PerimenopausePhase 4NCT04255160
Impact of Estradiol on Endothelial Function in Peri-Menopausal Women
A Phase 4 study testing Estradiol (mylan or vivelle dot patch) in people with Perimenopause and Vasodilation, run by University of Delaware at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 to 58 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Perimenopause, Vasodilation, Estrogen
- What is being tested?
- Estradiol (mylan or vivelle dot patch)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 31 Oct 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 58 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Estradiol (mylan or vivelle dot patch), Placebo
- Keywords
- Perimenopause, Vasodilation, Estrogen
- Medical subject headings
- Aneurysm
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Estradiol (mylan or vivelle dot patch)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.
PlaceboOther
A placebo patch that is visually similar to the estradiol patch will be used for the group not receiving estradiol.
| Study group | Role | What they receive |
|---|---|---|
| Estradiol | Experimental | Transdermal estradiol (0.1mg/day patch) Receives: Drug: Estradiol (mylan or vivelle dot patch) |
| Placebo | Placebo comparator | Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular Endothelial Function (Flow mediated dilation or FMD)
The capacity of the large and small blood vessels to dilate.
Measured: Change in FMD from Baseline to Day 7
Secondary outcomes (2)
Endothelial Cell Protein Expression
Venous endothelial cells will be harvested from peripheral veins of women during the hormone intervention and stained for expression of ET-1 and ETB receptors.
Measured: Change in fluorescent intensity from Baseline to Day 7
Endothelin Receptor Responses
The contribution of Endothelin A (ETA) and Endothelin B (ETB) receptors on changes in endothelial function will be assessed in the cutaneous circulation via microdialysis. Blood flow responses to local heating will be assessed under control and blockade sites in women during estradiol or placebo administration.
Measured: Change from Baseline to Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study start1 Oct 2020
- Primary completion1 Sep 2026 (estimated)
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PerimenopauseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Delaware
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Megan M. Wenner, University of Delaware
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04255160
- Sponsor's protocol ID
- 1508142
- Other IDs
- R01HL146558
- Status last verified
- Apr 2026
- First submitted
- 27 Jan 2020
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Estradiol on Endothelial Function in Peri-Menopausal Women
- ClinicalTrials.gov ID
- NCT04255160
- Acronym / sponsor ID
- 1508142
- Conditions
- Perimenopause, Vasodilation, Estrogen
- Keywords
- Perimenopause, Vasodilation, Estrogen
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of DelawareUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 5 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Estradiol | Experimental | Drug: Estradiol (mylan or vivelle dot patch)Transdermal estradiol (0.1mg/day patch) |
| Placebo | Placebo comparator | Other: PlaceboPlacebo |
Who may qualify
- Ages
- 40 to 58 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (8 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Estradiol |
| PlaceboA placebo patch that is visually similar to the estradiol patch will be used for the group not receiving estradiol. | Other | Placebo |
Primary outcome
Vascular Endothelial Function (Flow mediated dilation or FMD)
Time frame: Change in FMD from Baseline to Day 7
The capacity of the large and small blood vessels to dilate.
2 secondary outcomes
Endothelial Cell Protein Expression
Time frame: Change in fluorescent intensity from Baseline to Day 7
Endothelin Receptor Responses
Time frame: Change from Baseline to Day 7
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Estradiol (mylan or vivelle dot patch) in people with Perimenopause and Vasodilation, run by University of Delaware at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Vascular Endothelial Function (Flow mediated dilation or FMD) (time frame: Change in FMD from Baseline to Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.