ESPE Abstracts

Background: Spatial navigation is an essential human skill that helps individuals track their changes in position and orientation by integrating self-motion cues. Meta-analyses indicate that males, on average, perform better than females on a number of spatial tasks. Sex steroids, mainly androgens, modulate the remodeling of synapses in the prefrontal cortex and hippocampus, a limbic brain area with critical influence on spatial and contextual memory. Androgen-induced plasticity might be more pronounced during peri-adolescence to young adulthood when the executive network is under rapid development. In both males and females, testosterone levels have been associated with spatial ability. Transgender males receiving testosterone have been reported to have enhanced performance on visual memory, mental rotation and 3D spatial memory tasks. To date, performance on the virtual Morris Water Task, examining spatial navigation and memory, has not been examined in transgender male adolescents.

Objective: To examine spatial navigation and memory in transgender male adolescents receiving gender-affirming testosterone treatment compared to cisgender male and cisgender female adolescent controls.

Methods: Cross-sectional, single-center study from the Israeli Pediatric Gender Clinic. Spatial navigation was assessed using the Virtual Morris Water Maze Task in 28 transgender male adolescents receiving gender-affirming testosterone treatment, 26 cisgender male and 30 cisgender female adolescents. Participants were asked to find a hidden platform while navigating in a virtual water tank according to spatial cues located on the surrounding walls (4 blocks of 4 repeated attempts each). Data extracted from medical records included LH, FSH, estradiol and testosterone blood levels, and testosterone and Gonadotropin releasing hormone analogs (GnRHa) duration of treatment. Outcome measures: latency and path length to hidden platform.

Results: Transgender male adolescents (mean age 17.1±1.7 years) were treated with GnRHa and testosterone (mean duration of 17.9±11.2 and 19.4±14.8 months, respectively). Mean peak testosterone blood levels were 24.3±8.1 nmol/L. Transgender males and cisgender males performed significantly faster than cisgender females (P=0.022), with a shorter path length in the first block of the task (P=0.020). Correlations were not found between peak testosterone blood levels or duration of treatment and task performance.

Conclusion: Transgender male adolescents, receiving gender-affirming testosterone treatment, demonstrate spatial memory and learning that is comparable to cisgender males and enhanced compared to cisgender females. Further longitudinal research on the impact of gender-affirming hormonal treatment on cognitive functions is required, especially in peri-adolescence.