Brain Health in Transgender Adults

Official title

Cerebral Blood Flow and Neurocognitive Performance in Adults Undergoing Gender-affirming Hormone Therapy

Overview

The purpose of this study is to test whether and how a person's brain changes in the first few months after starting gender affirming hormone therapy (GAHT). The investigators want to know if GAHT changes: 1) cerebral blood flow (CBF), 2) brain structure, connectivity, and cognitive task performance, and 3) neurocognitive function (memory, attention, executive function, processing speed). 36 male at birth and 36 female at birth participants will conduct baseline studies prior to GAHT, with a second identical set of study visits 4-6 months after GAHT begins.

Detailed description

The purpose of this study is to assess the effects of GAHT on cerebral structure and function. To this end, this study has three aims:

Aim 1: To identify if transgender males and females demonstrate changes in

* A) basal CBF and * B) CBF responses to acute stress-particularly in areas involved in cognition, memory, and learning.

Aim 2: To identify if transgender adults will demonstrate significant changes in:

* A) overall brain structure, * B) functional connectivity, and * C) task activation.

Aim 3: To identify if neurocognitive function changes in transgender adults.

The investigators hypothesize that:

* Aim 1: Transgender females will demonstrate increased basal CBF and larger CBF responses to acute stress, particularly in areas involved in cognition, memory, and learning, whereas transgender males will display lower basal CBF and lower CBF responses to acute stress. * Aim 2: Transgender patients will demonstrate significant changes in: a) overall brain structure, b) functional connectivity, and c) task activation. * Aim 3: Neurocognitive function will increase in transgender females and decreases in transgender males, primarily in the domains of memory, attention, executive function, and processing speed.

Interventions

• Device Magnetic Resonance Imaging
  Two MRI visits (baseline and after 4-6 months of continuous GAHT) will involve structural scans of the brain, scans while performing cognitive tasks, and a scan taken while responding to an inhaled CO2 stressor. This visit will take approximately 1.5 hours.
• Other Cognition and Health Tests
  Two cognition and health test trials (baseline and after 4-6 months of continuous GAHT) will involve a body composition scan to determine body fat percentage, muscle mass, and bone density. This will be followed by a set of cognitive tasks using the NIH Toolbox.
• Other Optional Exercise Test
  Optional graded exercise test will be performed if the participant consents to this optional procedure (baseline and after 4-6months of continuous GAHT). to determine cardiorespiratory fitness. This test will be performed on a cycle ergometer, with a metabolic allowing for the measurement of maximal oxygen consumption via indirect calorimetry.

Primary outcome measures

• Change Cerebral Blood Flow (CBF) [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Brain Structure [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Brain Connectivity [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cognitive Function: Flanker Inhibitory Control and Attention [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cognitive Function: Pattern Comparison Processing Speed Test [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cognitive Function: List Sorting Working Memory Test [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cognitive Function: Dimensional Change Card Sort Test [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cognitive Function: Picture Vocabulary Test [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]

Secondary outcome measures (7)

• Change Cerebral Blood Flow (CBF) [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Changes in sex steroid concentrations [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Body Composition [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Blood Glucose [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Insulin [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Change in Cytokines [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]
• Optional Graded Exercise Test: VO2 Max [Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)]

Eligibility criteria

Inclusion criteria

• intention to undergo GAHT

Exclusion criteria

• BMI greater than 40 kg/m2
• Age greater than 45 yrs
• Blood pressure greater than 140/90 (stage II hypertension)
• A current diagnosis of type II diabetes
• History of traumatic brain injury/concussion, stroke, or seizures
• Are post-menopausal
• Previously taken hormone therapy medications
• Self-reported pregnancy (no pregnancy test)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Cohort

Study locations

United States · 1 center

• UW School of Medicine and Public Health — Madison

Identifiers

NCT: NCT07624747 · 2024-1861 · Protocol Version 1/12/26 · SOE/Kinesiology

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗