Testosterone Effects on the Brain in Transgender Men

Abstract

Transgender individuals experience incongruence between their gender identity and birth-assigned sex. The resulting gender dysphoria (GD), which some gender-incongruent individuals experience, is theorized to be a consequence of atypical cerebral sexual differentiation, but support for this assertion is inconsistent. We recently found that GD is associated with disconnected networks involved in self-referential thinking and own body perception. Here, we investigate how these networks in trans men (assigned female at birth with male gender identity) are affected by testosterone. In 22 trans men, we obtained T1-weighted, diffusion-weighted, and resting-state functional magnetic resonance imaging scans before and after testosterone treatment, measuring cortical thickness (Cth), subcortical volumes, fractional anisotropy (FA), and functional connectivity. Nineteen cisgender controls (male and female) were also scanned twice. The medial prefrontal cortex (mPFC) was thicker in trans men than controls pretreatment, and remained unchanged posttreatment. Testosterone treatment resulted in increased Cth in the insular cortex, changes in cortico-cortical thickness covariation between mPFC and occipital cortex, increased FA in the fronto-occipital tract connecting these regions, and increased functional connectivity between mPFC and temporo-parietal junction, compared with controls. Concluding, in trans men testosterone treatment resulted in functional and structural changes in self-referential and own body perception areas.

Gender-Affirming Hormone Use in Transgender Individuals: Impact on Behavioral Health and Cognition

“…Using both cross-sectional and longitudinal design, the studies generally show that GAHT is correlated with changes in the direction of gender identity rather than natal sex with respect to global and regional brain volumes [57•, 58], white matter microstructure [59, 60], and cognitive performance on sex-biased tasks requiring verbal and visual memory [61]. To the best of our knowledge, no studies thus far have looked at how GAHT influences executive function and cognitive domains used for daily living.…”

Cerebral sex dimorphism and sexual orientation

“…The present observations will, therefore, primarily be discussed in relation to sex hormones. Changes in testosterone and estrogen levels have indeed shown to coincide with changes in Cth/grey matter density and FA values, both in longitudinal studies of endogenous estrogen/testosterone, (Herting, Gautam, Spielberg, Dahl, & Sowell, ; Peper, van den Heuvel, Mandl, Hulshoff Pol, & van Honk, ), and studies of responses to cross sex hormone treatment in transsexual populations (Burke et al, ; Rametti et al, ; Zubiaurre‐Elorza, Junque, Gomez‐Gil, & Guillamon, ).…”

Sex differences in own and other body perception

“…A direct link between gender and own body perception also represents the hallmark of gender dysphoria, a condition gaining increasing public attention. This is possibly due to a disturbed own body perception with respect to gender identity (Burke, Manzouri, Dhejne, et al, 2018;Burke, Manzouri, & Savic, 2017;Feusner, Dervisic, et al, 2016;Feusner, Lidström, et al, 2017;Manzouri, Kosidou, & Savic, 2017). This is possibly due to a disturbed own body perception with respect to gender identity (Burke, Manzouri, Dhejne, et al, 2018;Burke, Manzouri, & Savic, 2017;Feusner, Dervisic, et al, 2016;Feusner, Lidström, et al, 2017;Manzouri, Kosidou, & Savic, 2017).…”

“…Gender dysphoria, termed "Gender Incongruence" in the latest ICD11 criteria of the World Health Organization (https://icd.who.int/ dev11/f/en#/http%3a%2f%2fid.who.int%2ficd%2fentity% 2f411470068), is characterized by a perceived incongruence between a person's gender identity and his/her sex assigned at birth (DSM-5, American Psychiatric Association, 2013). This is possibly due to a disturbed own body perception with respect to gender identity (Burke, Manzouri, Dhejne, et al, 2018;Burke, Manzouri, & Savic, 2017;Feusner, Dervisic, et al, 2016;Feusner, Lidström, et al, 2017;Manzouri, Kosidou, & Savic, 2017). Gender dysphoria has traditionally been regarded to have a male (sex assigned at birth) predominance, although this has been questioned more recently (Steensma, Cohen-Kettenis, & Zucker, 2018;Zucker, 2017).…”