Letter One ......
 
 

Many transgender people say that they feel as if they are trapped in the body of the wrong sex. Now, there is biological evidence in the brain that lends credence to those feelings. The research was published in the May issue of the esoteric Journal of Clinical Endocrinology and Metabolism.

Dr. Frank P.M. Kruijver and colleagues, working at the Netherlands Institute for Brain Research, knew from animal and human studies that the differences between male and female was more than genital. Hormones are one factor and so too is the brain, possibly in part as a result of those hormones.

Their research looked at the limbic portion of the brain, the center of emotion and basic body function. It is the most primitive core that is common to all animals, while man has evolved layers of brain beyond that, which allows for rational thought.

The Dutch sample included nine presumed heterosexual males, nine homosexual males, 10 presumed heterosexual females, six male-to-female transsexuals, and six brains (three male, three female) of patients with sex hormone disorders. They ranged in age from 20 to 53 and died of multiple causes from AIDS to suicide.

Kruijver's team took super-thin slices of human brains obtained at autopsy and performed a complex but standard series of preparations. Then they began counting neurons, the basic cellular component of the brain. They looked in particular at the somatostatin-expressing neurons, which are associated with growth hormone.

They found that heterosexual men had 71 percent more of these neurons than did heterosexual women. Homosexual men were clearly in the male range, in fact they averaged a fraction more neurons than their straight counterparts, though with the small size of the sample the difference did not reach statistical significance.

Male-to-female transsexuals mirrored heterosexual women in their neuronal patterns. It did not matter whether the person realized their transsexual identity early or later in life.

Nor did use or non-use of the feminizing hormone estrogen as an adult seem to have any impact upon brain structure. That was confirmed by examination of a straight male with an adrenal tumor that produced extremely high levels of estrogen but no change in brain neuron count. Post-menopausal women did not differ from their younger peers.

One hypothesis was that perhaps lack of testosterone in the transsexual person was responsible for the neuron count. But the pattern did not differ between those who had sexual reassignment surgery and those who retained testes. Nor did heterosexuals who lost their testicles to cancer show a change in their brain.

Kruijver also studied "the first collected brain ever of a female-to-male transsexual." The neuron pattern "was clearly in the male range." In fact, it was higher than all of the presumed heterosexual males and all but one of the homosexual males. The person had stopped taking testosterone three years before death.

This research adds to the body of evidence strongly suggesting that transsexualism has a biological origin that is prior to adulthood. It may be in part genetic, or a result of factors in the womb, or during early childhood development.
 

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LETTER TWO
 

Sexual Identity Hard-Wired by Genetics, Study Says
by Reuters News Service
10/20/2003
 

Refuting 30 years of scientific theory that solely credits hormones for brain development, UCLA scientists have identified 54 genes that may explain the different organization of male and female brains. Published in the October edition of the journal Molecular Brain Research, the UCLA discovery suggests that sexual identity is hard-wired into the brain before birth and may offer physicians a tool for gender assignment of babies born with ambiguous genitalia.

"Our findings may help answer an important question - why do we feel male or female?" explained Dr. Eric Vilain, assistant professor of human genetics and urology at the David Geffen School of Medicine at UCLA and a pediatrician at UCLA's Mattel Children's Hospital. "Sexual identity is rooted in every person's biology before birth and springs from a variation in our individual genome."

Since the 1970s, scientists have believed that estrogen and testosterone were wholly responsible for sexually organizing the brain. In other words, a fetal brain simply needed to produce more testosterone to become male. Recent evidence, however, indicates that hormones cannot explain everything about the sexual differences between male and female brains.

Vilain and his colleagues explored whether genetic influences could explain the variations between male and female brains. Using two genetic testing methods, they compared the production of genes in male and female brains in embryonic mice - long before the animals developed sex organs.

To their surprise, the researchers found 54 genes produced in different amounts in male and female mouse brains, prior to hormonal influence. Eighteen of the genes were produced at higher levels in the male brains; 36 were produced at higher levels in the female brains.

"We didn't expect to find genetic differences between the sexes' brains," admitted Vilain. "But we discovered that the male and female brains differed in many measurable ways, including anatomy and function."

In one intriguing example, the two hemispheres of the brain appeared more symmetrical in females than in males. According to Vilain, the symmetry may improve communication between both sides of the brain, leading to enhanced verbal expressiveness in females.

"This anatomical difference may explain why women can sometimes articulate their feelings more easily than men," he said.

Overall, the UCLA team's findings counter the theory that only hormones are responsible for organizing the brain.

"Our research implies that genes account for some of the differences between male and female brains," noted Vilain. "We believe that one's genes, hormones and environment exert a combined influence on sexual brain development."

The scientists will pursue further studies to distinguish specific roles in the brain's sexual maturation for each of the 54 different genes they identified. What their research reveals may provide insight into how the brain determines gender identity.

"Our findings may explain why we feel male or female, regardless of our actual anatomy," said Vilain. "These discoveries lend credence to the idea that being transgender --- feeling that one has been born into the body of the wrong sex -- is a state of mind.

"From previous studies, we know that transgender persons possess normal hormonal levels," he added. "Their gender identity likely will be explained by some of the genes we discovered."

Vilain's findings on the brain's sex genes may also ease the plight of parents of intersex infants, and help their physicians to assign gender with greater accuracy. Mild cases of malformed genitalia occur in 1 percent of all births - about 3 million cases. More severe cases - where doctors can't inform parents whether they had a boy or girl -- occur in one in 3,000 births.

"If physicians could predict the gender of newborns with ambiguous genitalia at birth, we would make less mistakes in gender assignment," said Vilain.

Lastly, Vilain proposes that the UCLA findings may help to explain the origin of homosexuality.

"It's quite possible that sexual identity and physical attraction is 'hard-wired' by the brain," he noted. "If we accept this concept, we must dismiss the myth that homosexuality is a 'choice' and examine our civil legal system accordingly."

The UCLA study was supported by the National Institute of Child Health and Human Development, the National Science Foundation and with start-up funds from the UCLA Department of Urology. Vilain's co-authors included Phoebe Dewing, Steve Horvath and Tao Shi, all of UCLA.

Molecular Brain Research, Oct. 21 issue, Vol. 118, pgs. 82-90.
 

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Letter Three
 

this was found here
http://www.symposion.com/ijt/ijtc0106.htm

A Sex Difference in the Human Brain and its Relation to Transsexuality
By J.-N. Zhou, M.A. Hofman, L.J. Gooren and D.F. Swaab

Citation: Zhou J.-N, Hofman M.A, Gooren L.J, Swaab D.F (1997) A Sex Difference in the Human Brain and its Relation to Transsexuality. IJT 1,1, http://www.symposion.com/ijt/ijtc0106.htm

Acknowledgements
References

Transsexuals have the strong feeling, often from childhood onwards, of having been born the wrong sex. The possible psychogenic or biological etiology of transsexuality has been the subject of debate for many years [1,2]. Here we show that the volume of the central subdivision of the bed nucleus of the stria terminalis (BSTc), a brain area that is essential for sexual behaviour [3,4], is larger in men than in women. A female-sized BSTc was found in male-to-female transsexuals. The size of the BSTc was not influenced by sex hormones in adulthood and was independent of sexual orientation. Our study is the first to show a female brain structure in genetically male transsexuals and supports the hypothesis that gender identity develops as a result of an interaction between the developing brain and sex hormones [5,6].

Investigation of genetics, gonads, genitalia or hormone level of transsexuals has not, so far, produced any results that explain their status [1,2]. In experimental animals, however, the same gonadal hormones that prenatally determine the morphology of the genitalia also influence the morphology and function of the brain in experimental animals in a sexually dimorphic fashion [6,7]. This led to the hypothesis that sexual differentiation of the brain in transsexuals might not have followed the line of sexual differentiation of the body as a whole. In the past few years, several anatomical differences in relation to sex and sexual orientation have been observed in the human hypothalamus (see [6] for a review), but so far no neuroanatomical investigations have been made in relation to the expression of cross-gender identity (transsexuality).
 
 
 

 Figure 1: Schematic frontal section through two subdivisions of the bed nucleus of the stria terminalis (BST) that are hatched. III: third ventricle; AC: anterior commissure; BSTc and BSTv: central and ventral subdivisions of the BST; FX: fornix; IC: internal capsule; LV: lateral ventricle; NBM: nucleus basalis of Meynert; OT: optic tract; PVN: paraventricular nucleus; SDN: sexually dimorphic nucleus; SON: supraoptic nucleus.
We have studied the hypothalamus of six male-to-female transsexuals (T1-T6); this material that was collected over the last eleven years. We searched for a brain structure that was sexually dimorphic, but not influenced by sexual orientation, as male-to-female transsexuals may be "oriented" to either sex with respect to sexual behaviour. Our earlier observations showed that the paraventricular nucleus (PVN), sexually dimorphic nucleus (SDN) and suprachiasmatic nucleus (SCN) did not meet these criteria ([6] and unpublished data). Although there is no accepted animal model for gender identity alterations, the bed nucleus of the stria terminalis (BST) turned out to be an appropriate candidate to study for the following reasons. First, it is known that the BST plays an essential part in rodent sexual behaviour [3,4]. Not only have oestrogen and androgen receptors been found in the BST [8,9], it is also a major aromatization centre in the developing rat brain [10]. The BST in the rat receives projections mainly from the amygdala and provides a strong input in the preoptic-hypothalamic region [11,12]. Reciprocal connections between hypothalamus, BST and amygdala are also well documented in experimental animals [13-15]. In addition, sex differences in the size and cell number of the BST have been described in rodents which are influenced by gonadal steroids in development [16-18]. Also in humans a particular caudal part of the BST (BNST-dspm) has been reported to be 2.5 times larger in men than in women [19].

The localization of the BST is shown in figure 1. The central part of the BST (BSTc) is characterized by its somatostatin cells and vasoactive intestinal polypeptide (VIP) innervation [20]. We measured the volume of the BSTc on the basis of its VIP innervation (Fig. 2).
 
 
 
 

Figure 2: Representative sections of the BSTc innervated by vasoactive intestinal polypeptide (VIP). A: heterosexual man; B: heterosexual woman; C: homosexual man; D: male-to-female transsexual. Bar=0.5 mm. LV: lateral ventricle. Note there are two parts of the BST in A and B: small sized medial subdivision (BSTm), and large oval-sized central subdivision (BSTc).

The BSTc volume in heterosexual men (2.49±0.16 mm3) was 44% larger than in heterosexual women (1.73±0.13 mm3) (P<0.005) (Fig. 3). The volume of the BSTc of heterosexual and homosexual men was found not to differ in any statistically significant way (2.81±0.20 mm3) (P=0.26). The BSTc was 62% larger in homosexual men than in heterosexual women (P<0.005). AIDS did not seem to influence the size of the BSTc: the BSTc size of two heterosexual AIDS-infected women and three heterosexual AIDS-infected men remained well within the range of the corresponding reference group (Fig. 3). The AIDS-infected heterosexuals were therefore included in the corresponding reference group for statistical purposes. A small volume of the BSTc (1.30±0.23 mm3) was found in the male-to-female transsexuals (Fig. 3). Its size was only 52% of that found in the reference males (P<0.005) and 46% of the BSTc of homosexual males (P<0.005). Although the mean BSTc volume in the transsexuals was even smaller than that in the female group, the difference did not reach statistical significance (P=0.13). The volume of the BSTc was not related to age in any of the reference groups studied (P>0.15), indicating that the observed small size of the BSTc in transsexuals was not due to the fact that they were, on average, 10 to 13 years older than the hetero- and homosexual men.

The BST plays an essential role in masculine sexual behaviour and in the regulation of gonadotrophin release, as shown by studies in the rat [3,4,21]. There has been no direct evidence that the BST has such a role in human sexual behaviour but our demonstration of a sexually dimorphic pattern in the size of the human BSTc, which is in agreement with the previously described sex difference in a more caudal part of the BST (BNST-dspm) [19], indicates that this nucleus may also be involved in human sexual or reproductive functions. It has been proposed that neurochemical sex differences in the rat BST may be due to effects of sex hormones on the brain during development and in adulthood [22,23]. Our data from humans however, indicate that BSTc volume is not affected by varying sex hormone levels in adulthood. The BSTc volume of a 46-year-old woman who had suffered for at least 1 year from a tumour of the adrenal cortex that produced very high blood levels of androstenedione and testosterone, was within the range of that of other women (Fig. 3: S1). Furthermore, two postmenopausal women (aged over 70 years) showed a completely normal female-sized BSTc (Fig. 3: M1, M2). As all the transsexuals had been treated with oestrogens, the reduced size of the BSTc could possibly have been due to the presence of high levels of oestrogen in the blood. Evidence against this comes from the fact that transsexual T2 and T3 both showed a small, female-like BSTc (Fig. 3), although T2 stopped taking oestrogen about 15 months before death, since her prolactin levels were too high and T3 stopped hormone treatment since a sarcoma was found about three months before death; also a 31-year-old man who suffered from a feminizing adrenal tumour which induced high blood levels of oestrogen, nevertheless had a very large BSTc (Fig. 3: S2).
 
 

Figure 3: Volume of the BSTc innervated by VIP fibres in presumed heterosexual males (M), homosexual males (HM), presumed heterosexual females (F) and male-to-female transsexuals (TM). The six transsexuals are numbered T1-T6. The patients with abnormal sex hormone levels are numbered S1-S4. M1 and M2: postmenopausal women. Bars indicate mean±SEM. Open symbols: individuals who died of AIDS. METHODS. Brains of 42 subjects matched for age, postmortem time and duration of formalin fixation were investigated. The autopsy was performed following the required permission. For immunocytochemical staining of VIP, the paraffin sections were hydrated and rinsed in TBS (Tris-buffered-saline: 0.05 M tris, 0.9% NaCl, pH 7.6). The sections were incubated with 200 µl anti-VIP (Viper, 18/9/86) 1:1000 in 0.5% triton in TBS overnight at 4° C. The immunocytochemical and morphometric procedures were performed as described extensively elsewhere [25-27]. In brief, serial 6 m m sections of the BSTc were studied by means of a digitizer (Calcomp 2000) connected to a HP-UX 9.0, using a Zeiss microscope equipped with a 2.5x objective and with 10x (PLAN) oculars. Staining was performed on every 50th section with anti-VIP. The rostral and caudal borders of the BSTc were assessed by staining every 10th section in the area. The volume of the BSTc was determined by integrating all the area measurements of the BSTc sections that were innervated by VIP fibres. In a pilot study, the size of the BSTc was measured on both sides in eight subjects (five females and three males) and no left-right asymmetries were observed: the left BSTc (1.71±0.16 mm3) was comparable in size to that of the right BSTc (1.83±0.30 mm3) (P=0.79). No asymmetry was observed in the BNST-dspm either [19]. The rest of our study was therefore performed on one side of the brain only. Brain weight of the male transsexuals (1385±75 g) was not different from that of the reference males (1453±25 g) (P=0.61) or that of the females (1256±35 g) (P=0.23). The cause of death of the six transsexuals was suicide (T1), cardiovascular disease (T2,T6), sarcoma (T3), AIDS, pneumonia, pericarditis (T4) and hepatitic failure (T5). Sexual orientation of the subjects of the reference group (12 men and 11 women) was generally not known, but presumably most of them were heterosexual. Sexual orientation of nine homosexuals was registered in the clinical records [28]. Differences among the groups were tested two-tailed using the Mann-Whitney U test. A 5% level of significance was used in all statistical tests.

Our results might also be explained if the female-sized BSTc in the transsexual group was due to the lack of androgens, because they had all been orchidectomized except for T4. We therefore studied two other men who had been orchidectomized because of cancer of the prostate (one and three months before death: S4 and S3, respectively), and found that their BSTc sizes were at the high end of the normal male range. The BSTc size of the single transsexual who had not been orchidectomized (T4) ranged in the middle of the transsexual scores (Fig. 3). Not only were five of the transsexuals orchidectomized, they all used the antiandrogen cyproterone acetate (CPA). A CPA effect on the BSTc does not seem likely, because T6 had not taken CPA for the past 10 years, and T3 took no CPA during the two years before death and still had a female-sized BSTc.

In summary, our observations suggest that the small size of the BSTc in male-to-female transsexuals cannot be explained by differences in adult sex hormone levels, but is established during development by an organizing action of sex hormones, an idea supported by the fact that neonatal gonadectomy of male rats and androgenization of the female rats indeed induced significant changes in the number of neurons of the BST and suppressed its sexual dimorphism [17,18].

Considered together with information from animals, then our study supports the hypothesis that gender identity alterations may develop as a result of an altered interaction between the development of the brain and sex hormones [5,6]. The direct action of genetic factors should also be considered on the basis of animal experiments [24].

We found no relationship between BSTc size and the sexual orientation of transsexuals, that is, whether they were male-oriented (T1,T6), female-oriented (T3,T2,T5), or both (T4). Furthermore, the size of the BSTc of heterosexual men and homosexual men did not differ, which reinforced the idea that the reduced BSTc size is independent of sexual orientation. In addition, there was no difference in BSTc size between early-onset (T2,T5,T6) and late-onset transsexuals (T1, T3), indicating that the decreased size is related to the gender identity alteration per se rather than to the age at which it becomes apparent. Interestingly, the very small BSTc in transsexuals appears to be a very local brain difference. We failed to observe similar changes in three other hypothalamic nuclei, namely, PVN, SDN or SCN in the same individuals (unpublished data). This might be due to the fact that these nuclei do not all develop at the same time, or to a difference between these nuclei and the BST with respect to the presence of sex hormone receptors or aromatase. We are now studying the distribution of sex hormone receptors and the aromatase activity in various hypothalamic nuclei in relation to sexual orientation and gender.
 

Acknowledgements

We thank Mr. B. Fisser, Mr. H. Stoffels, Mr. G. van der Meulen, and Ms. T. Eikelboom and Ms. W.T.P. Verweij for their help, and Drs. R.M. Buijs, M.A. Corner, E. Fliers, A. Walter and F.W. van Leeuwen for their comments. Brain material was provided by the Netherlands Brain Bank (coordinator Dr. R. Ravid). This study was supported by NWO.
 

References

Money, J. and Gaskin, Int. J. Psychiatry, 9 (1970/1971) 249.

Gooren, L.J.G., Psychoneuroencrinology, 15 (1990) 3-14.

Kawakami, M. and Kimura, F., Endocrinol. Jap., 21 (1974) 125-130.

Emery, D.E. and Sachs, B.D., Physiol. Behav., 17 (1976) 803-806.

Editorials Lancet, 338 (1991) 603-604.

Swaab, D.F. and Hofman, M.A., TINS, 18 (1995) 264-270.

Money, J., Schwartz, M. and Lewis, V.G., Psychoneuroendocrinology, 9 (1984) 405- 414.

Sheridan, P.J., Endocrinology, 104 (1979) 130-136.

Commins, D. and Yahr, D., J. Comp. Neurol., 231 (1985) 473-489.

Jakab, R.L., Horvath, T.L., Leranth, C., Harada, N. and Naftolin, F.J., Steroid Biochem. Molec. Biol., 44 (1993) 481-498.

Eiden, E.L., Hökfelt, T, Brownstein, M.J. and Palkovits, M., Neuroscience, 15 (1985) 999-1013.

De Olmos, J.S. In: Paxinos, G. (Ed.), The Human Nervous System, Academic Press, San Diego, 1990, pp. 597-710.

Woodhams, P.L., Roberts, G.W., Polak, J.M. and Crow, T.J., Neuroscience, 8 (1983) 677-703.

Simerly, R.B., TINS, 13 (1990) 104-110.

Arluison, M., et al., Brain Res. Bull., 34 (1994) 319-337.

Bleier, R., Byne, W. and Siggelkow, I., J. Comp. Neurol., 212 (1982) 118-130.

Del Abril, A., Segovia, S. and Guillamón, A., Dev. Brain Res., 32 (1987) 295-300.

Guillamón, A., Segovia, S. and Del Abril, A., Dev. Brain Res., 44 (1988) 281-290.

Allen, L.A. and Gorski, R.A., J. Comp. Neurol., 302 (1990) 697-706.

Walter, A., Mai, J.K., Lanta, L. and Görcs, T.J., Chem. Neuroanat., 4 (1991) 281-298.

Claro, F., Segovia, S., Guilamón, A. and Del Abril, A., Brain Res. Bull., 36 (1995) 1-10.

Simerly, R.B. and Swanson, L.W., Proc. Natl. Acad. Sci. U.S.A., 84 (1987) 2087- 2091.

De Vries, G.J., J. Neuroendocrinol., 20 (1990) 1-13.

Pilgrim, Ch. and Reisert, I., Horm. metab. Res., 24 (1992) 353-359.

Swaab, D.F., Zhou, J.N., Ehlhart, T. and Hofman, M.A., Brain Res., 79 (1994) 249- 259.

Zhou, J.N., Hofman, M.A. and Swaab, D.F., Neurobiol. Aging (1995) in press.

Zhou, J.N., Hofman, M.A. and Swaab, D.F., Brain Res. 672 (1995) 285-288.

Swaab D.F. and Hofman M.A., Brain Res., 537 (1990) 141-148.

Correspondence and requests for materials to:
J.-N. Zhou, M.A. Hofman and D.F. Swaab
Graduate School Neurosciences Amsterdam
Netherlands Institute for Brain Research
Meibergdreef 33
1105 AZ Amsterdam ZO
The Netherlands

L.J.G. Gooren
Department of Endocrinology
Free University Hospital
1007 MB Amsterdam
The Netherlands
Email: lgooren@inter.nl.net

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Letter Four
 

this was found here
http://gidinfo.home.comcast.net/research.htm

Medical Research for a Physical GID Cause

Most laypeople tend to view the concept that Gender Dysphoric individuals are "born" to the condition with some skepticism. This is only natural, since the very nature of the condition manifests itself as a perceptual (and therefore appearing to be only mental) disorder. The classification of Gender Identity Dysphoria (GID) within the International Classification of Diseases-10 (ICD-10) and Diagnostic and Statistical Manual of Mental Illnesses (DSM-IV) serve to support the belief that the transgender condition is a mental illness[1]. Much of the reasoning, however, for categorizing GID as a "Mental Illness" is based in science and psychology that is now decades old - beliefs which are being overturned by current research.

It has long been known that "floods" of various hormones are instrumental in the development of a fetus. What remains a vigorous area or research is to determine exactly what effects what hormones have on virtually every structure within the developing fetus. Large scale sexually differentiated structures are the easiest to observe, and the general effects of various hormones on gonadal structures have long been known. However, microstructures such as clusters of neurons in the brain, have proven to be much more difficult to observe. Coupled with that is the fact that the precise functions of neurons in brain is a field of study still in its infancy. Again, only large scale structures are known with very generalized concepts about the functions of those structures. Nevertheless, new research has shed light on the closest thing we have to "proof" that GID has an underlying congential cause.

Biologically, all fetuses start out the same, whether they will ultimately develop into male or female, the fetus contains a structure that has four ducts that can develop into male and/or female genitalia. The determining factor for "normal" development is the presence or absence of a "Y" chromosome. [ I say "normal" because there are numerous deviations from the XX/XY karotypes ] Generally, if the Y chromosome is not present, the fetus will develop as female, with enzymatic signals sent out for "floods" of Estrogenic hormones and Mullerian Hormone (which causes the Mullerian Ducts to develop into female genitalia). Without a flood of Testosterone, the other two ducts do not develop into testes and the tissue is reabsorbed. If there is a Y chromosome present, it sends out "enzymatic signals" during the pregnancy for a number of "Male" hormones. These include Androgen, Testosterone, and Mullerian Inhibiting Hormone. Testosterone is the best known to laypeople and is believed to be primarily responsible for the development of two of the ducts into testes, while the Mullerian Inhibiting Hormone prevents the other two ducts from developing into ovaries - the other ducts whither and the tissue is reabsorbed by the fetus. Androgen, it is believed, is primarily responsible for structural differentiation of neurological tissues. Because of this, Androgen is sometimes said to "hard wire" the brain to process as "male." [2] Of course there are numerous, well-documented cases where this "normal" process is interrupted or deviates, resulting in children born with Klienfelter's Syndrome, Intersexed (formerly known as "Hermaphrodites"), Turner's Syndrome, Down's Syndrome, and so on[3, 4, 5]. The deviations that cause easily observed physical deformity or mental inhibition are most readily diagnosed. However, milder forms of deviation often go undetected, sometimes for the individual's entire life. The mechanisms that cause such deviations are varied and mostly unknown, they result from genetic errors, susceptibility, environmental toxins, maternal stress, malnutrition, drugs, radiation, and probably a host of things that haven't yet been discovered.

Research carried out in the mid-1990's may have discovered just such a previously "undetected deviation" in the brain structures of transgender individuals. In 1995 the Journal Nature [6] reported on the findings in Holland concerning an area of the brain called the bed nucleus of the stria terminalis (BST) region and its put it forth as a possible explanation for Gender Identity Disphoria. The BST region had long been believed to influence sexual behavior, and is known to be larger in male vertebrates, which was why the researchers compared the brains of six transsexuals to the brains of non-transsexual men and women. Although the sampling was small, the BST regions in all six transsexuals were closer to the average size observed in female brains. [I should note that there have been similar comparisons of the size of the BST region between known homosexual and heterosexual men that found them to be comparable. I could find no references to studies comparing the relative size of BST regions in known homosexual and heterosexual women, however ]. The next challenge came in determining if the size of the BST region could be altered post-natally[7]. Tests performed on laboratory rats and primates have subsequently determined that the size of the BST region is determined in utero by the presence or absence of Androgen and is not affected by hormones after birth. The BST region is basically part of the Hypothalmus, which is part of the "primitive" brain and is known to be responsible for regulation of autonomic functions, hormone production, and sexual behavior. In laboratory animal tests, where normal fetal development was purposely altered, male subjects have been observed exhibiting female mating behaviors. Upon examination of the BST regions in these animals, the male brains more closely resembled those of typical females. As this has been tested and shown among primates, it is reasonable to believe that the same processes and results would be observed in human subjects as well.[8] Of course, ethically, such human trials can't be done and researchers must rely on data collected from the population. There are two factors that are impeding human research on the subject. One is that human beings have complex sexual social behaviors that do not often tolerate deviations from the norm (unlike with animal subjects, where homosexual mating behaviors have not social or moral constraints). Transgender individuals will often conceal their true nature and even act opposite to their own instincts as a method of self-preservation. It therefore becomes difficult to identify a significant portion of such individuals and gather data. Even if individuals are identified there is the second problem - the BST region currently must be examined post-mortem by dissection of the brain. Clearly this would be an easier hypothesis to prove if researchers were dealing with a society as uninhibited as the animal kingdom and also had a non-invasive method of observing the BST region in living subjects.

UPDATE 5 May 2002:

Another study researching the BST region has confirmed that the concentration of neurons in transsexual males is within the observed average female range, while heterosexual and homosexual males both had larger nuron counts in the BST region. Furthermore, supporting evidence that this region is unaffected by post-natal hormone levels was observed.[u1]

Another new study, conducted in 2002, discovered an unexpected finding: the BST region in human beings does not become significantly sexually dimorphic until adulthood. This was unexpected because it was not observed in lesser mammals. While some people believe this new study has "dealt a serious blow" to the assertion that the BST region is a significant factor in determining transsexuality, I would beg to differ. The researchers themselves conjectured that neonatal hormone levels could STILL affect gender identity by simultaneously producing changes in BST "synaptic density, neuronal activity, or neurochemical content" that might not occur early in life, but come to fruition during adulthood. No studies have yet been done to determine if exposure to hormones early in life may affect how the BST becomes sexually dimorphic, but previous studies seem to indicate that, once the region has already developed in adulthood, anti-androgens or supplemental hormones have no effect on altering BST size or structure.[u2]

While it appears that the BST region of the brain is a very important contributor to "Gender Identity," it is by no means the ONLY part of the brain researchers are exploring. Some research is also looking at the effects hormones have elsewhere in the brain, for example a number of Androgen Receptors have been observed in the Hippocampus of rats - and area that is associated with learning and memory, not sexual behavior.[9] It is currently unknown why it would be important for that region of the brain to recieve Androgen. In other research, scientists are studying the forebrain projections that product the neuropeptite "vasopressin." The density of these projections is greater in male brains than in female brains, and their activity is known to be linked to gonadal hormone production. However, even in cases of castration it takes months for the vasopressin to clear from the neural projections.[10] It is believed that vasopressin is partly responsible for male aggressive behavior and possibly contributes to libido. This may explain why sex offenders who are castrated do no immediately become less agressive or aroused, it may also help to explain the "shift" in sexual oriention experienced by many transsexuals usually months after they have had a bilateral orchiectomy. It is also believed that male hormones may be responsible for other, broader, changes in brain development. Male and female brains have both been observed "processing" under Magnetic Resonance Imaging. One of the most striking differences was that language skills appear to be centered in a specific region of the male brain, while language processing was observed to involve several areas of the female brain - including the visual cortex. There also appears to be more cross-hemispheric communication in the female brain. Science is well on its way to proving some of the long standing beliefs about the differences between the ways men and women think. Some of it appears to have been determined ("Hard Wired") prior to birth, while other things are more "plastic" in nature - effected by hormones or other environmental influences.

The bottom line: Gender Identity Dysphoria is NOT a mental problem and therefore psychotherapy will not make it "go away." It is a PHYSICAL CONDITION, the cause of which cannot be altered by any known methodology. Individuals with GID are often in need, however, of some form of therapy to deal with the SOCIAL problems that often go hand-in-hand with the condition. Those problems, though, are caused by something external - namely a society that will not accept the preferred gender identity of the individual. This is a problem FOR the transgender individual and a problem OF society that requires either better coping mechanisms for the individual and/or a more tolerant social environment.
 

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Letter Five
 

this was found here
http://transgenderwales.bravepages.com/gender_dysphoria.htm

Introduction

Gender Dysphoria is a biological condition, it's sufferers are people called transsexuals. This condition is recognised by the American Diagnostic and Statistical Manual of Mental Health Disorders, version four (DSM-IV, 1996) and the World Health Organisation's International Classification of Disorders (1992). This condition, according to these publications, is separate from homosexuality, transvestism and other transgender disorders.

Scientific research has been undertaken whilst conducting post mortem examinations, autopsies, on people born with gender dysphoria which has shown that they had the brain of the opposite sex to that given to them at birth. Studies have been undertaken showing that gender dysphoria does not only occur in humans, but also in other mammals including apes, dogs, cats, mice and rats. Also, since all foetuses begin life as female neuter, all males are born with nipples and the scar remnants of their original female sex.

Transsexuality is caused as a result of hormone changes in the uterus during the second month of development and their effect on the unborn baby. This condition may be brought on by the presence of chemicals similar to human hormones during this critical stage of the development of the baby's brain. These hormones are similar to androgens, especially testosterone and oestrogens, which create the male or female characteristics, respectively. The brain is extremely delicate and hence, sensitive at this crucial stage so a small change in chemicals such as hormones can make a major difference to the brain's developmen

Coming to terms with Transsexuality.

Transsexuals often realise themselves that there are problems at about age 5, but many repress these feelings in order to fit in with their parent's, family's and friend's expectations. Consequently, those sufferers who repress their true identities until later in life may not always recognise their transsexuality during puberty and later teenage years, even when this time creates inner conflicts for the individual.

Whilst growing up there can be evidence of the child being transsexual. In the case of socialisation, the transsexual child would find that they would receive rebuffs from they perceived peer group such as "You can't play with us, you're a boy" for the male to female child or "you can't play with us because you're a girl" for the female to male child. It is as a result of this incompatibility that repression occurs with many young transsexuals who try to "fit in" with their apparently correct peer group. This can then lead to the transsexual child being on the receiving end of bullying, this comes to the fore when the child enters their teens.

As adults, the transsexual can lose the support of their families and friends when repression is removed, and they start to live their lives as their true selves. Conversely, if the repressions are not removed, the result can unfortunately be fatal. The reason for this is that the transsexual cannot live the whole of their life without having very strong internal is incapable, for whatever reason, of coming to terms with their true identity, any fatalities normally occur by the age of 30 years.

The Next Steps

This condition is not curable, except by undergoing gender reassignment (a sex change), as the brain cannot be adapted to suit the body. In order to qualify for gender reassignment surgery, the transsexual has to undertake a "Real Life Test" (RLT); in the role of the gender they perceive themselves to be. The Real Life Test is over a period of time, not usually less than one year, but normally a two year period is required. This is to ensure that the transsexual person can adapt to their perceived gender role. During the Real Life Test, the transsexual will receive the required hormones, either androgens or oestrogens to further ensure their compatibility with their perceived gender. On completion of the Real Life Test, the transsexual could be recommended for surgery. After reassignment surgery, the individual is technically no longer transsexual but man to woman (or FTM) because the individual's sexual identity now matches their gender identity, their physical sex matches their brain sex.

Males and females are both affected by gender dysphoria in equal numbers, and there are estimated to be at least 25,000 transsexuals in the United Kingdom, according to the British Medical Authority. At the time of writing, there are some 500 or so Transsexuals in Wales (pre and post operative) who are under medical supervision for this condition. Of this number, only about 20 to 25 percent of transsexuals who do undergo gender reassignment surgery are Female to Male (FTM), since this transition requires more involved and intricate surgery than for Male to Female. At the risk of sounding a little simplistic, it's easier to take bits off than to put bits on.

Before gender reassignment, over 80% of transsexuals seriously consider, attempt or do commit suicide, whereas post-operatively, this figure reduces to less than one percent. This figure is very much in line with the rest of the population.

The History of Transsexualism.

Transsexuality and gender dysphoria has a long history, probably going back to palaeolithic periods of time. This can be deduced by considering the societies of aboriginal peoples who still live with "stone-age" technologies. These societies reserve honoured positions for transsexuals among their people, being considered magical, akin to gods or spirits and possessed of shamanic powers. Examples include the Gallae of ancient Rome, who were worshippers of the Goddess Cybele, the Nadles of the South West Navajos, the Winkte of the Sioux, the Sererr of the Kenyan Pokots, the Xanith of Islamic Oman, the Mahu of Tahiti, the Sekrata of Madagascar and the Hijiras of present day India.

Surgical gender reassignment was first attempted in Germany in 1930 on Herr Einar Wegener, who then became Lily Elbe. Sadly, Lily did not survive very long following the surgery due to tragic surgical complications. The first surviving post-operative person was an American GI. He was George Jorgensen who became Christine Jorgensen in 1953.

During the 1950's and 1960's, Doctor Harry Benjamin undertook the first research into gender dysphoria. In 1966, Dr Benjamin published "The Transsexual Phenomenon", a book based upon his documented studies. This first publication highlighted gender dysphoria as being of biological origin, which started much of the research which continues to the present day.
 

References

Transsexuality Reitz, J.D. (1998) www.transsexual.org
TearS: The facts Redding, K. www.kaffeine.freeuk.com/korner/bluboox/tears.htm
Myth, Stereotype and cross-gender Identity in the DSM-IV Wilson, K.K. & Hammond, B.E. www.transgender.org/tg/gic/awptext.html
Transsexualism: The current Medical Viewpoint (2nd Edition) Reid, R.W. www.kaffeine.freeuk.com/korner/bluboox/viewpt.htm
 

Research by Catherine Jones.

Copyright Transgender Wales © 2003. All rights reserved.