Causes of transsexualism
The etiology of transsexualism, meaning the cause or causes of transsexualism, is an area of interest for many people, including transgender and transsexual people, physicians, psychologists, other mental health professionals, and family members and friends of transgender people. Transsexualism usually presents with an expression of gender identity different from those associated with the biological sex determined at birth, behaviors considered norms for the associated gender, and discomfort called gender dysphoria. Currently, there are numerous possible explanations of the cause of transsexualism, including genetics, brain structure, brain function, and prenatal androgen exposure. Other theories have proposed linking the cause to psychological and behavioral reasons. These theories are not necessarily mutually exclusive.
The androgen receptor (AR), also known as 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. Hare et al. found that male-to-female transsexuals were found to have longer repetitions of the gene, which reduced its effectiveness at binding testosterone.
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 transsexualism but not MTF transsexualism. 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 transsexualism.
In a first-of-its-kind study, Zhou et al. (1995) found that in a region of the brain called the bed nucleus of the stria terminalis (BSTc), a region known for sex and anxiety responses, MTF transsexuals have a female-normal size while FTM transsexuals have a male-normal size. While the transsexuals studied had taken hormones, this was accounted for by including non-transsexual male and female controls who, for a variety of medical reasons, had experienced hormone reversal. The controls still retained sizes typical for their gender. No relationship to sexual orientation was found.
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 who matched up with the female neuron counts nonetheless.
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 failure to generate a gender identity consistent with one's anatomic sex.
In a review of the evidence in 2006, Gooren confirms the earlier research as supporting the concept that transsexualism is a sexual differentiation disorder of the sex dimorphic brain. Dick Swaab (2004) concurs.
In 2008, a new region with properties similar to that of BSTc in regards to transsexualism 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 once again, regardless of hormone exposure, MTF transsexuals lay within the female range and the FTM transsexual within the male range.
While the resolution of MRI tomographs in general can be fine enough, independent nuclei are not visible due to lack of contrast between different neurological tissue types. Therefore, such images do not show detailed structures such as BSTc and INAH3, and studies on BSTC were done by bisecting brains postmortem.
However, MRI does much more easily allow the study of larger brain structures. In Luders et al. (2009), 24 MTF transsexuals not-yet treated with cross-sex hormones were studied via MRI. While regional gray matter concentrations were more similar to men than women, there was a significantly larger volume of gray matter in the right putamen compared to men. As with many earlier studies, they concluded that transsexualism is associated with a distinct cerebral pattern.
An additional feature was studied in a group of FTM transsexuals who had not yet received cross-sex hormones: 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."
Hulshoff Pol et al. (2006), studied the gross brain volume of subjects undergoing hormone treatment. They discovered that whole brain volume for subjects changes toward the size of the opposite sex during hormone treatment. The conclusion of the study was, "The findings suggest that, throughout life, gonadal hormones remain essential for maintaining aspects of sex-specific differences in the human brain."
Brain structure differences associated with transsexualism do not exist in isolation. Similar brain structure differences have been noted between gay and heterosexual men, and between lesbian and heterosexual women.
More recent studies have found that circumstance and repeated activities such as meditation modify brain structures in a process called brain plasticity or neuroplasticity. In May 2014, the Proceedings of the National Academy of Sciences reported that parenting "rewires the male brain" for fathers.
Phantom limb syndrome is a common, often painful experience after the loss of an external organ. Ramachandran (2008) found that while nearly two thirds of non-transsexual males who have a penis surgically removed experience the sensation of a phantom penis, only one third of MTF transsexuals do so after sex reassignment surgery. This study, however, overlooks the differences between an amputation, where the nerves connecting the penis and the brain are severed, and male-to-female gender reassignment surgery, where some of the penis and scrotum may be reused to create a vaginal canal, labia and a clitoris. In this case, some of the nerves connecting the new genitalia to the brain remain largely intact. Also, two-thirds of FTM transsexuals reported the sensation of a phantom penis from childhood onwards, complete with phantom erections and other phenomena.
Berglund et al. (2008) tested the response of gynephilic MTF transsexuals to two 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 sexuality, the MTFs' hypothalamic networks activated in response to AND, like the androphilic female control groups. Both groups experienced amygdala activation in response to EST. Male control groups (gynephilic) experienced hypothalamic activation in response to EST. However, the MTF subjects also experienced limited hypothalamic activation to EST as well. The researchers' conclusion was, that in terms of pheromone activation, MTF's occupy an intermediate position with predominantly female features. 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.
Transsexuality among twins
In a 2013 study based on previously published research and conducted surveys it was found that in 39 monozygotic twin male pairs, 13 (33%) identified both of themselves as transsexual. This was found in 8 of 25 (22.5%) female pairs. Alternatively only 1 out of 38 (2.6%) coming from different fertilized eggs, dizygotic male and female pairs identified themselves as transsexual. The significant percentage of transsexual identification in both of the identical twins, and the virtual absence of this correspondence in dizygotic twins raised in the same family at the same time, supports the argument that one's transsexual identity is significantly influenced by genetics.
Prenatal androgen exposure
Prenatal androgen exposure, the lack thereof, or poor sensitivity to prenatal androgens are commonly cited mechanisms to explain the above discoveries. Schneider, Pickel, and Stalla (2006) found a correlation between digit ratio (a generally accepted marker for prenatal androgen exposure) and male to female transsexualism. MTF transsexuals were found to have a higher digit ratio than control males, but one that was comparable to control females.
Psychological and behavioral theories
For many years, many people, including psychiatrist and sexologist David Oliver Cauldwell, argued that transsexualism is a psychological/emotional disorder caused by psychological and environmental factors, due to personality conflicts.
Harry Benjamin wrote, "Our genetic and endocrine equipment constitutes either an unresponsive [or] fertile soil on which the wrong conditioning and a psychological trauma can grow and develop into such a basic conflict that subsequently a deviation like transsexualism can result."
The unsuccessful outcome of an attempt to raise David Reimer, the victim of an early accidental genital mutilation, as a girl from infancy through adolescence is cited as disproof of the theory that one's inborn sense of gender is developed through parenting. Nevertheless, no studies have been able to demonstrate this at a large scale, in part due to widespread disagreement with the study's methodology among scholars, primarily for ethical reasons. David Reimer's case is used by organizations such as The Intersex Society of North America as a cautionary tale about why one should not needlessly modify the genitals of unconsenting minors.
The theories of Ray Blanchard represent a taxonomy of male-to-female transsexualism and an explanation of its causes, built upon the work of his colleague, Kurt Freund. The theories state that male-to-female transsexuals can be broken up into two groups: "homosexual transsexuals", who transition because they are attracted to men, and "non-homosexual transsexuals", who transition because they are autogynephilic (sexually aroused by the thought or image of themselves as a woman). Prominent supporters of the theory include 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. Scientific criticism of the theory includes papers from Veale, Nuttbrock, Moser, and others who argue that the theory is poorly representative of MTF transsexuals, non-instructive, the experiments poorly controlled, or contradicted by other data. Many sources, including some supporters of the theory, criticize Blanchard's choice of wording as confusing or degrading. Though it has supporters, the transsexual community has for the most part vehemently rejected the theory. In her book Whipping Girl, evolutionary biologist, trans woman (MTF) and activist Julia Serano stated that she believed the evidence for autogynephilia was dubious and lacked scientific substantiation. Blanchard's ideas about trans women have also been rejected by the World Professional Association for Transgender Health (WPATH), the largest association of medical professionals who provides care for transgender people, as lacking empirical evidence and for stigmatizing behavior instead of focusing on treating distress.
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