Philosophy:Causes of transsexuality

From HandWiki

The study of the causes of transsexuality investigates gender identity formation of transgender people, especially those who are transsexual. Transgender people have a gender identity that does not match their assigned sex, often resulting in gender dysphoria.[1] The causes of transsexuality have been studied for decades. The most studied factors are biological, especially brain structure differences in relation to biology and sexual orientation. Environmental factors have also been proposed.

Transgender brain studies, especially those on trans women who are sexually attracted to women (gynephilic), and those on trans men who are sexually attracted to men (androphilic), are limited, as they include a small number of tested individuals.[2] The available research indicates that the brain structure of androphilic trans women with early-onset gender dysphoria is closer to the brain structure of cisgender women's and less like cisgender men's.[2] It also reports that both androphilic trans women and trans women with late-onset gender dysphoria who are gynephilic have different brain phenotypes, and that gynephilic trans women differ from both cisgender female and male controls in non-dimorphic brain areas.[2] Cortical thickness, 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.[2] 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.[2] Hormone use can also affect transgender people's brain structure; it can cause transgender women's brains to become closer to those of cisgender women, and morphological increments observed in the brains of trans men might be due to the anabolic effects of testosterone.[2]

<section begin="factors" />Twin studies suggest that there are likely genetic causes of transsexuality, although the precise genes involved are not fully understood.[3][4] One study published in the International Journal of Transgender Health found that 20% of identical twin pairs in which at least one twin was trans were both trans, compared to only 2.6% of non-identical twins who were raised in the same family at the same time, but were not genetically identical.[4]

Ray Blanchard created a taxonomy of male-to-female transsexualism that proposes two distinct etiologies for androphilic and gynephilic individuals that has become controversial, supported by J. Michael Bailey, Anne Lawrence, James Cantor and others, but opposed by Charles Allen Moser, Julia Serano, and the World Professional Association for Transgender Health.<section end="factors" />

Biological factors

Genetics

A 2008 study compared 112 male-to-female transsexuals (MtFs), both androphilic and gynephilic, and who were mostly already undergoing hormone treatment, with 258 cisgender male controls. Male-to-female transsexuals were more likely than cisgender males to have a longer version of a receptor gene (longer repetitions of the gene) for the sex hormone androgen, which reduced its effectiveness at binding testosterone.[5] The androgen receptor (NR3C4) is activated by the binding of testosterone or dihydrotestosterone, where it plays a critical role in the forming of primary and secondary male sex characteristics. The research suggests reduced androgen and androgen signaling contributes to the female gender identity of male-to-female transsexuals. The authors say that a decrease in testosterone levels in the brain during development might prevent complete masculinization of the brain in male-to-female transsexuals and thereby cause a more feminized brain and a female gender identity.[5][6]

A variant genotype for a gene called CYP17, which acts on the sex hormones pregnenolone and progesterone, has been found to be linked to female-to-male (FtMs) transsexuality but not MtF transsexuality. Most notably, the FtM subjects not only had the variant genotype more frequently, but had an allele distribution equivalent to male controls, unlike the female controls. The paper concluded that the loss of a female-specific CYP17 T -34C allele distribution pattern is associated with FtM transsexuality.[7]

Transsexuality among twins

In 2013, a twin study 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.[4] The significant percent 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.[4]

Brain structure

General

Several studies have found a correlation between gender identity and brain structure.[8] A first-of-its-kind study by Zhou et al. (1995) found that in a region of the brain called the bed nucleus of the stria terminalis (BSTc), a region which is known for sex and anxiety responses (and which is affected by prenatal androgens),[9] cadavers of six persons who were described as having been male-to-female transsexual or transgender persons in life had female-normal BSTc size, similar to the study's cadavers of cisgender women. While those identified as transsexual had taken hormones, this was accounted for by including cadavers of non-transsexual female and male controls who, for a variety of medical reasons, had experienced hormone reversal. The controls still had sizes typical for their gender. No relationship to sexual orientation was found.[10]

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 MtF subject, who had never gone on hormones, was also included and matched up with the female neuron counts nonetheless.[11]

In 2002, a follow-up study by Chung et al. found that significant sexual dimorphism (variation between sexes) in BSTc did not become established until adulthood. Chung et al. theorized that either 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 that the size of BSTc is affected by the generation of a gender identity inconsistent with one's assigned sex.[12]

It has been suggested that the BSTc differences may be due to the effects 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 paraphilias rather than transsexuality.[2]

In a review of the evidence in 2006, Gooren considered the earlier research as supporting the concept of transsexuality as a sexual differentiation disorder of the sex dimorphic brain.[13] Dick Swaab (2004) concurs.[14]

In 2008, a new region with properties similar to that of BSTc in regards to transsexuality was found by Garcia-Falgueras and Swaab: the interstitial nucleus of the anterior hypothalamus (INAH3), part of the hypothalamic uncinate nucleus. The same method of controlling for hormone usage was used as in Zhou et al. (1995) and Kruijver et al. (2000). The differences were even more pronounced than with BSTc; control males averaged 1.9 times the volume and 2.3 times the neurons as control females, yet regardless of hormone exposure, MtF transsexuals were within the female range and the FtM transsexual within the male range.[15]

A 2009 MRI study by Luders et al. of 24 MtF transsexuals not yet treated with cross-sex hormones found that regional gray matter concentrations were more similar to those of cisgender men than to those of cisgender women, but there was a significantly larger volume of gray matter in the right putamen compared to cisgender men. Like earlier studies, it concluded that transsexuality was associated with a distinct cerebral pattern.[16] (MRI 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.)

An additional feature was studied comparing 18 female-to-male transsexuals who had not yet received cross-sex hormones with 24 cisgender male and 19 female gynephilic controls, using an MRI technique called diffusion tensor imaging or DTI.[17] DTI is a specialized technique for visualizing white matter of the brain, and white matter structure is one of the differences in neuroanatomy between men and women. The study took into account fractional anisotropy values for white matter in the medial and posterior parts of the right superior longitudinal fasciculus (SLF), the forceps minor, and the corticospinal tract. Rametti et al. (2010) discovered that, "Compared to control females, FtM showed higher FA values in posterior part of the right SLF, the forceps minor and corticospinal tract. Compared to control males, FtM showed only lower FA values in the corticospinal tract."[17] The white matter pattern in female-to-male transsexuals was found to be shifted in the direction of biological males.

Hulshoff Pol et al. (2006) studied the gross brain volume of 8 male-to-female transsexuals and in six female-to-male transsexuals undergoing hormone treatment. They found that hormones changed the sizes of the hypothalamus in a gender consistent manner: treatment with male hormones shifted the hypothalamus towards the male direction in the same way as in male controls, and treatment with female 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."[18]

A 2016 review agreed with the other reviews when considering androphilic trans women and gynephilic trans men. It reported that hormone treatment may have large effects on the brain, and that cortical thickness, 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.[2] 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."[2]

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."[19]

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 trangender people. The review also found differences when comparing cisgender homosexual and heterosexual people, with the same limitations applying.[20]

Androphilic male-to-female transsexuals

A 2015 review reported that two studies found a pattern of white matter microstructure differences away from transsexuals' birth sex and toward their desired sex. In one of these studies, sexual orientation had no effect on the diffusivity measured.[21]

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.[2]

Gynephilic male-to-female transsexuals

Research on gynephilic trans women is considerably limited.[2] While MRI taken on gynephilic male-to-female transsexuals have likewise shown differences in the brain from non-transsexuals, no feminization of the brain's structure have been identified.[2] Neuroscientists Ivanka Savic and Stefan Arver at the Karolinska Institute used MRI to compare 24 gynephilic male-to-female transsexuals with 24 cisgender female and 24 cisgender male controls. None of the study participants were on hormone treatment. The researchers found sex-typical differentiation between the MtF transsexuals and cisgender females, and the cisgender males; but the gynephilic transsexuals "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".[22]

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).[22]

Berglund et al. (2008) tested the response of gynephilic MtF transsexuals 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 MtFs' hypothalamic networks activated in response to the AND pheromone, like the androphilic female control groups. Both groups experienced amygdala activation in response to EST. Gynephilic male control groups experienced hypothalamic activation in response to EST. However, the MtF subjects also experienced limited hypothalamic activation to EST. The researchers concluded that in terms of pheromone activation, MtFs occupy an intermediate position with predominantly female features.[23] The MtF transsexual 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.[23]

A 2016 review reported that gynephilic trans women differ from both cisgender female and male controls in non-dimorphic brain areas.[2]

Gynephilic female-to-male transsexuals

Fewer studies have been performed on the brain structure of transgender men than on transgender women.[2] A team of neuroscientists, led by Nawata in Japan, used a technique called single-photon emission computed tomography (SPECT) to compare the regional cerebral blood flow (rCBF) of 11 gynephilic FtM transsexuals with that of 9 androphilic cis females. Although the study did not include a sample of biological males so that a conclusion of "male shift" could be made, the study did reveal that the gynephilic FtM transsexuals showed significant decrease in blood flow in the left anterior cingulate cortex and a significant increase in the right insula, two brain regions known to respond during sexual arousal.[24]

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.[2] Morphological increments observed in the brains of trans men might be due to the anabolic effects of testosterone.[2]

Prenatal androgen exposure

Prenatal androgen exposure, the lack thereof, or poor sensitivity to prenatal androgens are commonly cited mechanisms to explain the above discoveries. To test this, studies have examined the differences between transsexual and cisgender individuals in digit ratio (a generally accepted marker for prenatal androgen exposure). A meta-analysis concluded that the effect sizes for this association were small or nonexistent.[25]

Congenital adrenal hyperplasia in persons with XX sex chromosomes results in what is considered to be excess exposure to prenatal androgens, resulting in masculinization of the genitalia and, typically, controversial prenatal hormone treatment[26] and postnatal surgical interventions.[27] Individuals with CAH are usually raised as girls and tend to have similar cognitive abilities to the typical female, including spatial ability, verbal ability, language lateralization, handedness and aggression. Research has shown that people with CAH and XX chromosomes will be more likely to be same sex attracted,[26] and at least 5.2% of these individuals develop serious gender dysphoria.[28]

In males with 5-alpha-reductase deficiency, conversion of testosterone to dihydrotestosterone is disrupted, decreasing the masculinization of genitalia. Individuals with this condition are typically raised as females due to their feminine appearance at a young age. However, more than half of males with this condition raised as females become males later in their 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.[28]

Psychological

Psychiatrist and sexologist David Oliver Cauldwell[29] argued in 1947 that transsexuality was caused by multiple factors. He believed that small boys tend to admire their mothers to such a degree that they end up wanting to be like them. However, he believed that boys would lose this desire as long as his parents set limits when raising him, or he had the right genetic predispositions or a normal sexuality. In 1966, Harry Benjamin[30] considered the causes of transsexuality to be badly understood, and argued that researchers were biased towards considering psychological causes over biological causes.

Gender dysphoria in those assigned male at birth 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 will stop for a while in this group and they will identify as gay or homosexual for a period of time, followed by recurrence of gender dysphoria. This group is usually sexually attracted to members of their natal sex 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 will usually be sexually 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 cross-dress with sexual excitement. In those assigned female at birth, 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.[31]

Ray Blanchard has developed a taxonomy of male-to-female transsexualism[32] built upon the work of his colleague Kurt Freund,[33] which argues that trans women have one of two primary causes of gender dysphoria.[34][35][36] Blanchard theorizes that "homosexual transsexuals" (a taxonomic category he uses to refer to trans women who are sexually 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" (a taxonomic category he uses to refer to trans women who are sexually attracted to women) as developing gender dysphoria primarily because they are autogynephilic (sexually aroused by the thought or image of themselves as a woman[32]), and as being either attracted to women, attracted to both women and men (a concept he calls pseudo-bisexuality as, considering attraction to males part of the performance of an autogynephilic sexual fantasy), or asexual.

Blanchard's theory has gained support from J. Michael Bailey, Anne Lawrence, James Cantor, and others who argue that there are significant differences between the two groups, including sexuality, age of transition, ethnicity, IQ, fetishism, and quality of adjustment.[37][38][32][39][34] However, the theory has been criticized in papers from Veale, Nuttbrock, Moser, and others who argue that it is poorly representative of MtF transsexuals and non-instructive, and that the experiments behind it are poorly controlled and/or contradicted by other data.[40][41][42] A 2009 study by Charles Moser 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.[43] This study was later criticized by Anne Lawrence, who argued that Moser's and Blanchard's scales differed significantly, and that Moser's questions "do not adequately assess the essential element of autogynephilia—sexual arousal simply to the thought of being a female."[44] Many authorities, including some supporters of the theory, criticize Blanchard's choice of wording as confusing or degrading because it focuses on trans women's assigned sex and disregards their sexual orientation identity.[2] Evolutionary biologist and trans woman Julia Serano wrote that "Blanchard's controversial theory is built upon a number of incorrect and unfounded assumptions, and there are many methodological flaws in the data he offers to support it."[45] The World Professional Association for Transgender Health (WPATH) argued against including Blanchard's typology in the DSM, stating that there was no scientific consensus on the theory, and that there was a lack of longitudinal studies on the development of transvestic fetishism.[46]

A 2016 review found support for the predictions of Blanchard's typology that androphilic and gynephilic trans women have different brain phenotypes. It stated that although Cantor seems to be right that Blanchard's predictions have been validated by two independent structural neuroimaging studies, there is "still only one study on nonhomosexual MtFs; to fully confirm the hypothesis, more independent studies on nonhomosexual MtFs are needed. A much better verification of the hypothesis could be supplied by a specifically designed study including homosexual and nonhomosexual MtFs." The review stated that "confirming Blanchard's prediction still needs a specifically designed comparison of homosexual MtF, homosexual male, and heterosexual male and female people."[2]

Parenting

The failure of an attempt to raise David Reimer from infancy through adolescence as a girl after his genitals were accidentally mutilated is cited as disproving the theory that gender identity is determined solely by parenting.[47][48] Between the 1960s and 2000, many other newborn and infant boys were surgically reassigned as females if they were born with malformed penises, or if they lost their penises in accidents. Many surgeons believed such males would be happier being socially and surgically reassigned female. Available evidence indicates that in such instances, parents were deeply committed to raising these children as girls and in as gender-typical a manner as possible. Six of seven cases providing orientation in adult follow-up studies identified as heterosexual males, with one retaining a female identity, but who is attracted to women. Such cases do not support the theory that parenting influences gender identity or sexual orientation of those assigned male at birth.[49]:72–73 Reimer's case is used by organizations such as the Intersex Society of North America to caution against needlessly modifying the genitals of unconsenting minors.[50]

In 2015, the American Academy of Pediatrics released a webinar series on gender, gender identity, gender expression, transgender, etc.[51][52] In the first lecture Dr. Sherer explains that parents' influence (through punishment and reward of behavior) can influence gender expression but not gender identity.[53] She cites a Smithsonian article that shows a photo of a 3 year old President Franklin D. Roosevelt with long hair, wearing a dress.[54][52] Children as old as 6 wore gender neutral clothing, consisting of white dresses, until the 1940s.[54] In 1927, Time (magazine) magazine printed a chart showing sex-appropriate colors, which consisted of pink for boys and blue for girls.[54] Dr. Sherer argued that kids will modify their gender expression to seek reward from their parents and society but this will not affect their gender identity (their internal sense of self).[53]

See also

References

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  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 "A Review of the Status of Brain Structure Research in Transsexualism". Archives of Sexual Behavior 45 (7): 1615–48. October 2016. doi:10.1007/s10508-016-0768-5. PMID 27255307. 
  3. ↑ "Gender identity disorder in twins: a review of the case report literature". The Journal of Sexual Medicine 9 (3): 751–7. March 2012. doi:10.1111/j.1743-6109.2011.02567.x. PMID 22146048. "Of 23 monozygotic female and male twins, nine (39.1%) were concordant for GID; in contrast, none of the 21 same‐sex dizygotic female and male twins were concordant for GID, a statistically significant difference (P = 0.005)... These findings suggest a role for genetic factors in the development of GID.". 
  4. ↑ 4.0 4.1 4.2 4.3 Diamond, Milton (2013). "Transsexuality Among Twins: Identity Concordance, Transition, Rearing, and Orientation". International Journal of Transgender Health 14 (1): 24–38. doi:10.1080/15532739.2013.750222. "Combining data from the present survey with those from past-published reports, 20% of all male and female monozygotic twin pairs were found concordant for transsexual identity... The responses of our twins relative to their rearing, along with our findings regarding some of their experiences during childhood and adolescence show their identity was much more influenced by their genetics than their rearing.". 
  5. ↑ 5.0 5.1 "Androgen receptor repeat length polymorphism associated with male-to-female transsexualism". Biological Psychiatry 65 (1): 93–6. January 2009. doi:10.1016/j.biopsych.2008.08.033. PMID 18962445. 
  6. ↑ "Transsexual study reveals genetic link". abc.net.au. 27 October 2008. http://www.abc.net.au/science/articles/2008/10/27/2401941.htm. 
  7. ↑ "A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism". Fertility and Sterility 90 (1): 56–9. July 2008. doi:10.1016/j.fertnstert.2007.05.056. PMID 17765230. 
  8. ↑ For a survey, see "The Human Brain and Gender: Sexual Differentiation of Our Brains.". Transsexuality in Theology and Neuroscience. Findings, Controversies, and Perspectives. Berlin and Boston: Walter de Gruyter. 2016. pp. 23–42. ISBN 978-3-11-044080-5. 
  9. ↑ Psychology: The Science of Behavior (7th ed.). Pearson Education. 2010. pp. 418. 
  10. ↑ "A sex difference in the human brain and its relation to transsexuality". Nature 378 (6552): 68–70. November 1995. doi:10.1038/378068a0. PMID 7477289. Bibcode: 1995Natur.378...68Z. https://pure.knaw.nl/portal/en/publications/a-sex-difference-in-the-human-brain-and-its-relation-to-transsexuality(9da6a0a1-f622-44f3-ac4f-fec297a7c6c2).html. 
  11. ↑ "Male-to-female transsexuals have female neuron numbers in a limbic nucleus". The Journal of Clinical Endocrinology and Metabolism 85 (5): 2034–41. May 2000. doi:10.1210/jcem.85.5.6564. PMID 10843193. 
  12. ↑ "Sexual differentiation of the bed nucleus of the stria terminalis in humans may extend into adulthood". The Journal of Neuroscience 22 (3): 1027–33. February 2002. doi:10.1523/jneurosci.22-03-01027.2002. PMID 11826131. 
  13. ↑ "The biology of human psychosexual differentiation". Hormones and Behavior 50 (4): 589–601. November 2006. doi:10.1016/j.yhbeh.2006.06.011. PMID 16870186. 
  14. ↑ "Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation". Gynecological Endocrinology 19 (6): 301–12. December 2004. doi:10.1080/09513590400018231. PMID 15724806. 
  15. ↑ "A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity". Brain 131 (Pt 12): 3132–46. December 2008. doi:10.1093/brain/awn276. PMID 18980961. 
  16. ↑ "Regional gray matter variation in male-to-female transsexualism". NeuroImage 46 (4): 904–7. July 2009. doi:10.1016/j.neuroimage.2009.03.048. PMID 19341803. 
  17. ↑ 17.0 17.1 "White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study". Journal of Psychiatric Research 45 (2): 199–204. February 2011. doi:10.1016/j.jpsychires.2010.05.006. PMID 20562024. 
  18. ↑ "Changing your sex changes your brain: influences of testosterone and estrogen on adult human brain structure". European Journal of Endocrinology 155: S107–S114. 2006. doi:10.1530/eje.1.02248. 
  19. ↑ Nguyen, Hillary B.; Loughead, James; Lipner, Emily; Hantsoo, Liisa; Kornfield, Sara L.; Epperson, C. Neill (January 2019). "What has sex got to do with it? The role of hormones in the transgender brain". Neuropsychopharmacology 44 (1): 22–37. doi:10.1038/s41386-018-0140-7. ISSN 1740-634X. PMID 30082887. 
  20. ↑ Frigerio, Alberto; Ballerini, Lucia; Valdes-Hernandez, Maria (2021). "Structural, Functional, and Metabolic Brain Differences as a Function of Gender Identity or Sexual Orientation: A Systematic Review of the Human Neuroimaging Literature". Archives of Sexual Behavior. doi:10.1007/s10508-021-02005-9. PMID 33956296. https://link.springer.com/article/10.1007/s10508-021-02005-9. Retrieved 2021-08-26. "Results suggest that, although the majority of neuroanatomical, neurophysiological, and neurometabolic features in transgenders resemble those of their natal sex rather than those of their experienced gender,...in the gender identity investigation, in MtF it was possible to find traits which are “feminine and demasculinized” and in FtM it was possible to find traits which are “masculine and defeminized” (Kreukels & Guillamon, 2016)....Due to conflicting results, it was, however, not possible to identify specific brain features which consistently differ between cisgender and transgender nor between heterosexual and homosexual groups. Very small brain changes, to date undetectable using the current neuroimaging tools, may affect behavior. The small number of studies, the small sample size of each study, the heterogeneity of investigations, the lack of negative results reported by some studies, and the fact that some studies did not report the sexual orientation of the individuals that composed their sample did not allow drawing general conclusions. Moreover, as the samples of the publications involved are not representative of the population analyzed, caution should be taken in the interpretation of the results of this review.". 
  21. ↑ Smith, Elke Stefanie; Junger, Jessica; Derntl, Birgit; Habel, Ute (1 December 2015). "The transsexual brain – A review of findings on the neural basis of transsexualism" (in en). Neuroscience & Biobehavioral Reviews 59: 251–266. doi:10.1016/j.neubiorev.2015.09.008. ISSN 0149-7634. PMID 26429593. https://www.sciencedirect.com/science/article/abs/pii/S0149763415002432. Retrieved 4 October 2021. 
  22. ↑ 22.0 22.1 "Sex dimorphism of the brain in male-to-female transsexuals". Cerebral Cortex 21 (11): 2525–33. November 2011. doi:10.1093/cercor/bhr032. PMID 21467211. 
  23. ↑ 23.0 23.1 "Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids". Cerebral Cortex 18 (8): 1900–8. August 2008. doi:10.1093/cercor/bhm216. PMID 18056697. 
  24. ↑ "Regional cerebral blood flow changes in female to male gender identity disorder". Psychiatry and Clinical Neurosciences 64 (2): 157–61. April 2010. doi:10.1111/j.1440-1819.2009.02059.x. PMID 20132527. 
  25. ↑ "Meta-Analysis Shows Associations of Digit Ratio (2D:4D) and Transgender Identity Are Small at Best". Endocrine Practice 24 (4): 386–390. April 2018. doi:10.4158/EP-2017-0024. PMID 29561190. 
  26. ↑ 26.0 26.1 "Prenatal Dexamethasone for Congenital Adrenal Hyperplasia: An Ethics Canary in the Modern Medical Mine". Journal of Bioethical Inquiry 9 (3): 277–294. September 2012. doi:10.1007/s11673-012-9384-9. PMID 22904609. 
  27. ↑ "Consensus statement on 21-hydroxylase deficiency from the European Society for Paediatric Endocrinology and the Lawson Wilkins Pediatric Endocrine Society". Hormone Research 58 (4): 188–95. 2002. doi:10.1159/000065490. PMID 12324718. 
  28. ↑ 28.0 28.1 Erickson-Schroth, Laura (2013). "Update on the Biology of Transgender Identity". Journal of Gay & Lesbian Mental Health 17 (2): 150–74. doi:10.1080/19359705.2013.753393. 
  29. ↑ Desire for Surgical Sex Transmutation: An Insane Fancy of Near Males. D.O. Cauldwell. 2001 reprint in the International Journal of Transgender Health Vol. 5 Number 2 of a paper published in 1947.
  30. ↑ The transsexual phenomenon.. New York: Julian Press. 1966. pp. 43–50. 
  31. ↑ Diagnostic and Statistical Manual of Mental Disorders (Fifth ed.). Arlington, VA: American Psychiatric Publishing. 2013. pp. 451–460. ISBN 978-0-89042-554-1. https://archive.org/details/diagnosticstatis0005unse/page/451. 
  32. ↑ 32.0 32.1 32.2 "The concept of autogynephilia and the typology of male gender dysphoria". The Journal of Nervous and Mental Disease 177 (10): 616–23. October 1989. doi:10.1097/00005053-198910000-00004. PMID 2794988. 
  33. ↑ "Two types of cross-gender identity". Archives of Sexual Behavior 11 (1): 49–63. February 1982. doi:10.1007/BF01541365. PMID 7073469. 
  34. ↑ 34.0 34.1 The Man Who Would Be Queen: The Science of Gender-Bending and Transsexualism. Washington, D.C.: Joseph Henry Press. 2003. pp. 170. ISBN 978-0-309-08418-5. OCLC 52779246. 
  35. ↑ "Early history of the concept of autogynephilia". Archives of Sexual Behavior 34 (4): 439–46. August 2005. doi:10.1007/s10508-005-4343-8. PMID 16010466. 
  36. ↑ "Transsexual subtypes: clinical and theoretical significance". Psychiatry Research 137 (3): 151–60. December 2005. doi:10.1016/j.psychres.2005.01.008. PMID 16298429. 
  37. ↑ "The classification and labeling of nonhomosexual gender dysphorias". Archives of Sexual Behavior 18 (4): 315–34. August 1989. doi:10.1007/BF01541951. PMID 2673136. 
  38. ↑ "Nonhomosexual gender dysphoria". Journal of Sex Research 24 (1): 188–93. January 1988. doi:10.1080/00224498809551410. PMID 22375647. 
  39. ↑ "Clinical observations and systematic studies of autogynephilia". Journal of Sex & Marital Therapy 17 (4): 235–51. Winter 1991. doi:10.1080/00926239108404348. PMID 1815090. 
  40. ↑ "Sexuality of male-to-female transsexuals". Archives of Sexual Behavior 37 (4): 586–97. August 2008. doi:10.1007/s10508-007-9306-9. PMID 18299976. 
  41. ↑ "Blanchard's Autogynephilia Theory: a critique". Journal of Homosexuality 57 (6): 790–809. 2010. doi:10.1080/00918369.2010.486241. PMID 20582803. 
  42. ↑ "A further assessment of Blanchard's typology of homosexual versus non-homosexual or autogynephilic gender dysphoria". Archives of Sexual Behavior 40 (2): 247–57. April 2011. doi:10.1007/s10508-009-9579-2. PMID 20039113. 
  43. ↑ "Autogynephilia in women". Journal of Homosexuality 56 (5): 539–47. 2009. doi:10.1080/00918360903005212. PMID 19591032. 
  44. ↑ "Something resembling autogynephilia in women: comment on Moser (2009)". Journal of Homosexuality 57 (1): 1–4. 2010. doi:10.1080/00918360903445749. PMID 20069491. 
  45. ↑ Serano, Julia (2007). Whipping girl: a transsexual woman on sexism and the scapegoating of femininity. Seal Press. p. 178. ISBN 978-1-58005-154-5. https://books.google.com/books?id=fR5ji5h5g1MC&pg=PT178. "While Blanchard's controversial theory is built upon a number of incorrect and unfounded assumptions, and there are many methodological flaws in the data he offers to support it, it has garnered some acceptance in the psychiatric literature..." 
  46. ↑ "Should Transvestic Fetishism Be Classified inDSM 5? Recommendations from the WPATH Consensus Process for Revision of the Diagnosis of Transvestic Fetishism". International Journal of Transgender Health 12 (4): 189–197. 2011. doi:10.1080/15532739.2010.550766. 
  47. ↑ "David Reimer, subject of 'sex reassignment,' dead at 38". http://the.honoluluadvertiser.com/article/2004/May/13/ln/ln52a.html. 
  48. ↑ As Nature Made Him: The Boy Who Was Raised as a Girl. Harper Perennial. 2001. ISBN 0-06-092959-6. https://archive.org/details/asnaturemadehim00john.  Revised in 2006[page needed]
  49. ↑ "Sexual Orientation, Controversy, and Science". Psychological Science in the Public Interest 17 (2): 45–101. September 2016. doi:10.1177/1529100616637616. PMID 27113562. 
  50. ↑ Intersex Society of North America | A world free of shame, secrecy, and unwanted genital surgery
  51. ↑ "American Academy of Pediatrics, Education, LGBT Health and Wellness" (in en-US). https://www.aap.org/en-us/about-the-aap/Committees-Councils-Sections/solgbt/Pages/Education.aspx. 
  52. ↑ 52.0 52.1 "American Academy of Pediatrics Webinar Series - What is Gender?". September 11, 2015. https://www.aap.org/en-us/Documents/solgbt_webinar_what_is_gender_sherer.pdf. 
  53. ↑ 53.0 53.1 Dr. Sherer (2015-09-15), "SOLGBTHW Webinar - What is Gender Terminology and Definitions", American Academy of Pediatrics, https://www.youtube.com/watch?v=LrqIq1oiwdY 
  54. ↑ 54.0 54.1 54.2 "When Did Girls Start Wearing Pink?" (in en). Smithsonian. http://www.smithsonianmag.com/arts-culture/when-did-girls-start-wearing-pink-1370097/?c=y&page=1. 




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