Developmental Correlates and Hormone Therapy Effects in Gender Dysphoria

The aim of the research is to study longitudinally the effects of reassignment hormonotherapy on the connectome of MtF (biological men who are transitioning to the female gender) dysphoric subjects after 6 months of hormone therapy. The subjects will be compared to a control group of healthy subjects taking into account sexual orientation

The pathophysiology of gender dysphoria is still poorly understood, but a number of clues point to an origin derived from biological and environmental factors, particularly studies of twins, birth order, and family groups. Several explanatory models have been put forward. In particular, the differentiation of genitals taking place in the first half of pregnancy while that of the brain in the second makes it possible to imagine a different differentiation between the external phenotype and the cerebral gender. Several developmental features have thus been found in gender dysphoric subjects, including the finger length ratio D2 / D4, lateralization. Some neuroimaging studies have shown brain features in gender dysphoric subjects that seem original compared to control subjects. Nevertheless, the results are scarce, poorly reproduced, and for some, the differences highlighted may be related to phenotypic variability including the non-consideration of sexual orientation. Moreover, some of these studies combine subjects treated or not with hormone therapy which is a bias because it is likely that hormone therapy may have structural and functional effects on brain function. The investigators team deals with dysphoric gender issues as part of a coordinated course of hormone-surgical reassignment. We wish to better characterize the brain effects, at the level of the "connectome" of the reassignment hormone therapy in a population of dysphoric subjects, taking into account signs of pre-natal hormonal impregnation (D2 / D4 ratio), developmental features (onset of dysphoria, lateralization, size), and controlling sexual orientation as a potential confounding factor. The aim of the research is then to study longitudinally the effects of reassignment hormonotherapy on the connectome of MtF dysphoric subjects after 6 months of hormone therapy. The subjects will be compared to a control group of healthy subjects taking into account sexual orientation. This is a prospective longitudinal study that includes, in a consecutive manner, open-label patients with MtF gender dysphoria (biological men who are transitioning to the female gender) attending the forensic psychiatric consultation for a request for hormone-surgical reassignment. Subjects will receive initial clinical assessment and MRI before and 6 months after initiation of hormone therapy; the imaging data will be compared to a control group (n = 20).