Cross-sex Hormone Therapy and Neuronal Plasticity

Gender Dysphoria Clinical Trial

Official title:

Neuroactive Sex Steroids And Their Influence In Glutamatergic Neurotransmission - Effects in Memory and Cognition in Transgender People

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03651427
• Other study ID #: 150199a
• Status: Recruiting
• Phase: N/A
• Start date: February 13, 2017
• Est. completion date: March 30, 2019

Study information

• Verified date: August 2018
• Source: Hospital de Clinicas de Porto Alegre
• Contact: Maiko Schneider, MD
• Phone: 5551997722606
• Email: maikoschneider[@]hcpa.edu.br
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Transgender women (male-to-female) were invited to participate in this study to test the impact of Cross-Sex Hormone Therapy (CSHT) in the brain.

Neuroimaging and cognitive assessment were performed in different time-points to compare the impact of CSHT in the brain.

Description:

Sex hormones are known to exert several effect on the brain white matter, cerebral cortex, functional connectivity and neurotransmission. Furthermore, in transgender people, CSHT is know to induce anatomical and functional changes in the brain. However, only a few studies have already been conducted to investigate the effects of sex hormones on the brain accounting for the interference of endogenous gonadal hormones. Also, there is a lack of knowledge about the importance of CSHT after Gender Affirming Surgery (GAS) regarding induced hypogonadism that follows this surgical procedure. Therefore, neuroimaging studies designed to isolate the effect of endogenous gonadal hormones in people with GD urge to be developed.

To fulfil this purpose, transgender women that have already performed GAS and/or were under Gonadotrophin Release Hormone analogues treatment (in order to induce hypogonadism similar to GAS) were invited to interrupt CSHT for at least 30 days to promote sex hormones washout. At the end of the washout, participants performed magnetic resonance imaging, laboratorial analyses for sex hormones and neuro-cognitive assessment. After this first time-point, participants received a new prescription for CSHT containing estradiol (without progesterone) to be used continuously for 60 days, when the same assessments from the end of washout were repeated 60 days after CSHT to compare brain and cognitive longitudinal changes.

At all the time-points, variations in depression scores and anxiety levels were assessed with specific scales.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: March 30, 2019
• Est. primary completion date: March 30, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Transgender women

• Age 18 to 60 years old.

Exclusion Criteria:

• Use of psychostimulant drugs

• Use of Antidepressive, Mood Stabiliser, Anti-psychotic, Benzodiazepines, anti-convulsivants, Anorexigenic

• Endocrinological disease (other than diabetes)

• Arterial Hypertensive Disease of Diabetes Mellitus out of control target

• Neurological disease, including stroke or recent cranial trauma with loss or consciousness

• HIV with low CD4 or high viral charge or symptomatic AIDS

• Neoplasia

Related Conditions & MeSH terms

• Gender Dysphoria

Intervention

Drug:
• Estradiol
Induced hypogonadism and re-institution of CSHT

Locations

Country	Name	City	State
Brazil	Hospital de Clínicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

Salgado JV, Malloy-Diniz LF, Abrantes SS, Moreira L, Schlottfeldt CG, Guimarães W, Freitas DM, Oliveira J, Fuentes D. Applicability of the Rey auditory-verbal learning test to an adult sample in Brazil. Rev Bras Psiquiatr. 2011 Sep;33(3):234-7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glutamate concentration in the left hippocampus	Proton Spectroscopy - magnetic resonance imaging; Glutamate concentration in the left hippocampus will be primarily correlated to working memory scores.	90 days
Secondary	Cortical Thickness	Anatomical magnetic resonance imaging	90 days
Secondary	Diffusion track imaging	Micro-Structural magnetic resonance imaging	90 days
Secondary	functional connectivity	functional magnetic resonance imaging	90 days
Secondary	Glutamate concentration in the anterior cingulate cortex and left dorsolateral prefrontal cortex	Proton spectroscopy - magnetic resonance imaging; Glutamate concentration in the left dorsolateral prefrontal cortex will be correlated to over all measures of cognition and executive functioning.	90 days
Secondary	Cognition	Instrument: Wechsler Adult Intelligence Scale (WAIS) version 3. Subscale: Full Scale Intelligence coefficient. Mean: 100 Standard deviation (SD):15 for Brazilian population. Range of classification: 69 and below - Extremely Low 70-79 - Borderline 80-89 - Low Average 90-109 - Average 110-119 - High Average 120-129 - Superior 130 and above - very superior	90 days
Secondary	Operational memory	Subscale from Wechsler Adult Intelligence Scale (WAIS) version 3. Mean: 100 Standard deviation (SD):15 for Brazilian population. 69 and below - Extremely Low 70-79 - Borderline 80-89 - Low Average 90-109 - Average 110-119 - High Average 120-129 - Superior 130 and above - very superior	90 days
Secondary	Verbal memory	Rey Auditory-Verbal Learning Test (RAVLT). Mean and range for Brazilian population: A1 (Verbal Memory - Immediate recall). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected; A5 (Verbal Memory - immediate recall). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected; A7 (Verbal Memory - late recall). Range in (Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected; Learning Over Trial (LOT) (Learning capacity). Range (in Z-scores): Z <-1.5 are classified as deficit; Z >-1.5 are expected (please, note the reference for Brazilian population in the section "references" where the mean and standard deviation according to Brazilian population are described for each of the subtest; Salgado et al. (2011).	90 days
Secondary	Language (Verbal Fluency)	Verbal Fluency Tests: (FAS) and Animals.; Mean and standard deviation (SD) according to age range and years of education: Age range for the test: 16-59 years; Score classification according to years of education: From 0 to 8 years of education: Mean: 38.8 SD: 12.0; From 9 to 12 years of education: Mean: 40.5 SD: 10.7; From 12 to 21 years of education: Mean: 44.7 SD:11.2; Range in Z-scores: Z <-1.5 are classified as deficit; Z >-1.5 are expected	90 days
Secondary	Executive function	Stroop Test -Victoria Version.; Mean and standard deviation (SD) according to the age range and years of education: For 19-39 years old + 5-8 years of education: Mean: 33.3 SD:11.35; For 19-39 years old + 9 or more years of education: Mean: 41.73 SD: 9.85; For 40-59 years old + 5-8 years of education: Mean: 28 SD: 7.76; For 40-59 years old + 9 or more years of education: Mean: 37.17 SD: 9.98; Range in Z-scores: Z <-1.5 are classified as deficit; Z >-1.5 are expected	90 days

External Links

•   This references is related to the "verbal memory" evaluation, described in the outcomes.