Pubertal Blockade and Estradiol Effects on Cardiometabolic Health for Transitioning Youth (PUBERTY)

To evaluate the effect of estradiol with or without a prior gonadotropin releasing hormone analogue on insulin sensitivity and vascular function in transgender females compared to cisgender controls.

Study Overview

• Status: Recruiting
• Conditions: Gender Dysphoria; Insulin Sensitivity; Transgenderism

• Study Type: Observational
• Enrollment (Estimated): 90

Contacts and Locations

• Study Contact: Name: Natalie Nokoff, MD, MSCS; Phone Number: 720-777-3607; Email: Natalie.Nokoff@childrenscolorado.org

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Children's Hospital Colorado
      • Contact: Natalie Nokoff, MD; Phone Number: 720-777-3607; Email: natalie.nokoff@childrenscolorado.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 16 years (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Transgender and cisgender adolescents

Description

Inclusion Criteria (transgender females):

• Identify as a transgender female
• Age 13-16 years at the time of enrollment
• If on a gonadotropin releasing hormone analogue, > 6 months exposure
• Plan to start estradiol clinically in < 4 months

Inclusion Criteria (cisgender males and females):

• Males and females ages 13-16 years

Exclusion Criteria:

• Cognitive, psychiatric, or physical impairment resulting in inability to tolerate the study procedures
• Antipsychotic medication use
• Type 1 or 2 diabetes (by medical history)
• Polycystic ovarian syndrome (PCOS for cisgender females)
• Hypertension (resting BP ≥ 140/90 mm/Hg)
• Weight> 400 lbs
• On oral progesterone medications (including oral progesterone or progestin, combined oral contraceptives or etonogestrel implant)
• Pregnancy (for cisgender females)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Transgender
Cisgender

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Insulin sensitivity	Change from baseline to 12 months
Brachial artery flow mediated dilation	Change from baseline to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Large artery stiffness	Carotid artery ultrasound	Change from baseline to 12 months
Cerebrovascular function	Middle cerebral artery blood flow	Change from baseline to 12 months
VO2 peak		Change from baseline to 12 months
Fat mass	DXA	Change from baseline to 12 months
Fat-free mass	DXA	Change from baseline to 12 months

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Natalie Nokoff, MD, MSCS, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 20, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): June 10, 2025
• Last Update Submitted That Met QC Criteria: June 5, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Glucose Metabolism Disorders; Hyperinsulinism; Sexual Dysfunctions, Psychological; Gender Dysphoria; Insulin Resistance
• Other Study ID Numbers: 19-1226; 1K23HL151868-01 (U.S. NIH Grant/Contract)

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