Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity

Women and men show marked differences in cardiovascular risk profile and outcome. Women experience fewer cardiovascular events than men before menopause, but this relationship seems to reverse at menopause. These disparities are probably due to hormonal factors, especially the female sex hormone estrogen seems to have a protective influence on the development of atherosclerotic plaques premenopausal.

The underlying mechanisms of the effect of estrogens on the vessel wall are still insufficiently investigated. In this study, menopause related effects on leukocyte distribution and function as well on platelets and their aggregational response will be evaluated.

Study Overview

• Status: Recruiting
• Conditions: Arteriosclerosis; Menopause; Acute Myocardial Infarction; Cardiovascular Events

Detailed Description

Sex-specific differences in the risk profile and outcome of cardiovascular diseases are evident, which are probably due to hormonal factors. Women suffer significantly fewer cardiovascular events than men before menopause, after menopause this relationship seems to reverse. Moreover, outcome is worse in female patients compared to men.

Platelets and leukocytes play an essential role in cardiovascular risk. Nevertheless, the underlying mechanisms of the mechanistic effects of the hormone transition in menopause on leukocytes and platelets have only been insufficiently investigated so far. Moreover, effects of a possible hormone replacement therapy are insufficiently understood with contradictive literature concerning cardiovascular effects.

The aim in this study, is to analyse leukocyte and platelet function in dependence from menopause related changes in hormone levels of estrogen, testosterone, progesterone, LH and FSH. Moreover, hormone replacement therapy will be investigated.

For this purpose, blood samples from male and female patients will be investigated with regard to age and menopause status. The blood samples are analysed by FACS to differentiate the leukocytes and test for inflammatory properties and reactive oxygen species. The monocyte distribution divided according to the surface markers CD14 and CD16 is analysed. In addition, plasma from the patient samples will be used to assess hormone levels in the blood. In addition, patient data such as general laboratory parameters, risk and lifestyle factors are collected and associated with the hormone and lipid levels.

For platelet function analysis, light-transmittance aggregometry, flow cytometry (platelet leukocyte crosstalk, investigation of platelet surface markers for platelet activation and cell-cell-adhesion) will be investigated. Platelets secretory potency will be analysed by ATP-release. Moreover, platelet adhesion will be investigated by collagen-coated flow chambers. Platelet proteomics and RNA sequencing will complement the data in an unbiased approach. In addition in-vitro incubation analyses with estrogen and testosterone will be conducted to investigate hormone replacement therapy effects.

• Study Type: Observational
• Enrollment (Estimated): 180

Contacts and Locations

• Study Contact: Name: Lisa Dannenberg, MD; Phone Number: +492118105315; Email: lisa.dannenberg@med.uni-duesseldorf.de

Study Locations

• Germany
  • Düsseldorf, Germany, 40225
    • Recruiting
    • University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine
    • Contact: Lisa Dannenberg, MD; Phone Number: +492118105315; Email: lisa.dannenberg@med.uni-duesseldorf.de
    • Contact: Clinical Trial Unit; Phone Number: +4921181105315; Email: ctu@med.uni-duesseldorf.de
    • Principal Investigator: Lisa Dannenberg, MD

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Male and female Patients with and without cardiovascular disease

Description

Inclusion Criteria:

• Age > 18 years
• Male, female, diverse patients with current treatment in the Department of Cardiology, Pneumology and Angiology.
• Persons who are able to understand and follow the instructions of the study staff
• Written informed consent

Exclusion Criteria:

• Age < 18 years
• Lack of written consent to participate in the study
• coagulation disorders

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Leukocyte distribution measured by flow cytometry	CD45 (Leukocytes), CD3 (T-cells), CD14 (Monocytes), CD16 (Granulocytes), CD19 (B-cells)	single time, up to one day after inclusion
Platelet function	measured by light transmittance aggregometry (Parameters: Maximum of Aggregation, Slope	single time, up to one day after inclusion
Platelet surface markers, platelet leukocyte crosstalk (CD40, CD40L)	measured by flow cytometry (FACS)	single time, up to one day after inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reactive Oxygen Species (ROS) Generation via CellRoxGreen [geometric mean]	measured by Flow Cytometry (FACS)	single time, up to one day after inclusion
Hormone levels of estrogen	measured by ELISA [ng/l]	single time, up to one day after inclusion
Hormone levels of testosterone measured by ELISA	measured by ELISA [ng/l]	single time, up to one day after inclusion
Hormone levels of progesterone	measured by ELISA [µg/l]	single time, up to one day after inclusion
Hormone levels of follicle stimulating hormone	measured by ELISA [µg/l]	single time, up to one day after inclusion
Hormone levels of luteinizing hormone	measured by ELISA [µg/l]	single time, up to one day after inclusion
Questionnaire including lifestyle factors, cardiovascular risk factors		single time, up to one day after inclusion

Collaborators and Investigators

• Sponsor: Heinrich-Heine University, Duesseldorf
• Investigators: Study Chair: Malte Kelm, Prof., Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2022
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 14, 2023
• First Submitted That Met QC Criteria: August 2, 2023
• First Posted (Actual): August 14, 2023

Study Record Updates

• Last Update Posted (Actual): August 14, 2023
• Last Update Submitted That Met QC Criteria: August 2, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: menopause; Atherosclerosis; cardiovascular risk; cardiovascular events; male; female; hormone replacement therapy; gender; sex
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arterial Occlusive Diseases; Myocardial Infarction; Infarction; Arteriosclerosis
• Other Study ID Numbers: Hormone

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No