Estrogen Deficiency on Cardiovascular Risk

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiovascular Diseases; Postmenopausal Symptoms
• Intervention / Treatment: Drug: Placebo; Drug: Estradiol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Lu Qin, PhD; Phone Number: 4026096068; Email: lqin@pennstatehealth.psu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Subjects will be assigned to 1 week of transdermal placebo patch.
Experimental: Estradiol	Drug: Estradiol; Subjects will be assigned to 1 week of transdermal estradiol (0.05 mg/day) patch.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
baseline plasma estrogen (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the first study visits up to 5 minutes
One week post-intervention plasma estrogen (pg/ml)	Measured by ELISA kits	Upon participants' arrival to the second study visit (1 week after the first visit)

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Principal Investigator: Lu Qin, PhD, Penn State College of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: April 11, 2024
• First Submitted That Met QC Criteria: April 11, 2024
• First Posted (Actual): April 17, 2024

Study Record Updates

• Last Update Posted (Actual): November 17, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Estradiol
• Other Study ID Numbers: STUDY000024245

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No