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

Overweight Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048606
• Other study ID #: IDionne_phyto_2008-2011
• Status: Completed
• Phase: Phase 4
• First received: January 12, 2010
• Last updated: December 18, 2013
• Start date: January 2009
• Est. completion date: November 2012

Study information

• Verified date: December 2013
• Source: Université de Sherbrooke
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Canadian Institutes of Health ResearchCanada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 50 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Overweight

Intervention

Behavioral:
• 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.

Dietary Supplement:
• 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.

Other:
• 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.

Locations

Country	Name	City	State
Canada	Centre de recherche sur le vieillissement du CSSS-IUGS	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Sherbrooke	Canadian Institutes of Health Research (CIHR)

Country where clinical trial is conducted

Canada, 

References & Publications (10)

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. — View 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. — View 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. Epub 2007 Feb 21. — View 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. — View 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. — View 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.

Lebon J, Aubertin-Leheudre M, Bobeuf F, Lord C, Labonté 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 — View 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. — View 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.met — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body Composition: Dual-energy X-ray Absorptiometry Method		Baseline	No
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)		Baseline	No
Primary	Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).		Baseline	No
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.		Baseline	No
Primary	Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.		Baseline	No
Primary	Plasma Fibrinogen Levels Measured With Luminescence.		Baseline	No
Primary	Body Composition: Dual-energy X-ray Absorptiometry Method		6 months	No
Primary	Body Composition: Dual-energy X-ray Absorptiometry Method		12 months	No
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)		6 months	No
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)		12 months	No
Primary	Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).		6 months	No
Primary	Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).		12 months	No
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.		6 months	No
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.		12 months	No
Primary	Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)		Baseline	No
Primary	Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)		6 months	No
Primary	Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)		12 months	No
Primary	Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale		6 months	No
Primary	Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale		12 months	No
Primary	Plasma Fibrinogen Levels Measured With Luminescence.		6 months	No
Primary	Plasma Fibrinogen Levels Measured With Luminescence.		12 months	No
Secondary	Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval)		0, 6 and 12 months	No
Secondary	Physical Activity Level: Physical Activity Scale for the Elderly (PASE)		0, 6 and 12 months	No
Secondary	Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method		0, 6 and 12 months	No
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.		0, 6 and 12 months	No
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).		0 and 12 months	No
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)		0, 6 and 12 months	No