Effects of Aging and Gender-Affirming Hormone Therapy on Vascular Endothelial Function and Metabolic Profiles in Transgender Women

Novel Evaluations of Aging and Gender-Affirming Hormone Therapy on Vascular Endothelial Function and Metabolic Profiles in Transgender Women Compared to Age Group-Matched Cisgender Adults

This study will examine markers of vascular endothelial function (vascular health) and metabolic profiles in younger versus older transgender women (people who were assigned male at birth but whose gender identity is female). Data will also be compared to those from cisgender women and men.

Study Overview

• Status: Recruiting
• Conditions: Blood Pressure; Vascular Stiffness; Lipid Disorder; Insulin Sensitivity; Appetitive Behavior; Gender Identity; Transgender; Vascular Inflammation

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Amanuail Gebregzabheir; Email: amanuail.gebregzabheir@cuanschutz.edu
• Study Contact Backup: Name: Sean Iwamoto, MD; Phone Number: 303-724-3662; Email: sean.iwamoto@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Amanuail Gebregzabheir; Email: amanuail.gebregzabheir@cuanschutz.edu
      • Contact: Sean Iwamoto, MD; Phone Number: 303-724-3662; Email: sean.iwamoto@cuanschutz.edu
      • Principal Investigator: Sean Iwamoto, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Transgender women from the Denver metropolitan area and/or who utilize health care at University of Colorado Hospital.

Description

Inclusion Criteria:

• Aged 18-40 years old or 50-75 years old
• Identify as a transgender woman
• Have taken estradiol and spironolactone for at least one year
• Currently taking oral or transdermal estradiol

Exclusion Criteria:

• Don't identify as a transgender woman
• Not currently taking estradiol or spironolactone
• Have been on estradiol and spironolactone for less than one year
• History of orchiectomy
• Current tobacco smoker
• Current illicit drug use
• History of prior or active estrogen-dependent neoplasms
• Acute liver or gallbladder disease
• Venous thromboembolism
• Hypertriglyceridemia >500 mg/dL
• Fasted plasma glucose >7.0 mmol/L or previously treated diabetes
• Resting blood pressure >140/90 mmHg

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Older transgender women; This cohort will consist of transgender women aged 50-75 years old who have taken estradiol and spironolactone for at least one year.
Younger transgender women; This cohort will consist of transgender women aged 18-40 years old who have taken estradiol and spironolactone for at least one year.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of endothelial function (flow-mediated dilation (FMD)	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin sensitivity		Baseline
Alcohol use		Baseline
Blood pressure		Baseline
Evaluation of carotid artery compliance	The carotid artery compliance index indicates how elastic the artery is. The index describes the change in arterial blood volume in response to a change in arterial blood pressure. Lower numbers are associated with worse outcomes (less elastic arteries).	Baseline
Carotid artery intimal-medial thickness		Baseline
Evaluation of oxidant burden: oxidized LDL	Oxidized low-density lipoprotein (LDL) measured in the blood and endothelial cells.	Baseline
Evaluation of oxidant burden: nitrotyrosine	Nitrotyrosine measured in the blood and endothelial cells.	Baseline
Evaluation of vascular endothelial cell inflammation: NFkB	Protein NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) measured in blood and endothelial cells.	Baseline
Evaluation of vascular endothelial cell inflammation: MCP-1	Monocyte Chemoattractant Protein-1 (MCP-1) measured in blood and endothelial cells.	Baseline
Evaluation of vascular endothelial cell inflammation: IL-6	Interleukin 6 (IL-6) measured in blood and endothelial cells.	Baseline
Evaluation of vascular endothelial cell inflammation: CRP	C-reactive protein (CRP) measured in blood and endothelial cells.	Baseline
Plasma lipid concentrations: total cholesterol	Total cholesterol will be determined at baseline.	Baseline
Plasma lipid concentrations: triglycerides	Triglycerides will be determined at baseline.	Baseline
Whole body composition: Percent Lean Mass	Percent lean mass will be determined using dual energy x-ray absorptiometry.	Baseline
Whole body composition: Percent Fat Mass	Percent fat mass will be determined using dual energy x-ray absorptiometry.	Baseline
Regional body composition: Percent Lean Mass	Regional percent lean mass will be determined using dual energy x-ray absorptiometry.	Baseline
Regional body composition: Percent Fat Mass	Regional percent fat mass will be determined using dual energy x-ray absorptiometry.	Baseline
Appetite ratings		Baseline
Appetite-related peptides		Baseline
D-Dimer		Baseline
Depression symptoms		Baseline
Physical activity monitoring	Physical activity will me monitored for 7 days with an ActivPALmonitor	7 days
Energy intake	Energy intake will be estimated with a 3-day food diary	3 days
Evaluation of carotid artery beta stiffness index	The carotid artery beta stiffness index indicates how stiff the artery is. Higher numbers are associated with worse outcomes (stiffer artery).	Baseline
Weight changes		Baseline

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Sean Iwamoto, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2019
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2024

Study Registration Dates

• First Submitted: June 17, 2019
• First Submitted That Met QC Criteria: August 21, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Estimated): December 4, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Inflammation; Insulin Resistance; Lipid Metabolism Disorders
• Other Study ID Numbers: 18-2258

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