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

NCT01048606 | Completed Phase 4 Results

• 1 other identifier: IDionne_phyto_2008-2011
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight

Keywords

Postmenopause; Overweight; Women; Phytoestrogens; Exercise; Cardiovascular Diseases; Risk Factors; Aging

Outcome Measures

Primary Outcomes (21)

• 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 Outcomes (6)

• 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

Study Arms (4)

Placeco + exercise

ACTIVE COMPARATOR

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

Phytoestrogens without exercise

ACTIVE COMPARATOR

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

Dietary Supplement: Phytoestrogens without exercise

Phytoestrogens + exercise

EXPERIMENTAL

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

Other: Phytoestrogens + exercise

Placebo without exercise

NO INTERVENTION

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

Interventions

Placebo + exercise BEHAVIORAL

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.

Placeco + exercise

Phytoestrogens without exercise DIETARY_SUPPLEMENT

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.

Phytoestrogens without exercise

Phytoestrogens + exercise OTHER

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.

Phytoestrogens + exercise

Eligibility Criteria

• Age: 50 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• soy allergy
• known hepatic diseases
• asthma
• family history of accident cerebro-vascular
• personal history of a feminine cancer

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Canadian Institutes of Health Research (CIHR): collaborator

Study Sites (1)

Centre de recherche sur le vieillissement du CSSS-IUGS

Sherbrooke, Quebec, J1H 4C4, Canada

Location

Related Publications (13)

• 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.

  PMID: 18788990 BACKGROUND

• 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.

  BACKGROUND

• 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.

  PMID: 17311051 BACKGROUND

• 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.

  PMID: 17290158 BACKGROUND

• 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.

  PMID: 22947543 RESULT

• 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.

  PMID: 22530610 RESULT

• 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.

  PMID: 22338607 RESULT

• 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.

  PMID: 21864865 RESULT

• 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.

  PMID: 21864137 RESULT

• 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.

  PMID: 20539245 RESULT

• 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.

  PMID: 33651744 DERIVED

• 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.

  PMID: 27326819 DERIVED

• 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.

  PMID: 21205384 DERIVED

MeSH Terms

Conditions

Overweight; Motor Activity; Cardiovascular Diseases

Interventions

Exercise; Phytoestrogens

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Estrogens, Non-Steroidal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Pr Isabelle Dionne, Ph.D., vice-dean to research and graduate studies
• Organization: Université de Sherbrooke

isabelle.dionne@usherbrooke.ca

1-819-821-8000

Study Officials

• Isabelle J Dionne, Ph.D.

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: January 12, 2010
• First Posted: January 13, 2010
• Study Start: January 1, 2009
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: February 12, 2014
• Results First Posted: February 12, 2014

Record last verified: 2013-12

Locations

CA (1)