NCT04255160

Impact of Estradiol on Endothelial Function in Peri-Menopausal Women

• Status: Active Not Recruiting
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: University of Delaware · Academic / Other
• Sex: Female
• Age: 40 Years – 58 Years
• Healthy volunteers: Accepted

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

Interventions

Type	Name	Description
DRUG	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.
OTHER	Placebo	A placebo patch that is visually similar to the estradiol patch will be used for the group not receiving estradiol.

Timeline

• Start date: 2020-10-01
• Primary completion: 2026-05-01
• Completion: 2026-06-30
• First posted: 2020-02-05
• Last updated: 2026-02-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study