Causes of gender incongruence

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Gender incongruence is the state of having a

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.[6]

In people with XX chromosomes,

Brain structure

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General

Transgender brain studies, especially those on

In a follow-up study, Kruijver et al. (2000) looked at the number of neurons in BSTc instead of volumes. They found the same results as Zhou et al. (1995), but with even more dramatic differences. One transfeminine subject who had never received hormone therapy was also included, and nonetheless matched up with the female neuron counts.[17]^{[non-primary source needed]}

In 2002, a follow-up study by Chung et al. found that significant sexual dimorphism 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.^{[18][non-primary source needed]}

It has been suggested that the BSTc differences may be a result of hormone replacement therapy. It has also been suggested that because pedophilic offenders have also been found to have a reduced BSTc, a feminine BSTc may be a marker for

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.[19] Dick Swaab (2004) concurred.^[20]

In 2008, Garcia-Falgueras & Swaab discovered that the interstitial nucleus of the

Hulshoff Pol et al. (2006) studied gross brain volume in 8 trans men and in 6 trans women undergoing hormone therapy. They found that hormones altered the sizes of the hypothalamus in a gender-consistent manner: treatment with masculinizing hormones shifted the hypothalamus towards the male direction in the same way as in male controls, and treatment with feminizing hormones shifted the hypothalamus towards the female direction in the same way as female controls. They concluded: "The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain."[24]^{[unreliable medical source?]}

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".^[25]

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.^[26]

A 2016 review reported that, for androphilic trans women and gynephilic trans men, hormone treatment may have large effects on the brain, and that

A 2019 review in Neuropsychopharmacology 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."^[27]

A 2020 paper^{[28][non-primary source needed]} tried to investigate and differentiate between the two competing hypotheses of a neurodevelopmental cortical hypothesis that suggests the existence of different brain phenotypes vs a functional-based hypothesis in relation to regions involved in the own body perception.^[28] Trans men, trans women, and cisgender women all had decreased connectivity compared with cisgender men in superior parietal regions, as part of the salience (SN) and the executive control (ECN) networks.^[28] Trans men also had weaker connectivity compared with cisgender men between intra-SN regions and weaker inter-network connectivity between regions of the SN, the default mode network (DMN), the ECN and the sensorimotor network.^[28] Trans women had lower small-worldness^{[clarification needed]}, modularity and clustering coefficient than cisgender men.^{[28][non-primary source needed]}

A 2021 review of brain studies published in the Archives of Sexual Behavior 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 and heterosexual people, with the same limitations applying.^[29]

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.^[3] It also reported that gynephilic trans women differ from both cisgender female and male controls in non-dimorphic brain areas.^[3]

The available research indicates that the brain structure of androphilic trans women with early-onset gender dysphoria is closer to that of

While MRI taken on gynephilic trans women have likewise shown differences in the brain from non-trans people, no feminization of the brain's structure has been identified.[3] Neuroscientists Ivanka Savic and Stefan Arver at the Karolinska Institute used MRI to compare 24 gynephilic trans women with 48 controls consisting of 24 cisgender men and 24 cisgender women. None of the study participants were undergoing hormone therapy. The researchers found sex-typical differentiation between the trans women and cisgender females, and the cisgender males; but the gynephilic trans women "displayed also singular features and differed from both control groups by having reduced thalamus and putamen volumes and elevated GM volumes in the right insular and inferior frontal cortex and an area covering the right angular gyrus".^{[30][non-primary source needed]}

The researchers concluded that:

Contrary to the primary hypothesis, no sex-atypical features with signs of 'feminization' were detected in the transsexual group ... The present study does not support the dogma that [male-to-female transsexuals] have atypical sex dimorphism in the brain but confirms the previously reported sex differences. The observed differences between MtF-TR and controls raise the question as to whether gender dysphoria may be associated with changes in multiple structures and involve a network (rather than a single nodal area).

Berglund et al. (2008) tested the response of gynephilic trans women to two steroids hypothesized to be sex pheromones: the progestin-like 4,16-androstadien-3-one (AND) and the estrogen-like 1,3,5(10),16-tetraen-3-ol (EST). Despite the difference in sexual orientation, the trans women's hypothalamic networks activated in response to the AND pheromone, like the androphilic cis women's control groups. Both groups experienced amygdala activation in response to EST. Gynephilic cis male control groups experienced hypothalamic activation in response to EST. However, the trans women also experienced limited hypothalamic activation to EST. The researchers concluded that in terms of pheromone activation, trans women occupy an intermediate position with predominantly female features.^[31] The transfeminine subjects had not undergone any hormonal treatment at the time of the study, according to their own declaration beforehand, and confirmed by repeated tests of hormonal levels.^{[31][non-primary source needed]}

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.[3] Morphological increments observed in the brains of trans men might be due to the anabolic effects of testosterone.^[3]

Onset

According to the

In the 1980s and 1990s, sexologist

• Genetic diagnosis of intersex
• Intersex and LGBT
• Sexual identity

References