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Title: High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain : a preliminary report
Authors: Kranz, GS 
Spies, M
Vraka, C
Kaufmann, U
Klebermass, EM
Handschuh, PA
Ozenil, M
Murgaš, M
Pichler, V
Rischka, L
Nics, L
Konadu, ME
Ibeschitz, H
Traub-Weidinger, T
Wadsak, W
Hahn, A
Hacker, M
Lanzenberger, R
Issue Date: Sep-2021
Source: Psychoneuroendocrinology, Nov. 2021, v. 133, 105381
Abstract: 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.
Keywords: Estradiol
Gender dysphoria
Gender-affirming hormone treatment
Monoamine oxidase A
Positron emission tomography
Testosterone
Transgender
Publisher: Pergamon
Journal: Psychoneuroendocrinology 
ISSN: 0306-4530
EISSN: 1873-3360
DOI: 10.1016/j.psyneuen.2021.105381
Rights: © 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
The following publication Kranz, G. S., Spies, M., Vraka, C., Kaufmann, U., Klebermass, E. M., Handschuh, P. A., ... & Lanzenberger, R. (2021). High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain: A preliminary report. Psychoneuroendocrinology, 133, 105381 is available at https://doi.org/10.1016/j.psyneuen.2021.105381
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