Clinical trial NCT05985447: Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity
Official title: Menopause Related Influences on Leukocyte Distribution, Monocyte Function and Platelet Reactivity
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Arteriosclerosis
Acute Myocardial Infarction
Cardiovascular Events
Menopause
Keywords: sex
gender
female
male
menopause
hormone replacement therapy
Atherosclerosis
cardiovascular events
cardiovascular risk
Lead sponsor: Heinrich-Heine University, Duesseldorf
Sponsor class: OTHER
First posted: 2023-08-14
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Male and female Patients with and without cardiovascular disease

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Leukocyte distribution measured by flow cytometry
timeFrame: single time, up to one day after inclusion
measure: Platelet function
timeFrame: single time, up to one day after inclusion
measure: Platelet surface markers, platelet leukocyte crosstalk (CD40, CD40L)
timeFrame: single time, up to one day after inclusion
Secondary outcomes:
measure: Reactive Oxygen Species (ROS) Generation via CellRoxGreen [geometric mean]
timeFrame: single time, up to one day after inclusion
measure: Hormone levels of estrogen
timeFrame: single time, up to one day after inclusion
measure: Hormone levels of testosterone measured by ELISA
timeFrame: single time, up to one day after inclusion
measure: Hormone levels of progesterone
timeFrame: single time, up to one day after inclusion
measure: Hormone levels of follicle stimulating hormone
timeFrame: single time, up to one day after inclusion
measure: Hormone levels of luteinizing hormone
timeFrame: single time, up to one day after inclusion
measure: Questionnaire including lifestyle factors, cardiovascular risk factors
timeFrame: single time, up to one day after inclusion
Other outcomes:
Locations:
city: Düsseldorf
country: Germany
facility: University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine
Study officials:
affiliation: Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf
name: Malte Kelm, Prof.
role: STUDY_CHAIR
References: