SAT412 Effects Of Gender-Affirming Hormone Therapy On The Connectivity Of Intrinsic Brain Networks
Authors: Pedreira Clarissa C , Tchir-Bourgeois Sophia , Tuli Shubhangi , Giancola Abigail , Loxton Caitlin , Keuroghlian Alex S , Misra Madhusmita , Andreano Joseph M 
Published: October 2023

Disclosure: C.C. Pedreira: None. S. Tchir-Bourgeois: None. S. Tuli: None. A. Giancola: None. C. Loxton: None. A.S. Keuroghlian: None. M. Misra: None. J.M. Andreano: None.

Background: Previous research has indicated that both acute gonadal hormone treatments and fluctuations in ovarian hormone levels over the course of the menstrual cycle can significantly alter patterns of communication between brain regions, particularly regions involved in affective processing. However, the neural effects of prolonged exogenous gonadal hormone exposure, as in gender-affirming hormone therapy (GAHT), are not presently well-understood. A better understanding of the influence of GAHT on intrinsic network connectivity could point the way towards improved GAHT treatment regimens that minimize affective side effects.Objective: To characterize the effects of estradiol and testosterone treatments in GAH on patterns of connectivity within and between the brain’s intrinsic networks.Methods: 5 transgender individuals receiving GAHT (estradiol n =3, testosterone n = 2) were scanned using functional magnetic imaging (fMRI) at rest at two timepoints: baseline, prior to treatment, and 6 months into GAHT. The time course of neural activity was computed for each voxel in the brain, then tested for correlation with each other voxel to develop a whole-brain connectome for each participant. Connectomes were then analyzed in two ways: 1) maps of average connectivity to two regions of interest found in previous research to differ between cis and transgender people (the anterior insula and temporal pole) were generated for each participant. These maps were then compared between baseline and 6-month timepoints. 2) Overall network structure of the brain was generated a priori for each participant at each timepoint using a community detection algorithm. Network assignments were then compared between timepoints, noting regions whose connectivity shifted between networks after GAHT.Results: 2 of 3 participants treated with estradiol exhibited a significant reduction of connectivity to the anterior insula throughout the brain, most notably within the medial temporal lobe and cingulate cortex. Both participants receiving testosterone treatment showed reduced anterior insula connectivity, although connectivity to the cingulate cortex, particularly the mid-cingulate, was preserved. Estradiol did not significantly affect connectivity of the frontal pole, although testosterone produced a widespread reduction in frontal pole connectivity. Community detection analysis indicated a shift in connectivity to the salience network from the default mode network in the medial temporal lobe following estradiol treatment. Testosterone treatment was associated with greater connectivity in medial frontal regions to the frontoparietal network. Conclusions: Preliminary evidence indicates that both estradiol and testosterone treatment can produce significant changes in the connectivity of affective regions in the brain, as well as reorganization of the brain’s network structure.

Presentation: Saturday, June 17, 2023