The Effects of Orchiectomy and Age on Vascular and Metabolic Health in Older Versus Younger Transgender Women

This study plans to learn more about differences in heart disease risk after gender-affirming orchiectomy (i.e., testes removal) in older transgender (trans) women compared to younger trans women.

Study Overview

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

Detailed Description

The global aim of this study is to characterize cardiometabolic risk (measured by vascular, metabolic and biochemical factors-which have not been extensively studied prospectively) in trans women before and after orchiectomy. Trans women appear to be at greater risk for cardiovascular disease (CVD) and blood clots compared to non-trans adults. The effect of orchiectomy on CVD risk among trans women is unknown, but orchiectomy may change blood vessel function and metabolic health. The investigators will examine blood vessel function and metabolic profiles of trans women before and at several timepoints after orchiectomy to identify age-related differences in CVD risk factors. This knowledge may lead to new approaches to prevent CVD in trans women as well as all people regardless of gender identity.

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

Contacts and Locations

• Study Contact: Name: Sean Iwamoto, MD; Phone Number: 303-724-8534; Email: sean.iwamoto@cuanschutz.edu
• Study Contact Backup: Name: Amanuail Gebregzabheir; Email: amanuail.gebregzabheir@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado
      • Contact: Sean Iwamoto, MD; Phone Number: 303-724-8534; Email: sean.iwamoto@cuanschutz.edu
      • Contact: Amanuail Gebregzabheir; Email: amanuail.gebregzabheir@cuanschutz.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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 years and older
• Identify as a transgender woman
• Have taken estradiol and spironolactone for at least one year
• Currently taking oral or transdermal or injectable estradiol
• Have not yet undergone but desire orchiectomy

Exclusion Criteria:

• Under 18 years of age
• 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
• Not deemed a candidate for 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 healthy transgender women aged 45 and above who have not undergone but desire orchiectomy, who have been on estrogen (history of oral, transdermal or injectable) and spironolactone for at least one year.
Younger transgender women; This cohort will consist of healthy transgender women aged 18-44 who have not undergone but desire orchiectomy, who have been on estrogen (history of oral, transdermal or injectable) 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) at Baseline	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.	Baseline
Evaluation of endothelial function (flow-mediated dilation (FMD) at 1 Month	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.	1 month
Evaluation of endothelial function (flow-mediated dilation (FMD) at 6 Months	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.	6 month
Evaluation of endothelial function (flow-mediated dilation (FMD) at 12 Months	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.	12 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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, 1 mo., 6 mo., 12 mo.
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, 1 mo., 6 mo., 12 mo.
Carotid artery intimal-medial thickness		Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of oxidant burden: oxidized LDL	Oxidized low-density lipoprotein (LDL) measured in the blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of oxidant burden: nitrotyrosine	Nitrotyrosine measured in the blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of vascular endothelial cell inflammation: nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)	Protein NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) measured in blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of vascular endothelial cell inflammation: MCP-1	Monocyte Chemoattractant Protein-1 (MCP-1) measured in blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of vascular endothelial cell inflammation: IL-6	Interleukin 6 (IL-6) measured in blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Evaluation of vascular endothelial cell inflammation: CRP	C-reactive protein (CRP) measured in blood and endothelial cells.	Baseline, 1 mo., 6 mo., 12 mo.
Blood pressure	Blood pressure will be measured at baseline, 1 mo., 6 mo. 12 mo.	Baseline, 1 mo., 6 mo., 12 mo.
Plasma lipid concentrations: total cholesterol	Total cholesterol will be determined at baseline, 1 mo., 6 mo., 12 mo.	Baseline, 1 mo., 6 mo., 12 mo.
Plasma lipid concentrations: triglycerides	Triglycerides will be determined at baseline, 1 mo., 6 mo., 12 mo.	Baseline, 1 mo., 6 mo., 12 mo.
Insulin sensitivity		Baseline, 1 mo., 6 mo., 12 mo.
Whole body composition: Percent Lean Mass	Percent lean mass will be determined using dual energy x-ray absorptiometry.	Baseline, 6 mo., 12 mo.
Whole body composition: Percent Fat Mass	Percent fat mass will be determined using dual energy x-ray absorptiometry.	Baseline, 6 mo., 12 mo.
Regional body composition: Percent Lean Mass	Regional percent lean mass will be determined using dual energy x-ray absorptiometry.	Baseline, 6 mo., 12 mo.
Regional body composition: Percent Fat Mass	Regional percent fat mass will be determined using dual energy x-ray absorptiometry.	Baseline, 6 mo., 12 mo.
Bone density	Bone density of femur and spine will be determined using dual energy x-ray absorptiometry.	Baseline, 12 mo.
Weight changes	Body weight will be measured at baseline, 1 mo., 6 mo., 12 mo.	Baseline, 1 mo., 6 mo., 12 mo.
Appetite ratings		Baseline, 1 mo., 6 mo., 12 mo.
Appetite-related peptides		Baseline, 1 mo., 6 mo., 12 mo.
D-Dimer		Baseline, 1 mo., 6 mo., 12 mo.
Alcohol use		Baseline, 1 mo., 6 mo., 12 mo.
Depression symptoms		Baseline, 1 mo., 6 mo., 12 mo.
Physical activity monitoring	Physical activity will me monitored for 7 days with an ActivPAL monitor	7 days at baseline, 1 mo., 6 mo., 12 mo.
Energy intake	Energy intake will be estimated with a 3-day food diary	3 days at baseline, 1 mo., 6 mo., 12 mo.
Sex hormone concentrations	Sex hormone concentrations of estradiol, testosterone, follicle stimulating hormone (FSH), luteinizing hormone (LH) and sex hormone-binding globulin (SHBG) will be measured	Baseline, 1 mo., 6 mo., 12 mo.

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institutes of Health (NIH)

Study record dates

Study Major Dates

• Study Start (Actual): March 22, 2021
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: October 22, 2021
• First Submitted That Met QC Criteria: January 12, 2022
• First Posted (Actual): January 18, 2022

Study Record Updates

• Last Update Posted (Estimate): March 7, 2023
• Last Update Submitted That Met QC Criteria: March 6, 2023
• Last Verified: March 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: 20-2141; NIH 5 K12 HD057022 (Other Grant/Funding Number: Building Interdisciplinary Research Careers in Women's Health (BIRCWH) - K12)

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