Effects of soy isoflavones on menopausal neurovegetative symptoms

AIM: Dietary soy supplementation may reduce the incidence of hot flushes in postmenopausal women due to the presence of phytoestrogens in soy foods. The aim of this study was to assess the effects of a 3-month administration of different doses of either oral or transdermal soy isoflavones on climacteric complaints in postmenopausal women. METHODS: Sixty postmenopausal women were assigned randomly to one of the following groups: groups A and B received 50 mg/day or 75 mg/day of oral isoflavones respectively, while groups C and D received 6 mg/day or 12 mg/day of transdermal isoflavones. A control group (group E) was composed of 15 patients that did not receive any treatment. Hot flushes, Kupper-man index and vaginal dryness at baseline and then after 5, 9 and 13 weeks were evaluated. RESULTS: The isoflavone treatment led to a progressive significant (p<0.01) reduction of the number of hot flushes in the groups A, B and D with a dose-related effect in group D. At week 13, the Kupperman index and hot flush score decreased significantly in all the treated groups, while vaginal dryness score was reduced only in group B. CONCLUSION: Our findings suggest that both oral and transdermal soy isoflavones are effective to attenuate slight to moderate menopausal neurovegetative symptoms with a dose-related effect.     

The effect of soy-derived isoflavones over hot flushes,menopausal symptoms and mood in climacteric women with increased body mass index

Background.?Risk-benefit issues raised after the WHI have significantly increased the use of alternative treatments for the menopause. Despite this, data regarding the effect of soy isoflavones over mood and menopausal symptoms in high risk populations is still lacking.

Objective.?To evaluate the effect of soy derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index (BMI).

Methods.?Fifty symptomatic climacteric women aged 40 to 59 with increased BMI (≥25) were recruited to receive oral 100?mg/day of soy derived isoflavones (Climasoy®) for 3 months. Hot flushes (frequency/intensity), menopausal symptoms (Menopause Rating Scale [MRS]) and mood (Hamilton Depressive Rating Scale [HDRS]) were evaluated at baseline and at 90 days.

Results.?A total of 45 women completed the study. After 3 months of soy isoflavone supplementation hot flushes significantly decreased in percentage, number and severity (100% to 31.1%; 3.9?±?2.3 to 0.4?±?0.8 and 2.6?±?0.9 to 0.4?±?0.8, respectively, p?<?0.001). MRS scores (total and for subscales) reflecting general menopausal symptoms also significantly decreased compared to baseline. Regarding mood, after three months total HDRS scores and the rate of women presenting depressed mood (scores?≥?8) significantly decreased (16.3?±?5.4 to 6.9?±?5.2 and 93.3% to 28.9%, respectively, p?<?0.05). There was no effect on blood pressure levels or BMI values after treatment.

Conclusion.?In this high risk climacteric population, soy derived isoflavone treatment improved mood as well as vasomotor and general menopausal symptoms. More research is required to determine if the positive effect over mood is a direct or an indirect one through hot flush alleviation.     

Phytoestrogens as hormone replacement therapy: an evidence-based approach

Postmenopausal women have sought nonestrogen alternatives to hormone replacement in order to avoid possible risks and side effects of the therapy. Selective estrogen receptor modulators have been developed to tailor therapy to a specific risk/benefit profile that will best fit the patient. More women have looked to phytoestrogens, such as the isoflavones found in the soy plant, to tailor their menopausal therapy in a “natural” way. This review examines the evidence regarding the risks and benefits of isoflavones as hormone replacement therapy. Controlled trials have shown a reduction in postmenopausal hot flashes when subjects’ diets were supplemented with soy. There is less evidence for a benefit in vaginal dryness symptoms. Furthermore, dietary supplementation also appears to lower total and low-density lipoprotein cholesterol in hypercholesterolemic subjects. A synthetic isoflavone, ipriflavone, has been shown in controlled trials to prevent postmenopausal bone loss, though there is much less evidence that soy isoflavones will accomplish this goal. Finally, although unopposed estrogen replacement may promote breast and endometrial cancer, there is no evidence that phytoestrogens will do the same. In contrast, great interest has been taken in the potential cancer-protective effects of phytoestrogens, though prospective evidence in postmenopausal women is not available. Although data regarding the use of isoflavone extracts are incomplete, dietary supplementation with soy foods appears to be a safe and possibly beneficial option for postmenopausal women.     

Red clover and soy isoflavones—an in vitro safety assessment

Isoflavones from red clover and soy plant extracts are used in highly concentrated food supplements as an alternative to hormone replacement therapy. Due to their estrogenic activity, isoflavones are a focus of safety concerns about their potential to promote the growth of hormone-dependent cancer cells. In this study, isoflavones and plant extracts were tested for their effect on cell proliferation, apoptosis induction and cell cycle arrest. Isoflavones and plant extracts were applied in proliferation assays on 11 human cancer cell lines (representing cancers of the colon, prostate, breast, cervix, liver, pancreas, stomach and ovaries) and a fibroblast line to detect cytotoxic activity. Fluorescence-activated cell sorting was used to detect the induction of apoptosis or cell cycle arrest. Isoflavones and plant extracts significantly reduced the proliferation activity of the treated cancer cell lines. Growth promotion was not observed, but apoptosis or necrosis induction was, as was cell cycle arrest, with genistein as the most potent isoflavone. Isoflavones and plant extracts from soy and red clover, respectively, do not promote the growth of human cancer cells but induce decreased cell proliferation, increased apoptosis and cell cycle arrest. These results indicate that isoflavones can be considered safe compounds.     

Soy intake related to menopausal symptoms, serum lipids, and bone mineral density in postmenopausal Japanese women

OBJECTIVE: To evaluate the effects of dietary isoflavones in soy products on menopausal symptoms, lipid profiles, and bone mineral densities in postmenopausal Japanese women. METHODS: We estimated the daily intakes of isoflavones in the diets of 478 postmenopausal Japanese women who reported soy consumption. We recorded serum values of fasting total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoproteins. Bone mineral density was measured at the lumbar spine (L2-L4) by dual energy x-ray absorptiometry. Women were assigned to two groups according to years since menopause (early and late postmenopausal groups), and each group was subcategorized into four groups according to dietary isoflavone intake. Relationships between isoflavone intake, menopausal symptoms, lipid profiles, and bone mineral density were examined in each group. RESULTS: The mean estimated intake of isoflavones among 478 women was 54.3 mg/day. With stepwise regression analysis we found that weight and years since menopause were significant independent predictors of bone mineral density. Bone mineral densities adjusted to years since menopause and weight were significantly different in the highest intake compared with lowest intake category (P <.001) within the early and late postmenopausal groups. In the early postmenopausal group, significant differences were found in palpitation and backaches between the high and low intake categories but were not significant in the late postmenopausal group. CONCLUSION: High consumption of soy products is associated with increased bone mass in postmenopausal women and might be useful for preventing hypoestrogenic effects.     

Posicionamiento de la Asociación Española para el Estudio de la Menopausia sobre el uso clínico de las isoflavonas en el climaterio

Introduction

Western countries have shown an increasing interest in the use of soya isoflavones to treat aging and menopause-related diseases and their associated symptoms, stimulating a proliferation of studies, many of which report contradictory results. Consequently, the role of isoflavones was assessed by the Spanish Menopause Society (SMS) using the most reliable scientific evidence.

Material and methods

A panel of experts on isoflavones was gathered. The selected studies were obtained by electronic search engines, Medline (1966-March 2007) and the Cochrane Controlled Clinical Trials Registry.

Results

The various reviews and meta-analysis on the effects of Isoflavones on women’s health are controversial. The contradictory results may be due, among other factors, to the lack of uniformity in the compounds under study. Data on doses and genisteine content have indicated beneficial effects on lipid profile, like antioxidants, as well as a mild decrease in hot flushes. Some studies suggest a positive effect on bone mass. However few data are available on other aspects such as breast, estrogendependent cancer, cognitive function, or skin

Conclusions

In certain situations, isoflavones can be a therapeutic alternative during the climacteric period. However, before general recommendations on the use of isoflavone supplements can be made, more specific clinical trials should be performed. These studies should be adequately designed, with supplements that are standarized according to isoflavone content and types, a sufficient number of patients and study duration     

Phytoestrogens and cardiovascular disease

The most extensively studied class of phytoestrogens, isoflavones, occur in soybeans and other legumes. Six systematic reviews have assessed the effects of soy isoflavones on lipid levels, and suggested that a diet supplemented with soy protein isolate (ISP) containing isoflavones reduces low-density lipoprotein (LDL) cholesterol by around 0.15 mmol/L, but without clear effects on triglycerides or high-density lipoprotein (HDL) cholesterol. However, no review has suggested that purified soy isoflavones or soy protein without isoflavones (where the isoflavones have been removed by an alcohol wash) have statistically significant effects. It remains unclear which are the active components of soy. They may include soy protein which has not been denatured by alcohol wash, interaction of isoflavones within the intact soy matrix, or other compounds removed in the alcohol-extracted fraction. The reduction in total cholesterol may be greater in men than in postmenopausal women. There is little evidence that the effectiveness of soy varies with baseline serum lipid levels, or the amount of isoflavone or soy protein consumed. However, changes in triglycerides may be related to baseline levels. While there is no evidence of beneficial effects of phytoestrogens on blood pressure, arterial compliance or oxidation of LDL cholesterol, there may be beneficial effects on endothelial function in postmenopausal women, and on homocysteine concentrations. There is little suggestion of adverse effects of soy or isoflavones at physiological doses, although those taking soy isoflavone supplements do appear to have higher levels of gastro intestinal and menstrual complaints. There have been no published trials on the effects of phytoestrogens on mortality or cardiovascular events, so studies currently rely on the above bio markers of risk. Most evidence relates to soy isoflavones, but there is some evidence for lignans. Further robust studies assessing the effects of whole soy foods on cardiovascular outcomes are needed.     

Behandlung von klimakterischen Beschwerden nach Brustkrebs

Background

Women with a history of breast cancer often suffer from climacteric symptoms. Hormonal therapies are known to reduce these symptoms but are not recommended in women with a history of breast cancer due to their potential adverse effects.

Objectives

The goal of this work is to give a literature overview on the efficacy of non-hormonal therapies as a therapy option for this patient group.

Materials and methods

In a PubMed search, relevant studies and meta-analyses from 1997–2014 that provided data on treatment of menopausal symptoms with hormonal replacement therapy versus nonhormonal therapies were identified.

Results

Hormone replacement therapy is not recommended in patients with history of breast cancer. Lifestyle modification is the basis in treating climacteric symptoms. Daily isoflavone intake of 50–60 mg can significantly reduce frequency and severity of hot flushes if not present more than 4 times/day. Cimicifuga racemosa allays hot flushes, depressive mood, and might be associated with prolonged disease-free survival. Its efficacy is comparable to transdermal estrogen. Off-label use of antidepressants like paroxetin and venlafaxin and anticonvulsants like gabapentin can be used as second line treatment with good efficacy.

Conclusion

Studies on nonhormonal therapies provide evidence for efficacy so that breast cancer patients do have an alternative treatment option for climacteric disorders. Nevertheless, hormone replacement is still more effective. More well-designed trials are needed to further investigate nonhormonal therapies.     

Alternatives To Hormonal Therapy During The Perimenopause

Two types of phyto-estrogens are available from food sources; isoflavones and lignons. Isoflavones are present in legumes, particularly soy, whereas grains and seeds contain lignons. These phyto-estrogens exhibit physiological effects and have been investigated for their potential usefulness in chronic disease, atherosclerosis, and cancer.Ingestion of soy protein, flax seed, and clover has had varying effects on FSH and LH level, luteal phase length, hot flushes, and vaginal epithelial proliferation. Herbal products have been used for centuries and are frequently recommended to relieve perimenopausal symptoms. Many herbals have ingredients with therapeutic effects while others experience only anecdotal success and tend to be exploited by the industry. The safety and efficacy of these products depends upon many factors. In Canada, the Health Protection Branch of Health Canada has been working on revision of existing legislation in order to adapt regulations to this product classification.Health care professionals must not blindly accept or reject alternative remedies but must be open-minded enough to evaluate critically the use of foods and plant medicines during the perimenopausal period.     

Red clover isoflavones in practice: a clinician's view

The subject of phytoestrogen use must be seen against the background of increasing controversy surrounding the role of hormone replacement therapy. Phytoestrogens such as those derived from red clover may help with hot flushes, which are a common menopausal complaint. Red clover isoflavones have more evidence base than most herbal medicinal products, although the literature is beset by difference in methodologies making direct comparison between studies difficult. There certainly does not appear to be any increased risk for women with breast cancer, who often suffer severely from sweats and flushes. There is currently insufficient evidence to recommend its use for bone protection in a group of women who are at high risk.     

Red clover isoflavones and menopausal health

Menopausal symptoms such as hot flushes and night sweats can be very disrupting. While hormone replacement therapy is an effective therapy, concerns about side effects and breast cancer risk have stimulated interest into alternative therapies such as phytoestrogens. These are oestrogen-like compounds made by plants. Two major sources of phytoestrogens are soy and red clover. Data on randomised controlled trials of red clover for the control of menopausal symptoms are presented. The conflicting data are encouraging and suggest that phytoestrogens are a treatment modality that needs pursuing.     

The effect of tibolone in postmenopausal women receiving tamoxifen after surgery for breast cancer: a randomised, double-blind, placebo-controlled trial

OBJECTIVE: To assess the effects of tibolone on climacteric symptoms, endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer. DESIGN: Double-blind, randomised, placebo-controlled, multicentre pilot study. SETTING: Hospital outpatient clinic. SAMPLE: Seventy postmenopausal women receiving tamoxifen following surgery for early breast cancer. METHODS: Women received 20 mg/day oral tamoxifen plus either 2.5 mg/day oral tibolone or placebo for 12 months. MAIN OUTCOME MEASURES: Frequency and severity of hot flushes (diary cards); intensity of hot flushes and sweats (Landgren scale); interference of hot flushes and sweats with normal life; frequency and intensity of other climacteric symptoms; endometrial thickness and histology; vaginal bleeding; breast cancer recurrence and serum lipid/lipoproteins. RESULTS: Daily card data showed no change in the daily number of hot flushes with either tibolone or placebo (P= 0.219) after three months. There was a significant reduction in the severity of flushes with tibolone compared with placebo (-0.4 vs 0.2, P= 0.031). The Landgren scale showed a mean change in the number of hot flushes of -0.6 with tibolone and +1.1 with placebo after 12 months (P= 0.022). Endometrial biopsies were normal and vaginal bleeding was similar in both groups. A significant decrease in triglycerides (-23% vs 1.4%) and HDL (-12% vs 19%) was seen with tibolone compared with placebo after 12 months. CONCLUSIONS: Tibolone prevented an increase in hot flushes in postmenopausal women given tamoxifen following surgery for breast cancer without untoward effects on the endometrium. Beneficial effects on serum lipid profile were noted.     

Menopausal symptoms in women treated for breast cancer: the prevalence and severity of symptoms and their perceived effects on quality of life.

OBJECTIVES: To determine, first, the prevalence and severity of various symptoms related to estrogen deficiency in women within a few years of receiving treatment for breast cancer, second, how women perceive the effects of these symptoms on their quality of life and, third, what measures have been taken to relieve vasomotor symptoms. METHODS: Two hundred women (aged 29-65 years) who had received treatment for breast cancer within the last 5 years were included in this cross-sectional survey. Information was collected about their breast cancer treatment, menopausal symptoms (Menopausal Rating Scale), the perceived effects of menopausal symptoms on their and their partner's quality of life and any treatments they were receiving for hot flushes. RESULTS: All but one woman reported at least one symptom related to the menopause (95.9% vasomotor; 83.3% psychological; 89.7% somatic). Current treatment with tamoxifen or previous chemotherapy did not influence the prevalence or the severity of hot flushes. Current antidepressant treatment was, however, significantly associated with a higher prevalence and severity of most menopausal symptoms, including hot flushes and sweats (p = 0.008). The severity of hot flushes and sweats was significantly correlated with self-assessed effects on overall quality of life (r(s) = 0.47); 56.4% of the respondents believed that menopausal symptoms had affected their partner's quality of life, the strongest correlations being with severity of sexual symptoms (r(s) = 0.56) and vaginal dryness (r(s) = 0.5). Only 21% of women experiencing hot flushes were receiving any treatment for hot flushes, with most women describing no knowledge or poor knowledge of treatment options. CONCLUSIONS: The majority of women receiving treatment for breast cancer report menopausal symptoms, which negatively correlate, not only with their own, but also with their partner's quality of life. Most women experiencing hot flushes are not receiving treatment due to lack of both awareness and confidence in the existing treatment options.     

Phytoestrogens

The soy-isoflavones genistein and daidzein and the flaxseed-lignans secoisolariciresinol and matairesinol belong to the group of phytoestrogens. Epidemiological data suggest that phytoestrogens have a preventive effect against various estrogen-related diseases/symptoms such as breast cancer, menopausal symptoms, cardiovascular diseases, and osteoporosis. To prove these assumptions, available controlled clinical trials have been critically reviewed. Especially soy-isoflavones have been extensively studied. There is no scientific evidence for an effect of phytoestrogens on menopausal symptoms and risk factors of breast cancer. However, isoflavones-containing soy protein can lower total cholesterol, LDL cholesterol, and triglyceride serum levels. The strongest evidence exists for a preventive effect of soy isoflavones on postmenopausal bone loss of the lumbar spine. Distinct effects on estrogen-related diseases can be explained at least in part by the different affinity of isoflavones to estrogen receptors alpha and beta and the distinct tissue distribution of these receptors.     

Evaluation of the isoflavones and estrogen effects on the rat adrenal

The aim of this study was to evaluate the morphometry and the gene expression of Ki-67, VEGF and caspase 3 and the stress oxidative in the adrenal gland of ovariectomized rats treated with estrogen or isoflavones. We used 15 Wistar rats ovariectomized treated with isoflavones or estrogen during 30?days. At the end of the treatment, the left adrenal gland was removed for subsequent histological studies and the right was used to evaluate gene expression of angiogenesis (VEGF-A), cell proliferation (Ki-67), apoptose (caspase 3 clivated) and oxidative stress. Treatment with estrogen showed a largest increase in the layers of the adrenal cortex than with isoflavones. These hypertrofic effects agree with higher expression elevation of Ki67 and VEGF, which did not occur with the caspase 3, indicating that isoflavones have great proliferative effect on the adrenal gland. Similar results were also observed on superoxide quantification show that isoflavone has a protective effect against oxidative stress. Our results indicate positively the trophic therapeutic potential of isoflavones has a protective effect and can contribute to the development of effective therapies to decrease the symptoms of menopause.     

Alternative Therapiemöglichkeiten zur Hormontherapie in der Postmenopause

Despite increasing interest in alternative therapies for menopausal hot flashes that avoid use of estrogens, the efficacy and safety of other options currently are not well supported. In women who need relief for mild vasomotor symptoms isoflavones or black cohosh are recommended. Non-hormonal treatments are not as effective as estrogens in relieving hot flashes. There is a suggestion, but no conclusive evidence, that isoflavones have a beneficial effect on bone health and that there is an association between lifelong soya bean intake und reduced risk of breast cancer. Recommended options for women with contraindications relating to estrogen-containing treatments include serotonin reuptake inhibitors and gabapentin.     

Effect of soy-derived isoflavones on hot flushes,endometrial thickness,and the pulsatility index of the uterine and cerebral arteries

OBJECTIVE: To determine the effect of soy-derived isoflavones on hot flushes, endometrial thickness, and the vascular reactivity of uterine and cerebral arteries. DESIGN: Double-blind, randomized, placebo-controlled trial. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Sixty-two postmenopausal women aged 45-60 years attending the Outpatient Menopause Clinic of our gynecological departments. INTERVENTION(S): 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. MAIN OUTCOME MEASURE(S): The daily number of hot flushes, endometrial thickness, and arterial pulsatility index (PI). RESULT(S): 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. CONCLUSION(S): 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.     

Isoflavones are safe compounds for therapeutical applications – Evaluation of in vitro data

Isoflavone-rich food and food supplements have gained increasing popularity also in the Western world. Their weak estrogenic effect has been considered as a potential risk, although all epidemiological studies and clinical trials show a significant cancer protection and decreased risk of cardiovascular diseases. In vitro data suggest that the concerted action of the isoflavones and their metabolites show antiproliferative behaviour, reduce angiogenesis, reduce tumor progression and exert antiinflammatory effects. For the evaluation of the biological effects, special emphasis has to be put on the concerted action between the isoflavones and their metabolites. For instance, while isolated genistein shows some growth promoting effect at low concentrations, the metabolite equol or soy extract show growth retardation as well as higher concentrations of genistein do. The isoflavones have multiple affinities to other members of the steroid hormone receptor superfamily. The beneficial effect on metabolic diseases and weight reduction by isoflavone consumption can be partly explained by its affinity for the PPAR family. In light of the in vitro experiments, together with the epidemiological observations and the clinical experience, isoflavones can be considered as safe compounds and their consumption as food and food supplements has to be promoted.     

A natural alternative to menopausal hormone replacement therapy. Phytoestrogens

Phytoestrogens are non-steroidal plant molecules whose structure differs from gonadal hormones, but with an estrogen-type bioactivity: they are capable of interacting with estrogen receptors, showing both agonist and antagonist methods of action. The beneficial effects of various classes of phytoestrogens present in nature are now known, but the main isoflavone present in soya, genistein, appears to be particularly effective. Interest in this substance is concentrated in particular on its therapeutic role in menopause. This paper is a review of the main studies published to date on the efficacy of phytoestrogens in reducing the symptoms of menopause. A diet rich in isoflavones is associated with a reduced incidence of vasomotor episodes; the average supplement of genistein is approximately 50 mg/day. After supplementing the diet with phytoestrogens, studies show a reduction in total cholesterol and LDL fraction. This is accompanied by an increase in BMD (Bone mineral density) after taking 90 mg of isoflavones for 6 months. Isoflavones may reduce the risk of developing breast cancer. The data examined confirm the excellent clinical efficacy of supplementing the diet with soy extracts, particularly genistein which is indicated to alleviate both the short-term symptoms of menopause and the long-term effects, although the latter finding requires further subsantiation.     

Soy, fat and other dietary factors in relation to premenstrual symptoms in Japanese women

OBJECTIVE: To evaluate the relations of intakes of soy, fat and other dietary components to premenstrual symptoms. DESIGN: Cross sectional study. SETTING: Three colleges and two nursing schools. POPULATION: One hundred and eighty-nine Japanese women aged 19 to 34 years. METHODS: Intakes of nutrients and foods, including soy products and isoflavones, were estimated by a semiquantitative food frequency questionnaire. Change in menstrual cycle symptoms were assessed by the Moos Menstrual Distress Questionnaire (MDQ). MAIN OUTCOME MEASURES: Spearman rank correlation of soy and other dietary factors with changes in MDQ scores between the follicular and the premenstrual phases after controlling for age, marital status, exercise, smoking status, age at menarche and number of days of bleeding. RESULTS: Neither soy product nor isoflavone intake was significantly associated with change in MDQ score in the premenstrual phase. Intakes of total, saturated and monounsaturated fats were significantly correlated with change in scores for total MDQ and subscale 'pain' in the premenstrual phase after controlling for the covariates. Intake of cereals/potatoes/starches was significantly inversely correlated with a change in total MDQ score in the premenstrual phase. CONCLUSIONS: High intake of fats and low intake of foods with high concentration of carbohydrate may be associated with premenstrual symptoms.