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

Sponsor

Heinrich-Heine University, Duesseldorf (Other)

Overall Status

Recruiting

CT.gov ID

NCT05985447

Collaborator

(none)

180

Enrollment

Location

56.8

Anticipated Duration (Months)

3.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Arteriosclerosis Acute Myocardial Infarction Cardiovascular Events Menopause

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 Design

Study Type:

Observational

Anticipated Enrollment :

180 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Mar 7, 2022

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2026

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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