Clinical trial NCT06369363: Estrogen Deficiency on Cardiovascular Risk
Official title: Estrogen Deficiency on Cardiovascular Risk: Sympathetic Responses and Pro-inflammatory Cytokines
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Postmenopausal Symptoms
Cardiovascular Diseases
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
First posted: 2024-04-17
Enrollment: 20
Sex: FEMALE
Minimum age (years): 54
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Red blood cell flux
timeFrame: Recorded continuously for up to 4 hours during the study visit
measure: Mean arterial pressure (mmHg)
timeFrame: Recorded continuously for up to 4 hours during the study visit
measure: baseline plasma TNF-α concentration (pg/ml)
timeFrame: Upon participants' arrival to the first study visit up to 5 minutes
measure: One week post-intervention plasma TNF-α concentration (pg/ml)
timeFrame: Upon participants' arrival to the second study visit (1 week after the first visit)
measure: baseline plasma IL-1β concentration (pg/ml)
timeFrame: Upon participants' arrival to the first study visits up to 5 minutes
measure: One week post-intervention plasma IL-1β concentration (pg/ml)
timeFrame: Upon participants' arrival to the second study visit (1 week after the first visit)
measure: baseline plasma IL-6 concentration (pg/ml)
timeFrame: Upon participants' arrival to the first study visits up to 5 minutes
measure: One week post-intervention plasma IL-6 concentration (pg/ml)
timeFrame: Upon participants' arrival to the second study visit (1 week after the first visit)
Secondary outcomes:
measure: baseline plasma estrogen (pg/ml)
timeFrame: Upon participants' arrival to the first study visits up to 5 minutes
measure: One week post-intervention plasma estrogen (pg/ml)
timeFrame: Upon participants' arrival to the second study visit (1 week after the first visit)
Other outcomes:
Locations:
Study officials:
affiliation: Penn State College of Medicine
name: Lu Qin, PhD
role: PRINCIPAL_INVESTIGATOR
References: