Structural, Functional, and Metabolic Brain Differences as a Function of Gender Identity or Sexual Orientation: A Systematic Review of the Human Neuroimaging Literature

Abstract

This review systematically explored structural, functional, and metabolic features of the cisgender brain compared with the transgender brain before hormonal treatment and the heterosexual brain compared to the homosexual brain from the analysis of the neuroimaging literature up to 2018, and identified and discussed subsequent studies published up to March 2021. Our main aim was to help identifying neuroradiological brain features that have been related to human sexuality to contribute to the understanding of the biological elements involved in gender identity and sexual orientation. We analyzed 39 studies on gender identity and 24 on sexual orientation. Our results suggest that some neuroanatomical, neurophysiological, and neurometabolic features in transgender individuals resemble those of their experienced gender despite the majority resembling those from their natal sex. In homosexual individuals the majority resemble those of their same-sex heterosexual population rather than their opposite-sex heterosexual population. However, it is always difficult to interpret findings with noninvasive neuroimaging. Given the gross nature of these measures, it is possible that more differences too subtle to measure with available tools yet contributing to gender identity and sexual orientation could be found. Conflicting results contributed to the difficulty of identifying specific brain features which consistently differ between cisgender and transgender or between heterosexual and homosexual groups. The small number of studies, the small-to-moderate sample size of each study, and the heterogeneity of the investigations made it impossible to meta-analyze all the data extracted. Further studies are necessary to increase the understanding of the neurological substrates of human sexuality.

Whole‐brain dynamics differentiate among cisgender and transgender individuals

“…Second, the menstrual cycle of cis women and trans men was not accounted as a variable of interest, while there is growing evidence of functional dynamic differences between the phases of the menstrual cycle (De Filippi et al, 2021 ). Likewise, the sexual orientation of all participants was not systematically assessed as a variable of interest (Frigerio et al, 2021 ; Guillamon et al, 2016 ; Skorska et al, 2021 ). Including minority gender groups when investigating the gender phenomenon in the brain is imperative to understand the complexity of the gender experience.…”

Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria

“…A second theoretical perspective is the neurohormonal hypothesis, which posits that prenatal androgen exposure organizes parts of the brain (in terms of structure (23) and function (24)) as well as sex-differentiated psychological and behavioral characteristics (25), including gender identity and sexual orientation. The surge in sex hormones during adolescence is argued to influence parts of the brain to be further expressed in a relatively male-or female-typical manner, based on the earlier prenatal brain organization (6)(7)(8)(9)(26)(27)(28). On average, sex differences in functional connectivity that are consistent with the neurohormonal hypothesis have been reported (e.g., 13,[29][30][31][32], although there are ongoing debates regarding the extent of sex differences in various brain features, including functional connectivity (e.g., [33][34][35][36].…”

Same Sexual Orientation as a Potential Risk Factor for Severe Mental Illness

“…According to a growing body of research, prenatal factors impacts on sexual gender orientation, neuroanatomical and other biological connections have been discovered [13]. Multiple studies conducted have shown differences between structures and activities of the brain in homosexuality compared to heterosexuality [14][15][16]. Sexual minority adolescents are also more vulnerable to child abuse [17], peer bullying [18], and other types of violence than their heterosexual counterparts, which further contribute to the manifestation of mental disorder like schizophrenia [19].…”