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

Kranz, Georg S.; Spies, Marie; Vraka, Chrysoula; Kaufmann, Ulrike; Klebermass, Eva‐Maria; Handschuh, Patricia; 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

doi:10.1016/j.psyneuen.2021.105381

Cited by 15 publications

(9 citation statements)

References 53 publications

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“…NCT02715232). Transgender individuals as well as age-matched cis controls were assessed before and after at least 12 weeks into GHT, see (Kranz, 2021). The current study focusses on the assessment of MRS data.…”

Section: Methodsmentioning

confidence: 99%

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Spurny-Dworak

Handschuh

Spies

et al. 2022

Psychoneuroendocrinology

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Section: Methodsmentioning

confidence: 99%

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Spurny-Dworak

Handschuh

Spies

et al. 2022

Psychoneuroendocrinology

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“…On the other hand, sevoflurane anesthesia, which is not a direct inhibitor of MAO, decreased deuterated L-[ 11 C]deprenyl uptake in non-human primate brain by 80%, which is certainly consistent with some novel regulation of MAO-B availability (Varnäs, 2021). Hormones may also play a role here; testosterone treatment for gender dysphoria slightly decreased (−10%) the [ 11 C]harmine binding in human brain (Kranz, 2021).…”

Section: Pet Imaging Of Mao In Vivomentioning

confidence: 56%

Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca

2022

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The monoamine oxidases (MAOs) are flavin-containing amine oxidoreductases responsible for metabolism of many biogenic amine molecules in the brain and peripheral tissues. Whereas serotonin is the preferred substrate of MAO-A, phenylethylamine is metabolized by MAO-B, and dopamine and tyramine are nearly ambivalent with respect to the two isozymes. β-Carboline alkaloids such as harmine, harman(e), and norharman(e) are MAO inhibitors present in many plant materials, including foodstuffs, medicinal plants, and intoxicants, notably in tobacco (Nicotiana spp.) and in Banisteriopsis caapi, a vine used in the Amazonian ayahuasca brew. The β-carbolines present in B. caapi may have effects on neurogenesis and intrinsic antidepressant properties, in addition to potentiating the bioavailability of the hallucinogen N,N-dimethyltryptamine (DMT), which is often present in admixture plants of ayahuasca such as Psychotria viridis. Tobacco also contains physiologically relevant concentrations of β-carbolines, which potentially contribute to its psychopharmacology. However, in both cases, the threshold of MAO inhibition sufficient to interact with biogenic amine neurotransmission remains to be established. An important class of antidepressant medications provoke a complete and irreversible inhibition of MAO-A/B, and such complete inhibition is almost unattainable with reversible and competitive inhibitors such as β-carbolines. However, the preclinical and clinical observations with synthetic MAO inhibitors present a background for obtaining a better understanding of the polypharmacologies of tobacco and ayahuasca. Furthermore, MAO inhibitors of diverse structures are present in a wide variety of medicinal plants, but their pharmacological relevance in many instances remains to be established.

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“…In contrast, in a prior analysis of MAO-A density after GHT performed by our group, we found statistically significant reductions of MAO-A V T in six of twelve previously defined regions of interest in TM after GHT for at least 4 months. These regions included the 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)) (33). Of note, in the study by Kranz et al regional MAOA V T was estimated based on a priori defined regions-of-interest (ROIs) from a modified AAL atlas (33, 82), whereas here, MAO-A analysis was performed in regions that showed significant GMD and GMM changes after GHT.…”

Section: Discussionmentioning

confidence: 99%

“…These regions included the 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)) (33). Of note, in the study by Kranz et al regional MAOA V T was estimated based on a priori defined regions-of-interest (ROIs) from a modified AAL atlas (33, 82), whereas here, MAO-A analysis was performed in regions that showed significant GMD and GMM changes after GHT.…”

Section: Discussionmentioning

confidence: 99%

Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects

Handschuh

Reed

Murgaš

et al. 2022

Preprint

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Alterations in gray matter (GM) and monoamine oxidase A (MAO-A) distribution across the brain have been found in various neuropsychiatric conditions. MAO-A catalyzes the oxidative degradation of various monoamines and is thus implicated in neuroplastic processes that influence GM density (GMD) and microstructure (GMM) of the brain. Sex-specific differences in these patterns are well documented, however studying the long-term effects of certain sex steroids on the brain are limited due to hormonal fluctuations under naturalistic conditions. Due to the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy represent a valuable cohort to investigate such changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term gender-affirming hormone therapy over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men were recruited. All participants underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. Between baseline and follow-up imaging, transgender subjects underwent gender-affirming hormone therapy. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. The present results are indicative of a reliable influence of gender-affirming hormone therapy on GMD and GMM following an interregional pattern. Nevertheless, future studies with larger sample sizes are needed to further investigate the relationship between sex steroids, gray matter alterations and MAO-A density.

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

Cited by 15 publications

References 53 publications

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Monoamine Oxidase Inhibition by Plant-Derived β-Carbolines; Implications for the Psychopharmacology of Tobacco and Ayahuasca

Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects

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