Sex steroid-related genes and male-to-female transsexualism
Journal article, 2005

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.

Estrogen receptor beta



Androgen receptor


Gender identity disorder

Sexual differentiation


Susanne Henningsson

University of Gothenburg

Lars Westberg

University of Gothenburg

Staffan Nilsson

University of Gothenburg

Chalmers, Mathematical Sciences, Mathematical Statistics

Bengt Lundström

University of Gothenburg

Lisa Ekselius

Uppsala University

Owe Bodlund

Umeå University

Eva Lindström

Uppsala University

Monika Hellstrand

University of Gothenburg

Roland Rosmond

University of Gothenburg

Elias Eriksson

University of Gothenburg

Mikael Landén

Karolinska Institutet


0306-4530 (ISSN)

Vol. 30 7 657-664

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