High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: A preliminary report

The sex hormones testosterone and estradiol influence brain structure and function and are implicated in the pathogenesis, prevalence and disease course of major depression. Recent research employing gender-affirming hormone treatment (GHT) of gender dysphoric individuals and utilizing positron emission tomography (PET) indicates increased serotonin transporter binding upon high-dosages of testosterone treatment. Here, we investigated the effects of GHT on levels of monoamine oxidase A (MAO-A), another key target of antidepressant treatment. Participants underwent PET with the radioligand [¹¹C]harmine to assess cerebral MAO-A distribution volumes (V_T) before and four months after initiation of GHT. By the time this study was terminated for technical reasons, 18 transgender individuals undergoing GHT (11 transmen, TM and 7 transwomen, TW) and 17 cis-gender subjects had been assessed. Preliminary analysis of available data revealed statistically significant MAO-A V_T reductions in TM under testosterone treatment in six of twelve a priori defined regions of interest (middle frontal cortex (-10%), anterior cingulate cortex (-9%), medial cingulate cortex (-10.5%), insula (-8%), amygdala (-9%) and hippocampus (-8.5%, all p<0.05)). MAO-A V_T did not change in TW receiving estrogen treatment. Despite the limited sample size, pronounced MAO-A V_T reduction could be observed, pointing towards a potential effect of testosterone. Considering MAO-A's central role in regulation of serotonergic neurotransmission, changes to MAO-A V_T should be further investigated as a possible mechanism by which testosterone mediates risk for, symptomatology of, and treatment response in affective disorders.