Brain development, brain functioning, growth and metabolic aspects in the clinical management of transsexual adolescents.

The present study will focus on the consequences of long-term delay of puberty induced by treatment with Decapeptyl-CR. We will investigate the effects of this treatment in regard to brain functioning, brain development, various endocrine, metabolic and anthropometric aspects before, during and after treatment with Decapeptyl-CR alone and in combination with cross-sex hormones in juvenile transsexuals. Hereby we will focus on sex differences between transsexual adolescents and similar aged individuals of both sexes by investigating brain development and brain functioning, as well as on possible determinants of the aetiology of transsexuality by means of structural and functional MRI and family pedigree research.

The hypothesis of this study is that the pubertal delay in transsexual adolescents, induced by treatment with GnRH analogues, will cause a difference in the development of brain structures and brain function between transsexuals and age matched control subjects without transsexuality. If cross-sex hormones are added from the age of sixteen, a catch up of brain development is expected. It is of great interest to investigate if this brain development will occur in the direction of the biologic or desired sex.
Gender dysphoria is associated with atypical levels of sex hormones during pregnancy. The hypothesis of this study is that already at a young age, development of brain structures and brain function in gender dysphoric children will occur in the direction of the desired instead of the biologic sex.

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Patients: measurements will be performed at a prepubertal stage, before start of GNrH analogue Triptoreline/ Decapeptyl-CR (current puberty delaying medication for transsexual adolescents in the VUmc from the age of 12 and if puberty has already started i.e. Tanner stage B2 in girls, G1-2 in boys), before start of cross-sex hormones (17 beta oestradiol in male-to-female transsexuals and sustanon in female-to-male transsexuals), one year after start of cross-sex hormones and 1-2 years after gender reassignment surgery.



Age matched control subjects (friends of the transsexual patients): measurements will be performed if the transsexual friend starts with puberty delaying treatment, if the transsexual friend starts with cross-sex hormones and 1-2 years after surgery of the transsexual friend.




Interventions:

1. Structural MRI, method used: voxel based morphometry, ROI analysis;

2. Functional MRI (BOLD) during which 3 cognition tasks will be performed (mental rotation, verbal fluency and emotional faces);

3. Physical examination with anthropometric measurements and gathering of information about pubertal stage according to Tanner;

4. Digital photographs and physical appearance list;

5. Salivary testosterone measurements;

6. Family pedigree research: homosexuality/ transsexuality in family.




The duration of the intervention will be approximately three hours for every visit, which means at maximum 5 visits (if patients will be followed longitudinally) for the patients and three visits (if control subjects will be followed longitudinally) for the control subjects.