Impact of Estradiol on Endothelial Function in Peri-Menopausal Women

NCT ID: NCT04255160

Last Updated: 2025-12-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2025-12-31

Brief Summary

The purpose of this study is to identify the impact of estradiol (E2) on the mechanisms that regulate vascular endothelial function in peri-menopausal (PERI) women. This study is the first step in understanding factors contributing to endothelial dysfunction in women with advancing reproductive age and in response to E2 administration.

Detailed Description

Cardiovascular disease (CVD) is the leading cause of death in women. Although overall CVD-related mortality has declined, there has been an increase in CVD mortality in women aged 35-54 years, prior to menopause. It is unclear what contributes to this increased mortality rate, and is a significant problem for women's health. Endothelial function is considered a biomarker of cardiovascular health; declines in endothelial function are considered a precursor to the development of atherosclerosis and CVD. Thus, changes in endothelial function in women as they advance through reproductive stages towards menopause may play a role in the greater prevalence of CVD mortality. However, very few studies have focused on cardiovascular health in women leading up to menopause, during the PERI transition. The PERI period is a critical time point where reproductive hormones and ovarian function change rapidly. Recent data demonstrate that endothelial function begins to decline during PERI. Furthermore, despite women being of similar biological age, significant differences in endothelial function were noted when classified based on reproductive age - specifically between early PERI and late PERI. These data show that the decline initially occurs in the early PERI phase, making this a key time point for intervention to offset the future development of CVD. Our central hypothesis is that increased Endothelin-1 (ET-1) and a loss of Endothelin-1 B (ETB) mediated vasodilation play a primary role in contributing to impaired endothelial function with advancing reproductive age. We will assess macro- and micro- vascular endothelial function, assess intracellular ET-1 protein and ETB receptor expression in harvested endothelial cells from peripheral veins, and use the cutaneous circulation as an in vivo model to explore the receptor mechanisms (ETBR and ETAR) in early and late PERI in response to E2 or placebo.

Conditions

Perimenopause; Vasodilation; Estrogen

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Estradiol

Transdermal estradiol (0.1mg/day patch)

Group Type: EXPERIMENTAL

Estradiol (mylan or vivelle dot patch)

Intervention Type: DRUG

Transdermal estradiol (0.1mg/day patch) will be used by women for 7 days. Administration of the patch will follow the package guidelines to change the patch after 3-4 days of use.

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

A placebo patch that is visually similar to the estradiol patch will be used for the group not receiving estradiol.

Interventions

Estradiol (mylan or vivelle dot patch)

Transdermal estradiol (0.1mg/day patch) will be used by women for 7 days. Administration of the patch will follow the package guidelines to change the patch after 3-4 days of use.

Intervention Type: DRUG

Placebo

A placebo patch that is visually similar to the estradiol patch will be used for the group not receiving estradiol.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Peri-menopausal women between 40-58 years of age with variable cycles as defined by increase in cycle length of greater than 7 days within ten consecutive cycles, or amenorrhea for more than 2 months, but less than 12 months.

Exclusion Criteria

• Women who are pregnant, planning on becoming pregnant, or are breast feeding;
• Women who have a history of cardiovascular disease, blood clots (e.g, pulmonary embolism or deep vein thrombosis), stroke, cancer, or liver disease;
• Women who have a body mass index less than 18 or greater than 35kg/m2;
• Women who use tobacco products;
• Women who's blood pressure is greater than 140/90 mmHg, have been diagnosed by a physician with hypertension or are taking medication for high blood pressure;
• Women who have a neurological disease, or diabetes;
• Women who have had a hysterectomy or have used hormones (birth control or hormone replacement) within the past 3 months;
• Women who have a latex allergy.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 58 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

University of Delaware

OTHER

Sponsor Role: lead

Responsible Party

Megan M. Wenner

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Delaware

Newark, Delaware, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kathy Masso, BS

Role: CONTACT

kcmasso@udel.edu

(302) 831-3493

Megan M Wenner, PhD

Role: CONTACT

mwenner@udel.edu

(302) 831-7343

Facility Contacts

Kathy Masso, BS

Role: primary

kcmasso@udel.edu

302-831-3493

Megan M Wenner, PhD

Role: backup

mwenner@udel.edu

302-831-7343

Other Identifiers

R01HL146558

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1508142

Identifier Type: -

Identifier Source: org_study_id