Puberty, Testosterone, and Brain Development

Effect of Testosterone on Brain Imaging and Headache in Transmasculine Adolescents

Transmasculine youth (female sex assigned at birth, male gender identity) who begin clinical gender affirming hormone therapy (GAHT) with testosterone (T) may experience changes in headache. Researchers think this because studies published on effects of giving testosterone to cisgender females (female sex, female gender identity) and transmasculine adults seem to show an effect on pain.

This research will help us learn more about changes in headache and in brain structure and function in transmasculine youth during the first two years of T. Youth who will be starting T within 6 months, either on puberty blocker or not, as part of their regular medical care can participate and will be asked to attend 4 visits:

• before starting T
• after 6 months on T
• after 1 year on T
• after 2 years on T

At the visits, they will be asked to:

• answer questions and surveys about their health
• have a brain MRI done
• give a small sample of blood

and at their first visit, complete a physical exam. Some participants can also do a brief test of pain sensitivity. All participants will be asked to complete a headache diary for the first 6 months, for 1 month after the 1 year visit, and for 1 month after the 2 year visit.

Study Overview

• Status: Recruiting
• Conditions: Headache; Gender Identity; Transgender; Gender Dysphoria in Adolescents and Adults
• Intervention / Treatment: Drug: Testosterone

Detailed Description

This will be conducted at Childrens Hospital Colorado (CHCO) Clinical & Translational Research Centers (CTRC) facilities. Physical examination will include vital signs, anthropometric measurements, and breast/pubic hair staging, as applicable, by a medical provider.

Visits will be in the morning to capture peak hormone levels.

The following questionnaires will be administered: PROMIS Pediatric Anxiety Short Form, PROMIS Pediatric Depressive Symptoms Short Form, and PedMIDAS form (headache disability measure).

The daily headache diary is tailored to be brief on days when no headache occurs, and to capture more detail including medications taken and headache and aura characteristics on days a headache does occur.

The medical chart will be reviewed for relevant health information and medications.

MR-based imaging will be conducted at the Brain Imaging Center at the University of Colorado Anschutz Medical Campus.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Jennifer Hranilovich, MD; Phone Number: (720)-777-6895; Email: headache-research@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Jennifer Hranilovich; Phone Number: 720-777-6895; Email: headache-research@childrenscolorado.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

transmasculine and gender diverse youth

Description

Inclusion Criteria:

1. transmasculine and gender diverse
2. assigned female at birth
3. age 12-20 years at the time of enrollment
4. plan to start testosterone clinically in < 6 months
5. if taking gonadotropin releasing hormone agonist (GnRHa, puberty blocker), was started on this type of drug 3+ months prior to enrollment

Exclusion Criteria:

1. cognitive or psychiatric impairment resulting in inability to tolerate or perform the study procedures
2. known history of stroke, multiple sclerosis, or other serious neurologic condition
3. prior diagnosis of Turner Syndrome (monosomy X) or other difference of sexual development
4. prior diagnosis of polycystic ovarian syndrome (PCOS)
5. uncontrolled or untreated hypothyroidism
6. MRI-specific exclusion criteria: (Weight > 500 lbs, severe claustrophobia, certain type of metal in body)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
On blocker; Transmasculine youth who will begin taking testosterone clinically in < 6 months with or without headache and who have been on pubertal blocker, a gonadotropin hormone releasing (GnRH) agonist for at least 3 months.	Drug: Testosterone; Clinical testosterone therapy No research interventions will be used as a part of the study since the research is observational. Testosterone treatment will be prescribed and followed by participant's clinical physician.
No blocker; Transmasculine youth who will begin taking testosterone clinically in < 6 months with or without headache and who have no history of pubertal blocker.	Drug: Testosterone; Clinical testosterone therapy No research interventions will be used as a part of the study since the research is observational. Testosterone treatment will be prescribed and followed by participant's clinical physician.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amygdala volume	As measured by volumetric MRI	At the end of the two years of study
Change in headache burden	Change in number of headache days per month	Over the two years of the study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Headache diagnosis	Application of ICHD-3 criteria to headaches, if any	At baseline visit before start of T

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Investigators: Principal Investigator: Jennifer Hranilovich, Children's Hospital Colorado

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2024
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 23, 2024
• First Submitted That Met QC Criteria: October 31, 2024
• First Posted (Actual): November 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: April 2, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: MRI; fMRI; migraine; testosterone; resting-state functional connectivity; pain task; gender affirming hormone therapy
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Mental Disorders; Sexual Dysfunctions, Psychological; Gender Dysphoria; Headache; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Androgens; Testosterone
• Other Study ID Numbers: 23-1113

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No