Male-to-Female Transsexuals Show Sex-Atypical Hypothalamus Activation When Smelling Odorous Steroids

Abstract

One working hypothesis behind transsexuality is that the normal sex differentiation of certain hypothalamic networks is altered. We tested this hypothesis by investigating the pattern of cerebral activation in 12 nonhomosexual male-to-female transsexuals (MFTRs) when smelling 4,16-androstadien-3-one (AND) and estra-1,3,5(10),16-tetraen-3-ol (EST). These steroids are reported to activate the hypothalamic networks in a sex-differentiated way. Like in female controls the hypothalamus in MFTRs activated with AND, whereas smelling of EST engaged the amygdala and piriform cortex. Male controls, on the other hand, activated the hypothalamus with EST. However, when restricting the volume of interest to the hypothalamus activation was detected in MFTR also with EST, and explorative conjunctional analysis revealed that MFTR shared a hypothalamic cluster with women when smelling AND, and with men when smelling EST. Because the EST effect was limited, MFTR differed significantly only from male controls, and only for EST-AIR and EST-AND. These data suggest a pattern of activation away from the biological sex, occupying an intermediate position with predominantly female-like features. Because our MFTRs were nonhomosexual, the results are unlikely to be an effect of sexual practice. Instead, the data implicate that transsexuality may be associated with sex-atypical physiological responses in specific hypothalamic circuits, possibly as a consequence of a variant neuronal differentiation.

Roles of sex and gonadal steroids in mammalian pheromonal communication

“…Lesbian women failed to show hypothalamic PET responses to AND (Berglund et al, 2006), and in this respect resembled heterosexual men. In another study (Berglund et al, 2008) 46 XY male to female transsexuals, who were all gynaphilic (heterosexual), showed a significant hypothalamic PET response to AND that resembled the response seen in heterosexual women. Finally, (Ciumas et al, 2009) significant AND-induced PET activation in the hypothalamus was seen in women with congenital adrenal hyperplasia and in whom fetal testosterone signaling was very likely higher than in the normal control women.…”

Intrinsic Cerebral Connectivity Analysis in an Untreated Female-to-Male Transsexual Subject: A First Attempt Using Resting-State fMRI

“…Feminization (in MtF) and masculinization (in FtM) are well-known processes that could involve both cognitive, neurobiological and psychological profile of transsexual subjects [13,14]. Nevertheless, there is a larger body of research focusing on MtF subjects than FtM, with a large number of studies founding no specific effect for FtM condition in behavioral and neuroimaging investigations [6].…”

Neuroimaging studies in people with gender incongruence

“…A sex difference in the hypothalamic response is already apparent in prepubertal children (Burke et al, 2014). Gynephilic MtF adults show similarities with control women in hypothalamic activation while smelling odorous steroids (Berglund et al, 2008). Adolescents with gender incongruence showed a response to androstadienone that was similar to their experienced gender (Burke et al, 2014).…”