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Reproductive Endocrinology

MON-187 - Testosterone Gender-Affirming Hormone Therapy and Its Effect on Grey Matter Volumes and Cerebral Blood Flow

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Evolene Bon de Sousa Pernes: No financial relationships to disclose
Gender-affirming hormone therapy (GAHT) has seen an important rise throughout the last decade, most notably amongst transgender teenagers. Transmasculine youth receive testosterone hormone therapy to support gender congruence. While the neurovascular effects of estrogen have received growing research attention, the impact of exogenous testosterone on the developing brain remains largely unexplored.
Therefore, this study’s objective is to determine the effects exogenous testosterone has on grey matter volume (GMV) and cerebral blood flow (CBF) via non-invasive cerebral magnetic resonance imaging (MRI).
For this longitudinal pilot study, eight adolescent transmen were recruited through their pediatric endocrinology clinic and underwent two MRI scans: one before starting testosterone GAHT and one 3-9 months after, when the target dose had been reached. Cortical thickness and GMV were estimated from T1 weighted MRI using FastSurfer, and ExploreASL was used to estimate CBF from arterial spin labeling. Blood draws were done to measure concentrations of serum total testosterone and estradiol. GMV and CBF were compared for each session in a repeated measures study design, with a mean follow-up time of 8 months between sessions.
Cortical GMV decreased by 1.7% (SE = 1.23, p = 0.007) while cortical CBF decreased by 16.7% (SE = 11.98, p = 0.010). No significant differences were observed in subcortical GMV (p = 0.559) and subcortical CBF (p = 0.070), nor was the relationship between change in cortical GMV and cortical CBF (R-squared = 0.49, p = 0.093). Together, these results suggest that grey matter changes are relatively small in testosterone GAHT, compared to changes observed in CBF, potentially indicating a neurovascular uncoupling.
These preliminary results suggest that testosterone GAHT seems to have a minor impact on MRI biomarkers of neuronal health despite its relatively strong impact on the cerebrovascular system during the first eight months of testosterone GAHT. These findings, although preliminary, highlight the importance of further deepening our knowledge of testosterone-GAHT and its potential effects on the cerebrovascular system.

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