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

Study Overview
=================
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.

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

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

Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Older transgender women<br>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<br>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. |