Endocrine Abstracts

JOINT2880

Background: Gender incongruency potentially has a multifactorial etiology but little is known about specific neuroanatomic regions consistently associated with this condition. We aimed to recognize the potential role of hypothalamic subregions in therapy-naïve transgender population to provide a better understanding on neuroendocrine pathways involved in gender identity.

Methods: Transgender and age-matched cisgender participants were recruited from a national tertiary center and from the local community, respectively, during the same temporal period. All subjects were right-handed. Gender incongruence was diagnosed according to ICD-10-CM criteria following independent psychiatric evaluations. T1-weighted structural data were acquired using a 3T Siemens MAGNETOM Prisma MRI scanner. Automated hypothalamic subunits segmentation was conducted using FreeSurfer v7.3.2. Blood samples were collected to measure anterior pituitary hormone levels. Preliminary statistical analyses were performed in SPSS v28 at a 5% significance level.

Results: From 40 participants, 34 were included in the final sample (9 CisMale, 10 CisFemale, 9 TransMale, 6 TransFemale). Mean age was 24.5±7.38 y in the transgender group and 25.5±5.69 y in the cisgender group. Specifically, the TransFemale group exhibited a significantly larger left inferior tubular (infTub) hypothalamic subunit volume (153.6±15.50 mm³) compared to TransMale group (121.2±18.44 mm³). No significant differences were found for this region between cisgender and transgender subgroups (CisMale 140.7±24.96 mm³, CisFemale 127.7± 16.62 mm³). No additional significant volumetric differences were found in the right infTub or the other subunits, bilaterally (anterior-inferior, anterior-superior, posterior, superior tubular regions). Exploratory correlation analysis between hypothalamic left infTub volumes and anterior pituitary hormone levels (FSH, LH, total testosterone, TSH, T4I and prolactin) in each transgender group was performed. There was a strong significant negative correlation (r=-0.872, P = 0.024) between left infTub volumes and total testosterone levels in TransFemale participants. No other significant correlations were found.

Conclusion: Our findings suggest a potential neuroanatomical region of interest in therapy-naïve TransFemale individuals, characterized by increased volume in the left infTub hypothalamic subregion. Interestingly, the hypothalamic hormone kisspeptin, a key regulator of reproductive behavior, is predominantly expressed in the infundibulum. Given the functional association of infTub with the infundibular (arcuate), preoptic, and ventromedial nuclei—critical regulators of metabolic function and sexual behavior—further research is warranted to elucidate its role in gender identity and neuroendocrine regulation.