Department of Pharmacology, Institute of Physiology and Pharmacology, Göteborg University, Göteborg, Sweden.

Transsexualism is characterised by lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The cause of transsexualism is unknown, but it has been suggested that an aberration in the early sexual differentiation of various brain structures may be involved. Animal experiments have revealed that the sexual differentiation of the brain is mainly due to an influence of testosterone, acting both via androgen receptors (ARs) and-after aromatase-catalyzed conversion to estradiol-via estrogen receptors (ERs). The present study examined the possible importance of three polymorphisms and their pairwise interactions for the development of male-to-female transsexualism: a CAG repeat sequence in the first exon of the AR gene, a tetra nucleotide repeat polymorphism in intron 4 of the aromatase gene, and a CA repeat polymorphism in intron 5 of the ERβ gene. Subjects were 29 Caucasian male-to-female transsexuals and 229 healthy male controls. Transsexuals differed from controls with respect to the mean length of the ERβ repeat polymorphism, but not with respect to the length of the other two studied polymorphisms. However, binary logistic regression analysis revealed significant partial effects for all three polymorphisms, as well as for the interaction between the AR and aromatase gene polymorphisms, on the risk of developing transsexualism. Given the small number of transsexuals in the study, the results should be interpreted with the utmost caution. Further study of the putative role of these and other sex steroid-related genes for the development of transsexualism may, however, be worthwhile.

Keywords:
Aromatase; Androgen receptor; Estrogen receptor beta; Gender identity disorder; Polymorphisms; Sexual differentiation; Transsexualism

Done is done—and gone is gone
sex change presently the best remedy for transsexuals

Sweden was the first country to legislate on sex reassignment procedures in 1972. Patients with gender dysphoria are in Sweden referred to one of six university clinics specialised in the field; all surgery, however, is centralised to the Karolinska Hospital in Stockholm. The aetiological strivings regarding transsexualism have to date been inconclusive; however, several lines of evidence speak in favour of an early biological influence on gender identity. The vast majority of studies addressing outcome have provided convincing evidence for the benefit of sex reassignment surgery in carefully selected cases. The current article summarises the state of the art regarding work-up and treatment of transsexuals.

Transsexualism is characterized by a lifelong discomfort with the assigned sex and a strong identification with the opposite sex. The etiology of transsexualism is unknown, but several authors have suggested that it is related to an aberration in the early sexual differentiation of various brain structures. Animal experiments have shown that this sexual differentiation of the brain is mainly due to an influence of testosterone, acting via androgen receptors (ARs) but also, after aromatase-catalyzed conversion to estradiol, via estrogen receptors (ERs). The aim of the present study was to examine the possible importance of three different sex steroid-related genes for the susceptibility of male-to-female transsexualism. The polymorphisms investigated were 1) a tetra nucleotide polymorphism in intron 4 of the aromatase gene, 2) a CAG repeat sequence in the first exon of the AR gene, and 3) a CA repeat polymorphism of the ER beta gene. Subjects were 28 genetically male transsexuals and 30 healthy male controls. Transsexuals more often had a long variant of the tetra nucleotide repeat polymorphism of the aromatase gene (187 bp) and less often a shorter variant (171 bp) than did controls. The lengths of the CAG repeat sequence of the AR gene did not differ between transsexuals and controls; however, transsexuals with a short variant of the aromatase gene had a long variant of the AR gene significantly more often than did controls with a short variant of the aromatase gene. The longest variants of the ER beta gene polymorphism were more frequent in Transsexuals than in controls, particularly in those with a long variant of the AR gene polymorphism. The results indicate that a long variant of the aromatase gene, a long variant of the AR gene, and a long variant of the ER beta gene are three independent risk factors for the development of transsexualism.

Departments of Clinical Neuroscience amd Pharmacology, Göteborg University, and Sahlgrenska University Hospital/Möndahl, SE-431 80 Mölndahl, Sweden.

A girl with high functioning autism who developed transsexualism is described. The literature to date has, to the authors‘ knowledge, not documented any similar case. The diagnosis of a coexisting psychiatric disorder in transsexualism has implications for the evaluation, prognosis, and appropriate management of the patient. The question of a possible relationship between autism and transsexualism and whether there is a predisposition to gender dysphoria in autism, is discussed.