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New Study: Cross Sex Hormones Lower Neurotransmitter Level in Hippocampus

In a study titled “Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort”, researchers out of the Department of Psychiatry and Psychotherapy at the Medical University of Vienna, Austria report cross-sex hormones lower neurotransmitter levels in the hippocampus of transgender men.

The researchers collected data on 15 transgender men with a DSM-5 diagnosis of gender dysphoria and compared their hippocampal neurotransmitter levels with that of 15 women. In their publication, the researchers note their interest of the neurotransmitter in question, GABA (Gamma-aminobutyric acid) “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 …

GABA is the primary inhibitory neurotransmitter in the brain and is associated with leveling anxiety. Low levels of GABA signaling are associated with general anxiety disorder (GAD) and other psychopathologies that are prevalent among the transgender population. “Here we report GABA+/tCr reductions after testosterone treatment for the first time in human TM (transgender male) subjects with GD (gender dysphoria) compared to cisgender women. GD is often accompanied by psychiatric disorders and increased rates in suicidality (Peterson, 2017). Especially major depressive disorder (MDD), characterized by altered neurotransmission and BDNF levels, shows a high prevalence in individuals with GD (Heylens, 2014).” the researchers state in their publication.

The decrease in GABA is linked to the cross-sex hormone administration according to the researchers. “Here, we describe a significant reduction of GABA+/tCr ratios in the hippocampus after gender-affirming hormone therapy in TM (transgender male) individuals compared to a female cisgender cohort.” They note past studies show androgen exposure can impact the structure and function of the hippocampus, though the effect has only been shown in animal studies.

This study is the first of its kind, however, because a link between hippocampal GABA reduction and cross-sex hormone treatment has been detected in humans.

This study is not the only one reporting the negative effects of cross-sex hormones. Though the study looked at the effects of cross-sex hormones on adults, there are many suggesting cross-sex hormones impact adolescents the most. One study found suppressing puberty via gonadotropin-releasing hormone agonists lowers bone mineral density. Another study published in Reproductive Biomedicine Online found exogenous testosterone exposure caused hyperplasia and was associative with polycystic ovarian syndrome.

Other studies and academic reviews report adolescent grow out of their gender dysphoria as well. Last year, a study was published in Frontiers of Psychiatry wherein the authors found 88% of children desisted from their gender dysphoria in a sample size of 139.

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