Effects of Sex Steroid Hormones on Human Brain Function, Structure and Connectivity

Study Overview
=================
Brief Summary
-----------------
This ultrahigh-field MRI study gives us the unique opportunity to measure changes in brain function and structure induced by long-term opposite-sex steroid hormone administration in transsexual subjects. Our aim is 1. to prove the influence of high-dose, long-term opposite-sex steroid hormone treatment on functional brain response in transsexuals. 2. to investigate the influence of hormone treatment on resting state functional connectivity and brain morphology. 3. to investigate differences between transsexuals and healthy control subjects in brain function and functional connectivity, brain morphology and structural connectivity. In this longitudinal study, transsexuals and healthy control subjects will undergo three 7 Tesla ultrahigh-field MRI scan sessions: 1. baseline (before hormone treatment), 2. after 4 weeks of treatment and 3. after 4 months of treatment.

Official Title
-----------------
Effects of Sex Steroid Hormones on Human Brain Function, Structure and Connectivity: A Longitudinal Study Using 7 Tesla Ultrahigh-field Magnetic Resonance Imaging

Conditions
-----------------
Gender Identity Disorder

Intervention / Treatment
-----------------
* Drug: Hormones


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria for transsexuals are: DSM-IV diagnosis of Gender Identity Disorder (DSM-IV: 302.85, 302.6; ICD-10: F64.9, F64.8) by a structured clinical interview (SCID) general health based on history, physical examination, ECG, laboratory screening, SCID willingness and competence to sign the informed consent form Exclusion criteria for transsexuals are: severe neurological or internal diseases steroid hormone treatment within 2 months prior to inclusion (including birth control pill, phytohormones) treatment with psychotropic agents such as SSRIs any implant or stainless steel graft abnormal values in routine laboratory screening or general physical examination current substance abuse (determined using drug screening at the screening visit) pregnancy (determined at screening visit and first MRI scan) failure to comply with the study protocol or to follow the instructions of the investigating team. Inclusion criteria for healthy controls are: general health based on history, physical examination, ECG, laboratory screening, SCID willingness and competence to sign the informed consent form Exclusion criteria for healthy controls are: severe diseases any implant or stainless steel graft steroid hormone treatment within 2 months prior to inclusion (including birth control pill, phytohormones) abnormal values in routine laboratory screening or general physical examination current substance abuse (determined using drug screening at the screening visit) pregnancy (determined at screening visit and first MRI scan) failure to comply with the study protocol or to follow the instructions of the investigating team

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Transsexual<br>Female-to-Male and Male-to-Female Transsexuals receiving hormonal therapy | Drug: Hormones<br>* FtM will receive 1000mg testosterone undecanoate every 12 weeks (Nebido® 4ml i.m.), or alternatively 50mg testosterone transdermally (Testogel® 5g-bag per day) and if menstruation still occurs, additionally either lynestrenol Orgametril® (2-3 tablets/day) or in some cases 0.075mg desogestrel (Cerazette®, 1 tablet/day). MtF will receive 50mg cyproterone acetate daily (Androcur®) estradiol 100µg transdermal therapeutic system (TTS) twice a week (Estradot®, Estramon®), especially if subjects age is > 40 years, or p.o. estradiol 2x2mg (Estrofem®) if subjects age is < 40 years; alternatively estradiol 0,75-1,5mg (1-2 hubs) transdermally (Estrogel-Gel®) and 2,5mg alpha-5-reductase-inhibitor every 2nd day (Finasterid Actavis/ Arcana/ Aurobindo®) in case of extensive hair loss.<br>|
| Healthy control subjects<br>receiving no hormonal therapy | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| BOLD response to experimental fMRI paradigms | task-related BOLD (blood oxygen level dependent) responses are evaluated before, and 4 weeks, as well as 4 months of hormonal treatment in transsexual subjects and healthy control subjects | at baseline, 1 and 4 months after treatment start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Psychological Questionaires | Psychological questionaires measuring different aspects of emotion and cognitive processing are used to infer effects of hormonal therapy on these measures | at baseline, 1 and 4 months after treatment start |