Estrogen Deficiency on Cardiovascular Risk

NCT06369363 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: STUDY000024245
• Study Type: interventional
• Target: 20
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Postmenopausal Symptoms; Cardiovascular Diseases

Outcome Measures

Primary Outcomes (8)

• Red blood cell flux

  Percentage relative to the maximum flux level

  Recorded continuously for up to 4 hours during the study visit

• Mean arterial pressure (mmHg)

  Calculated from the systolic and diastolic blood pressure

  Recorded continuously for up to 4 hours during the study visit

• baseline plasma TNF-α concentration (pg/ml)

  Measured by ELISA kits

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

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

  Measured by ELISA kits

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

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

  Measured by ELISA kits

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

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

  Measured by ELISA kits

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

• baseline plasma IL-6 concentration (pg/ml)

  Measured by ELISA kits

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

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

  Measured by ELISA kits

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

Secondary Outcomes (2)

• baseline plasma estrogen (pg/ml)

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

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

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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Estradiol

EXPERIMENTAL

Drug: Estradiol

Interventions

Placebo DRUG

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

Placebo

Estradiol DRUG

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

Estradiol

Eligibility Criteria

• Age: 54 Years - 75 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• \<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.

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead

MeSH Terms

Conditions

Cardiovascular Diseases

Interventions

Estradiol

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Lu Qin, PhD

  Penn State College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lu Qin, PhD

CONTACT

4026096068; lqin@pennstatehealth.psu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor in Department of Medicine

Study Record Dates

• First Submitted: April 11, 2024
• First Posted: April 17, 2024
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: November 17, 2025

Record last verified: 2025-11