The Effects of Testosterone on the Brain of Transgender Men

Abstract

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.

Keywords: MRI; androgenic anabolic steroids; astrocytes; glutamine; testosterone; transgender men.

FIG. 1.

Experimental design of a longitudinal study to androgenize adult female rats. Animals were weekly injected with testosterone or vehicle. Every 15 days, blood from the tail was collected for immunoassay and MRI was acquired. At the end of the experiment, animals were euthanized and brain was dissected to obtain the metabolic spectrum. DTI, diffusion tensor imaging; MRI, magnetic resonance imaging; NMR, nuclear magnetic resonance; RIA, radioimmunoassay.

FIG. 2.

Effects of testosterone on the cortical volume (A) and fractional anisotropy (B) in adult androgenized female rats. Androgenized rats showed a sharper decrease in cortical volume while maintaining fractional anisotropy values against/despite aging effect seen in control animals. Data from Perez-Laso et al. *p < 0.05; **p < 0.01. FA, fractional anisotropy.

FIG. 3.

Suggested mechanism to explain cortical volume decrease in subjects under supraphysiological doses of testosterone. Increased protein synthesis attracts water into the astrocytes. In turn, to maintain the osmotic equilibrium, astrocytes efflux water to the extracellular space by means of osmolytes such as mI and Gln whose relative content decreases. Decreases in the Gln concentration might affect the Gln–Glu cycle. Gln, glutamine; Glu, glutamate; GluRs, glutamate receptors; mI, myo-Inositol.