Brain Health in Transgender Adults

NCT07624747 | Recruiting DMC

• 3 other identifiers: 2024-1861Protocol Version 1/12/26SOE/Kinesiology
• Study Type: observational
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Gender Dysphoria

Keywords

Gender-Affirming Hormone Therapy; brain health

Outcome Measures

Primary Outcomes (8)

• Change Cerebral Blood Flow (CBF)

  CBF at rest and in response to cognitive stressors.

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

• Change in Brain Structure

  Grey matter and White matter volumes.

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

• Change in Brain Connectivity

  Measured using MRI.

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

• Change in Cognitive Function: Flanker Inhibitory Control and Attention

  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.

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

• Change in Cognitive Function: Pattern Comparison Processing Speed Test

  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.

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

• Change in Cognitive Function: List Sorting Working Memory Test

  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.

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

• Change in Cognitive Function: Dimensional Change Card Sort Test

  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.

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

• Change in Cognitive Function: Picture Vocabulary Test

  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.

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

Secondary Outcomes (7)

• Change Cerebral Blood Flow (CBF)

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

• Changes in sex steroid concentrations

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

• Change in Body Composition

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

• Change in Blood Glucose

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

• Change in Insulin

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

Study Arms (2)

Male at birth undergoing GAHT with their Clinical Care Team

Device: Magnetic Resonance Imaging; Other: Cognition and Health Tests; Other: Optional Exercise Test

Female at birth undergoing GAHT with their Clinical Care Team

Device: Magnetic Resonance Imaging; Other: Cognition and Health Tests; Other: Optional Exercise Test

Interventions

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.

Also known as: MRI

Female at birth undergoing GAHT with their Clinical Care Team; Male at birth undergoing GAHT with their Clinical Care Team

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.

Female at birth undergoing GAHT with their Clinical Care Team; Male at birth undergoing GAHT with their Clinical Care Team

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.

Female at birth undergoing GAHT with their Clinical Care Team; Male at birth undergoing GAHT with their Clinical Care Team

Eligibility Criteria

• Age: 18 Years - 45 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Adults (18-45 years) undergoing gender affirming hormone therapy with their clinical health care team.

You may qualify if:

• intention to undergo GAHT

You may not qualify if:

• 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)

Sponsors & Collaborators

• University of Wisconsin, Madison: lead

Study Sites (1)

UW School of Medicine and Public Health

Madison, Wisconsin, 53792, United States

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

de-identified blood samples

MeSH Terms

Conditions

Gender Dysphoria

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Sexual Dysfunctions, Psychological; Mental Disorders

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• William Schrage, PhD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shawn Bolin, MS

CONTACT

608-263-6308; sbolin@wisc.edu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2026
• First Posted: June 3, 2026
• Study Start: October 14, 2025
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: June 3, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)