Causes of transsexualism
The etiology of transsexualism, meaning the cause or causes of transsexualism, is an area of interest for many transgender and transsexual people, physicians, psychologists, other mental health professionals, and family members and friends of transsexual people. Transsexualism usually presents with an expression of gender identity different from the gender assigned at birth, behaviors typical of that gender, and discomfort called gender dysphoria. Currently, there are numerous scientific explanations of the cause of transsexualism, linking the cause to genetics, brain structure, brain function and prenatal androgen exposure; in addition other theories have proposed linking the cause to psychological and behavioral reasons. These theories are not necessarily mutually exclusive.
Psychological and behavioral theories
Rearing / Trauma
Harry Benjamin wrote, "Our genetic and endocrine equipment constitutes either an unresponsive [or] fertile soil on which the wrong conditioning and a psychic 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. His 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.
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 repeat lengths on 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 the first of its kind, 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 which, 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 followup 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 followup study by Chung, De Vries, and Swaab 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. 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 MRI images cannot resolve as fine details as structures such as BSTc and INAH3, they can 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."
A cautionary note is sounded in Hulshoff Pol et al (2006), which studied the changes in transsexual brains on hormone administration over four months via MRI. They discovered that whole brain volume for subjects, as well as hypothalamic volume for androgen treatment, and potentially more sexually dimorphic structures in that region, change significantly toward the size of the opposite gender during hormone treatment. The study does not criticize the controls used to account for this in the BSTc or INAH3 studies. The study additionally concluded that before hormonal treatment, total brain volumes of the subjects were equivalent according to birth sex.
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. Perhaps more remarkably, two-thirds of FTM transsexuals reported the sensation of a phantom penis from childhood onwards, replete with phantom erections and other phenomena. Ramachandran theorizes that transsexualism is an innate form of phantom limb syndrome involving the mismapping of body regions in the brain.
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 female control groups. Both groups experienced amygdala activation in response to EST. Male control groups 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.
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.
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