Changes to hypothalamic volume and associated subunits during gender-affirming hormone therapy

Area of Science:

• Neuroendocrinology
• Neuroimaging
• Endocrinology

Background:

• Gender-affirming hormone therapy (GHT) has pleiotropic effects, including alterations in regional brain volumes.
• The hypothalamus, crucial for neuroendocrine, emotional, and cognitive functions, is a key target for studying GHT effects.
• Investigating hypothalamic subunit volumes is essential due to the region's anatomical and functional heterogeneity.

Purpose of the Study:

• To assess changes in total and subunit hypothalamic volumes following gender-affirming hormone therapy (GHT).
• To explore the impact of GHT on brain structure in transgender individuals compared to cisgender controls.
• To understand the subunit-specific effects of GHT on the hypothalamus.

Main Methods:

• 106 participants (38 transgender men [TM], 15 transgender women [TW], 32 cisgender women [CW], 21 cisgender men [CM]) underwent two MRI scans.
• TW and TM received GHT (estrogen/anti-androgen or testosterone) between scans (median interval 145 days).
• Hypothalamic volumes were segmented using FreeSurfer; repeated-measures ANCOVA tested GHT effects.

Main Results:

• Significant group × time interaction effects were found for total and subunit hypothalamic volumes.
• Transgender women (TW) showed decreased volumes in several hypothalamic subunits after GHT (p_corr < 0.01).
• Changes in TW differed significantly from cisgender men (CM) and cisgender women (CW) in specific subunits (p_corr < 0.05).

Conclusions:

• Gender-affirming hormone therapy (GHT) exerts subunit-specific effects on hypothalamus volumes in transgender women (TW).
• Findings align with known effects of estrogens and androgens on brain volumes.
• Further research is needed to explore psychological and behavioral changes associated with GHT.