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Cerebral Cortex Advance Access originally published online on December 3, 2007
Cerebral Cortex 2008 18(8):1900-1908; doi:10.1093/cercor/bhm216
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© The Author 2007. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

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

H. Berglund1, P. Lindström2, C. Dhejne-Helmy3 and I. Savic2

1 Department of Medicine, 2 Division of Neurology, Department of Clinical Neuroscience, Stockholm Brain Institute, 3 Department of Psychiatry, Karolinska University Hospital, Karolinska Institute, 171 76 Stockholm, Sweden

Address correspondence to Ivanka Savic, Department of Clinical Neuroscience, Stockholm Brain Institute, Karolinska University Hospital, Karolinska Institute, MR centre, M8, 171 76 Stockholm, Sweden. Email: ivanka.savic-berglund{at}ki.se.

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.

Key Words: hypothalamus • odor • PET • pheromones • transsexuality


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