This  has information that is applicable to not only those that are TS but other gender variant states. The language is aimed at the clinician but wade through it and you will find a good bit of information. I do highly recommend the book I have found something new each time I read it.  Sandra

  

Etiology of Gender Dysphoria

By Randi Ettner from Gender Loving Care

 

 

Etiology of Gender Dysphoria

 

No true transsexual has yet been persuaded, bullied, drugged, analyzed, shamed, ridiculed, or electrically shocked into an acceptance of his physique.

Jan Morris, Conundrum

 

Owing to the intricate relationship of etiology and treat­ment, it is not surprising that early therapies were designed to cure people of what was considered a psychiatric disorder or, falling short of that goal, to ameliorate their discomfort.

Early hypotheses about the genesis of transsexualism pointed to environmental factors in the nature vs. nurture antipodal paradigm.

The psychoanalytic model presupposed serious object-relation disturbances and pathologically introjected, highly cathected motherchild relations (Lothstein, 1979). Those advancing this model maintained that close, retrospective observations would reveal that the adult transsexual was a child who could not separate without intense anxiety, on the part of both mother and child (Gilpin, Raza, & Gilpin, 1979; Moberly, 1986; Ovesey & Person, 1976). The difficulty lay in the patient's inability to adequately regulate the intrapsychic distance between self and others (Macvicar, 1978).

Psychoanalytic literature focused on the dynamics beneath the desire to change sex. Various mechanisms were suggested to account for transsexual wishes. While some psychoanalytically oriented professionals described the psychopathology to be of a psychotic nature (Socarides, 1978), others conceptualized a borderline personality organization. In this theoretical model, the male-to-female patient seeks to "discard bad and aggressive features and to replace them with a new, idealized perfection" (Lothstein, 1984). These analysts suggested that sex reassign­ment surgery could best be conceptualized as "a new type of psychosurgery" (Kavanaugh & Volkan, 1978). In the case of the female-to-male transsexual, the dynamically oriented explanation was that the need to change sex arose from the child's desire to protect mother and self from a threatening father (Bradley, 1980).

By 1982, the psychoanalytic theory of gender disorders had crystallized into the following summary position: 

Sex reassignment is a symptomatic compromise formation serving defensive and expressive functions. The symptoms are the outgrowth of developmental trauma affecting body ego and archaic sense of self caused by peculiar symbiotic and separation-individuation phase relationships. The child exists in the pathogenic (and reparative) maternal fantasy in order to repair her body image and to demonstrate the interconvertability of the sexes .... gender pathology bears common features with other preoedipal syndromes. Transsexualism is closely linked to perversions and the clinical syndromes may shade from one into another. However, what is kept at the symbolic level in the perversions must be made concrete in transsexualism. The clinical complaint of the transsexual is a condensation of remarkable proportions. When the transsexual says that he is a girl trapped in a man's body, he sincerely means what he says. As with other symptoms, however, it takes a long time before he begins to say what he means. (Meyer, 1982)  

The successful treatment of transsexualism via psychoanalysis is claimed in the literature in scattered case studies (Haber, 1991), with analysis of a full-blown transference neurosis being viewed as the ultimate resolution (Loeb, 1992; Loeb & Shane, 1982). A literature review of the last three decades also reports one case of transsexualism having been cured through exorcism and faith healing! (Barlow, Abel, & Blanchard, 1977).

Throughout the aforementioned psychiatric literature, one finds frequent mention of the transsexual's unwillingness to engage in the psychotherapeutic process and resistance to therapeutic interventions (e.g., Shtasel, 1979). White (1997), a psychiatrist, has observed similar language invoked in early psy­chiatric response to patients who were diagnosed with obsessive-compulsive disorders. When analysis fails, a "blame the victim" dictum prevails.

Running parallel to the psychoanalytic theories of pathogesesis are the endeavors to find a biological basis for the condition (Buhrich, Barr,& Lam Po Tang, 1978). Early attempts to find an organic genesis range from roentgenological examination of the skulls of transsexuals (Lundberg, Sjovall, & Walinder, 1975) to a search for an anomalous hormonal milieu (Gooren, 1986; Kula, Dulko, Pawlikowski, Imelinski, & Slowikowska, 1986).

Some early studies, first appearing in 1979, looked promising in detecting incongruous H-Y antigen status in transsexuals (Eicher et al., 1980; Spoljar, Eicher, Eiermann, & Cleve, 1981). Through cytotoxicity assays, initial reports found H-Y antigen expression to be discordant with anatomic sex and to correspond instead to the gender identity of the transsexual (Eicher et al., 1981; Engel, Pfafflin, & Wiedeking, 1980). HY antigen, thought to be a presumptive inducer of the testis, is present in the cells of normal males and not in the cells of normal females. Researchers felt that these results would "help to replace emotional controversy by rational assessment of facts" (Vogel, 1981).

By 1982, Meyer-Bahlburg concluded that attempts to impli­cate the H-Y antigen in the etiology of the condition had failed (Wachtel et al., 1986); nevertheless, some researchers felt strongly that hormonal-dependent structural brain changes, though not yet demonstrated, seemed likely (Gooten, 1990).

Similarly failing to bear fruit were studies that documented a high rate of temporal EEG abnormalities in transsexuals. Despite early accounts of this phenomenon (Hoenig, & Kenna, 1979; Nusselt & Kockott, 1976), subsequent reports, which refuted the reliability of visual EEG analyses and utilized quan­titative frequency EEG analysis, found no significant differ­ences between transsexuals and normals (Grasser, Keidel, & Kockott, 1989 ). And in 1991 a study using magnetic resonance imaging ruled out differences in shape and size of the splenium of the corpus callosum as a marker of transsexualism (Emory, Williams, Cole, Amparo, & Meyer).

Clinical psychologists had a unique contribution to make in this search for causality. Through the use of psychological tests they could substantiate, or fail to substantiate, the claim that transsexuals had rampant psychopathology. Once again, find­ings reported in the literature could buttress either position. For example, a 1985 study hypothesized that transsexuals mani­fested a borderline personality organization and operationalized Kernberg's criteria for borderline personality with the use of Rorschach protocols. This study found that, compared to normals, transsexuals and borderlines display intense levels of aggression, poor object relations, poor reality testing, and impaired boundary differentiation. The author concluded that male gender dysphorics are a subgroup of borderline disorders (Murray, 19851.  

Studies that looked at sex-change applicants' responses to Minnesota Multiphasic Personality Inventory testing were evenly divided in concluding that they do or do not shows signs of, phychopathology (Greenberg & Laurence, 1981). Some of these differences were clarified when researchers distinguished between sex-reassignment applicants who were living as men and those who were living in their preferred female gender. The latter group showed no elevations in the clinical scales, which the authors described as a "a notable absence of psychopathol­ogy'' (Greenberg 8,5 Laurence, 1981; Tsushima & Wedding, 1979). One study found length of hormonal treatment to be related to emotional adjustment on four clinical scales: scores indicating greater adjustment correlated positively with longer periods of hormonal treatment (Leavitt, Berger, Hoeppner, & Northrop, 1980).  

In a well-designed research study, Cole, O'Boyte, Emory, and Meyer (1997) retrospectively examined the comorbidity between gender dysphoria and psychopathology by reviewing the charts of 435 gender dysphoric individuals (318 males and 117 females). Extensive information existed for this group, including MMPI data. They reported an absence of Axis I and Axis II diagnoses and concluded that transsexualism "is usually an isolated diagnosis and not part of any general psychopathological disorder." In other words, transsexuals did not inevitably have a coexisting psychiatric disorder, which seemed to be the operating assumption of many professionals (Bodlund, Kullgren, Sundbom, & Hojerback, 1993).

In a discussion of Dutch adolescent transsexuals who had been surgically reassigned, Cohen Kettenis and Van Goozen (1997) noted that adolescent transsexuals are psychologically healthier than adult transsexuals. This suggests that the longer an individual suffers by living unsuccessfully in his or her phenotypic role, the more vulnerable he or she is to depression ensuing from the social and emotional difficulties of trying to hide the condition. Another study of adolescent transsexuals in the Netherlands compared them to adolescent psychiatric out­patients. These authors concluded that "the argument that gross psychopatholgy is a required condition for the develop­ment of transsexualism appears indefensible" (Cohen, de Ruiter, Ringelberg, & Cohen-Kettenis, 1997).

As more and more people came forth requesting treatment and medical resources, interested investigators began to compile substantial data about the medical and psychological histories of these individuals. While the histories were consistent, in that all of these individuals had suffered similar distress, there was no commonality in terms of environmental features or in any of the particulars of their biographical data. Some reported unhappy childhoods and broken homes or blatantly dysfunctional families, while others were born to privilege or claimed to have had happy childhoods (Buhrich & McConaghy, 1978). Few of the population were sexually abused, as some theorists had speculated, and there were no similarities in terms of birth order, sexual experiences in childhood, or childrearing practices of the parents. In short, there was no empirical evidence that environmental factors alone could account for the origin of the condition.

Interestingly, the most compelling clues as to the origin of the condition came from a seemingly unrelated group of people: baby girls who were born with adrenogenital syndrome. In this syndrome, baby girls are born without an important enzyme necessary for the making of an adrenal hormone called cortisol. They have mixed genitalia, which include an oversized clitoris that resembles a penis. Left untreated, at four years of age their appearance will begin to show signs of masculinity.

Treatment for this condition became available in the 1950s. It consists of administering corticosteroids from birth on and surgically correcting the appearance of the genitals so that they become decidedly female. With this treatment, these babies are indistinguishable from other infant girls. But as they mature, they show behavior more typical of boys than girls (Zucker et al., 1996). Longitudinal studies of these children found them to be tomboys, and as they grew, they all remarked that they would have preferred to have been male. This paralleled the transsexual experience and cast further doubt on the nurture component of the nature vs. nurture controversy.

If it is indeed true that there is a biological etiology of transsexualism, it is based on the belief that gender identity derives from hormone-induced cephalic differentiation at some critical gestational stage (Dorner, Poppe, Stahl, Kolzsch, & Uebelhack, 1991; Elias & Valenta, 1992; Giordano & Giusti, 1995). A derivative designed to test this belief would be to determine if any phenotypic differences separate the transsexual population from the general population. A 1992 report published in the Journal of the American Medical Association documented that three times as many male-to-female transsexuals were left-handed, compared to the general population (Watson & Coren, 1992). In a 1996 study that looked at height as a phenotypic variable, Ettner, Schacht, Brown, Niederberger, and Schrang demonstrated that the male transsexual population tends to be of greater than average height.

Looking at pathophysiology of the female-to-male transsexual, Van Straalen, Hage, and Bloemena (1995) used histological investigation to conclude that an anomalous inframammary ligament extending from the sternum to the lateral margin of the pectoralis major muscle is present in female-to-male transsexuals. Several studies have documented a higher rate of potycystic ovaries in this population (Bosinski et al., 1997a; Futterweit, 1983; Futterweit & Deligdisch, 1986; Futterweit & Krieges; 1979; Futterweit, Weiss, & Fagerstrom, 1986; Spinder, Spijkstra, Gooren, & Burger, 1989).

Bosinski et al. (1997b) examined the relationship between body build, androgens, and female-to-male transsexualism. They assessed anthropometrical measurements in hormonally untreated female-to-males in comparison to healthy female and male controls. The female-to-male group differed from control females on seven of fourteen sex-dimorphic indices of masculinity/femininity in body build. The transsexuals were more masculine in body shape, primarily in bone proportion and fat distribution. Levels of testosterone and androstenedione were significantly higher in the female-to-males than in the control females. Unbound testosterone was also higher in female-to-males than in control females, and correlated positively with masculine body configuration.

White has theorized that "neuronal pruning" may be the process responsible for normal gender identity development as well as transsexualism--a common filial pathway encompassing varying degrees of nature and nurture. It is assumed that gender identity is a process that begins in-utero and is consolidated by three years of age. White suggests that the fetal brain is primed for gender identity development by an anatomic "sculpting" of location. This location is impacted by an active pruning of neurons during the third trimester of fetal life. The mechanisms involved in gender identity consolidation may fol­low patterns similar to those of other developmental processes, such as language acquisition:  

The neural proliferation within the neural tube undergoes a caudal migration ending between weeks 18 to 24. Over half of the neurons and glial cells generated undergo an active pruning process--a programmed cell death known as apoptosis. Genes become activated to prune specific brain cells and once pruned they cannot regenerate. Acti­vation of these cellular "suicide" genes involves genetic, hormonal, and immunologic factors, although chance may also play a role.  

It has been shown that the right hemisphere develops approximately ten days before the left. In most individuals, there is an active pruning of the right hemisphere such that when the left hemisphere develops it claims dominance. If this active pruning on the right does not occur; and if this involves the motor strip of the brain, the right hemisphere may attain dominance resulting in a lefthanded individual. If this process involves the language center, the result may be dyslexia. Since testosterone is involved in cell survival, it potentially can effect pruning and thus may account for the increased rates of dyslexia in boys. If this same process involves the area in the brain wherein lies one's sense of gender identity (one promising possibility is the central subdivision of the bed nucleus of the stria terminalis [BSTc] in the hypothalamus noted by Zhou et al., 1995, to be a sexually dimorphic nucleus),'then it could potentially result in a discordant gender identity. In some manner that is poorly understood, within the 'structural components of the brain, within these connections of neurons and synapses, lies one's core sense of gender self. As with any developmental process, the route taken may be quite different than expected. Neurons, too, can take the "road less traveled."

Yet neurons are only one piece of the equation and the potential etiologic factors span from neuronal migration to synaptic pruning, the latter being mainly a postnatal phenomenon. Differentiation of the primary sexual fea­tures occurs during approximately the third month of uterine life. At this stage of development, the neurons are undergoing a rapid proliferation and migration. Testoterone not only serves as the key ingredient propagating primary sexual development in the normal male but may also differentiate brain development through modulation of either the migration or pruning process. Whether via a receptor defect, inadequate hormonal levels, or genetic abnormalities of migration or pruning, the brain region responsible for gender identity may be either predisposed or set to a specific gender identity. In light of the developmental processes at this time, this period is certainly wor­thy of consideration in exploring the etiologic cascade.

If gender identity consolidation relies heavily on nurture, then synaptic pruning within an epigenetic frame­work is an etiologic candidate. Synaptogenesis, or the creation of synapses, begins during the second trimester and is most rapid during the first year of life, although this is somewhat dependent on the region of the brain. As with neurons, the synapses also undergo an active pruning process that correlates with a decline in brain plasticity. Since synaptic activity accounts for approximately fifty percent of this pruning process, it is feasible that certain environmental triggers could augment a discordant gender identity--most probably in the context of an underlying predisposition. Nurture can modulate nature through mechanisms such as immediate-early genes. Whichever pathway, be it migration, neuronal genesis, or pruning and/or synaptogenesis or pruning, gender identity becomes fixed over time with the decrement of brain plasticity. Once crystallized, it becomes as difficult to change as forgetting one's mother tongue. (1997)  

With sophisticated new technologies, such as functional mag­netic resonance imaging and positron emission tomography, brain activity and structure can be envisaged as never before. At present, there is a rapidly mounting assemblage of brain struc­ture research. These studies reveal differences in the structure and function of female and male brains. Zhou, Hofman, Gooren, and Swaab at the Netherlands Institute for Brain Research in Amsterdam broke new ground in announcing, in 1995, that there exists a detectable difference in transsexual brains, as viewed at autopsy.

The specific region under study is the area of the bed nucleus of the stria terminals, BSTc, an area essential for sexual behavior. The autopsied brains revealed that the genetically male transsexuals had a female brain structure, for the volume of the central sulcus of the stria terminalis of the hypothalamus was similar in male-to-female transsexuals and genetic females. Heterosexual and homosexual males displayed a larger volume. This supports the hypothesis that gender identity develops as an interactive affair between the brain and sex hormones.

This research has had an enormous impact. Some European laws have been changed to reflect this new recognition that transsexuals are born, not made, and as such deserve medical care and legal protection. We in the United States have not followed suit, as yet.

An unfortunate surgical accident and its widely reported consequences seemed to buttress this view of gender identity as existing independent of gonadal and anatomical sex. In 1973, researchers at Johns Hopkins University published the case of an infant male twin whose penis was injured, and then ampu­tated. The child was reared as a girl, and the case seemed to offer proof that infants are genderless at birth and that the process of socialization establishes gender identity.

But in 1997, Milton Diamond and H. Keith Sigmundson presented a long term followup of this highly publicized case that sharply contradicted the alleged success of this child's reassignment to a female gender. The patient, who was raised as a girl, knew nothing of the accident that occurred at birth, and though given female hormones, steadfastly maintained a male identity. "Joan" as the infant was named, would tear off her dresses anti reject dolls, and consistently preferred male companions. She rebuked her mother's attempts to have her wear makeup and tried to urinate standing. As she entered puberty and grew breasts, she stopped taking the female hormones because she so disliked the changes that were occurring. At that point she was suicidal. At age 14, still unaware of her past, she refused to continue life as a girl. Her father broke down and revealed the surgical accident, the subsequent removal of the testes, and the creation of the neovagina. This information proved to be a great relief to Joan. For the first time, life made sense. Joan requested male hormones, had mastectomy, and began phalloplasty to try to regain a male anatomy. At 25, "John" married. Even though the reassignment surgeries were only moderately successful, John was happier than ever before.

In a second documented case of a boy similarly reared as a girl after the genitals were damaged during circumcision, the outcome was unlike that described above. In this newly publi­cized case, the reassigned child adapted to a female identity, lives as a woman, and describes herself as bisexual ("Manipulating Gender," 1998). In the first case the reassign­ment took place at twenty-one months, whereas in the second case surgery was performed at seven months. These cases sug­gest that, while gender identity is not solely a result of social­ization, there appears to be a critical period--a window of time after birth--during which gender identity consolidates.