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NCT Number: NCT06369363

Estrogen Deficiency on Cardiovascular Risk

To explore how estrogen deficiency impacts the blood pressure (BP) and sympathetic nerve activity (SNA), and how it impacts the production of the key pro-inflammatory mediators such as Tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). It is hypothesized that estrogen deficiency increases BP, SNA and the pathway activities of the key pro-inflammatory mediators. Those effects are impacted through the downregulation of the estrogen receptor.

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Key information

Age range

54 year–75 year

Sex eligibility

Female

Study type

Interventional

Phase

Early Phase 1

About this study

In the United States, cardiovascular disease (CVD) is one of the major health concerns and affects approximately 6.5 million people over 40. As the number of elderly women increases, CVD becomes an increasing problem. Estrogen is cardioprotective, and the menopause condition in the aging female population induces the loss of this protective effect. There has been a dilemma for medical treatment in CVD patients with comorbidities including endometriosis or breast cancer history. Overall, these patients lose the cardioprotective effect of estrogen and increase the risk of CVD development. However, there is still little understanding regarding the mechanism for how estrogen suppression in women accelerates CVD development. The proposed studies are, therefore, the essential first step to elucidating how estrogen alters mechanisms underlying CVD and provide the preclinical data to design studies for future alternative intervention strategies for CVD patients undergoing estrogen suppression therapies.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Age 54-75 years
  • Healthy participants who are capable of giving informed consent
  • Classified as postmenopausal or stop having period >1year or had a full hysterectomy surgery
  • Any race or ethnicity
  • Have satisfactory history and physical exam
  • Free of acute medical conditions

Exclusion criteria

  • <54 or >75 years
  • Medications that could alter cardiovascular, thermoregulatory, or peripheral vascular control (e.g. Angiotensin converting enzyme inhibitors, statins, beta blockers, etc.);
  • Self-reported history of long-term menstrual irregularities, vaginal bleeding, or other gynecological conditions that could influence study outcomes
  • Use of hormone therapy during 6 months prior to study enrollment
  • Allergy to latex
  • Current smoker
  • Have any clinically relevant history or the presence of metabolic (e.g., diabetes), respiratory, renal, hepatic, gastrointestinal, hematological, lymphatic, neurological, cardiovascular, or other disease or diseases that, in the opinion of the research team, exclude the subject from participation.
  • Presenting with a resting blood pressure of 150/100 or higher
  • Contraindications to a maximal exercise test or an indication for early termination of an exercise test
  • Taking any medications that affect vascular control or autonomic function (e.g. beta blockers, ACE inhibitors, calcium channel blockers, etc.)
  • Contraindications to estrogen patch: include undiagnosed vaginal bleeding; known, suspected, or history of breast cancer; known or suspected E2-sensitive neoplasm; history of deep venous thrombosis or pulmonary embolism; current or recent arterial thromboembolic disease; liver dysfunction and disease; known or suspected pregnancy.
  • Past/current history of venous thromboembolism, hypercoagulation or thrombopenia
  • Past/current history of hormone-responsive cancer
  • Past/current history of endometrial hyperplasia
  • Patient has a recent drug or alcohol abuse history (less than 6 months) or is currently using or abusing excessive alcohol or drugs. Excessive alcohol will be defined as greater than 14 drinks per week.

Treatment and study plan

Placebo

Drug

Subjects will be assigned to 1 week of transdermal placebo patch.

Estradiol

Drug

Subjects will be assigned to 1 week of transdermal estradiol (0.05 mg/day) patch.

Primary outcomes

  1. Red blood cell flux

    Time frame: Recorded continuously for up to 4 hours during the study visit

    Percentage relative to the maximum flux level

  2. Mean arterial pressure (mmHg)

    Time frame: Recorded continuously for up to 4 hours during the study visit

    Calculated from the systolic and diastolic blood pressure

  3. baseline plasma TNF-α concentration (pg/ml)

    Time frame: Upon participants' arrival to the first study visit up to 5 minutes

    Measured by ELISA kits

  4. One week post-intervention plasma TNF-α concentration (pg/ml)

    Time frame: Upon participants' arrival to the second study visit (1 week after the first visit)

    Measured by ELISA kits

  5. baseline plasma IL-1β concentration (pg/ml)

    Time frame: Upon participants' arrival to the first study visits up to 5 minutes

    Measured by ELISA kits

  6. One week post-intervention plasma IL-1β concentration (pg/ml)

    Time frame: Upon participants' arrival to the second study visit (1 week after the first visit)

    Measured by ELISA kits

  7. baseline plasma IL-6 concentration (pg/ml)

    Time frame: Upon participants' arrival to the first study visits up to 5 minutes

    Measured by ELISA kits

  8. One week post-intervention plasma IL-6 concentration (pg/ml)

    Time frame: Upon participants' arrival to the second study visit (1 week after the first visit)

    Measured by ELISA kits

Secondary outcomes

  1. baseline plasma estrogen (pg/ml)

    Time frame: Upon participants' arrival to the first study visits up to 5 minutes

    Measured by ELISA kits

  2. One week post-intervention plasma estrogen (pg/ml)

    Time frame: Upon participants' arrival to the second study visit (1 week after the first visit)

    Measured by ELISA kits

Study contacts

Contact information is provided by the study sponsor or research team.

Lu Qin, PhD

CONTACT

[email protected]

4026096068

Sponsors and collaborators

Lead sponsor

Milton S. Hershey Medical Center

Other

Registry information

Official study title

Estrogen Deficiency on Cardiovascular Risk: Sympathetic Responses and Pro-inflammatory Cytokines

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Apr 17, 2024
Registry last updated
Nov 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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