TY - JOUR
T1 - Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort
AU - Spurny-Dworak, Benjamin
AU - Handschuh, Patricia
AU - Spies, Marie
AU - Kaufmann, Ulrike
AU - Seiger, Rene
AU - Klobl, Manfred
AU - Konadu, Melisande
AU - Reed, Murray
AU - Ritter, Vera
AU - Baldinger-Melich, Pia
AU - Bogner, Wolfgang
AU - Kranz, Georg
AU - Lanzenberger, Rupert
N1 - Funding Information:
This research was funded or in part by the Austrian Science Fund (FWF) [KLI 504 and KLI 516 PI: R. Lanzenberger], Brain and Behavior Research Foundation (formerly NARSAD) Young Investigator grants (23741, PI: M. Spies) and grant number P 30701 to W. Bogner, the Medical Imaging Cluster of the Medical University of Vienna, and by the grant „Interdisciplinary translational brain research cluster (ITHC) with highfield MR" from the Federal Ministry of Science, Research and Economy (BMWFW), Austria. M. Klöbl and M.B. Reed are recipients of a DOC Fellowship of the Austrian Academy of Sciences.
Funding Information:
This research was funded or in part by the Austrian Science Fund (FWF) [ KLI 504 and KLI 516 PI: R. Lanzenberger], Brain and Behavior Research Foundation (formerly NARSAD) Young Investigator grants ( 23741 , PI: M. Spies) and grant number P 30701 to W. Bogner, the Medical Imaging Cluster of the Medical University of Vienna, and by the grant „Interdisciplinary translational brain research cluster (ITHC) with highfield MR" from the Federal Ministry of Science, Research and Economy (BMWFW), Austria. M. Klöbl and M.B. Reed are recipients of a DOC Fellowship of the Austrian Academy of Sciences.
Publisher Copyright:
© 2022
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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, undergoing GHT, and 15 age-matched cisgender women (CW), receiving no therapy, underwent MRSI before and after at least 12 weeks. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (combination of GABA and macromolecules) and Glx (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. Data availability statement: Due to data protection laws processed data is available from the authors upon reasonable request. Please contact [email protected] with any questions or requests.
AB - 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, undergoing GHT, and 15 age-matched cisgender women (CW), receiving no therapy, underwent MRSI before and after at least 12 weeks. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (combination of GABA and macromolecules) and Glx (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. Data availability statement: Due to data protection laws processed data is available from the authors upon reasonable request. Please contact [email protected] with any questions or requests.
KW - GABA
KW - Gender-affirming hormone treatment
KW - Glutamate
KW - MRS
KW - Transgender
UR - http://www.scopus.com/inward/record.url?scp=85124470295&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2022.105683
DO - 10.1016/j.psyneuen.2022.105683
M3 - Journal article
SN - 0306-4530
VL - 138
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
M1 - 105683
ER -
