Exercise Training and Thrombotic Risk in Post-menopausal Women (TIME)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Thrombosis; Menopause; Exercise Training; Vascular Dilation
• Intervention / Treatment: Other: Early and late postmenopausal women

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Ylva Hellsten

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Copenhagen
• Collaborators: Swansea University
• Investigators: Principal Investigator: Ylva Hellsten, Dr.Med.Sci., Nutrition, Exercise and Sports, 2200 Copenhagen, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Actual): December 1, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: October 8, 2020
• First Submitted That Met QC Criteria: October 15, 2020
• First Posted (Actual): October 22, 2020

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis
• Other Study ID Numbers: Thrombosis in PM Women

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