Sarah M. Burke, PhD; Baudewijntje P.C. Kreukels, PhD; Peggy T. Cohen-Kettenis, PhD; Dick J. Veltman, MD, PhD; Daniel T. Klink, MD, PhD; Julie Bakker, PhD
Background: Sex differences in performance and regional brain activity during mental rotation have been reported repeatedly and reflect organizational and activational effects of sex hormones. We investigated whether adolescent girls with gender dysphoria (GD), before and after 10 months of testosterone treatment, showed male-typical brain activity during a mental rotation task (MRT).
Methods: Girls with GD underwent fMRI while performing the MRT twice: when receiving medication to suppress their endogenous sex hormones before onset of testosterone treatment, and 10 months later during testosterone treatment. Two age-matched control groups participated twice as well.
Results: We included 21 girls with GD, 20 male controls and 21 female controls in our study. In the absence of any group differences in performance, control girls showed significantly increased activation in frontal brain areas compared with control boys (pFWE = 0.012). Girls with GD before testosterone treatment differed significantly in frontal brain activation from the control girls (pFWE = 0.034), suggesting a masculinization of brain structures associated with visuospatial cognitive functions. After 10 months of testosterone treatment, girls with GD, similar to the control boys, showed increases in brain activation in areas implicated in mental rotation.
Limitations: Since all girls with GD identified as gynephilic, their resemblance in spatial cognition with the control boys, who were also gynephilic, may have been related to their shared sexual orientation rather than their shared gender identity. We did not account for menstrual cycle phase or contraceptive use in our analyses.
Conclusion: Our findings suggest atypical sexual differentiation of the brain in natal girls with GD and provide new evidence for organizational and activational effects of testosterone on visuospatial cognitive functioning.
Submitted Apr. 27, 2015; Revised Nov. 19, 2015; Revised Dec. 20, 2015; Accepted Dec. 20, 2015; Early-released Apr. 12, 2016
Acknowledgements: The authors thank Ms. Willeke Menks for her help with participant recruitment and support during the fMRI and neuropsychological data acquisition and Mr. Ton Schweigmann for his efforts in coordinating and supporting the fMRI data acquisition. This work was supported by a VICI grant (453-08-003) from the Dutch Science Foundation (Nederlandse Organisatie voor Wetenschappelijk Onderzoek) to J. Bakker. J. Bakker is a senior research associate of the Belgian Fonds National de la Recherche Scientifique.
Affiliations: From the Center of Expertise on Gender Dysphoria, Department of Medical Psychology, VU University Medical Center, Amsterdam, the Netherlands (Burke, Kreukels, Cohen-Kettenis, Bakker); the Netherlands Institute for Neuroscience, Neuroendocrinology group, Meibergdreef 47, Amsterdam, the Netherlands (Burke, Bakker); the Karolinska Institute, Department of Women’s and Children’s Health, Karolinska Hospital, Stockholm, Sweden (Burke); the Department of Psychiatry, VU University Medical Center, De Boelelaan, Amsterdam, the Netherlands (Veltman); the Department of Pediatric Endocrinology, VU University Medical Center, De Boelelaan, Amsterdam, the Netherlands (Klink); and the GIGA Neuroscience, University of Liege, Avenue Hippocrate, Liege, Belgium (Bakker).
Competing interests: None declared.
Contributors: S. Burke, P. Cohen-Kettenis and J. Bakker designed the study. S. Burke and D. Klink acquired the data, which S. Burke, B. Kreukels, P. Cohen-Kettenis, D. Veltman and J. Bakker analyzed. S. Burke and J. Bakker wrote the article, which all authors reviewed and approved for publication.
Correspondence to: S.M. Burke, Karolinska Institute, Department of Women’s and Children’s Health, Karolinska Hospital, Stockholm, Sweden; email@example.com