Background In contrast to cisgender persons, transgender persons identify with a different gender than the one assigned at birth. Although research on the underlying neurobiology of transgender persons has been accumulating over the years, neuroimaging studies in this relatively rare population are often based on very small samples resulting in discrepant findings. Aim To examine the neurobiology of transgender persons in a large sample. Methods Using a mega-analytic approach, structural MRI data of 803 non-hormonally treated transgender men (TM, n = 214, female assigned at birth with male gender identity), transgender women (TW, n = 172, male assigned at birth with female gender identity), cisgender men (CM, n = 221, male assigned at birth with male gender identity) and cisgender women (CW, n = 196, female assigned at birth with female gender identity) were analyzed. Outcomes Structural brain measures, including grey matter volume, cortical surface area, and cortical thickness. RESULTS Transgender persons differed significantly from cisgender persons with respect to (sub)cortical brain volumes and surface area, but not cortical thickness. Contrasting the 4 groups (TM, TW, CM, and CW), we observed a variety of patterns that not only depended on the direction of gender identity (towards male or towards female) but also on the brain measure as well as the brain region examined. Clinical Translation The outcomes of this large-scale study may provide a normative framework that may become useful in clinical studies. Strengths and Limitations While this is the largest study of MRI data in transgender persons to date, the analyses conducted were governed (and restricted) by the type of data collected across all participating sites. CONCLUSION Rather than being merely shifted towards either end of the male-female spectrum, transgender persons seem to present with their own unique brain phenotype.

Sexual responding in transgender people has typically been investigated from a medical and functional perspective. Aligning with the biopsychosocial model, it is however equally important to consider psychological aspects of sexuality in this population. We propose that the Sexual Self-Concept (SSC) theory offers a valuable framework to understand (sexual) wellbeing in transgender people, while Self-Concept Discrepancy (SCD) theory could offer an explanation of the mechanisms underlying negative SSCs related to gender dysphoria. We investigated differences in SSC (consisting of sexual esteem, sexual attitudes, and sexual self-efficacy) in 197 binary transgender and 205 cisgender individuals using an online survey and explored the mediating role of actual/ideal self-discrepancies in explaining the relation between gender dysphoria and SSC. Transgender and cisgender individuals differed significantly in seven out of eight components related to sexual esteem and sexual attitudes. Actual/ideal selfdiscrepancies mediated the relationship between gender dysphoria and the SSC in transgender individuals for the sexual esteem components related to body perception, conduct, and attractiveness, as well as for sexual anxiety. We found no relation between gender dysphoria and the other SSC components in this group. We conclude that SSC discrepancies could be a valuable treatment target to improve transgender individuals' sexual esteem and sexual attitudes.

Background It is currently unknown whether there are differences in desire for gender affirming medical treatment (GAMT) between binary and non-binary transgender individuals, although the latter seek treatment less prevalently. Aim To investigate differences between binary and non-binary individuals on received GAMT, desire for GAMT, and motives for (not) wanting GAMT, and to explore the association between having an unfulfilled treatment desire and general and sexual well-being. Methods We conducted an online questionnaire in a community sample of 125 transgender men, 72 transgender women, and 62 non-binary transgender individuals (age: M = 30.4, SD = 11.31, range 18-69). Outcome measures Undergone GAMT, GAMT desire, motives for (not) wanting (further) GAMT, Utrecht Gender Dysphoria Scale, Satisfaction With Life Scale, Hospital Anxiety and Depression Scale, Global Measure of Sexual Satisfaction, transgender-specific body image worries, and sexual self-concept discrepancies. Results Binary transgender participants reported having undergone more GAMT procedures than non-binary transgender participants (P < .001 for both gender affirming hormone treatment (GAHT) and gender affirming surgery (GAS)). While binary participants reported a stronger desire for GAHT compared to non-binary participants (X2(1, N = 93) = 32.63, P < .001), the groups did not differ in their desire for GAS (X2(1, N = 247) = 0.68, P = .411). Binary and non-binary participants reported similar reasons for wanting treatment, mostly related to body and/or gender incongruence and gender affirmation. In terms of not wanting treatment, the non-binary group reported their gender identity as the most important reason, while the binary group mostly mentioned possible medical complications. The majority of both groups had an unfulfilled treatment desire (69% of binary participants and 64.5% of non-binary participants), which was related to lower levels of general life satisfaction (P < .001) and sexual satisfaction (P = .005), more anxiety (P = .006) and transgender-specific body image worries (P < .001), and larger sexual self-concept discrepancies (P < .001 for actual and/or ideal, P < .001 for actual and/or ought). Clinical implications Systemic barriers to GAMT (especially GAS) should be removed not only for binary but also for non-binary identifying transgender individuals to decrease the discrepancy between treatment desire and actually seeking treatment. Strengths & limitations This study was the first to systematically investigate differences in treatment desire motives between binary and non-binary transgender individuals, while also showing the possible negative consequences of an unfulfilled treatment desire. Given the online character of the study, results may not generalize to the broader transgender community. Conclusion Similarly to binary transgender individuals, many non-binary transgender individuals have a desire for GAMT, and not being able to receive GAMT has a negative effect on their mental and sexual health. Further efforts should be made to make GAMT accessible for all transgender individuals, regardless of gender identity.

Background Non-binary and genderqueer (NBGQ) individuals do not identify with a binary gender identity. Some but not all NBGQ individuals identify as transgender, and it is currently unclear on which aspects of mental and sexual well-being NBGQ and binary transgender individuals may differ. Aim To compare NBGQ, binary transgender and cisgender individuals on variables related to mental well-being, sexual well-being, and sexual self-concept discrepancies. Methods We conducted an online questionnaire study in 125 transgender men, 72 transgender women, 78 NBGQ individuals, 98 cisgender men, and 107 cisgender women. Results For most variables, NBGQ individuals did not differ from binary transgender individuals. These two groups differed only on gender dysphoria and transgender specific body image worries, which were both lower in the NBGQ group. Compared to the cisgender group, NBGQ individuals scored higher on gender dysphoria, actual/ought sexual self-concept discrepancies, and actual/ideal sexual self-concept discrepancies, and lower on general life satisfaction and sexual esteem related to body perception. Discussion These results offer a first quantitative analysis of sexual well-being in NBGQ individuals, and highlight that – while both groups face unique challenges – NBGQ individuals encounter similar difficulties concerning mental and sexual well-being as binary transgender individuals.