M. Lipovac, P. Chedraui, C. Gruenhut, A. Gocan, C. Kurz, B. Neuber & M. Imhof
The effect of red clover isoflavone supplementation over vasomotor and menopausal symptoms in postmenopausal women
Published in Gynecological Endocrinology 2011, 1-5
Number of patients: 109
|Study Setting||MF11RCE® Group||Control Group|
|Inclusion Criteria||Postmenopausal women (amenorrhea >12 months), 40 years or older with moderate-to-severe menopausal symptoms (Kupperman index ≥15)||Postmenopausal women (amenorrhea >12 months), 40 years or older with moderate-to-severe menopausal symptoms (Kupperman index ≥15)|
|Exclusion Criteria||positive pregnancy test, nonwillingness,on hormonal therapy (HT), known isoflavone hypersensitivity||positive pregnancy test, nonwillingness,on hormonal therapy (HT), known isoflavone hypersensitivity|
|Parameter||Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days.||Daily hot flush and night sweat frequency and overall menopausal symptom intensity (Kupperman Index) were measured at baseline, 90, 97 and 187 days.|
|Treatment||MF11RCE® 80 mg for a 90-day period. After a 7 day washout period, subjects switched to receive the opposite treatment for another 90 days.||Plazebo for a 90-day period. After a 7 day washout period, subjects switched to receive the opposite treatment for another 90 days.|
Despite the fact that worldwide hormone therapy (HT) has proved to be effective in the alleviation of the climacteric syndrome and prevention of osteoporosis and other age related conditions, long term compliance is low and related to several factors, among them risk-benefit concerns. Nearly a decade has passed since the Women’s Health Initiative study (WHI) found that one HT regimen significantly increased the risk for cardiovascular events and breast cancer. During this period physicians and patients have changed their attitude towards the use of hormonal compounds for the management of the menopause.
Within the category of alternatives one can mention phytoestrogens which are plant derived molecules, basically represented by isoflavones. These exhibit estrogenic effects and although being less potent than conventional estrogenic compounds, their selective beta-estrogenic receptor binding properties allow positive effects over various organs.
MF11RCE® supplementation has reported positive effects over menopausal symptoms, vaginal health and lipids, with a promising safety profile.
Aim of the Study
The aim of the present analysis was to evaluate the effect of MF11RCE® supplementation over vasomotor and overall menopausal symptoms in postmenopausal women.
Materials and Methods
Women were recruited in accordance to the following inclusion criteria: postmenopausalstatus (amenorrhea > 12 months), 40 years or older, moderate-severe menopausal symptoms (Kupperman index ≥ 15) with more than 5 hot flushes per day, a negative pregnancytest, willingness.
Those on HT or with known isoflavone hypersensitivity were excluded.
Participants were randomly assigned to receive either MF11RCE® or placebo of equal appearance (Group B) for a 90-day period. After a 7 day washout period, subjects switched to receive the opposite treatment for another 90 days. Number of daily hot flushes/night sweats and menopausal symptom intensity (Kupperman index) were measured at baseline, 90, 97 and 187 days. Additional examinations comprised anamnesis, medication anamnesis and height, weight and blood pressure determinations at proposed intervals. Blood pressure determinations were performed after women had been sitting for 15 min. Bodymass index (BMI) was calculated as: weight/squared height.
Patients & Study Design
A prospective randomized, double-blind, placebo controlled trial was carried out at the Study Center Med XIX and the Department for Gynecological Endocrinology and Reproductive Medicine, General Hospital, Vienna, Austria.
Fifty-three were randomized to group A and 60 to group B. Four women started HT and were excluded. Thus, data of 109 women who completed treatment (Group A: 50 and Group B: 59) was used for analysis. No significant differences were observed between study groups regarding basal characteristics.
Statistical analysis was performed on an intention-to-treat basis using SPSS software package (Version 10.0 for Windows, SPSSInc., Chicago, IL). Data are presented as means, standard deviations, confidence intervals and percentages. The Kolmogorov Smirnov test was used to determine the normality of data distribution. Differences between groups were analyzed with the Mann–Whitney (continuous non parametric data) or the chi-square test (percentages). Changes after each treatment phase within groups were assessed using the Wilcoxon rank test. A p value < 0.05 was considered as statistically significant. Assuming that hot flush frequency would be reduced 50% in the red clover group (15% in the placebo group) a sample size of 49 individuals per group was calculated in order to achieve an 80% power at a two-sided alpha level of 0.05.
No significant differences were observed between study groups regarding basal characteristics. Daily hot flush/night sweat frequency and Kupperman Index values were similar in both studied groups at baseline. All indices significantly decreased after MF11RCE® in Group A, corresponding respectively to a 73.5%, 72.2% and 75.4% average decrement. These decrements were significantly higher than those observed for Group B after placebo phase (8.2%, 0.9% and 6.7%, respectively). In Group A, after washout and placebo phases all values significantly increased. In Group B, all indices remained similar after placebo and washout phases, however significantly dropping after red clover treatment. These values were also significantly lower than those observed in Group A after placebo phase. No side effects were encountered after treatment with the active compound or the placebo group.
Risk-benefit issues raised after the publication of the WHI results have changed physicians’ and women’s attitude toward HT use. Indeed, nowadays women simply just do not want to take hormonal compounds.
As a consequence, current trend is to individualize treatment and focus on alternatives for the menopause. This tendency seems to be more pronounced among those with contraindications or with high risk situations.
Superiority of red clover supplementation over placebo in the treatment of vasomotor and menopausal symptoms was clearly demonstrated in the present series. Finally the present series found that vasomotor symptom improvement correlated with a concomitant decrease in depressive and anxiety symptoms. In this regard, red clover isoflavones may well be exerting a positive effect over mood through hot flush improvement. However, a direct or combined effect of the active compound over mood cannot be totally ruled out, for which more research is warranted. In any case, red clover treatment in women presenting both conditions seems promising.
MF11RCE® supplementation was more effective than placebo in reducing daily vasomotor frequency and overall menopausal intensity in postmenopausal women.
In postmenopausal women, MF11RCE® supplementation may
- reduce daily frequency of hot flushes,
- reduce daily frequency of night sweats,
- alleviate overall vasomotor symptoms’ intensity,
- concomitantly decrease depression and anxiety symptoms,
- and thus, improve quality of life in menopause.