Testosterone and Neurovascular Control in Humans

Study Overview
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Brief Summary
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The purpose of these studies are to evaluate the role of testosterone on autonomic and vascular function in men.

Detailed Description
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Sex hormones play a pivotal role in neurovascular function in humans. In recent years, great strides have been made in elucidating the roles of estrogen and progesterone on autonomic and vascular control in women; however, very little is known about the impact of testosterone in men. Given that low testosterone levels are associated with an increased risk of cardiovascular disease, reduced exercise capacity and vascular dysfunction, it is evident that testosterone plays a pivotal role in autonomic and vascular function in men. Our current understanding of testosterone's effects on neurovascular control are confounded by numerous factors that independently alter autonomic and vascular function such as aging and chronic disease (e.g. cardiovascular disease, metabolic disease). The purpose of these studies are to evaluate the role of testosterone on autonomic and vascular function in young men to better isolate the effects of testosterone from the aforementioned confounding factors. The outcomes of these studies will provide novel information regarding the role of male sex hormones in autonomic and vascular control, and further our understanding of the influence of sex hormones on human physiology.

Official Title
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Exploring the Role of Testosterone on Neurovascular Control in Humans

Conditions
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Healthy

Intervention / Treatment
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* Drug: Cetrorelix Acetate
* Drug: Testosterone gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderately active Free of chronic disease Exclusion Criteria: congenital or acquired hypogonadism drug/alcohol dependence hypertension current smoker current opioid or cannabis user diabetes inability to provide written consent parkinson's disease cardiovascular disease testosterone use within the last year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Male

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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GnRH antagonist alone<br>Intervention: Cetrorelix acetate (Cetrotide) | Drug: Cetrorelix Acetate<br>* GnRH antagonist - subcutaneous injection. Day 1: 1-3 mg; Days 2-14: 0.25mg/daily.<br>* Other names: Cetrotide;|
| Experimental: GnRH antagonist + Testosterone add-back<br>Intervention: Cetrorelix acetate (Cetrotide) + Testosterone gel (Androgel) | Drug: Cetrorelix Acetate<br>* GnRH antagonist - subcutaneous injection. Day 1: 1-3 mg; Days 2-14: 0.25mg/daily.<br>* Other names: Cetrotide;Drug: Testosterone gel<br>* Testosterone gel - transdermal application of 5mg/day on Day 7-14 of GnRH antagonist<br>* Other names: Androgel 1%;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle sympathetic nerve activity | Multi-unit postganglionic muscle sympathetic nerve activity (MSNA) will be measured by inserting a unipolar tungsten microelectrode into the peroneal nerve near the fibular head of the leg. Neural signals will be amplified, filtered (bandwidth, 700-2,000 Hz), rectified, and integrated (time constant, 0.1 s) to obtain mean voltage neurograms. MSNA will be measured during both trials to evaluate the effect of testosterone on sympathetic activity directed toward the musculature. | After 7 days GnRH antagonist alone and 7 days GnRH antagonist + Testosterone | 
| Endothelial function | Brachial artery flow-mediated dilation (FMD). Brachial artery FMD measures will be performed non-invasively via Doppler ultrasound. | After 7 days GnRH antagonist alone and 7 days GnRH antagonist + Testosterone | 
| Forearm blood flow | Forearm blood flow will be measured using Doppler ultrasound at baseline and during stress (e.g. exercise) | After 7 days GnRH antagonist alone and 7 days GnRH antagonist + Testosterone | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle microvascular blood flow | Microvascular blood flow will be measured using Diffuse correlation spectroscopy. | After 7 days GnRH antagonist alone and 7 days GnRH antagonist + Testosterone |