The influence of sex steroid treatment on insular connectivity in gender dysphoria

Murray B Reed; Patricia A Handschuh; Manfred Klöbl; Melisande E Konadu; Ulrike Kaufmann; Andreas Hahn; Georg S Kranz; Marie Spies; Rupert Lanzenberger

doi:10.1016/j.psyneuen.2023.106336

The influence of sex steroid treatment on insular connectivity in gender dysphoria

Psychoneuroendocrinology. 2023 Sep:155:106336. doi: 10.1016/j.psyneuen.2023.106336. Epub 2023 Jul 20.

Authors

Murray B Reed¹, Patricia A Handschuh¹, Manfred Klöbl¹, Melisande E Konadu¹, Ulrike Kaufmann², Andreas Hahn¹, Georg S Kranz³, Marie Spies¹, Rupert Lanzenberger⁴

Affiliations

¹ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
² Department of Obstetrics and Gynecology, Medical University of Vienna, Austria.
³ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria; Department of Rehabilitation Sciences, Hong Kong Polytechnic University, Hong Kong, China.
⁴ Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria. Electronic address: rupert.lanzenberger@meduniwien.ac.at.

PMID: 37499299
DOI: 10.1016/j.psyneuen.2023.106336

Abstract

Background: Sex-specific differences in brain connectivity were found in various neuroimaging studies, though little is known about sex steroid effects on insular functioning. Based on well-characterized sex differences in emotion regulation, interoception and higher-level cognition, gender-dysphoric individuals receiving gender-affirming hormone therapy represent an interesting cohort to investigate how sex hormones might influence insular connectivity and related brain functions.

Methods: To analyze the potential effect of sex steroids on insular connectivity at rest, 11 transgender women, 14 transgender men, 20 cisgender women, and 11 cisgender men were recruited. All participants underwent two magnetic resonance imaging sessions involving resting-state acquisitions separated by a median time period of 4.5 months and also completed the Bermond-Vorst alexithymia questionnaire at the initial and final examination. Between scans, transgender subjects received gender-affirming hormone therapy.

Results: A seed based functional connectivity analysis revealed a significant 2-way interaction effect of group-by-time between right insula, cingulum, left middle frontal gyrus and left angular gyrus. Post-hoc tests demonstrated an increase in connectivity for transgender women when compared to cisgender men. Furthermore, spectral dynamic causal modelling showed reduced effective connectivity from the posterior cingulum and left angular gyrus to the left middle frontal gyrus as well as from the right insula to the left middle frontal gyrus. Alexithymia changes were found after gender-affirming hormone therapy for transgender women in both fantasizing and identifying.

Conclusion: These findings suggest a considerable influence of estrogen administration and androgen suppression on brain networks implicated in interoception, own-body perception and higher-level cognition.

Keywords: Gender-affirming hormone therapy; Insula; Interoception; Resting-state; Transgender.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Brain
Female
Gender Dysphoria* / drug therapy
Gender Identity
Gonadal Steroid Hormones / pharmacology
Humans
Magnetic Resonance Imaging / methods
Male
Steroids
Transsexualism* / drug therapy

Substances

Gonadal Steroid Hormones
Steroids

Grants and funding

KLI 504/FWF_/Austrian Science Fund FWF/Austria