Expanding upon the relationship between gender-affirming hormone therapy, neural connectivity, mental health, and body image dissatisfaction

Connor Grannis*, Whitney I. Mattson, Scott Farrell Leibowitz, Leena Nahata, Diane Chen, John F. Strang, Heather Thobe, Justin A. Indyk, Eric E. Nelson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Objective: Transgender/non-binary (TNB) youth are at increased risk for anxiety, depression, and suicidality compared to cisgender youth. Gender affirming hormone therapy (GAHT, i.e., testosterone or estrogen) is a standard of care option for TNB youth, and we have recently shown that GAHT (testosterone) in transgender youth assigned a female sex at birth is associated with reductions in internalizing symptomatology. The current analysis explores: 1) whether these benefits are observed in both TNB youth assigned female at birth (TNBAFAB) and TNB youth assigned male at birth (TNBAMAB) and 2) the extent to which body image dissatisfaction and alteration in neural circuitry relate to internalizing symptoms. Method: The current study is an expansion of a previous publication from our lab that explored the association between gender-affirming testosterone and internalizing symptomatology. While participants in our previous study consisted of 42 TNBAFAB youth, participants in the current study included adolescent TNBAFAB receiving GAHT (n = 21; GAHT+) and not receiving GAHT (n = 29; GAHT-) as well as adolescent GAHT+ TNBAMAB (n = 15) and GAHT- TNBAMAB (n = 17). Participants reported symptoms of trait and social anxiety, depression, suicidality in the past year, and body image dissatisfaction. Brain activation was measured during a face processing task designed to elicit amygdala activation during functional MRI. Results: GAHT+ TNBAFAB had significantly lower rates of social anxiety, depression, and suicidality compared to GAHT- TNBAFAB. While there were no significant relationships between estrogen and depression and anxiety symptoms, longer duration of estrogen was related to less suicidality. Both testosterone and estrogen administration were related to significantly lower rates of body image dissatisfaction compared to GAHT- youth. No significant differences emerged for BOLD response in the left or right amygdala during the face processing task, however, there was a significant main effect of GAHT on functional connectivity between the right amygdala and the ventromedial prefrontal cortex, such that GAHT+ youth had stronger co-activation between the two regions during the task. Body image dissatisfaction, greater functional connectivity, their interaction effect, and age predicted depression symptomatology and body image dissatisfaction additionally predicted suicidality in the past year. Conclusion: The current study suggests that GAHT is associated with fewer short-term internalizing symptoms in TNBAFAB than in TNBAMAB, although internalizing symptoms among TNBAMAB may diminish with longer durations of estrogen treatment. Controlling for age and sex assigned at birth, our findings indicate that less body image dissatisfaction and greater functional connectivity between the amygdala and ventromedial prefrontal cortex were both predictors of fewer levels of internalizing symptoms following GAHT.

Original languageEnglish (US)
Article number106319
JournalPsychoneuroendocrinology
Volume156
DOIs
StatePublished - Oct 2023

Funding

Support for REDCap is provided by a Vanderbilt Institute for Clinical and Translational Research grant ( UL1 TR000445 from the National Center for Advancing Translational Sciences/National Institutes of Health) from the National Institutes of Health (NIH). Funding was provided by internal funds from the Abigail Wexner Research Institute at Nationwide Children’s Hospital . Support for REDCap is provided by a Vanderbilt Institute for Clinical and Translational Research grant (UL1 TR000445 from the National Center for Advancing Translational Sciences/National Institutes of Health) from the National Institutes of Health (NIH). Funding was provided by internal funds from the Abigail Wexner Research Institute at Nationwide Children's Hospital.

Keywords

  • Estrogen
  • Gender dysphoria
  • Gender incongruence
  • MRI
  • Testosterone
  • Transgender

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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