Developmental Correlates and Hormone Therapy Effects in Gender Dysphoria (DCHGD)

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

Study Overview

• Status: Withdrawn
• Conditions: Gender Dysphoria
• Intervention / Treatment: Other: MRI

Detailed Description

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).

• Study Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• gender dysphoric subjects MtF
• right handed
• androphilic orientation
• without hormone therapy

Control group of male subjects:

• right handed
• without any psychiatric or medical history
• androphilic orientation

Exclusion Criteria:

• MRI contraindication
• vulnerable adults
• mental retardation
• psychiatric or neurological disease including autism spectrum disorders, psychotropic medication
• hormonal or genetic condition

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: gender dysphoria subjects; 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	Other: MRI; Subjects will receive structural and functional (resting state) MRI
Other: control subjects; Control group inclusions, of open-label patients without gender dysphoria.	Other: MRI; Subjects will receive structural and functional (resting state) MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain connectome 6 months after the hormone therapy beginning	Structural and functional MRI before and after 6 months of hormone therapy will be analysed in order to make a comparison before/after	6 months after the beginning of the hormone therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain connectome in gender dysphoric and control subjects	The MRI images will be analysed in order to construct a brain " connectome " which reflects brain connectivity, using the graph theory. At baseline, these networks will be compared between dysphoric and control subjects.	baseline
Gender dysphoria phenotype description	The MRI images will be analysed in order to construct a brain " connectome " which reflects brain connectivity, using the graph theory. Correlations will be made at baseline between brain connectome of the dysphoric subjects and testosteronemia, and developmental measures : age at beginning of gender dysphoria, finger lenghth D2/D4 ratio, birth weight, laterality using Edimbourg scale.	baseline and 6 months after the beginning of the hormone therapy
Brain connectome variations	The MRI images will be analysed in order to construct a brain " connectome " which reflects brain connectivity, using the graph theory. Evolutions of the brain connectome of dysphoric subjects will be compared after 6 months of hormone therapy, taking into acount gender dysphoria decrease measured using Utrecht Gender Dysphoria Scale.	6 months after the beginning of the hormone therapy

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2021
• Primary Completion (Anticipated): June 15, 2021
• Study Completion (Actual): March 15, 2022

Study Registration Dates

• First Submitted: February 18, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 16, 2020

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 23, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: neuroimaging; gender dysphoria; hormone-surgical reassignment
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Sexual Dysfunctions, Psychological; Depressive Disorder; Gender Dysphoria; Depressive Disorder, Major
• Other Study ID Numbers: 2019-A01997-50

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No