Androgens Modulate Brain Networks of Empathy in Female-to-Male Transsexuals: An fMRI Study

Women show higher sensitivity than men to emotional and social cues and are therefore better in showing empathy with others and in deciphering other's intentions and mental states. These sex differences have been linked to hormonal levels. However, it remains unclear how hormones modulate neural mechanisms underlying empathic processes. To assess effects of chronic hormonal treatment, functional magnetic resonance imaging was used in a group of female-to-male transsexuals before and during androgen therapy and a group of female and male controls while they watched pictures portraying emotionally negative or neutral situations (emotional content) involving one or two persons (social relation). Before therapy, the medial superior frontal gyrus and left inferior frontal gyrus showed greater activations for emotional than neutral stimuli. The posterior superior temporal sulcus showed greater activations for emotional vs. neutral stimuli and for social relations relative to pictures of single persons. Long-term androgen administration reduced the pSTS activity in response to emotional stimuli as well as its response to social relation. More importantly, the functional connectivity among frontal, temporal and striatal regions was weakened while the connectivity among limbic regions was strengthened as the androgen level increased during hormone therapy. This pattern of change was similar to the sex difference observed between female vs. male controls. Thus, making a brain more male by the application of androgens not only reduced the activity of a core neural hub but also markedly altered the organization of the brain network supporting emotional and social cognitive processes related to empathy and mentalizing.