Effects of gender-affirming hormone therapy on gray matter density, microstructure and monoamine oxidase A levels in transgender subjects

Abstract

AbstractAlterations in gray matter (GM) and monoamine oxidase A (MAO-A) distribution across the brain have been found in various neuropsychiatric conditions. MAO-A catalyzes the oxidative degradation of various monoamines and is thus implicated in neuroplastic processes that influence GM density (GMD) and microstructure (GMM) of the brain. Sex-specific differences in these patterns are well documented, however studying the long-term effects of certain sex steroids on the brain are limited due to hormonal fluctuations under naturalistic conditions. Due to the exact monitoring of plasma hormone levels and sex steroid intake, transgender individuals undergoing gender-affirming hormone therapy represent a valuable cohort to investigate such changes of GM and concomitant MAO-A density. Here, we investigated the effects of long-term gender-affirming hormone therapy over a median time period of 4.5 months on GMD and GMM as well as MAO-A distribution volume. To this end, 20 cisgender women, 11 cisgender men, 20 transgender women and 10 transgender men were recruited. All participants underwent two MRI scans in a longitudinal design. PET scans using [11C]harmine were performed before each MRI session in a subset of 35 individuals. Between baseline and follow-up imaging, transgender subjects underwent gender-affirming hormone therapy. GM changes determined by diffusion weighted imaging (DWI) metrics for GMM and voxel based morphometry (VBM) for GMD were estimated using repeated measures ANOVA. Regions showing significant changes of both GMM and GMD were used for the subsequent analysis of MAO-A density. These involved the fusiform gyrus, rolandic operculum, inferior occipital cortex, middle and anterior cingulum, bilateral insula, cerebellum and the lingual gyrus (post-hoc tests: pFWE+Bonferroni < 0.025). In terms of MAO-A distribution volume, no significant effects were found. The present results are indicative of a reliable influence of gender-affirming hormone therapy on GMD and GMM following an interregional pattern. Nevertheless, future studies with larger sample sizes are needed to further investigate the relationship between sex steroids, gray matter alterations and MAO-A density.