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

This study has been completed.
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
Centre de recherche sur le vieillissement du CSSS-IUGS
Information provided by (Responsible Party):
Isabelle J Dionne, Université de Sherbrooke
ClinicalTrials.gov Identifier:
NCT01048606
First received: January 12, 2010
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Overweight
Behavioral: Placebo + exercise
Dietary Supplement: Phytoestrogens without exercise
Other: Phytoestrogens + exercise
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Exercise and Phytoestrogens: a Synergistic Effect on Factors Predisposing to CVD in Postmenopausal Women

Resource links provided by NLM:


Further study details as provided by Université de Sherbrooke:

Primary Outcome Measures:
  • Body Composition: Dual-energy X-ray Absorptiometry Method [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Plasma Fibrinogen Levels Measured With Luminescence. [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Body Composition: Dual-energy X-ray Absorptiometry Method [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Body Composition: Dual-energy X-ray Absorptiometry Method [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis). [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) [ Time Frame: Baseline ] [ Designated as safety issue: No ]
  • Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Plasma Fibrinogen Levels Measured With Luminescence. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Plasma Fibrinogen Levels Measured With Luminescence. [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval) [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Physical Activity Level: Physical Activity Scale for the Elderly (PASE) [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method [ Time Frame: 0, 6 and 12 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: January 2009
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Placeco + exercise
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

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.

Active Comparator: Phytoestrogens without exercise
Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session)
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.

Experimental: Phytoestrogens + exercise
Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week)
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.

No Intervention: Placebo without 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) No exercise

  Eligibility

Ages Eligible for Study:   50 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01048606

Locations
Canada, Quebec
Centre de recherche sur le vieillissement du CSSS-IUGS
Sherbrooke, Quebec, Canada, J1H 4C4
Sponsors and Collaborators
Université de Sherbrooke
Canadian Institutes of Health Research (CIHR)
Centre de recherche sur le vieillissement du CSSS-IUGS
Investigators
Principal Investigator: Isabelle J Dionne, Ph.D. Université de Sherbrooke
  More Information

Publications:
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Isabelle J Dionne, PhD, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT01048606     History of Changes
Other Study ID Numbers: IDionne_phyto_2008-2011
Study First Received: January 12, 2010
Results First Received: December 18, 2013
Last Updated: December 18, 2013
Health Authority: Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee

Keywords provided by Université de Sherbrooke:
Postmenopause
Overweight
Women
Phytoestrogens
Exercise
Cardiovascular Diseases
Risk Factors
Aging

Additional relevant MeSH terms:
Cardiovascular Diseases
Overweight
Body Weight
Signs and Symptoms
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 16, 2014