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. 2021 Nov;50(8):3329-3352.
doi: 10.1007/s10508-021-02005-9. Epub 2021 May 6.

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

Alberto Frigerio  1 , Lucia Ballerini  1 , Maria Valdés Hernández  2
Affiliations

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

Alberto Frigerio et al. Arch Sex Behav. 2021 Nov.

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.

Keywords: Gender identity; Neuroimaging; Sexual orientation; Transgender; Transsexual.

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Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1
Fig. 1
Flowcharts summarizing the study selection process for the analyses on gender identity (left) and sexual orientation (right)
Fig. 2
Fig. 2
3D pie charts summarizing the number and percentage of studies included in the analyses, conducted with different neuroimaging techniques: overall information (top), analysis on gender identity (bottom left), and analysis on sexual orientation (bottom right)
Fig. 3
Fig. 3
3D bubble charts of the mean age and sample size of: a cisgenders and transgenders involved in the selected studies (left) (Note: the graph does not include the study by Yokota et al., because of the lack of data), and b heterosexuals and homosexuals involved in the selected studies (right) (Note: the graph does not include the study by Hu et al., because of the lack of data. Four studies (Kagerer et al., ; Perry et al., ; Sylva, ; Zeki & Romaya, 2010) reported just the mean age of all the sample size, and we assumed that it was the same in heterosexual and homosexual subsamples)
Fig. 4
Fig. 4
Six representative sagittal slices showing the foci resultant from the meta-analyses of stereotaxic coordinates where significant differences were found between groups with opposite gender identity (result from GingerAle 2.3.6; figure generated with micron.exe) (Purple = Transgender_vs_Natal sex; red = Transgender_vs_Opposite sex; blue = Transgender_vs_Natal and Opposite Sex)
Fig. 5
Fig. 5
Six representative axial slices showing the foci resultant from the meta-analyses of stereotaxic coordinates where significant differences were found between groups with opposite sexual orientation (result from GingerAle 2.3.6; figure generated with micron.exe) (Red = Homosexual_vs_Heterosexual Natal Sex; cyan = Homosexual_vs_Heterosexual Opposite Sex; blue = Transgender_vs_Natal and Opposite Sex; indigo = Homosexual_vs_Heterosexual)
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