Specifically, the individual Brain Sex estimates were used to calculate the receiver operator characteristic (ROC) and its area under the curve (AUC). All participants provided informed consent, and ethics approval was granted by the Institutional Review Board of the University of California, Los Angeles (UCLA protocol 041106703, 27 April 2007) and by the University of Auckland (UOA protocol 022375, 30 November 2021).īefore the main analysis, we assessed the classifier performance, both in the independent training sample (305 females/242 males) using a 10-fold cross-validation and in our 48 cisgender brains (24 males/24 females). The cisgender sample-selected from the International Consortium for Brain Mapping (ICBM) database ( )-was close in age and handedness and consisted of 24 males (45.9 ± 13.7, 23–69 years) and 24 females (46.2 ± 14.0, 23–73 years). The mean age of the transgender sample was 45.7 ± 13.8 years (range 23–72 years). Six transgender women reported to be androphile (attracted to men) and 18 transgender women stated to be gynephile (attracted to women). Moreover, participants were confirmed to be genetic males as defined by the presence of the SRY gene in their genome. To be included in this study, participants needed to self-identify as transgender women, report no history of hormone therapy, and declare the intention of undergoing estrogen replacement therapy. Twenty-four transgender women (biological sex: male perceived gender: female) were recruited through local community organizations and through professionals who offer services to the transgender community.
We hypothesized that the estimated brain sex in transgender women is shifted away from their biological sex (male) towards their gender identity (female), but still significantly different from both. Our study sample consisted of 24 cisgender men, 24 cisgender women, and 24 transgender women before hormone therapy in order to rule out any modifying effects of circulating sex steroids. For this purpose, we employed a recently developed multivariate classifier that yields a continuous (rather than a binary) estimate for being male or female, in accordance with current biological models. The current study was designed to shed further light on the question of whether the brains of transgender people resemble their birth sex or their gender identity. The reasons for divergences in study outcomes may be due to including individuals at different points in their gender-affirming process, using univariate classifiers and/or applying binary classifiers contrary to the notion that a mere binary classification may be insufficient to capture interactions between biological sex and gender identity. Interestingly, some studies reported that the classification accuracy was reduced in transgender individuals, albeit not all studies observed this effect. The overarching question addressed in those recent studies is whether the brains of transgender people are concordant with their birth sex or their gender identity, which is usually based on a so-called “classification accuracy” (i.e., how well can a brain be classified as male or as female). A possible solution is to study brain patterns rather than single features, as lately accomplished using modern machine learning algorithms in both cisgender samples and transgender samples. The latter is a concern in particular as even within cisgender studies there are large discrepancies in terms of reported sex differences, apart from the larger male and smaller female brain on average. Possible reasons include analyzing small and/or heterogeneous samples, applying different morphometric methods across studies, as well as focusing on single brain features. However, despite this wealth of research, a clear consensus is still missing in terms of which brain structures are altered in transgender individuals. Some (or perhaps all) of the aforementioned variables may have contributed to neuroanatomical variations in transgender brains, as repeatedly observed in both post mortem and in vivo studies published over the past three decades. Social explanations pointing to psychosocial and environmental influences are complemented by biological explanations that include genetic predispositions and hormonal exposures. Worldwide, the reported prevalence of transgender identities is rising, but our scientific understanding of how gender identity develops is still limited. Transgender women are assigned male at birth but identify as female transgender men are assigned female at birth but identify as male. Transgender people report discomfort with their birth sex and a strong identification with the opposite sex.
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