Estrogen Deficiency on Cardiovascular Risk

Official title

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

Overview

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.

Interventions

• Drug Placebo
  Subjects will be assigned to 1 week of transdermal placebo patch.
• Drug Estradiol
  Subjects will be assigned to 1 week of transdermal estradiol (0.05 mg/day) patch.

Primary outcome measures

• Red blood cell flux [Time frame: Recorded continuously for up to 4 hours during the study visit]
• Mean arterial pressure (mmHg) [Time frame: Recorded continuously for up to 4 hours during the study visit]
• baseline plasma TNF-α concentration (pg/ml) [Time frame: Upon participants' arrival to the first study visit up to 5 minutes]
• 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)]
• baseline plasma IL-1β concentration (pg/ml) [Time frame: Upon participants' arrival to the first study visits up to 5 minutes]
• 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)]
• baseline plasma IL-6 concentration (pg/ml) [Time frame: Upon participants' arrival to the first study visits up to 5 minutes]
• 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)]

Secondary outcome measures (2)

• baseline plasma estrogen (pg/ml) [Time frame: Upon participants' arrival to the first study visits up to 5 minutes]
• One week post-intervention plasma estrogen (pg/ml) [Time frame: Upon participants' arrival to the second study visit (1 week after the first visit)]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06369363 · STUDY000024245

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗