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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Transgender, Gender Identity, Vascular Stiffness, Vascular Inflammation, Insulin Sensitivity, Blood Pressure, Lipid Disorder, Appetitive Behavior

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Older transgender women<br>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<br>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?
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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 |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| Blood pressure |  | 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 | 
| Insulin sensitivity |  | 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 | 
| Weight changes |  | Baseline | 
| Appetite ratings |  | Baseline | 
| Appetite-related peptides |  | Baseline | 
| D-Dimer |  | Baseline | 
| Alcohol use |  | 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 |