Effect of Hormones on Frequency of Headache and Brain Structure and Function in Puberty

With a rising population of transgender adults and youth, there is a need for more research to meet the needs of this community. Transfemale (MTF) youth (male sex, female gender identity) who begin clinical Gender Affirming Hormone Therapy (GAHT) with estrogen may be at a higher risk for headache since estrogen has been linked to headache in cisgender females (female sex, female gender identity). This research hopes to learn more about headache in MTF youth.

Study Overview

• Status: Recruiting
• Conditions: Headache; Gender Identity
• Intervention / Treatment: Other: Clinical estrogen therapy

Detailed Description

MTF youth who will begin estrogen clinically will be enrolled in the study and will be seen twice, once before starting estrogen and then one year after beginning estrogen. Cisgender males (male sex, male gender identity) will also be enrolled as a control group and will be seen once at the beginning of the study and then once a year later. The researchers will track how often youth have headaches during this time to see if it is different between groups. In a subset of the youth enrolled, an MRI will be completed to also look at brain structure and function.

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Emily Albertson; Phone Number: 720-777-9941; Email: emily.albertson@childrenscolorado.org
• Study Contact Backup: Name: Lauren Mitchell; Phone Number: 720-777-5282; Email: lauren.2.mitchell@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Emily Albertson; Phone Number: 720-777-9941; Email: emily.albertson@childrenscolorado.org
      • Principal Investigator: Jennifer Hranilovich, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Study population is limited to transgender females (male sex, female gender identity) for the case population and cisgender males (male sex, male gender identity) for the purposes of the study analysis as outlined in the protocol.

Description

Inclusion Criteria:

For MTF youth (cases):

• Identify as MTF
• Age 11-20 years at the time of enrollment
• Plan to start estrogen clinically in < 6 months

For cisgender male youth (controls):

• Identify as cisgender male
• Age 9-20 years at the time of enrollment
• No diagnosis of Klinefelter Syndrome (XXY)

Exclusion Criteria:

• Cognitive, or psychiatric impairment resulting in inability to tolerate the study procedures not including depression or anxiety

• Known history of stroke, multiple sclerosis, or other serious neurologic condition

  • MRI-specific exclusion criteria (Weight > 500 lbs, claustrophobia, metal in body)

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cases; MTF youth who will begin taking estrogen clinically in < 6 months with or without headache	Other: Clinical estrogen therapy; No research interventions will be used as a part of the study since the research is observational. Estrogen treatment will be prescribed and followed by participant's clinical physician.
Controls; Cisgender males with or without headache

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in frequency of headache.	Measured by headache count from daily headache diary.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in amygdala structure.	Amygdala volume as measured on MRI.	1 year
Change in resting state functional connectivity pattern.	Measured by proportion of between-module connectivity patterns vs. within-module connectivity patterns.	1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): December 14, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Estimated): February 5, 2024
• Last Update Submitted That Met QC Criteria: January 31, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Headache; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens
• Other Study ID Numbers: 20-1824

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