Testosterone and Neurovascular Control in Humans

Exploring the Role of Testosterone on Neurovascular Control in Humans

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

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy
• Intervention / Treatment: Drug: Cetrorelix Acetate; Drug: Testosterone gel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andrew D'Souza, MSc; Phone Number: 88084 519-661-2111; Email: adsouz58@uwo.ca
• Study Contact Backup: Name: Arlene Fleischhauer, RN; Email: afleisc@uwo.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5B9
      • The University of Western Ontario

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sex hormones	Serum concentrations of total testosterone, estradiol, albumin, and sex hormone binding globulin (SHBG) will be measured to document changes in hormone concentrations. Free testosterone will be calculated using total testosterone, SHBG and albumin.	After 7 days GnRH antagonist alone and 7 days GnRH antagonist + Testosterone

Collaborators and Investigators

• Sponsor: Western University, Canada
• Investigators: Principal Investigator: Joel K Shoemaker, Ph.D., University of Western Ontario, Canada

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: March 22, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 26, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Reproductive Control Agents; Fertility Agents, Female; Fertility Agents; Androgens; Cetrorelix; Testosterone
• Other Study ID Numbers: 117996

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
• product manufactured in and exported from the U.S.: No