Clinical trial NCT01048606: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Overweight
Keywords: Postmenopause
Overweight
Women
Phytoestrogens
Exercise
Cardiovascular Diseases
Risk Factors
Aging
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2010-01-13
Enrollment: 45
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Body Composition: Dual-energy X-ray Absorptiometry Method
timeFrame: Baseline
measure: 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)
timeFrame: Baseline
measure: Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
timeFrame: Baseline
measure: 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.
timeFrame: Baseline
measure: Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.
timeFrame: Baseline
measure: Plasma Fibrinogen Levels Measured With Luminescence.
timeFrame: Baseline
measure: Body Composition: Dual-energy X-ray Absorptiometry Method
timeFrame: 6 months
measure: Body Composition: Dual-energy X-ray Absorptiometry Method
timeFrame: 12 months
measure: 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)
timeFrame: 6 months
measure: 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)
timeFrame: 12 months
measure: Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
timeFrame: 6 months
measure: Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).
timeFrame: 12 months
measure: 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.
timeFrame: 6 months
measure: 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.
timeFrame: 12 months
measure: Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
timeFrame: Baseline
measure: Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
timeFrame: 6 months
measure: Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)
timeFrame: 12 months
measure: Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
timeFrame: 6 months
measure: Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale
timeFrame: 12 months
measure: Plasma Fibrinogen Levels Measured With Luminescence.
timeFrame: 6 months
measure: Plasma Fibrinogen Levels Measured With Luminescence.
timeFrame: 12 months
Secondary outcomes:
measure: Dietary Intakes: 3-days Food Record. Dietary Analyses Will be Completed Using the Nutifiq Software (Université Laval)
timeFrame: 0, 6 and 12 months
measure: Physical Activity Level: Physical Activity Scale for the Elderly (PASE)
timeFrame: 0, 6 and 12 months
measure: Plasma Isoflavones (Diadzein) - a Marker of Phytoestrogen Compliance - Will be Measured by the ELISA Method
timeFrame: 0, 6 and 12 months
measure: 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.
timeFrame: 0, 6 and 12 months
measure: 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).
timeFrame: 0 and 12 months
measure: 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)
timeFrame: 0, 6 and 12 months
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Centre de recherche sur le vieillissement du CSSS-IUGS
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Isabelle J Dionne, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.