Causes of gender incongruence

The etiology of transsexualism, meaning the cause or causes of transsexualism, is an area of interest for many transsexual people, physicians, psychologists, other mental health professionals, and family members and friends of transsexual people. Currently, there is no scientifically proven cause of transsexualism; however, there are a number of theories, many of which are not mutually exclusive.

Rearing / Trauma

For many years, many people, for example the psychiatrist and sexologist David Oliver Cauldwell, argued that transsexualism was a psychological/emotional disorder caused by psychological factors.

Harry Benjamin wrote, "Summarizing my impression, I would like to repeat here what I said in my first lecture on the subject more than 10 years ago: Our genetic and endocrine equipment constitutes either an unresponsive [or] fertile soil on which the wrong conditional and a psychic trauma can grow and develop into such a basic conflict that subsequently a deviation like transsexualism can result."

The case of David Reimer is cited as a criticism of these theories , that one's inborn sense of gender is immutable, and 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.

Regardless of the accuracy of these theories, the American Medical Association Committee on Human Sexuality has long held that psychotherapy is generally ineffective for curing transsexual adults.

Sexuality

See also: Blanchard, Bailey, and Lawrence theory

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 M2F 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. The theory has created a firestorm of protest in the transsexual community, although it has its supporters.

Genetics

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 male-to-female transsexualism. Most notably, the F2M 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.

Brain structure

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 -- male-to-female transsexuals have a female-normal size while female-to-male 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. Two other sexually dimorphic brain structures studied (the sexually dimorphic nucleus and the suprachiasmatic nucleus) matched the transsexuals' anatomic gender.

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 male-to-female transsexual 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, male-to-female transsexuals lay within the female range and the female-to-male 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 M2F 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 female-to-male 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 Hillekke et al (2006), which studied the changes in transsexual brains on hormone administration over four months via MRI. They discovered that whole brain size, as well as a variety of sexually dimorphic structures within the brain, 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.

Brain function

Phantom limb syndrome is a common, often painful experience after the loss of an external organ. Ramachandran (2008) found that while nearly 2/3rds of non-transsexual males who have a penis surgically removed experience the sensation of a phantom penis, only 1/3rd of male-to-female transsexuals do after sex-reassignment surgery. Perhaps more remarkable, 2/3rds of female-to-male transsexuals reported the sensation of a phantom penis from childhood, complete 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 male-to-female 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 M2Fs hypothalamic networks activated in response to AND, like the female control groups, and both experienced amygdala activation in response to EST. Male control groups experienced hypothalamic activation in response to EST. However, the M2Fs also experienced limited hypothalamic activation to EST as well. The conclusion was that in terms of pheromone activation, M2Fs occupy an intermedite position with predominantly female features.

Prenatal androgen exposure

Schneider, Pickel, and Stalla (2006) found a correlation between digit ratio (a generally accepted marker for prenatal androgen exposure) and male to female transsexualism. Male-to-female transsexuals were found to have a higher digit ratio than control males, but one that was comparable to control females.