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

• Published in: Psychoneuroendocrinology Vol. 133; p. 105381
• Main Authors: Kranz, Georg S., Spies, Marie, Vraka, Chrysoula, Kaufmann, Ulrike, Klebermass, Eva-Maria, Handschuh, Patricia A., Ozenil, Marius, Murgaš, Matej, Pichler, Verena, Rischka, Lucas, Nics, Lukas, Konadu, Melisande E., Ibeschitz, Harald, Traub-Weidinger, Tatjana, Wadsak, Wolfgang, Hahn, Andreas, Hacker, Marcus, Lanzenberger, Rupert
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2021
• Subjects: Brain - diagnostic imaging; Brain - metabolism; Dose-Response Relationship, Drug; Estradiol; Female; Gender dysphoria; Gender-affirming hormone treatment; Humans; Male; Monoamine Oxidase - drug effects; Monoamine Oxidase - metabolism; Monoamine oxidase A; Positron emission tomography; Testosterone; Testosterone - administration & dosage; Testosterone - pharmacology; Testosterone; Monoamine oxidase A; Gender-affirming hormone treatment; Transgender; Estradiol; Gender dysphoria; Positron emission tomography
• ISSN: 0306-4530; 1873-3360; 1873-3360
• DOI: 10.1016/j.psyneuen.2021.105381

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 (VT) 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 VT 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 VT did not change in TW receiving estrogen treatment. Despite the limited sample size, pronounced MAO-A VT 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 VT should be further investigated as a possible mechanism by which testosterone mediates risk for, symptomatology of, and treatment response in affective disorders. •Gender-affirming hormone treatment (GHT) allows assessment of high-dose cross-sex hormone effects.•Here we assess effects of GHT on brain MAO-A, previously shown as increased in depression.•MAO-A was downregulated under testosterone treatment in female to male individuals.•Observed effects are a human in vivo confirmation of previous animal data.•Future studies should explore MAO-A as a potential correlate for testosterone’s antidepressant properties.