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

Recruiting

• Conditions: Insulin Sensitivity; Lipid Disorder; Transgender; Vascular Inflammation; Gender Identity; Vascular Stiffness; Blood Pressure; Appetitive Behavior
• Interventions: Other: No intervention

• Registration Number: NCT05195164
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

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 Timeline

• Study Start: 2021-03-22
• Study First Submitted: 2021-10-22
• Study First Submitted QC: 2022-01-12
• Study First Posted: 2022-01-18
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-06
• Last Update Posted: 2023-03-07
• Primary Completion: 2024-03
• Study Completion: 2024-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Younger transgender women	No intervention	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.
Older transgender women	No intervention	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.

Primary Outcome Measures

Name	Time	Method
Evaluation of endothelial function (flow-mediated dilation (FMD) at 1 Month	1 month	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.
Evaluation of endothelial function (flow-mediated dilation (FMD) at Baseline	Baseline	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.
Evaluation of endothelial function (flow-mediated dilation (FMD) at 6 Months	6 month	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.
Evaluation of endothelial function (flow-mediated dilation (FMD) at 12 Months	12 month	Brachial artery flow-mediated dilation (FMD), as measured by ultrasound.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Colorado; 🇺🇸 Aurora, Colorado, United States