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

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

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.

Study Overview

• Status: Completed
• Conditions: Gender Identity Disorder
• Intervention / Treatment: Drug: Hormones

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Department of Psychiatry and Psychotherapy, Medical University of Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Transsexuals urging sex reassignment in a clinical setting will be enrolled at the Unit for Gender Identity Disorder at the General Hospital in Vienna. 20 female-to-male (FtM) and 20 male-to-female (MtF) transsexuals will be asked to undergo this fMRI, MRI, DTI and resting-state functional connectivity study. Transsexual subjects are aged between 18 and 50 years old and free from hormone-treatment at baseline.

40 healthy control subjects, matched for age, sex and sexual orientation to transsexual subjects will be recruited.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Transsexual; Female-to-Male and Male-to-Female Transsexuals receiving hormonal therapy	Drug: Hormones; 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.
Healthy control subjects; 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

Collaborators and Investigators

• Sponsor: Medical University of Vienna
• Investigators: Principal Investigator: Rupert R Lanzenberger, A/Prof. MD, Department of Psychiatry and Psychotherapy, Medical University of Vienna

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 9, 2011
• First Posted (Estimate): February 10, 2011

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 8, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Sexual Dysfunctions, Psychological; Gender Dysphoria; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: P23021FWF