Gender-affirming hormone treatment – A unique approach to study the effects of sex hormones on brain structure and function

Kranz, Georg S.; Zhang, Bella B.B.; Handschuh, Patricia; Ritter, Vera; Lanzenberger, Rupert

doi:10.1016/j.cortex.2020.04.005

Cited by 27 publications

(26 citation statements)

References 79 publications

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“…In different studies, increased GMV in this region was found both for TW who had not started GAHT [9] and for TW who were already receiving GAHT (including the present study) [34]. Another aspect that further complicates the issue of GAHT influences in neuroanatomical studies of GI was reported by Kranz and colleagues [37]. In their review, the authors pointed out that the different hormones given to TM and TW might have opposite effects on GMV.…”

Section: Discussionsupporting

confidence: 57%

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals

Clemens

Votinov

Puiu

et al. 2021

JCM

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The brain structural changes related to gender incongruence (GI) are still poorly understood. Previous studies comparing gray matter volumes (GMV) between cisgender and transgender individuals with GI revealed conflicting results. Leveraging a comprehensive sample of transmen (n = 33), transwomen (n = 33), cismen (n = 24), and ciswomen (n = 25), we employ a region-of-interest (ROI) approach to examine the most frequently reported brain regions showing GMV differences between trans- and cisgender individuals. The primary aim is to replicate previous findings and identify anatomical regions which differ between transgender individuals with GI and cisgender individuals. On the basis of a comprehensive literature search, we selected a set of ROIs (thalamus, putamen, cerebellum, angular gyrus, precentral gyrus) for which differences between cis- and transgender groups have been previously observed. The putamen was the only region showing significant GMV differences between cis- and transgender, across previous studies and the present study. We observed increased GMV in the putamen for transwomen compared to both transmen and ciswomen and for all transgender participants compared to all cisgender participants. Such a pattern of neuroanatomical differences corroborates the large majority of previous studies. This potential replication of previous findings and the known involvement of the putamen in cognitive processes related to body representations and the creation of the own body image indicate the relevance of this region for GI and its potential as a structural biomarker for GI.

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Section: Discussionsupporting

confidence: 57%

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals

Clemens

Votinov

Puiu

et al. 2021

JCM

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“…What can we learn from the animal model with respect to TM and AAS consumers? The structural brain MRI data we know come from TM during short-medium administration (around a year or less), 31 , 72 whereas data from AAS consumers are from long-term consumption. 73 , 74 Over 1-year's consumption of AASs by weightlifters is associated with a thinner cortex and smaller volumes of total gray matter, cerebral cortex, and putamen, 74 but right amygdala enlargement and higher Gln/Glu ratio have also been reported.…”

Section: Discussionmentioning

confidence: 99%

The Effects of Testosterone on the Brain of Transgender Men

Zubiaurre‐Elorza

Cerdán

Uribe

et al. 2021

Androgens: Clinical Research and Therapeutics

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Transgender men (TM) experience an incongruence between the female sex assigned when they were born and their self-perceived male identity. Some TM seek for a gender affirming hormone treatment (GAHT) to induce a somatic transition from female to male through continuous administration of testosterone. GAHT seems to be relatively safe. However, testosterone produces structural changes in the brain as detected by quantitative magnetic resonance imaging. Mainly, it induces an increase in cortical volume and thickness and subcortical structural volume probably due to the anabolic effects. Animal models, specifically developed to test the anabolic hypothesis, suggest that testosterone and estradiol, its aromatized metabolite, participate in the control of astrocyte water trafficking, thereby controlling brain volume.

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“…An ROI-based quantification (described in (Spurny, 2019)) was applied for the analysis of GABA+ (a combination of GABA and macromolecules) and Glx (glutamate+glutamine) ratios to total creatine (GABA+/tCr and Glx/tCr) in the hippocampus, insula, putamen, pallidum and thalamus. ROI selection was based on previous studies showing structural adaptions after GHT in trans cohorts (Spizzirri, 2018; Kranz, 2020). In short, FreeSurfer was used for automated segmentation of structural images and mask extraction, spectral maps of GABA+, Glx and tCr were interpolated to the resolution of structural images (288×288×208), overlaid with the derived masks and mean GABA+/tCr and Glx/tCr ratios calculated within each ROI.…”

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. 2021

Preprint

Self Cite

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Sex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals. Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, and 15 age-matched cisgender women (CW) underwent MRSI before and after at least 12 weeks of GHT. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (a combination of GABA and macromolecules) and Glx (a combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus). Linear mixed models analysis revealed a significant measurement by gender identity effect (pcorr. = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (pcorr. = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men. Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies.

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Gender-affirming hormone treatment – A unique approach to study the effects of sex hormones on brain structure and function

Cited by 27 publications

References 79 publications

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals

Replication of Previous Findings? Comparing Gray Matter Volumes in Transgender Individuals with Gender Incongruence and Cisgender Individuals

The Effects of Testosterone on the Brain of Transgender Men

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

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