Cortical structure and brain size in Thai transfeminine individuals with and without gender-affirming hormone use compared with cisgender heterosexual men, heterosexual women, and gay men.

Transfeminine individuals' cortical phenotype has been shown to resemble cisgender women's. However, prior studies lacked tests of the generalizability of this finding beyond clinic populations in Europe and the Americas, and of the specificity of this phenotype to gender identity rather than the often-confounding factor of sexual orientation. Also, in clinic-based studies, transfeminine individuals' brain size and cortical thickness have been shown to decrease following the use of gender-affirming hormones (GAH). Focusing on a Thai population, this study provides a test of cross-population generalizability and helps disentangle effects of sex, gender identity, sexual orientation, and self-regulated use of GAH-a widespread but underexamined practice. Brain size and cortical structure were examined in 140 Thai adults (aged 18-44): heterosexual and gay cisgender men, heterosexual cisgender women, and transfeminine individuals attracted to men known locally as sao praphet song ("second kind of woman") with or without histories of GAH use. Regional cortical thickness and, to a limited extent, surface area were associated with gender identity and use of GAH, but not with sexual orientation. Gay men's cortical structure aligned with heterosexual men's. Feminine gender identity-in cisgender women and GAH-naïve sao praphet song-was associated with greater frontal and parietal cortical thickness. Among sao praphet song, GAH use was associated with smaller brain size and thinner cortices. These findings support the generalizability of the previously observed cortical phenotype of transfeminine individuals, and its specificity to gender identity rather than sexual orientation, as well as inform GAH-related brain differences in the context of self-regulated GAH use.