title: Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria.
abstract: Adolescents with gender dysphoria (GD) may be treated with gonadotropin releasing hormone analogs (GnRHa) to suppress puberty and, thus, the development of (unwanted) secondary sex characteristics. Since adolescence marks an important period for the development of executive functioning (EF), we determined whether the performance on the Tower of London task (ToL), a commonly used EF task, was altered in adolescents with GD when treated with GnRHa. Furthermore, since GD has been proposed to result from an atypical sexual differentiation of the brain, we determined whether untreated adolescents with GD showed sex-atypical brain activations during ToL performance. We found no significant effect of GnRHa on ToL performance scores (reaction times and accuracy) when comparing GnRHa treated male-to-females (suppressed MFs, n=8) with untreated MFs (n=10) or when comparing GnRHa treated female-to-males (suppressed FMs, n=12) with untreated FMs (n=10). However, the suppressed MFs had significantly lower accuracy scores than the control groups and the untreated FMs. Region-of-interest (ROI) analyses showed significantly greater activation in control boys (n=21) than control girls (n=24) during high task load ToL items in the bilateral precuneus and a trend (p<0.1) for greater activation in the right DLPFC. In contrast, untreated adolescents with GD did not show significant sex differences in task load-related activation and had intermediate activation levels compared to the two control groups. GnRHa treated adolescents with GD showed sex differences in neural activation similar to their natal sex control groups. Furthermore, activation in the other ROIs (left DLPFC and bilateral RLPFC) was also significantly greater in GnRHa treated MFs compared to GnRHa treated FMs. These findings suggest that (1) GnRHa treatment had no effect on ToL performance in adolescents with GD, and (2) pubertal hormones may induce sex-atypical brain activations during EF in adolescents with GD.
authors.affiliation: Neuroendocrinology Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands.
authors.forename: Annemieke S
authors.initials: AS
authors.lastname: Staphorsius
authors.affiliation: Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Baudewijntje P C
authors.initials: BP
authors.lastname: Kreukels
authors.affiliation: Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Peggy T
authors.initials: PT
authors.lastname: Cohen-Kettenis
authors.affiliation: Department of Psychiatry, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Dick J
authors.initials: DJ
authors.lastname: Veltman
authors.affiliation: Neuroendocrinology Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands; Center of Expertise on Gender Dysphoria, Department of Medical Psychology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Burke
authors.affiliation: Department of Pediatric Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands; Department of Pediatrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Sebastian E E
authors.initials: SE
authors.lastname: Schagen
authors.affiliation: Department of Pediatric Endocrinology, Neuroscience Campus Amsterdam, VU University Medical Center, De Boelelaan 1117, 1081 HZ Amsterdam, The Netherlands.
authors.forename: Femke M
authors.initials: FM
authors.lastname: Wouters
authors.affiliation: Department of Pediatrics, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
authors.forename: Henriëtte A
authors.initials: HA
authors.lastname: Delemarre-van de Waal
authors.affiliation: Neuroendocrinology Group, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA Amsterdam, The Netherlands; GIGA Neurosciences, University of Liège, Avenue de l'Hôpital 1B36, 4000 Liège, Belgium. Electronic address: jbakker@ulg.ac.be.
authors.forename: Julie
authors.initials: J
authors.lastname: Bakker
mesh_terms: D000293:Adolescent; D039721:Diagnostic and Statistical Manual of Mental Disorders; D056344:Executive Function; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D000068116:Gender Dysphoria / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000503:physiopathology; D011597:Psychomotor Performance; D011627:Puberty / Q000523:psychology*; D011930:Reaction Time / Q000502:physiology; D012733:Sex Differentiation
chemical_list: D007987:Gonadotropin-Releasing Hormone
keywords: Adolescents; Gender dysphoria; Gonadotropin releasing hormone analog; Sex difference; Tower of London; fMRI