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

Phase 4

Completed

Conditions: Overweight

Interventions: Behavioral: Placebo + exercise
Dietary Supplement: Phytoestrogens without exercise
Other: Phytoestrogens + exercise

Registration Number: NCT01048606

Lead Sponsor: Université de Sherbrooke

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 45

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

Study Type: INTERVENTIONAL

Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Placeco + exercise	Placebo + 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)
Phytoestrogens without exercise	Phytoestrogens without exercise	Phytoestrogens (70mg/day of soy isoflavone) Without exercise (no structured exercise session)
Phytoestrogens + exercise	Phytoestrogens + exercise	Phytoestrogens (70 mg/day soy isoflavone) Exercise (1h-sessions 3 times/week)

Primary Outcome Measures

Name	Time	Method
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
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)	12 months
Plasma Fibrinogen Levels Measured With Luminescence.	12 months
Glucose Metabolism: 2h-75g Oral Glucose Tolerance Test (OGTT) + Plasma Insulin and Glucose Concentrations (Blood Sample Analysis).	12 months
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale.	Baseline
Quality of Life: Assessed With Questionnaires (SF-36 (General Health Perceptions), Kupperman Index, Perceived Stress Scale	12 months
Sex-hormone Levels. Estradiol, Estrone, Progesterone, Testosterone and SHBG Will be Obtained by Enzyme Immuno Assay (EIA)	12 months

Secondary Outcome Measures

Name	Time	Method
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
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
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