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

Primary Purpose

Overweight

Status
Completed
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Placebo + exercise
Phytoestrogens without exercise
Phytoestrogens + exercise
Sponsored by
Université de Sherbrooke
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Overweight focused on measuring Postmenopause, Overweight, Women, Phytoestrogens, Exercise, Cardiovascular Diseases, Risk Factors, Aging

Eligibility Criteria

50 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Centre de recherche sur le vieillissement du CSSS-IUGS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Active Comparator

Experimental

No Intervention

Arm Label

Placeco + exercise

Phytoestrogens without exercise

Phytoestrogens + exercise

Placebo without exercise

Arm Description

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)

Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session)

Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week)

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

Outcomes

Primary Outcome Measures

Body Composition: Dual-energy X-ray Absorptiometry Method
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)
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
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.
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.
Plasma Fibrinogen Levels Measured With Luminescence.
Body Composition: Dual-energy X-ray Absorptiometry Method
Body Composition: Dual-energy X-ray Absorptiometry Method
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)
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)
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
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.
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.
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Plasma Fibrinogen Levels Measured With Luminescence.
Plasma Fibrinogen Levels Measured With Luminescence.

Secondary Outcome Measures

Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval)
Physical Activity Level: Physical Activity Scale for the Elderly (PASE)
Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method
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.
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).
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)

Full Information

First Posted
January 12, 2010
Last Updated
December 18, 2013
Sponsor
Université de Sherbrooke
Collaborators
Canadian Institutes of Health Research (CIHR)
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1. Study Identification

Unique Protocol Identification Number
NCT01048606
Brief Title
Exercise and Phytoestrogens: Effect on Factors Predisposing to Cardiovascular Disease(CVD) in Postmenopausal Women
Official Title
Exercise and Phytoestrogens: a Synergistic Effect on Factors Predisposing to CVD in Postmenopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Université de Sherbrooke
Collaborators
Canadian Institutes of Health Research (CIHR)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Overweight
Keywords
Postmenopause, Overweight, Women, Phytoestrogens, Exercise, Cardiovascular Diseases, Risk Factors, Aging

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Factorial Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placeco + exercise
Arm Type
Active Comparator
Arm Description
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)
Arm Title
Phytoestrogens without exercise
Arm Type
Active Comparator
Arm Description
Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session)
Arm Title
Phytoestrogens + exercise
Arm Type
Experimental
Arm Description
Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week)
Arm Title
Placebo without exercise
Arm Type
No Intervention
Arm Description
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
Intervention Type
Behavioral
Intervention Name(s)
Placebo + exercise
Intervention Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Phytoestrogens without exercise
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Phytoestrogens + exercise
Intervention Description
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.
Primary Outcome Measure Information:
Title
Body Composition: Dual-energy X-ray Absorptiometry Method
Time Frame
Baseline
Title
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
Title
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time Frame
Baseline
Title
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
Title
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.
Time Frame
Baseline
Title
Plasma Fibrinogen Levels Measured With Luminescence.
Time Frame
Baseline
Title
Body Composition: Dual-energy X-ray Absorptiometry Method
Time Frame
6 months
Title
Body Composition: Dual-energy X-ray Absorptiometry Method
Time Frame
12 months
Title
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
Title
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
Title
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time Frame
6 months
Title
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
Time Frame
12 months
Title
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
Title
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
Title
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time Frame
Baseline
Title
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time Frame
6 months
Title
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
Time Frame
12 months
Title
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Time Frame
6 months
Title
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
Time Frame
12 months
Title
Plasma Fibrinogen Levels Measured With Luminescence.
Time Frame
6 months
Title
Plasma Fibrinogen Levels Measured With Luminescence.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval)
Time Frame
0, 6 and 12 months
Title
Physical Activity Level: Physical Activity Scale for the Elderly (PASE)
Time Frame
0, 6 and 12 months
Title
Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method
Time Frame
0, 6 and 12 months
Title
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
Title
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
Title
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

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Isabelle J Dionne, Ph.D.
Organizational Affiliation
Université de Sherbrooke
Official's Role
Principal Investigator
Facility Information:
Facility Name
Centre de recherche sur le vieillissement du CSSS-IUGS
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 4C4
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
18788990
Citation
Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Isoflavones and clinical cardiovascular risk factors in obese postmenopausal women: a randomized double-blind placebo-controlled trial. J Womens Health (Larchmt). 2008 Oct;17(8):1363-9. doi: 10.1089/jwh.2008.0836.
Results Reference
background
Citation
Choquette, S., D.-A. Lalancette, et al. (2009). Soy Isoflavones and Exercise: Possible Benefits for Postmenopausal Women's Cardiovascular Health. Current Women's Health Reviews 5(2): 56-62.
Results Reference
background
PubMed Identifier
17311051
Citation
Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial. Eur J Clin Nutr. 2007 Dec;61(12):1442-4. doi: 10.1038/sj.ejcn.1602695. Epub 2007 Feb 21.
Results Reference
background
PubMed Identifier
17290158
Citation
Aubertin-Leheudre M, Lord C, Khalil A, Dionne IJ. Effect of 6 months of exercise and isoflavone supplementation on clinical cardiovascular risk factors in obese postmenopausal women: a randomized, double-blind study. Menopause. 2007 Jul-Aug;14(4):624-9. doi: 10.1097/gme.0b013e31802e426b.
Results Reference
background
PubMed Identifier
22947543
Citation
Lebon J, Aubertin-Leheudre M, Bobeuf F, Lord C, Labonte M, Dionne IJ. Is a small muscle mass index really detrimental for insulin sensitivity in postmenopausal women of various body composition status? J Musculoskelet Neuronal Interact. 2012 Sep;12(3):116-26.
Results Reference
result
PubMed Identifier
22530610
Citation
Barsalani R, Riesco E, Lavoie JM, Dionne IJ. Effect of exercise training and isoflavones on hepatic steatosis in overweight postmenopausal women. Climacteric. 2013 Feb;16(1):88-95. doi: 10.3109/13697137.2012.662251. Epub 2012 Apr 24.
Results Reference
result
PubMed Identifier
22338607
Citation
Choquette S, Dion T, Brochu M, Dionne IJ. Soy isoflavones and exercise to improve physical capacity in postmenopausal women. Climacteric. 2013 Feb;16(1):70-7. doi: 10.3109/13697137.2011.643515. Epub 2012 Feb 16.
Results Reference
result
PubMed Identifier
21864865
Citation
Riesco E, Choquette S, Audet M, Lebon J, Tessier D, Dionne IJ. Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial. Metabolism. 2012 Feb;61(2):273-80. doi: 10.1016/j.metabol.2011.06.025. Epub 2011 Aug 23.
Results Reference
result
PubMed Identifier
21864137
Citation
Riesco E, Choquette S, Audet M, Tessier D, Dionne IJ. Effect of exercise combined with phytoestrogens on quality of life in postmenopausal women. Climacteric. 2011 Oct;14(5):573-80. doi: 10.3109/13697137.2011.566652. Epub 2011 Aug 24.
Results Reference
result
PubMed Identifier
20539245
Citation
Riesco E, Aubertin-Leheudre M, Maltais ML, Audet M, Dionne IJ. Synergic effect of phytoestrogens and exercise training on cardiovascular risk profile in exercise-responder postmenopausal women: a pilot study. Menopause. 2010 Sep-Oct;17(5):1035-9. doi: 10.1097/gme.0b013e3181da7915.
Results Reference
result
PubMed Identifier
33651744
Citation
Ghachem A, Marcotte-Chenard A, Tremblay D, Prud'homme D, Rabasa-Lhoret R, Riesco E, Brochu M, Dionne IJ. Obesity among postmenopausal women: what is the best anthropometric index to assess adiposity and success of weight-loss intervention? Menopause. 2021 Mar 1;28(6):678-685. doi: 10.1097/GME.0000000000001754.
Results Reference
derived
PubMed Identifier
27326819
Citation
Myette-Cote E, Archambault-Therrien C, Brochu M, Dionne IJ, Riesco E. Physical fitness improvement in overweight postmenopausal women who do not lose fat mass in response to exercise training. Menopause. 2016 Oct;23(10):1122-9. doi: 10.1097/GME.0000000000000677.
Results Reference
derived
PubMed Identifier
21205384
Citation
Choquette S, Riesco E, Cormier E, Dion T, Aubertin-Leheudre M, Dionne IJ. Effects of soya isoflavones and exercise on body composition and clinical risk factors of cardiovascular diseases in overweight postmenopausal women: a 6-month double-blind controlled trial. Br J Nutr. 2011 Apr;105(8):1199-209. doi: 10.1017/S0007114510004897. Epub 2010 Dec 17.
Results Reference
derived

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

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