White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging

Area of Science:

• Neuroscience
• Endocrinology
• Human Behavior

Background:

• Gender dimorphisms in human behavior, cognition, and emotion are well-documented.
• Diffusion-weighted magnetic resonance imaging (dMRI) allows detailed investigation of white matter microstructure.
• Understanding biological influences on brain structure is crucial for neuroscience and psychology.

Purpose of the Study:

• To investigate the influence of biological sex, gender identity, sex hormones, and sexual orientation on white matter microstructure.
• To compare white matter microstructure between female-to-male (FtM) and male-to-female (MtF) transsexuals and cisgender controls (FC and MC).
• To explore correlations between white matter metrics and plasma hormone levels.

Main Methods:

• Diffusion Tensor Imaging (DTI) was performed on 23 FtM, 21 MtF transsexuals, 23 female controls (FC), and 22 male controls (MC) at 3 tesla.
• Tract-Based Spatial Statistics (TBSS) and fiber tractography were used to calculate fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD).
• Plasma levels of testosterone, estradiol, and progesterone were measured, and sexual orientation was recorded.

Main Results:

• Significant differences in mean diffusivity (MD) were observed across all white matter tracts between groups.
• Female controls (FC) exhibited the highest MD, followed by FtM, MtF, and then male controls (MC) with the lowest MD.
• Axial diffusivity changes primarily accounted for the observed MD differences; no significant differences in fractional anisotropy (FA) were found.
• Plasma testosterone levels correlated significantly with MD, AD, and RD, but controlling for hormone levels or sexual orientation did not alter group differences.

Conclusions:

• White matter microstructure, specifically diffusivity, differs significantly between cisgender men and women, and these patterns are partially observed in transgender individuals.
• The findings support the hypothesis that the hormonal environment during prenatal and early postnatal development influences white matter tract development.
• Hormonal milieu, rather than solely biological sex or gender identity, may play a key role in shaping white matter microstructure.