TY - JOUR
T1 - High-dose testosterone treatment reduces monoamine oxidase A levels in the human brain
T2 - A preliminary report
AU - Kranz, Georg S.
AU - Spies, Marie
AU - Vraka, Chrysoula
AU - Kaufmann, Ulrike
AU - Klebermass, Eva Maria
AU - Handschuh, Patricia A.
AU - Ozenil, Marius
AU - Murgaš, Matej
AU - Pichler, Verena
AU - Rischka, Lucas
AU - Nics, Lukas
AU - Konadu, Melisande E.
AU - Ibeschitz, Harald
AU - Traub-Weidinger, Tatjana
AU - Wadsak, Wolfgang
AU - Hahn, Andreas
AU - Hacker, Marcus
AU - Lanzenberger, Rupert
N1 - Funding Information:
Without any relevance to this work, R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. Without relevance to this work, W. Wadsak received within the last three years research grants from ITM Medical Isotopes GmbH (Munich, Germany) and Scintomics (Fürstenfeldbruck, Germany). He is a part-time employee of CBmed GmbH (Graz, Austria) and a co-founder of MINUTE medical GmbH (Vienna, Austria). G.S. Kranz received travel grants from Roche, AOP Orphan Pharmaceuticals and Pfizer. M. Spies received travel grants from Janssen and AOP Orphan Pharmaceuticals, speaker honoraria from Janssen and Austroplant, and workshop participation from Eli Lilly. All other authors report no potential conflict of interest regarding this publication.
Funding Information:
This study was supported by a grant from the Austrian Science Fund to R. Lanzenberger (FWF grant number K LI 50 4 ). M. Murgas is funded by the Austrian Science Fund (FWF), D OC 33-B2 7 . L. Rischka was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy, Medical University of Vienna.
Funding Information:
This study was supported by a grant from the Austrian Science Fund to R. Lanzenberger (FWF grant number KLI 504). M. Murgas is funded by the Austrian Science Fund (FWF), DOC 33-B27. L. Rischka was a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy, Medical University of Vienna. The authors are grateful to S. Kasper, K. Papageorgiou, A. Komorowski, T. Vanicek, A. Kautzky, G. Gryglewski, M. Hienert, J. Jungwirth, J. Unterholzner, M. Godbersen, P. Michenthaler, A. Basaran for medical support, and G. James, S. Ganger, M. Kl?bl, B. Spurny, R. Seiger, H. Sigurdardottir, B. Zhang for technical support, and E. Sittenberger, V. Ritter and the diploma students of the Neuroimaging Labs for subject recruitment and administrative support. We thank N. Berroteran-Infante and N. Schindler for support in radiosyntheses and the PET team for the measurements. The authors are especially grateful to all study subjects for participating. The scientific project was performed with the support of the Medical Imaging Cluster of the Medical University of Vienna., Without any relevance to this work, R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR, Heel, and support from Siemens Healthcare regarding clinical research using PET/MR. He is a shareholder of the start-up company BM Health GmbH since 2019. Without relevance to this work, W. Wadsak received within the last three years research grants from ITM Medical Isotopes GmbH (Munich, Germany) and Scintomics (F?rstenfeldbruck, Germany). He is a part-time employee of CBmed GmbH (Graz, Austria) and a co-founder of MINUTE medical GmbH (Vienna, Austria). G.S. Kranz received travel grants from Roche, AOP Orphan Pharmaceuticals and Pfizer. M. Spies received travel grants from Janssen and AOP Orphan Pharmaceuticals, speaker honoraria from Janssen and Austroplant, and workshop participation from Eli Lilly. All other authors report no potential conflict of interest regarding this publication.
Publisher Copyright:
© 2021 The Authors
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Estradiol
KW - Gender dysphoria
KW - Gender-affirming hormone treatment
KW - Monoamine oxidase A
KW - Positron emission tomography
KW - Testosterone
KW - Transgender
UR - https://www.scopus.com/pages/publications/85112491439
U2 - 10.1016/j.psyneuen.2021.105381
DO - 10.1016/j.psyneuen.2021.105381
M3 - Journal article
AN - SCOPUS:85112491439
SN - 0306-4530
VL - 133
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
M1 - 105381
ER -
SDG 3 Good Health and Well-being