Overweight
Conditions
Keywords
Postmenopause, Overweight, Women, Phytoestrogens, Exercise, Cardiovascular Diseases, Risk Factors, Aging
Brief summary
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.
Interventions
BEHAVIORALPlacebo + exercise
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.
DIETARY_SUPPLEMENTPhytoestrogens without exercise
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.
OTHERPhytoestrogens + exercise
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.
Sponsors
Canadian Institutes of Health Research (CIHR)
Université de Sherbrooke
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale | 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) | 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 |
| Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) | Baseline |
| Body Composition: Dual-energy X-ray Absorptiometry Method | Baseline |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval) | 0, 6 and 12 months |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placeco + Exercise Placebo (no phytoestrogen) Exercise (three 1h-sessions/week)
Placebo + exercise: 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. | 28 |
| Phytoestrogens Without Exercise Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session)
Phytoestrogens without exercise: 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. | 15 |
| Phytoestrogens + Exercise Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week)
Phytoestrogens + exercise: 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. | 26 |
| Placebo Without Exercise Placebo (no phytoestrogens) Without exercise (no structured exercise session) 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). | 10 |
| Total | 79 |
Baseline characteristics
| Characteristic | Placeco + Exercise | Phytoestrogens Without Exercise | Phytoestrogens + Exercise | Placebo Without Exercise | Total |
|---|---|---|---|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 5.7 | 58.4 years STANDARD_DEVIATION 4.3 | 60.5 years STANDARD_DEVIATION 3.8 | 61.7 years STANDARD_DEVIATION 3.9 | 60.4 years STANDARD_DEVIATION 4.8 |
| Body Mass Index | 29.8 kg/m2 STANDARD_DEVIATION 4.7 | 33.8 kg/m2 STANDARD_DEVIATION 5.8 | 30.3 kg/m2 STANDARD_DEVIATION 5.3 | 31.1 kg/m2 STANDARD_DEVIATION 2.9 | 30.9 kg/m2 STANDARD_DEVIATION 5.1 |
| Region of Enrollment Canada | 28 participants | 15 participants | 26 participants | 10 participants | 79 participants |
| Sex: Female, Male Female | 28 Participants | 15 Participants | 26 Participants | 10 Participants | 79 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 28 | 0 / 15 | 0 / 26 | 0 / 10 |
| serious Total, serious adverse events | 0 / 28 | 0 / 15 | 0 / 26 | 0 / 10 |
Outcome results
Primary
Body Composition: Dual-energy X-ray Absorptiometry Method
Time frame: 6 months
Primary
Body Composition: Dual-energy X-ray Absorptiometry Method
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placeco + Exercise | Body Composition: Dual-energy X-ray Absorptiometry Method | 44.5 percent of total fat mass | Standard Deviation 5.5 |
| Phytoestrogens Without Exercise | Body Composition: Dual-energy X-ray Absorptiometry Method | 48.8 percent of total fat mass | Standard Deviation 5 |
| Phytoestrogens + Exercise | Body Composition: Dual-energy X-ray Absorptiometry Method | 43.8 percent of total fat mass | Standard Deviation 4.8 |
| Placebo Without Exercise | Body Composition: Dual-energy X-ray Absorptiometry Method | 46.6 percent of total fat mass | Standard Deviation 2.8 |
Primary
Body Composition: Dual-energy X-ray Absorptiometry Method
Time frame: 12 months
Primary
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time frame: 12 months
Primary
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time frame: 6 months
Primary
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time frame: Baseline
Primary
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.
Time frame: Baseline
Primary
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.
Time frame: 6 months
Primary
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.
Time frame: 12 months
Primary
Plasma Fibrinogen Levels Measured With Luminescence.
Time frame: 12 months
Primary
Plasma Fibrinogen Levels Measured With Luminescence.
Time frame: 6 months
Primary
Plasma Fibrinogen Levels Measured With Luminescence.
Time frame: Baseline
Primary
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)
Time frame: 12 months
Primary
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)
Time frame: Baseline
Primary
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)
Time frame: 6 months
Primary
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Time frame: 12 months
Primary
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Time frame: 6 months
Primary
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.
Time frame: Baseline
Primary
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time frame: 6 months
Primary
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time frame: 12 months
Primary
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time frame: Baseline
Secondary
Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval)
Time frame: 0, 6 and 12 months
Secondary
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).
Time frame: 0 and 12 months
Secondary
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.
Time frame: 0, 6 and 12 months
Secondary
Physical Activity Level: Physical Activity Scale for the Elderly (PASE)
Time frame: 0, 6 and 12 months
Secondary
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)
Time frame: 0, 6 and 12 months
Secondary
Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method
Time frame: 0, 6 and 12 months