XVI Harry Benjamin International Gender Dysphoria Association Symposium
17 - 21 August 1999, London

Reflections on "Transsexualism and Sex Reassignment" 1969 -1999

Gender Transpositions: The Brain Has Not Followed Other Markers of Sexual Differentiation?

Gooren, Louis J.G. Endocrinology, Free University Hospital, Amsterdam, the Netherlands

Traditionally gender transpositions have been conceptualized as purely psychological phenomena, and indeed there is no evidence that gender transpositions can be explained by variations in chromosomal patterns, or by gonadal, genital or hormonal anomalies. Very recent research on brains of male-to-female transsexuals demonstrated that one of the brain nuclei that is sex-dimorphic in the human, the bed nucleus of the stria terminalis, shows all characteristics of female differentiation. This finding may lead to a concept of gender transpositions as a state of being, wherein the sexual differentiation of the brain (which in mammals also undergoes sexual differentiation) is not consistent with the other variables of sex, such as chromosomal pattern, nature of the gonad and nature of internal/external gonads.

The brain undergoes a sexual differentiation process. In other words: sexual differentiation is not completed with the differentiation of the external genitalia into either male or female. The sexual differentiation of the brain can be demonstrated neuroanatomically or in psychological function tests. In lower mammals it expresses itself in sex-dimorphic sexual behavior but also in sex-dimorphic non-sexual behaviors (such as aggression, defense of territory, and caring for the young). This process has been termed the organization, the "wiring" of the brain, to prepare it for future sexual/reproductive and non-sexual behavior in agreement with the gonadal/genital status. Following exposure of the brain to androgens, male and female rat brains differ in their neuroanatomical structure. Sex differences in size and shape of certain nuclei in the hypothalamus have been described in the human. One of the sex-dimorphic nuclei becomes differentiated not earlier than between the ages of two to four. The time of differentiation is not known for other sex dimorphic nuclei. Nor is the mechanism subserving sexual differentiation of the human brain known, whether it is hormonally (co)determined or not. From clinical observations in patients with an intersex condition or cross-sex hormone exposure during pregnancy, the a priori evidence for solely hormonal determination is not strong. Postnatal rearing is in all likelihood a significant factor in the development of gender identity/role; this is no longer irreconcilable with the existence of a biological substrate of gender identity since one’s life history is a factor in shaping brain anatomy/function. If it becomes accepted that humans also undergo a differentiation of the brain as an integral part of the process of becoming man or woman, gender transpositions could be conceptualized as a state wherein sexual differentiation of the brain has not followed the course set by the chromosomes, the gonad and the genitalia, but has crossed over to the course of development of the other sex.

This finding of a biological index of a female brain differentiation of male-to-female transsexuals could be a conceptual turning point in the approach of gender transpositions.