Estrogen and Microvascular Function

Effects of Continuous Estrogen on Human in Vivo Microvascular Function

The goal of this study is to learn how long-term use of estrogen affects blood vessels in healthy adults.

Participants will:

• give one blood draw of 5 mL
• have one Dexa Scan taken to measure adipose and muscle mass
• have a camera placed under the tongue to take pictures of blood vessels
• have 2 laser Doppler microdialysis catheters placed on the forearm to monitor blood vessels before and after local drug infusion

Researchers will compare blood vessel function of those who take estrogen to those who do not.

Study Overview

• Status: Active, not recruiting
• Conditions: Cardiovascular Diseases; Estrogen; Oral Contraceptive Use; Microvasculature
• Intervention / Treatment: Drug: Nω-nitro-L-arginine methyl ester (L-NAME); Drug: Acetylcholine; Drug: Sodium Nitroprusside

• Study Type: Observational
• Enrollment (Estimated): 45

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Wauwatosa, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Community sample

Description

Inclusion Criteria:

Estrogen/Progestin Group

• Adults aged 18-40 years
• Females with estrogen/progestin treatment for a minimum of 1 year.
• Blood pressure <140/ < 90 mmHg
• No more than 1 cardiovascular risk factor Control Groups
• Adults aged 18-40 years
• Female with no estrogen/progestin treatment for minimum of 5 years.
• Female undergoing progestin only treatment for a minimum of 1 year.
• Blood pressure <140/ < 90 mmHg
• No more than 1 cardiovascular risk factor

Exclusion Criteria:

• Medications that could alter cardiovascular control
• Rash, skin disease, or pigmentation disorders on both forearms
• Anemia
• Kidney Disease
• Known skin allergies
• Smoking or tobacco use within last 6 months

• Coronary Artery Disease

  -1 cardiovascular risk factor Hypertension Diabetes Hypercholesterolemia Hyperlipidemia

• Bleeding disorders
• Use of anti-coagulants
• Allergies to study drugs
• Use of topical/non-topical steroids in last 6 months
• Internal mouth sores
• Forearms covered with tattoos
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Continuous estrogen/progestin; Females who have had continuous estrogen/progestin treatment for a minimum of 1 year.	Drug: Nω-nitro-L-arginine methyl ester (L-NAME); L-NAME will be infused locally through microdialysis catheters.; Drug: Acetylcholine; ACh will be infused locally through microdialysis catheters.; Drug: Sodium Nitroprusside; SNP will be infused locally through microdialysis catheters.
No Estrogen/progestin; Females who have not had continuous estrogen treatment for a minimum of 5 years.	Drug: Nω-nitro-L-arginine methyl ester (L-NAME); L-NAME will be infused locally through microdialysis catheters.; Drug: Acetylcholine; ACh will be infused locally through microdialysis catheters.; Drug: Sodium Nitroprusside; SNP will be infused locally through microdialysis catheters.
Continuous progestin; Females who have had continuous progestin treatment for a minimum of 1 year.	Drug: Nω-nitro-L-arginine methyl ester (L-NAME); L-NAME will be infused locally through microdialysis catheters.; Drug: Acetylcholine; ACh will be infused locally through microdialysis catheters.; Drug: Sodium Nitroprusside; SNP will be infused locally through microdialysis catheters.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Perfused Vessel Density	Total vessel density (TVD) will be calculated using the DeBacker Score manual analysis on all images that have a minimum microcirculation image quality score (MIQS) of 10. Perfused vessel density (PVD) will be calculated by multiplying total vessel density (TVD) x proportion of perfused vessels (PPV%).	0.5 hours
Change in blood vessel dilation	Cutaneous vascular conductance in response to acetylcholine, L-NAME, and sodium nitroprusside infusions will be calculated as percentage of cardiovascular conductance.	2 hours

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2023
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: September 12, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): July 4, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Female; oral contraceptive
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Vasodilator Agents; Antihypertensive Agents; Cholinergic Agents; Cholinergic Agonists; Nitric Oxide Donors; Acetylcholine; Nitroprusside
• Other Study ID Numbers: PRO40920

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No