Exercise and Phytoestrogens: Effect on Factors Predisposing to Cardiovascular Disease(CVD) in Postmenopausal Women

Study Overview
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Brief Summary
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Menopause is characterized by a decrease of estrogen and progesterone levels and is associated with various changes in body composition, including an accumulation of total fat mass, a relocation of adiposity to the abdomen, deterioration of plasma lipid profile, increased risk of type 2 diabetes, and increased oxidative stress. Taken together, these changes increase the risk of developing cardiovascular disease (CVD). Physical activity and hormone-replacement therapy (HRT) have been shown to act in synergy to improve total fat mass in postmenopausal (PM) women. Because the progesterone component of HRT has been associated with an increased CVD risk in older women with a family history of CVD, the use of HRT has become controversial. As a result, a large decrease of the use of HRT in the community has been observed and postmenopausal women (PM) have developed interest in alternative therapies. Among the possibilities, phytoestrogens have shown beneficial effects on menopausal symptoms and plasma lipids. Phytoestrogens are structurally and functionally similar to estradiol (the major estrogen in humans) but found only in plants such as soybean isoflavones. They do not exert any effect on breast cancer or/and endometrial tissue. AIMS To examine the effects of phytoestrogens, exercise and the combination of both on lean body mass, total fat mass, visceral fat, blood lipid profile, oxidative stress markers, antioxidant system, glucose metabolism, and sex-hormone levels in obese PM women. HYPOTHESES Women undergoing a combination of phytoestrogen treatment and an exercise program will display a greater increase in lean body mass, decrease in total and visceral fat mass, improvements in blood lipid profile, decrease in oxidative stress markers, increase in antioxidant system, improvement in glucose metabolism, and increase in sex-hormone levels than those submitted to any or one of the treatments. A total of 120 women will be recruited. There will be 4 groups (30 women/group) undergoing exercise or not and supplemented with phytoestrogens or a placebo. The intervention is planned to last 12 mo. Key variables will be measured at baseline, and after 6 and 12 mo of intervention. Three weekly 1h-sessions of exercise will be held on 3 non-consecutive days. The phytoestrogen supplements will consist of 70 mg/d of soy isoflavones taken as 4 caps/day.

Official Title
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Exercise and Phytoestrogens: a Synergistic Effect on Factors Predisposing to CVD in Postmenopausal Women

Conditions
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Overweight

Intervention / Treatment
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* Behavioral: Placebo + exercise
* Dietary Supplement: Phytoestrogens without exercise
* Other: Phytoestrogens + exercise


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 50-70 years francophone or understanding French body mass index > 27kg/m² without physical disability without medical treatment influencing metabolism non smoker light drinker (<15 g ethanol/day = 1 alcoholic beverage) weight stable (< 2 kg) for 6 mo no participation in a supervised exercise program for 6 mo without HRT for at least 3 yrs and without menses for at least 12 mo Exclusion Criteria: soy allergy known hepatic diseases asthma family history of accident cerebro-vascular personal history of a feminine cancer

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Placeco + exercise<br>Placebo (no phytoestrogen): Non-active capsules of the same size and appearance than phytoestrogens capsules will be used as a placebo (same posology, i.e. 4 caps/day) Exercise (three 1h-sessions/week) | Behavioral: Placebo + exercise<br>* Placebo: Non-active capsules of the same size and appearance than phytoestrogens capsules will be used as a placebo (same posology, i.e. 4 caps/day) Exercise intervention: Three weekly 1h-sessions will be held on 3 non-consecutive days. Each session comprises a total of 60 min of aerobic exercise (on an ergometer device) and resistance exercise (with elastic bands, free weights, exercise ball, etc.), and a 5-min cool down. Cues regarding exercise intensity will be offered to maintain intensity in a range of 60 to 80% of maximal heart rate (with the use of a target pulse, etc.). The exercise sessions will be led by a physical activity specialist.<br>|
| Active Comparator: Phytoestrogens without exercise<br>Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session) | Dietary Supplement: Phytoestrogens without exercise<br>* Phytoestrogens: The phytoestrogen supplements will consist of 70 mg/day of soy isoflavones taken as 4 caps/day. More specifically, the daily dose of isoflavones contains 44 mg of diadzein, 16 mg of glycitein and 10 mg of genestein extracted from natural soy. Without exercise: participants will be asked to do only their usual activities without being involved in any kind of structured exercise sessions.<br>|
| Experimental: Phytoestrogens + exercise<br>Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week) | Other: Phytoestrogens + exercise<br>* Phytoestrogens: The phytoestrogen supplements will consist of 70 mg/day of soy isoflavones taken as 4 caps/day. More specifically, the daily dose of isoflavones contains 44 mg of diadzein, 16 mg of glycitein and 10 mg of genestein extracted from natural soy. Exercise intervention: Three weekly 1h-sessions will be held on 3 non-consecutive days. Each session comprises a total of 60 min of aerobic exercise (on an ergometer device) and resistance exercise (with elastic bands, free weights, exercise ball, etc.), and a 5-min cool down. Cues regarding exercise intensity will be offered to maintain intensity in a range of 60 to 80% of maximal heart rate (with the use of a target pulse, etc.). The exercise sessions will be led by a physical activity specialist.<br>|
| No Intervention: Placebo without exercise<br>Placebo: Non-active capsules of the same size and appearance than phytoestrogens capsules will be used as a placebo (same posology, i.e. 4 caps/day) No exercise | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body Composition: Dual-energy X-ray Absorptiometry Method |  | Baseline | 
| Plasma Lipid Profile: the Apolipoproteins (Apo-AI, Apo-AII, Apo-B), Cholesterol HDL, LDL and Triglycerides Levels Will be Determined by Clinical Analyses of Blood Sample (Obtained After 12 h Fasting State) |  | Baseline | 
| Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). |  | Baseline | 
| Markers of Oxidative Stress: Conjugated Diene Formation, Malondialdehyde, Alpha-tocopherol and Its Oxidised Form Alpha-tocopheryl Quinone. TAS Constitutes the Most Reliable Method for the Evaluation of Oxidative Stress in Vivo. |  | Baseline | 
| Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale. |  | Baseline | 
| Plasma Fibrinogen Levels Measured With Luminescence. |  | Baseline | 
| Body Composition: Dual-energy X-ray Absorptiometry Method |  | 6 months | 
| Body Composition: Dual-energy X-ray Absorptiometry Method |  | 12 months | 
| Plasma Lipid Profile: the Apolipoproteins (Apo-AI, Apo-AII, Apo-B), Cholesterol HDL, LDL and Triglycerides Levels Will be Determined by Clinical Analyses of Blood Sample (Obtained After 12 h Fasting State) |  | 6 months | 
| Plasma Lipid Profile: the Apolipoproteins (Apo-AI, Apo-AII, Apo-B), Cholesterol HDL, LDL and Triglycerides Levels Will be Determined by Clinical Analyses of Blood Sample (Obtained After 12 h Fasting State) |  | 12 months | 
| Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). |  | 6 months | 
| Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). |  | 12 months | 
| Markers of Oxidative Stress: Conjugated Diene Formation, Malondialdehyde, Alpha-tocopherol and Its Oxidised Form Alpha-tocopheryl Quinone. TAS Constitutes the Most Reliable Method for the Evaluation of Oxidative Stress in Vivo. |  | 6 months | 
| Markers of Oxidative Stress: Conjugated Diene Formation, Malondialdehyde, Alpha-tocopherol and Its Oxidised Form Alpha-tocopheryl Quinone. TAS Constitutes the Most Reliable Method for the Evaluation of Oxidative Stress in Vivo. |  | 12 months | 
| Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) |  | Baseline | 
| Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) |  | 6 months | 
| Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) |  | 12 months | 
| Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale |  | 6 months | 
| Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale |  | 12 months | 
| Plasma Fibrinogen Levels Measured With Luminescence. |  | 6 months | 
| Plasma Fibrinogen Levels Measured With Luminescence. |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval) |  | 0, 6 and 12 months | 
| Physical Activity Level: Physical Activity Scale for the Elderly (PASE) |  | 0, 6 and 12 months | 
| Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method |  | 0, 6 and 12 months | 
| Metabolic Rate at Rest: During 30 Minutes With a Breathing Mask by Indirect Calorimetry (CCM/D, Medgraphics Corp, St-Paul, MN, USA) After a 12-hour Fast, in the Early Morning. |  | 0, 6 and 12 months | 
| Maximal Oxygen Uptake Measured Using a Continuous, Incremental Protocol (Balke Modified Protocol) on a Treadmill With a Breathing Mask by Indirect Calorimetry (CCM/D, Medgraphics Corp, St-Paul, MN, USA). |  | 0 and 12 months | 
| Physical Capacity: 3 Tests From the Senior Fitness Test (Chair Stand Test, Chair Sit-and-Reach Test, Back Scratch Test) + Handgrip Strength Test (Lafayette Hand Dynamometer, Indiana) |  | 0, 6 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postmenopause, Overweight, Women, Phytoestrogens, Exercise, Cardiovascular Diseases, Risk Factors, Aging