the previous diagnostic label of gender i ...
. The causes of gender incongruence have been studied for decades. Transgender brain studies, especially those on
trans women A trans woman or transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity and may experience gender dysphoria (distress brought upon by the discrepancy between a person's gender identity and their ...
attracted to women ( gynephilic), and those on
trans men A trans man or transgender man is a man who was assigned female at birth. Trans men have a male gender identity, and many trans men undergo Gender transition, medical and social transition to alter their appearance in a way that aligns with th ...
attracted to men (
androphilic In behavioral science, androphilia and gynephilia are sexual orientations: Androphilia is sexual attraction to men and/or masculinity; gynephilia is sexual attraction to women and/or femininity. Ambiphilia describes the combination of both androp ...
), are limited, as they include only a small number of tested individuals.
Twin studies Twin studies are studies conducted on Identical twin, identical or Fraternal twin, fraternal twins. They aim to reveal the importance of environmental and genetics, genetic influences for traits, phenotypes, and disorders. Twin research is consid ...
indicate that genes play a role in gender incongruence, although the precise genes involved are not known or well understood. Environmental factors, such as prenatal hormone exposure, have also been investigated but are difficult to test.


Genetics

Gender identity is genetically heritable, but no convincing candidate genes are known. Gender incongruence has been associated with certain
allele An allele is a variant of the sequence of nucleotides at a particular location, or Locus (genetics), locus, on a DNA molecule. Alleles can differ at a single position through Single-nucleotide polymorphism, single nucleotide polymorphisms (SNP), ...
s relevant to
steroidogenesis A steroid is an organic compound with four fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes that alter memb ...
. In 2013, a
twin study Twin studies are studies conducted on identical or fraternal twins. They aim to reveal the importance of environmental and genetic influences for traits, phenotypes, and disorders. Twin research is considered a key tool in behavioral genetics ...
combined a survey of pairs of twins where one or both had undergone, or had plans and medical approval to undergo, gender transition, with a literature review of published reports of transgender twins. The study found that one third of identical twin pairs in the sample were both transgender: 13 of 39 (33%) monozygotic or identical pairs of assigned males and 8 of 35 (22.8%) pairs of assigned females. Among dizygotic or genetically non-identical twin pairs, there was only 1 of 38 (2.6%) pairs where both twins were trans. The significant percentage of identical twin pairs in which both twins are trans and the virtual absence of dizygotic twins (raised in the same family at the same time) in which both were trans would provide evidence that transgender identity is significantly influenced by genetics if both sets were raised in different families. In 2018 a review of family and twin studies found that there was "significant and consistent evidence" for gender identity being genetically heritable.


Prenatal hormonal environment

Sex hormones in the prenatal environment differentiate the male and female brain. One hypothesis proposes that transgender individuals may have been exposed to atypical levels of sex hormones during later stages of fetal development, leading to brain structures atypical of their sex assigned at birth. In people with XX chromosomes,
congenital adrenal hyperplasia Congenital adrenal hyperplasia (CAH) is a group of Genetic disorder#Autosomal recessive, autosomal recessive disorders characterized by impaired cortisol synthesis. It results from the deficiency of one of the five enzymes required for the Biosy ...
(CAH) results in heightened exposure to prenatal androgens, resulting in masculinization of the genitalia. Individuals with CAH are typically subjected to medical interventions including prenatal hormone treatment and postnatal genital reconstructive surgeries. Such treatments are sometimes criticized by
intersex rights Intersex people are born with sex characteristics, such as chromosomes, gonads, or genitals, that, according to the UN Office of the High Commissioner for Human Rights, "do not fit typical binary notions of male or female bodies." Intersex pers ...
organizations as non-consensual, invasive, and unnecessary interventions. Individuals with CAH are usually
assigned female Sex assignment (also known as gender assignment) is the discernment of an infant's sex, typically made at birth based on an examination of the baby's external genitalia by a healthcare provider such as a midwife, nurse, or physician. In the v ...
and tend to develop similar cognitive abilities to the typical females, including
spatial ability Spatial ability or visuo-spatial ability is the capacity to understand, reason, and remember the visual and spatial relations among objects or space. Visual-spatial abilities are used for everyday use from navigation, understanding or fixing equ ...
, verbal ability, language lateralization,
handedness In human biology, handedness is an individual's preferential use of one hand, known as the dominant hand, due to and causing it to be stronger, faster or more Fine motor skill, dextrous. The other hand, comparatively often the weaker, less dext ...
and
aggression Aggression is behavior aimed at opposing or attacking something or someone. Though often done with the intent to cause harm, some might channel it into creative and practical outlets. It may occur either reactively or without provocation. In h ...
. Research has shown that people with CAH and XX chromosomes will be more likely to experience same-sex attraction, and at least 5.2% of these individuals develop serious gender dysphoria. In males with 5-alpha-reductase deficiency, conversion of
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
to
dihydrotestosterone Dihydrotestosterone (DHT, 5α-dihydrotestosterone, 5α-DHT, androstanolone or stanolone) is an endogenous androgen sex steroid and hormone primarily involved in the growth and repair of the prostate and the penis, as well as the production o ...
is disrupted, decreasing the masculinization of genitalia. Individuals with this condition are typically assigned female and raised as girls due to their feminine appearance at a young age. However, more than half of males with this condition raised as females come to identify as male later in life. Scientists speculate that the definition of masculine characteristics during puberty and the increased social status afforded to men are two possible motivations for a female-to-male transition.


Brain structure

Transgender brain studies, especially those on
trans women A trans woman or transgender woman is a woman who was assigned male at birth. Trans women have a female gender identity and may experience gender dysphoria (distress brought upon by the discrepancy between a person's gender identity and their ...
attracted to women ( gynephilic), and those on
trans men A trans man or transgender man is a man who was assigned female at birth. Trans men have a male gender identity, and many trans men undergo Gender transition, medical and social transition to alter their appearance in a way that aligns with th ...
attracted to men (
androphilic In behavioral science, androphilia and gynephilia are sexual orientations: Androphilia is sexual attraction to men and/or masculinity; gynephilia is sexual attraction to women and/or femininity. Ambiphilia describes the combination of both androp ...
), are limited, as they include only a small number of tested individuals. Several studies have found a correlation between gender identity and brain structure. A first-of-its-kind study by Zhou ''et al.'' (1995) found that in the bed nucleus of the
stria terminalis The stria terminalis (or terminal stria) is a structure in the brain consisting of a band of fibers running along the lateral margin of the ventricular surface of the thalamus. Serving as a major output pathway of the amygdala, the stria termina ...
(BSTc), a region of the brain known for sex and anxiety responses (and which is affected by prenatal androgens), cadavers of six trans women had female-normal BSTc size, similar to the study's cadavers of cisgender women. While the trans women had undergone hormone therapy, and all but one had undergone sex reassignment surgery, this was accounted for by including cadavers of cisgender men and cisgender women as controls who, for a variety of medical reasons, had experienced hormone reversal. The controls still had sizes typical for their sex, and thus no relationship to post-natal hormone levels (nor to sexual orientation) was found. Other post-mortem studies also found brain differences between cisgender and transgender individuals. In 2002, a follow-up study by Chung ''et al.'' found that significant
sexual dimorphism Sexual dimorphism is the condition where sexes of the same species exhibit different Morphology (biology), morphological characteristics, including characteristics not directly involved in reproduction. The condition occurs in most dioecy, di ...
in BSTc did not establish until adulthood. Chung ''et al.'' theorized that changes in fetal hormone levels produce changes in BSTc synaptic density, neuronal activity, or neurochemical content which later lead to size and neuron count changes in BSTc, or alternatively, that the size of BSTc is affected by the generation of a gender identity inconsistent with one's assigned sex. In the textbook Adult Psychopathology and Diagnosis, 7th edition, Lawrence and Zucker suggested that the BSTc may not be a valid biomarker for gender incongruence, as differences in size could be caused by gender-affirming hormone therapy or paraphilias, and might not occur in homosexual transsexuals. In a review of the evidence in 2006, Gooren considered the earlier research as supporting the concept of gender incongruence as a "sexual differentiation disorder" of the sexually dimorphic brain.
Dick Swaab Dick Frans Swaab (born 17 December 1944) is a Dutch physician and neurobiologist (brain researcher). He is a professor of neurobiology at the University of Amsterdam and was until 2005 Director of the Netherlands Institute for Brain Research (N ...
(2004) concurred. In 2008, Garcia-Falgueras & Swaab discovered that the interstitial nucleus of the
anterior hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituit ...
( INAH-3), part of the hypothalamic uncinate nucleus, had properties similar to the BSTc with respect to sexual dimorphism and gender incongruence, likewise in line with the trans individuals’ declared genders and likewise regardless of if hormonal transition had occurred or not. A 2009
MRI Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and rad ...
study by Luders et al. found that among 24 trans women not treated with hormone therapy, regional
gray matter Grey matter, or gray matter in American English, is a major component of the central nervous system, consisting of neuronal cell bodies, neuropil (dendrites and unmyelinated axons), glial cells (astrocytes and oligodendrocytes), synapses, and ...
concentrations were more similar to those of cisgender men than of cisgender women, but there was a significantly greater volume of gray matter in the right
putamen The putamen (; from Latin, meaning "nutshell") is a subcortical nucleus (neuroanatomy), nucleus with a rounded structure, in the basal ganglia nuclear group. It is located at the base of the forebrain and above the midbrain. The putamen and c ...
compared to cisgender men. Like earlier studies, researchers concluded that transgender identity was associated with a distinct cerebral pattern. MRI scanning allows easier study of larger brain structures, but independent nuclei are not visible due to lack of contrast between different neurological tissue types, hence other studies on e.g. BSTc were done by dissecting brains post-mortem. Rametti et al. (2011) studied 18 trans men who had not undergone hormone therapy using
diffusion tensor imaging Diffusion-weighted magnetic resonance imaging (DWI or DW-MRI) is the use of specific MRI sequences as well as software that generates images from the resulting data that uses the diffusion of water molecules to generate contrast in MR images. It ...
(DTI), an MRI technique which allows visualizing
white matter White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
, the structure of which is sexually dimorphic. Rametti ''et al.'' discovered that the trans men's white matter, compared to 19 cisgender gynephilic females, showed higher
fractional anisotropy Fractional anisotropy (FA) is a scalar (mathematics), scalar value between zero and one that describes the degree of anisotropy of a diffusion process. A value of zero means that diffusion is isotropic, i.e. it is unrestricted (or equally restricted ...
values in posterior part of the right SLF, the forceps minor and
corticospinal tract The corticospinal tract is a white matter motor pathway starting at the cerebral cortex that terminates on lower motor neurons and interneurons in the spinal cord, controlling movements of the limbs and trunk. There are more than one million neu ...
". Compared to 24 cisgender males, they showed only lower FA values in the corticospinal tract. The white matter patterns in trans men were found to be shifted in the direction of cis men. A 2011 review published in '' Frontiers in Neuroendocrinology'' found that "Female INAH3 and BSTc have been found in MtF transsexual persons. The only female-to-male (FtM) transsexual person available to us for study so far had a BSTc and INAH3 with clear male characteristics. (...) These sex reversals were found not to be influenced by circulating hormone levels in adulthood, and seem thus to have arisen during development" and that "All observations that support the neurobiological theory about the origin of transsexuality, i.e. that it is the sizes, the neuron numbers, and the functions and connectivity of brain structures, not the sex of their sexual organs, birth certificates or passports, that match their gender identities". In 2012 and 2016 studies by Taziaux et al. reported that MtF subjects had infundibular nuclei similar to those of cis women. A 2015 review reported that two studies found a pattern of white matter microstructure differences away from a transgender person's birth sex, and toward their desired sex. In one of these studies, sexual orientation had no effect on the diffusivity measured. A 2016 review reported that, for androphilic trans women and gynephilic trans men, hormone treatment may have large effects on the brain, and that
cortical thickness The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...
, which is generally thicker in cisgender women's brains than in cisgender men's brains, may also be thicker in trans women's brains, but is present in a different location to cisgender women's brains. It also stated that for both trans women and trans men, "cross-sex hormone treatment affects the gross morphology as well as the white matter microstructure of the brain. Changes are to be expected when hormones reach the brain in pharmacological doses. Consequently, one cannot take hormone-treated transsexual brain patterns as evidence of the transsexual brain phenotype because the treatment alters brain morphology and obscures the pre-treatment brain pattern." A 2019 review in ''
Neuropsychopharmacology Neuropsychopharmacology, an interdisciplinary science related to psychopharmacology (study of effects of drugs on the mind) and fundamental neuroscience, is the study of the neural mechanisms that drugs act upon to influence behavior. It entails ...
'' found that among transgender individuals meeting diagnostic criteria for gender dysphoria, "cortical thickness, gray matter volume, white matter microstructure, structural connectivity, and corpus callosum shape have been found to be more similar to cisgender control subjects of the same preferred gender compared with those of the same natal sex." A 2021 review of brain studies published in the ''
Archives of Sexual Behavior The ''Archives of Sexual Behavior'' is a bimonthly peer-reviewed medical journal in sexology. It is the official publication of the International Academy of Sex Research. History The journal was established in 1971 by Richard Green, who served a ...
'' found that "although the majority of neuroanatomical, neurophysiological, and neurometabolic features" in transgender people "resemble those of their natal sex rather than those of their experienced gender", for trans women they found feminine and demasculinized traits, and vice versa for trans men. They stated that due to limitations and conflicting results in the studies that had been done, they could not draw general conclusions or identify-specific features that consistently differed between cisgender and transgender people. The review also found differences when comparing cisgender
homosexual Homosexuality is romantic attraction, sexual attraction, or sexual behavior between people of the same sex or gender. As a sexual orientation, homosexuality is "an enduring pattern of emotional, romantic, and/or sexual attractions" exc ...
and
heterosexual Heterosexuality is romantic attraction, sexual attraction, or sexual behavior between people of the opposite sex or gender. As a sexual orientation, heterosexuality is "an enduring pattern of emotional, romantic, and/or sexual attractions ...
people, with the same limitations applying.


Androphilic vs. gynephilic trans women

A 2016 review reported that early-onset androphilic transgender women have a brain structure similar to cisgender women's and unlike cisgender men's, but that they have their own brain phenotype. It also reported that gynephilic trans women differ from both cisgender female and male controls in non-dimorphic brain areas. The available research indicates that the brain structure of androphilic trans women with early-onset gender dysphoria is closer to that of
cisgender The word ''cisgender'' (often shortened to ''cis''; sometimes ''cissexual'') describes a person whose gender identity corresponds to their sex assigned at birth, i.e., someone who is not ''transgender''. The prefix '' cis-'' is Latin and ...
women than that of cisgender men. It also reports that gynephilic trans women differ from both cisgender female and male controls in non-dimorphic brain areas.
Cortical thickness The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of neural integration in the central nervous system, and plays a key ...
, which is generally thicker in cisgender women's brains than in cisgender men's brains, may also be thicker in trans women's brains, but is present in a different location to cisgender women's brains. For trans men, research indicates that those with early-onset gender dysphoria and who are gynephilic have brains that generally correspond to their assigned sex, but that they have their own phenotype with respect to cortical thickness, subcortical structures, and white matter microstructure, especially in the right hemisphere.
Hormone therapy Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are hormonal therap ...
can also affect transgender people's brain structure;
estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...
can cause transgender women's brains to become closer to those of cisgender women, and morphological changes observed in the brains of trans men might be due to the anabolic effects of
testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...
. MRI taken on gynephilic trans women have likewise shown differences in the brain from non-trans people, though in ways not directly related to sexual dimorphism.


Gynephilic trans men

Fewer brain structure studies have been performed on transgender men than on transgender women. A 2016 review reported that the brain structure of early-onset gynephilic trans men generally corresponds to their assigned sex, but that they have their own phenotype with respect to cortical thickness, subcortical structures, and white matter microstructure, especially in the right hemisphere. Morphological increments observed in the brains of trans men might be due to the anabolic effects of testosterone.


Onset

According to the
DSM-5 The ''Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition'' (DSM-5), is the 2013 update to the '' Diagnostic and Statistical Manual of Mental Disorders'', the taxonomic and diagnostic tool published by the American Psychiat ...
, gender dysphoria in those
assigned male at birth Sex assignment (also known as gender assignment) is the discernment of an infant's sex, typically made at birth based on an examination of the baby's external genitalia by a healthcare provider such as a midwife, nurse, or physician. In the v ...
tends to follow one of two broad trajectories: early-onset or late-onset. Early-onset gender dysphoria is behaviorally visible in childhood. Sometimes, gender dysphoria may stop for a while in this group, and they may identify as gay or homosexual for a period of time, followed by recurrence of gender dysphoria. This group is usually androphilic in adulthood. Late-onset gender dysphoria does not include visible signs in early childhood, but some report having had wishes to be the opposite sex in childhood that they did not report to others. Trans women who experience late-onset gender dysphoria are more likely be attracted to women and may identify as lesbians or bisexual. It is common for people assigned male at birth who have late-onset gender dysphoria to experience sexual excitement from cross-dressing. In those
assigned female at birth Sex assignment (also known as gender assignment) is the discernment of an infant's sex, typically made at birth based on an examination of the baby's external genitalia by a healthcare provider such as a midwife, nurse, or physician. In the ...
, early-onset gender dysphoria is the most common course. This group is usually sexually attracted to women. Trans men who experience late-onset gender dysphoria will usually be sexually attracted to men and may identify as gay. In general, onset of symptoms may begin at any time after an individual reaches the age of two or three.


Blanchard's typology

In the 1980s and 1990s, sexologist
Ray Blanchard Ray Milton Blanchard III ( ; born October 9, 1945) is an American-Canadian sexologist who researches pedophilia, sexual orientation and Transgender, gender identity. He has found that men with more older brothers are more likely to be gay than m ...
developed a taxonomy of male-to-female transsexualism built upon the work of his colleague
Kurt Freund Kurt Freund (17 January 1914 – 23 October 1996) was a Czech-Canadian physician and sexologist best known for developing the penile plethysmograph (a measurement of sexual arousal in males), research studies in pedophilia, and for the " court ...
, which argues that trans women have one of two primary causes of gender dysphoria. Blanchard theorized that " homosexual transsexuals" (a taxonomic category referring to trans women attracted to men) are attracted to men and develop gender dysphoria typically during childhood, and characterizes them as displaying overt and obvious femininity since childhood; he characterizes "non-homosexual transsexuals" (trans women who are sexually attracted to women) as developing gender dysphoria primarily due to autogynephilia (sexual arousal by the thought or image of themselves as a woman), and as attracted to women, attracted to both women and men (Blanchard calls this "pseudo-bisexuality", believing attraction to males to be not genuine, but part of the performance of an autogynephilic sexual fantasy), or
asexual Asexual or Asexuals may refer to: *Asexual reproduction **Asexual reproduction in starfish *Asexuality, the lack of sexual attraction to anyone or lack of interest in or desire for sexual activity. **Gray asexuality, the spectrum between asexualit ...
. Blanchard's theory has received support from J. Michael Bailey,
Anne Lawrence Anne Alexandra Lawrence (born November 17, 1950) is an American psychologist, sexologist, and physician who has published extensively on gender dysphoria, transgender people, and paraphilias. Lawrence is a transgender woman and self-identifies ...
, and
James Cantor James M. Cantor is an American-Canadian clinical psychologist and sexologist specializing in hypersexuality and paraphilias. A former senior scientist with the Centre for Addiction and Mental Health (CAMH) in Toronto, Blanchard argued that there are significant differences between the two groups, including sexuality, age of transition, ethnicity, IQ,
fetishism A fetish is an object believed to have supernatural powers, or in particular, a human-made object that has power over others. Essentially, fetishism is the attribution of inherent non-material value, or powers, to an object. Talismans and amulet ...
, and quality of adjustment. Blanchard's typology has been criticized in papers from Veale, Nuttbrock, Moser, and others who argue that it is poorly representative of trans women and non-instructive, and that the experiments behind it are poorly controlled and/or contradicted by other data. Charles Moser conducted a survey of 29 cisgender women in the healthcare field based on Blanchard's methods for identifying autogynephilia, found that 93% of respondents qualified as autogynephiles based on their own responses. Anne Lawrence criticized the methodology of Mosers survey. Blanchard proposed that "homosexual transsexuals", but not "autogynephilic transsexuals", would have feminized brain structure, stating: "if there is any neuroanatomic intersexuality, it is in the homosexual group". James Cantor has argued that MRI studies of transgender women offer support for Blanchard's prediction. A 2016 review of transgender brain structure states: "Cantor seems to be right. Nonhomosexual MtFs present differences with heterosexual males in structures that are not sexually dimorphic (Savic & Arver, 2011), while homosexual MtFs (as well as homosexual FtMs) show differences with respect to male and female controls in a series of brain fascicles". The review notes that only one study has compared gynephilic and androphilic transgender women, and that "more independent studies on nonhomosexual MtFs are needed".


See also

* * * * * Wrong-body narrative


References


Further reading

* Kauffman et al. (2022
Concordance for Gender Dysphoria in Genetic Female Monozygotic (Identical) Triplets
''Archives of Sexual Behavior'' {{DEFAULTSORT:Causes Of Transsexualism Transgender studies Psychological theories Neuroscience Behavioral neuroscience
Transsexualism A transsexual person is someone who experiences a gender identity that is inconsistent with their assigned sex, and desires to permanently transition to the sex or gender with which they identify, usually seeking medical assistance (incl ...
Behavioural genetics Gender identity Transgender health care