Effects of Sex Steroids on the Serotonin System

NCT02715232 | Unknown Phase 4

• 1 other identifier: 1.1-20150511
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to prove the modulatory influence of sex hormones on serotonergic neurotransmission by determining the enzymatic processes involved in serotonin synthesis and degradation using positron emission tomography (PET) in humans in vivo with the radiotracers \[11C\]AMT and \[11C\]harmine.

Conditions

Gender Dysphoria

Outcome Measures

Primary Outcomes (2)

• blood-to-brain clearance/trapping (K*) of [11C]AMT

  \[11C\]AMT trapping as an estimation of brain serotonin synthesis in vivo in humans

  <5 months

• distribution volume (DV) of [11C]harmine

  distribution volume of specifically bound radioligand \[11C\]harmine in brain regions

  <5 months

Secondary Outcomes (5)

• white and gray matter microstructure

  <5 months

• gray matter volume/density and cortical thickness

  <5 months

• cerebral blood flow (CBF)

  <5 months

• Scores on the Klein Sexual Orientation Grid (KSOG)

  <5 months

• Scores on the Utrecht Gender Dysphoria Scale

  <5 months

Study Arms (4)

Female-to-Males

EXPERIMENTAL

Female-to-Male Transsexuals receiving Testosterone treatment

Drug: Testosterone; Drug: Lynestrenol; Drug: Triptorelin acetate

Male-to-Females

EXPERIMENTAL

Male-to-Female Transsexuals receiving Estradiol and Anti-androgen treatment

Drug: Cyproterone Acetate; Drug: Estradiol; Drug: Triptorelin acetate

Female Controls

NO INTERVENTION

Female Controls receiving no intervention

Male Controls

NO INTERVENTION

Male controls receiving no intervention

Interventions

Testosterone DRUG

100mg testosterone undecanoat every 8-12 weeks, or alternatively 50mg testosterone transdermally, or 50mg testosterone creme

Female-to-Males

Lynestrenol DRUG

2-3 tablets/day, if menstruation still occurs

Female-to-Males

Cyproterone Acetate DRUG

25mg daily

Male-to-Females

Estradiol DRUG

75 microgram transdermal therapeutic system twice a week, or p.o. estradiol 2x2mg/day, or estradiol gel 1,5-3mg

Male-to-Females

Triptorelin acetate DRUG

4,12mg every 4-6 weeks (powder for suspension for injection s.c. or i.m.

Female-to-Males; Male-to-Females

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• DSM-5 diagnosis of Gender Dysphoria (DSM-5: 302.85; ICD-10: F64.1) (for transsexuals only)
• Somatic health based on history, physical examination, ECG, laboratory screening, SCID
• willingness and competence to sign the informed consent form

You may not qualify if:

• concomitant major medical or neurological illness
• internal or neurologic medical histories as well as pregnancy (positive urine pregnancy test) or breastfeeding
• other DSM-5 Axis-I comorbidities, determined by a structured clinical interview (SCID), especially body dysphoric disorder (DSM-5: 300.7; ICD-10: F45.22), schizophrenia spectrum and other psychotic disorders
• 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 or current or past substance related disorder
• for participants who participated in an earlier neuroimaging study using ionizing radiation, the total radiation exposure dose of 20 mSv over the last 10 years must not be exceeded, as specified in the legislation on radiation protection (Allg. Strahlenschutzverordnung 2010; www.ris.bka.gv.at)
• failure to comply with the study protocol or to follow the instructions of the investigating team

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Department of Psychiatry and Psychotherapy, Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (8)

• Kranz GS, Wadsak W, Kaufmann U, Savli M, Baldinger P, Gryglewski G, Haeusler D, Spies M, Mitterhauser M, Kasper S, Lanzenberger R. High-Dose Testosterone Treatment Increases Serotonin Transporter Binding in Transgender People. Biol Psychiatry. 2015 Oct 15;78(8):525-33. doi: 10.1016/j.biopsych.2014.09.010. Epub 2014 Sep 23.

  PMID: 25497691 BACKGROUND

• Kranz GS, Hahn A, Kaufmann U, Kublbock M, Hummer A, Ganger S, Seiger R, Winkler D, Swaab DF, Windischberger C, Kasper S, Lanzenberger R. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging. J Neurosci. 2014 Nov 12;34(46):15466-75. doi: 10.1523/JNEUROSCI.2488-14.2014.

  PMID: 25392513 BACKGROUND

• Hahn A, Kranz GS, Kublbock M, Kaufmann U, Ganger S, Hummer A, Seiger R, Spies M, Winkler D, Kasper S, Windischberger C, Swaab DF, Lanzenberger R. Structural Connectivity Networks of Transgender People. Cereb Cortex. 2015 Oct;25(10):3527-34. doi: 10.1093/cercor/bhu194. Epub 2014 Sep 12.

  PMID: 25217469 BACKGROUND

• Hahn A, Kranz GS, Sladky R, Kaufmann U, Ganger S, Hummer A, Seiger R, Spies M, Vanicek T, Winkler D, Kasper S, Windischberger C, Swaab DF, Lanzenberger R. Testosterone affects language areas of the adult human brain. Hum Brain Mapp. 2016 May;37(5):1738-48. doi: 10.1002/hbm.23133. Epub 2016 Feb 15.

  PMID: 26876303 BACKGROUND

• Smith LJ, Henderson JA, Abell CW, Bethea CL. Effects of ovarian steroids and raloxifene on proteins that synthesize, transport, and degrade serotonin in the raphe region of macaques. Neuropsychopharmacology. 2004 Nov;29(11):2035-45. doi: 10.1038/sj.npp.1300510.

  PMID: 15199371 BACKGROUND

• Aggarwal M, Puri V, Puri S. Effects of estrogen on the serotonergic system and calcitonin gene-related peptide in trigeminal ganglia of rats. Ann Neurosci. 2012 Oct;19(4):151-7. doi: 10.5214/ans.0972.7531.190403.

  PMID: 25205989 BACKGROUND

• Purves-Tyson TD, Handelsman DJ, Double KL, Owens SJ, Bustamante S, Weickert CS. Testosterone regulation of sex steroid-related mRNAs and dopamine-related mRNAs in adolescent male rat substantia nigra. BMC Neurosci. 2012 Aug 6;13:95. doi: 10.1186/1471-2202-13-95.

  PMID: 22867132 BACKGROUND

• Klobl M, Reed MB, Handschuh P, Kaufmann U, Konadu ME, Ritter V, Spurny-Dworak B, Kranz GS, Lanzenberger R, Spies M. Gender Dysphoria and Sexual Euphoria: A Bayesian Perspective on the Influence of Gender-Affirming Hormone Therapy on Sexual Arousal. Arch Sex Behav. 2024 May;53(5):1859-1871. doi: 10.1007/s10508-023-02778-1. Epub 2024 Jan 12.

  PMID: 38216784 DERIVED

MeSH Terms

Conditions

Gender Dysphoria

Interventions

Testosterone; Lynestrenol; Cyproterone Acetate; Estradiol; Triptorelin Pamoate

Condition Hierarchy (Ancestors)

Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Norpregnenes; Norpregnanes; Norsteroids; Cyproterone; Pregnadienes; Pregnanes; Steroids, Chlorinated; Estrenes; Estranes; Estradiol Congeners; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Study Officials

• Rupert Lanzenberger, MD

  Department of Psychiatry and Psychotherapy, Medical University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rupert Lanzenberger, MD

CONTACT

+43 40400; rupert.lanzenberger@meduniwien.ac.at

Georg S Kranz, PhD

CONTACT

+43 40400; georg.kranz@meduniwien.ac.at

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assoc. Prof.

Study Record Dates

• First Submitted: March 16, 2016
• First Posted: March 22, 2016
• Study Start: February 6, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: October 15, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)