Exercise Training and Thrombotic Risk in Post-menopausal Women

Study Overview
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Brief Summary
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At menopausal transition, the risk of cardiovascular diseases increases. This is partly due to aging, but largely also the loss of estrogen, which has many positive effects on the circulation and protects against cardiovascular diseases. It has been suggested that the loss of estrogen may have a negative impact on the otherwise well-documented health promoting effects of exercise training, and that the time after menopause may be crucial for the effect of exercise training on the vascular function, and therefore also for the risk of thrombosis. Literature regarding the effect of exercise training on the risk of thrombosis is limited, and especially in women. The purpose of the present study is to investigate whether the same effects of exercise training in relation to thrombosis is achieved if the exercise is initiated early compared to late after menopause. The aim is to provide knowledge-based recommendations regarding exercise. Teams sports will be used as the training intervention, because team sports benefits physical health and also includes a social element.

Detailed Description
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Part of the novelty of this project is to link functional measurements of cardiovascular health at whole body level to cell studies. Cells will be isolated from muscle samples obtained from the post-menopausal women before and after the training intervention. This will enhance the understanding of the changes that occur after prolonged loss of estrogen on thrombotic risk and vascular function, and whether exercise training can alter these parameters.

Official Title
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Susceptibility to Thrombosis in Post-menopausal Women- Influence of Exercise Training

Conditions
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Thrombosis, Menopause, Exercise Training, Vascular Dilation

Intervention / Treatment
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* Other: Early and late postmenopausal women


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 50-70 years Physical activity ≤ 2 hours per week (except transportation by bike or by walking) BMI ≤ 30 Exclusion Criteria: Age <50 years Injuries that prevent the performance of team sports Participation in other clinical projects Smokes or has smoked within the last 10 years On hormone therapy Not entered menopause Has chronic diseases that are not expected, cf. the groups sought. Including heart problems, atrial fibrillation, cancer, immune diseases and previous strokes with functionally significant sequelae Being treated with oral steroids Has alcohol / drug abuse or is being treated with disulfiram (Antabus) Is unable to understand the contents of the document with informed consent or the experimental procedures

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early postmenopausal women<br>Healthy sedentary early postmenopausal women | Other: Early and late postmenopausal women<br>* The intervention involves supervised team sports 1 h 3 x/week for 16 weeks.<br>|
| Experimental: Late postmenopausal women<br>Healthy sedentary late postmenopausal women | Other: Early and late postmenopausal women<br>* The intervention involves supervised team sports 1 h 3 x/week for 16 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in clot microstructure in early and late postmenopausal women after 16 weeks of exercise training | Clot microstructure is measured in a rheometer using unaltered whole blood | 16 weeks | 
| Changes in platelet reactivity in early and late postmenopausal women after 16 weeks of exercise training | Platelet reactivity is measured with Light Transmission Aggregometry using platelet rich and platelet poor plasma | 16 weeks | 
| Plasma concentration of coagulation factors in early and late postmenopausal women after 16 weeks of exercise training | Coagulation factors II, VII, X, VIII, D-dimer, fibrinogen and thrombin | 16 weeks | 
| Changes in vascular function in early and late postmenopausal women after 16 weeks of exercise training | Vascular function is assessed by flow-mediated dilation (FMD) in the brachial artery using ultrasound doppler | 16 weeks | 
| Changes in capillary density after 16 weeks of team sports in early and late postmenopausal women | Capillary density will be assessed by histochemistry | 16 weeks | 
| Changes in proliferative capacity of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women | From a biopsy sample we isolate endothelial cells and run a proliferation assay | 16 weeks | 
| Changes in mitochondrial function of endothelial cells after 16 weeks of exercise training in early and late postmenopausal women | High resolution respirometry | 16 weeks | 
| Changes in skeletal muscle protein content important for vascular function after 16 weeks of exercise training in early and late postmenopausal women | Western blots will be used to determine endothelial nitric oxide synthase (eNOS), cyclo-oxygenase 1 and 2, prostacyclin synthase, endothelin receptor A and B, VEGF (vascular endothelial growth factor), Thrombospondin-1, Flk-1 (VEGF receptor). All protein content measures will be presented as arbitrary units. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood pressure after 16 weeks of team sports in early and late postmenopausal women | Blood pressure measured at home with an automated blood pressure device. Systolic blood pressure, diastolic blood pressure and mean arterial pressure will be collected. | 16 weeks | 
| Changes in maximal oxygen uptake after 16 weeks of team sports in early and late postmenopausal women | Maximal oxygen uptake will be measured using a metabolic cart. The test protocol will be performed on a cycle ergometer using an incremental step test. | 16 weeks | 
| Changes in body composition after 16 weeks of team sports in early and late postmenopausal women | Dual-energy x-ray absorptiometry (DXA) will be used to determine fat free mass, fat mass as well as bone mineral content. These values will be presented in absolute (g) as well as relative values (percentage) | 16 Weeks |