Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07624747

Brain Health in Transgender Adults

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Gender Dysphoria Mental Disorders Sexual Dysfunctions, Psychological

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Observational

Primary location

UW School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

Location status: Recruiting

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Magnetic Resonance Imaging

Device

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 names: MRI

Cognition and Health Tests

Other

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.

Optional Exercise Test

Other

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 outcomes

  1. Change Cerebral Blood Flow (CBF)

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    CBF at rest and in response to cognitive stressors.

  2. Change in Brain Structure

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Grey matter and White matter volumes.

  3. Change in Brain Connectivity

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Measured using MRI.

  4. Change in Cognitive Function: Flanker Inhibitory Control and Attention

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    NIH Toolbox to assess neurocognitive function. The Flanker test is a measure of executive function and is scored using a T-score where 100 is the average, higher scores indicate better performance.

  5. Change in Cognitive Function: Pattern Comparison Processing Speed Test

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    NIH Toolbox to assess neurocognitive function. The Pattern Comparison Processing Speed Test measures how many correct responses the participant has within 90 seconds. There is a maximum of 130 items.

  6. Change in Cognitive Function: List Sorting Working Memory Test

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    NIH Toolbox to assess neurocognitive function. The List Sorting Working Memory Test is a measure of recall and sorting. Participants scores reflect the number of items recalled and appropriately sorted up to 28 items maximum.

  7. Change in Cognitive Function: Dimensional Change Card Sort Test

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    NIH Toolbox to assess neurocognitive function. The Dimensional Change Card Sort Test measures accuracy: the number of accurate responses, up to a maximum of 40.

  8. Change in Cognitive Function: Picture Vocabulary Test

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    NIH Toolbox to assess neurocognitive function. The Picture Vocabulary Test has the participant hear a word and then pick from one of four pictures that best represents the word. It is scored using a T-score where 100 is the average, higher scores indicate better performance.

Secondary outcomes

  1. Change Cerebral Blood Flow (CBF)

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Changes in CBF in response to inhaled mixture of room air and CO2

  2. Changes in sex steroid concentrations

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

  3. Change in Body Composition

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Dual-energy X-ray absorptiometry (DEXA)

  4. Change in Blood Glucose

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Glucose is a marker of metabolic health

  5. Change in Insulin

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Insulin is a marker of metabolic health.

  6. Change in Cytokines

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    Cytokines are a marker of inflammation.

  7. Optional Graded Exercise Test: VO2 Max

    Time frame: baseline and up to 6 months (after 4-6 months of continuous GAHT)

    An optional graded exercise test will be performed 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. This will be a ramped exercise test, starting at a wattage of 50W and increasing in difficulty by 1 watt every 2 seconds. The purpose of this is to begin at a low intensity and gradually increase the difficulty until exhaustion is reached.

Study contacts

Contact information is provided by the study sponsor or research team.

Shawn Bolin, MS

CONTACT

[email protected]

608-263-6308

Sponsors and collaborators

Lead sponsor

University of Wisconsin, Madison

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Jun 3, 2026
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.