The effect of soy protein with or without isoflavones relative to milk protein on plasma lipids in hypercholesterolemic postmenopausal women. Isoflavones and clinical cardiovascular risk factors in obese postmenopausal women: a randomized double-blind placebo-controlled trial. The effect of red clover isoflavones on menopausal symptoms, lipids and vaginal cytology in menopausal women: a randomized, double-blind, placebo-controlled study. Benefits of soy isoflavone therapeutic regimen on menopausal symptoms. The effect of Promensil, an isoflavone extract, on menopausal symptoms. Randomized placebo-controlled trial of an isoflavone supplement and menopausal symptoms in women. The effects of soy protein in women and men with elevated plasma lipids. Effects on menopausal symptoms and acceptability of isoflavone-containing soy powder dietary supplementation. Effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries.
Clinical trial data and the results of a meta-analysis suggest a hypocholesterolemic effect of soy protein. The effect may be partially attributable to the isoflavones in soy. Few studies have examined the separate effects of soy protein and isoflavones.
                The objective of this study was to determine the effect of soy protein and isoflavones on plasma lipid concentrations in postmenopausal, moderately hypercholesterolemic women.
                This was a randomized, double-blind, placebo-controlled clinical trial with 3 treatment groups. After a 4-wk run-in phase during which the women consumed a milk protein supplement, the subjects were randomly assigned to 12 wk of dietary protein supplementation (42 g/d) with either a milk protein (Milk group) or 1 of 2 soy proteins containing either trace amounts of isoflavones (Soy- group) or 80 mg aglycone isoflavones (Soy+ group).
                LDL-cholesterol concentrations decreased more in the Soy+ group (n = 31) than in the Soy- group (n = 33) (0.38 compared with 0.09 mmol/L; P = 0.005), but neither of these changes was significantly different from the 0.26-mmol/L decrease observed in the Milk group (n = 30). The results for total cholesterol were similar to those for LDL cholesterol. There were no significant differences in HDL-cholesterol or triacylglycerol concentrations between the 3 groups.
                The difference in total- and LDL-cholesterol lowering between the 2 soy-protein supplements suggests an effect attributable to the isoflavone-containing fraction. However, the unexpected LDL-cholesterol lowering observed in the Milk group, and the fact that there was no significant difference between either soy group and the Milk group, suggests that changes may have been due to other factors related to participation in the study. To investigate whether 6 months of isoflavone supplementation, which has been shown to be sufficient to improve menopausal symptoms, could also improve clinical cardiovascular disease (CVD) risk factors in obese postmenopausal women, compared with a placebo.
                A randomized double-blind placebo-controlled trial in which 50 obese postmenopausal women were divided into two groups (isoflavones vs. placebo) to examine the effect of 6 months of isoflavone supplement (70 mg) on clinical CVD risk factors. Body composition (DXA), medical and social characteristics, daily energy expenditure (accelerometry), dietary intake (3-day dietary record), and blood biochemical analyses (lipid profile, insulin, glucose) were obtained.
                At baseline, no differences were found between groups except for fasting insulin level. Women were thus considered at risk of CVD based on body composition but not biochemical variables. After 6 months, we observed that isoflavones did not favorably affect risk factors predisposing to CVD (biochemical or body composition) compared with placebo.
                Isoflavones given for 6 months should not be considered protective against clinical CVD risk factors in obese postmenopausal women. Nevertheless, further research is needed to verify if isoflavones protect against CVD disease risk factors when administered for a longer duration or when combined with nutritional or exercise interventions. It would also be pertinent to study their effects in women with specific metabolic abnormalities. Background: The unexpected results of the Women's Health Initiative study have decreased the use of conventional hormone therapy (HT), changing physicians' and patients' attitudes towards HT and increasing their interest in alternative options.
                The present study aimed to evaluate the effect of isoflavones contained in red clover extracts (Trifolium pratense) on menopausal symptoms, lipids and vaginal cytology in menopausal women.
                Sixty postmenopausal women aged >40 years, non-users of HT, with Kupperman index score 15, were double-blindly randomized to receive either a commercially available red clover isoflavone supplement (80 mg/day) or placebo for 90 days. Subsequently, after a 7-day washout period, subjects switched to receive the opposite treatment for a further 90 days. Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline, 90 and 180 days.
                Fifty-three women (88.3%) completed the trial. Mean age was 51.3 +/- 3.5 years, 69.7% of the women were aged 50 years or more. There was no significant effect on body mass index, weight or blood pressure after either treatment phase. Baseline Kupperman index score decreased significantly after each treatment phase, with the decrease more pronounced after the isoflavone phase (baseline: 27.2 +/- 7.7; after isoflavone: 5.9 +/- 3.9; after placebo: 20.9 +/- 5.3, p < 0.05). Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic, cornification and basal cell maturation indices. Mean total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels also decreased; however, only the latter was significantly lower compared with placebo.
                Compared with placebo, red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels. To examine the change in menopausal symptoms and cardiovascular risk factors in response to 4 months of daily 100-mg soy isoflavone in postmenopausal women.
                In this double-blind, placebo-controlled study, 80 women were randomly assigned to isoflavone (n = 40) and placebo (n = 40) treatment. The menopausal Kupperman index was used to assess change in menopausal symptoms at baseline and after 4 months of treatment. Cardiovascular risk factors were assessed by evaluating plasma lipid levels, body mass index, blood pressure, and glucose levels in the participants. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and 17 beta-estradiol were measured. Transvaginal sonography was performed to quantify endometrial thickness.
                The data showed a decrease in menopausal symptoms (P <.01, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). Total cholesterol and low-density lipoprotein decreased significantly in the isoflavone group compared with the baseline or placebo group (P <.001, paired t test, two-tailed, between baseline and isoflavone groups, and P <.01, unpaired t test, between placebo and isoflavone groups). The isoflavone treatment appeared to have no effect on blood pressure, plasma glucose, and high-density lipoprotein and triglyceride levels.
                This study suggests that isoflavone 100-mg regime treatment may be a safe and effective alternative therapy for menopausal symptoms and may offer a benefit to the cardiovascular system. The primary aim was to assess whether the use of an isoflavone extract containing 40 mg or 160 mg of total isoflavones affects the frequency of menopausal flushes and other symptoms. The secondary aims were assessments of possible effects on menopause symptom scores and biological measures of estrogen activity.
                A randomized, double-blind, placebo-controlled prospective trial of 37 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to three treatment groups: placebo, 40 mg or 160 mg, delivered in tablet form.
                There was no significant difference in the incidence of flushes between the three groups at trial conclusion. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal pH, levels of follicle stimulating hormone (FSH), sex hormone binding globulin (SHBG) or total cholesterol, liver function or blood parameters. A statistically significant increase in high-density lipoprotein (HDL) cholesterol of 18.1% (p = 0.038) occurred in the 40-mg group.
                A large placebo response and inadvertent use of dietary isoflavones in the placebo group may have obscured a significant change in flushing frequency. Previous uncontrolled studies claiming a beneficial effect of foods with a high isoflavone content on menopausal symptoms may have been confounded by a large placebo response. To test the hypothesis that increasing the intake of isoflavones by dietary supplementation may produce a therapeutic effect in reducing the incidence and severity of hot flushes in menopausal women.
                Fifty-one postmenopausal women were randomized to placebo and active (one tablet per day of a 40-mg isoflavone supplement) groups in a cross-over design trial. After a 1-week run-in period, subjects were commenced on a 12-week period of treatment (active or placebo), followed by a 1-month placebo wash-out period, then crossed over to the alternative treatment regimen for a further 14 weeks. Symptom diaries were maintained throughout the trial and at the start and end of treatment. Plasma sex hormone binding globulin (SHBG) assay, full blood count, biochemical profiles, vaginal swabs and vaginal ultrasound scans were performed and isoflavones determined in 24-h urine collections by high-pressure liquid chromatography (HPLC) analysis.
                There was no significant difference between active and placebo groups in the reduction in hot flushes between start and finish time-points. Analysis performed on interim data time-points revealed a substantially greater reduction in flushing in the active group than placebo at 4 and 8 weeks after commencement of treatment, but this was not statistically significant. There were no significant differences between groups for Greene scores or in SHBG levels, hematological or biochemical parameters and vaginal swab or ultrasound findings. The combined values for all subjects, regardless of treatment group, revealed a strong negative correlation between the level of urinary isoflavone excretion and the incidence of hot flushes.
                These data do not indicate a therapeutic benefit from dietary supplementation with isoflavones in women experiencing menopausal symptoms, but do indicate that the apparent placebo effect in many studies of menopausal symptoms may be attributable to dietary sources of isoflavones. The study also demonstrates that 3 months of isoflavone supplementation did not cause adverse events or endometrial changes. Fifty four postmenopausal women with elevated cholesterol were recruited for a randomised, double-blind controlled trial of soy protein containing isoflavones. (ISP+) or a soy protein with a low isoflavone content (ISP-), taken daily for 12 weeks. There was an overall reduction after 12 weeks in total cholesterol (TC), LDL cholesterol (LDL-C), sex hormone binding globulin (SHBG), and luteinizing hormone (LH). There were no significant differences between treatment groups. In a separate study 27 male subjects with a TC > 5.5 mmol/l were given ISP+ for 12 weeks. In this male study there was a significant increase in HDL cholesterol (HDL-C) and SHBG. Soy protein has a cholesterol lowering effect in both women and men. These studies suggest that this effect is independent of isoflavones. Soy protein also reduces SHBG levels in both sexes. To assess the acceptability of the delivery of an isoflavone supplementation in the form of a powdered drink, and whether the supplementation of dietary isoflavones in this manner decreased the incidence of menopausal flushes. The secondary aims included assessment of other symptoms or parameters of estrogen deficiency and responses to isoflavones.
                A randomized, double-blind, placebo-controlled, parallel-group trial comprising 24 postmenopausal women with symptoms of estrogen deficiency was performed over a 12-week period. The women were randomized to receive a dietary beverage containing isoflavones or an isoflavone-free, isocaloric placebo preparation.
                Although there was a high compliance rate among individual patients, there was a 25% withdrawal rate from the study in the active group. The incidence of complaints of bad taste tended to be higher in the active group (p = 0.07), and the total number of adverse events was significantly higher in this group (p < 0.001). There was no statistically significant difference in the incidence of flushes between the groups. There was no difference between the groups in Greene Menopause Symptom Scores, vaginal maturation value, levels of follicle stimulating hormone (FSH) or sex hormone-binding globulin (SHBG), or bone turnover markers.
                Powdered energy drinks are not commonly consumed in Australia and were poorly tolerated in this study. The high withdrawal rate and reporting of side-effects suggests that other methods of isoflavone delivery may be more appropriate in this culture, in future trials. At the dose used no benefit was seen in relief from menopausal symptoms, although for the sample size, the study could only have been expected to detect major differences between the groups. To determine the effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the vascular reactivity of uterine and cerebral arteries.
                Double-blind, randomized, placebo-controlled trial.
                Healthy volunteers in an academic research environment.
                Sixty-two postmenopausal women aged 45-60 years attending the Outpatient Menopause Clinic of our gynecological departments.
                The patients were administered 72 mg of soy-derived isoflavones or placebo under double-blind conditions. The daily number of hot flushes was recorded in a diary. Endometrial thickness was measured by means of transvaginal ultrasound; the uterine, internal carotid, and middle cerebral arteries were evaluated using Doppler ultrasound.
                The daily number of hot flushes, endometrial thickness, and arterial pulsatility index (PI).
                Both treatments led to a 40% reduction in the number of hot flushes. Soy-derived isoflavones had no effect on endometrial thickness or the PI of the uterine and cerebral arteries.
                The daily administration of 72 mg of soy-derived isoflavones is no more effective than placebo in reducing hot flushes in postmenopausal women. It also has no effect on endometrial thickness or the PI of the uterine and cerebral arteries.
We found no evidence for effects of isoflavones on patient-important outcomes or lowering of cholesterol levels in people with hypercholesterolaemia. Our findings have to be interpreted with caution due to high or unclear risk of bias in several risk of bias domains, and low number of participants in trials.