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.     

Use of alternative and complementary medicine in menopause.

OBJECTIVES: To review the clinical evidence available for the treatment of menopausal symptoms with alternative and complementary medicine. METHODS: The MEDLINE, PREMEDLINE and COCHRANE electronic databases for the years 1980-2002 were searched for articles concerning soy products, black cohosh, dong quai, acupuncture, ginseng and evening primrose oil. Studies pertaining to menopausal vasomotor symptoms, lipid profiles and bone mineral densities of postmenopausal women were included. The data from clinical trials were reviewed. RESULTS: Soy isoflavones slightly decrease total cholesterol and LDL levels. The clinical significance of this small change is yet to be determined. The synthetic isoflavone derivative ipriflavone increases bone mineral density in healthy peri- and postmenopausal women with moderate bone mineral densities. Although earlier reports have claimed that soy is beneficial for the improvement of vasomotor symptoms, recent data do not support this claim. There are insufficient data on the other alternative therapies for treating menopausal symptoms at this time. CONCLUSION: Alternative and complementary medicine may play a role in the management of menopause, however, well-designed large studies are still needed.     

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.     

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.     

Sinnvolle komplementärmedizinische Maßnahmen in der gynäkologischen Onkologie

The results from studies on the prevalence of utilization of naturopathy or complementary medicine show substantial variation. According to Weis et al. in Germany approximately 70?% of patients with gynecological cancers, particularly patients with breast cancer, make use of complementary treatment. The term complementary medicine is not precisely defined and has to be confined to the commonly used synonymous terms alternative medicine and alternative therapy procedures. Complementary forms of treatment are utilized as extended supportive treatment options accompanying and supplementary to conventional oncological treatment. The reasons and motivations for the utilization of complementary medicine are varied and are mostly based on and characterized by the salutogenic therapy strategy of patients. This strategy supports coping, healing and overcoming the disease. From the patient perspective the aspects with the highest priority are ensuring autonomy, integration of self-participation and optimization of resilience, in a phase of life that often appears threatening and has to be overcome. Complementary therapies can be integrated into acute phase treatment and also into the rehabilitation phase. Safety and compatibility of the multitude of complementary measures with the conventional tumor treatment has the highest priority.     

Phytoestrogens and the risk of breast cancer: a review of the literature

BACKGROUND: Over the last decade, interest in the physiological role of bioactive compounds in plants has increased dramatically. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of nonsteroidal estrogens that are widely distributed within the plant kingdom, including isoflavones and lignans. Epidemiological studies suggest that diets rich in phytoestrogens, particularly soy and unrefined grain products, may be associated with low risk of breast cancer. This review presents the studies published so far exploring a link between dietary phytoestrogens and breast cancer risk. METHODS: A Medline search was conducted using the key words below. Further articles were obtained by cross-matching references of relevant articles. Twenty-one case-control and 15 prospective studies were identified since 1978. One meta-analysis and several review articles also were noted. RESULTS: Results from previous studies were analyzed and comparisons were made between each type of study. Controversy exists regarding this subject, and we found conflicting evidence in recent literature regarding this hypothesis. CONCLUSION: There is no clear evidence that phytoestrogen intake influences the risk of developing breast cancer.     

CAM research in Britain: the last 10 years

Research into complementary and alternative medicine (CAM) is not as new as it might appear from a U.K. perspective. Most continental European countries have a long tradition in CAM research. Many studies of homoeopathy, for instance, were published decades ago in languages other than English [The trials of homeopathy. Origins, structure and development. Stiftung: Essen, Karl und Veronica Carstens, 2004]. However, it is probably true to say that, in the English speaking world and particularly in the U.K., CAM has become a respectable area of scientific investigation only during the last decade. In this article, we review the 10 years of CAM research in Britain.     

Complementary medicine in Germany.

Generally speaking, complementary medicine is increasingly popular. But there are considerable national and regional differences, and the reasons for them are not always well understood. In this issue, Schwarz and colleagues publish data suggesting that, in the German region of West Pomerania, the 1-year prevalence of use of complementary medicine is 6%. This contrasts sharply with the 1-year prevalence figure of 62% in the rest of Germany. The reasons for this difference relate to health policies of the Nazis 70 years ago and to the former communist East German government, as well as to the fact that complementary medicine is, at least partly, private health care.     

Soy and red clover for mid-life and aging.

INTRODUCTION: Menopause is associated with mid-life, a time when many women begin to experience the signs and symptoms of aging, such as increases in blood pressure, changes in lipid profiles, loss of bone mass density, and diminished memory and cognition. Given the result of the Women's Health Initiative, many women no longer consider hormone therapy the first option for promoting healthy aging. Instead, they are turning to botanical and dietary supplement (BDS) products in place of hormone therapy. This paper reviews the evidence available for use of isoflavones from soy and red clover for the treatment or prevention of these health issues. METHODS: The MEDLINE and EMBASE databases were searched for articles relating to soy or red clover supplement use for prevention and/or treatment of heart disease, hyperlipidemia, osteoporosis, mood disorders and cognitive abilities. Studies were included if they were randomized, controlled trials and included peri- or postmenopausal women. RESULTS: Isoflavone products appear to be the most useful for improving lipid profiles; however, the evidence suggests that isoflavone extracts from soy are less effective than products containing soy protein or red clover isoflavones. Soy protein appears to reduce levels of total cholesterol and low density lipoprotein cholesterol, while red clover reduces levels of triglycerides and increases high density lipoprotein cholesterol. The data were somewhat less convincing, although promising, for increasing bone mass density and improving cognitive abilities. CONCLUSIONS: Research suggests that isoflavones found in soy foods and red clover appear to have a small but positive health effect on plasma lipid concentrations, bone mass density, and cognitive abilities. Given the lack of serious safety concerns in the short term, it would appear that including soy and red clover in the diet of postmenopausal women, not withstanding a soy allergy, might be beneficial.     

Education in naturopathy and western herbal medicine in Australia: results of a survey of education providers

BACKGROUND: Questions about the risks and regulatory requirements of naturopathy and western herbal medicine (WHM) in Australia prompted research by the Department of Human Services Victoria. This article offers findings from a survey of education providers, which was one of several studies carried out for the report. (The full report can be found at http://www.health.vic.gov.au/pracreg/naturopathy.htm.) METHOD: Questionnaires were sent to 43 Australian providers of naturopathy and WHM education. RESULTS: Unsustainable variation was found in award types, contact hours, clinical education, length of courses, and course content. CONCLUSIONS: Naturopaths and WHM practitioners are primary contact health professionals but educational standards vary widely, with some practitioners not likely to be adequately prepared. The degree of risk in their practice, and the need for better integration of complementary care with mainstream healthcare, require education at least to the level of a bachelor degree. Courses should be subject to independent external accreditation. However, attempts to determine appropriate minimum educational standards are unlikely to succeed without the support of a regulatory system that can mandate those minimum requirements.     

The acceptability of isoflavones as a treatment of menopausal symptoms: a European survey among postmenopausal women.

OBJECTIVE: To investigate determinants of the acceptability of isoflavone products among postmenopausal women with regard to social and lifestyle factors, dietary habits, health concerns, food beliefs, menopausal symptoms and therapies, and to elucidate preferences for specific products. METHODS: A consumer survey was conducted among postmenopausal women in four European countries (Germany, Denmark, Italy and the UK), including a total of 465 respondents. RESULTS: The declared acceptability of isoflavones was highest in Germany (80%), followed by Italy (75%), the UK (59%) and Denmark (55%; p < 0.001). Among other factors, prior information about isoflavones (odds ratio (OR) 2.64, 95% confidence interval (CI) 1.54-4.51, p < 0.001) and belief that foods can be used to treat medical conditions (OR 2.18, 95% CI 1.17-4.05, p = 0.014) were the strongest predictors of potential acceptability. The preferred forms in which isoflavones might be taken differed markedly between countries. CONCLUSIONS: Information about the health effects of isoflavones and health-diet links should be considered the most important factors in attempts to influence the potential acceptability of isoflavone products. Foods enriched with isoflavones need to be developed with regard to specific cultural demands in order to assure consumer acceptance on the marketplace.     

The role of naturopathy in pregnancy, labour and post-natal care: broadening the evidence-base

It is known that women are high users of complementary and alternative medicine (CAM) including naturopathy and that CAM is frequently used by pregnant women. However, we still know little about the consumption, practice and role of naturopathy in pregnancy, labour and post-natal care. With this in mind, this paper proposes a possible framework for advancing further research on this topic. The framework is divided into issues associated with three core stakeholder groups - pregnant women, naturopaths/herbalists and other maternity health professionals including obstetricians, midwives and general practitioners. The development of a rigorous health services research agenda around this topic has much to offer maternity-care users, practitioners and policy makers and the framework outlined here is offered with the hope of inspiring further inquiry into this significant issue in women's health.     

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.     

Effects of phytoestrogens genistein and daidzein on production of human chorionic gonadotropin in term trophoblast cells in vitro.

BACKGROUND: Phytoestrogens are a diverse group of non-steroidal compounds that occur naturally in many plants. Because they possess a ring system similar to estrogens they are able to bind to estrogen receptors in humans. In the present study we tested the effects of the phytoestrogens genistein and daidzein on the production of human chorionic gondaotropin (hCG) in isolated trophoblast cells of term placentas in vitro. METHODS: Genistein and daidzein were incubated at different concentrations with trophoblast cells. Untreated cells were used as controls. At designated times aliquots were removed and tested for hCG production. RESULTS: Production of the protein hormone hCG was influenced by the phytoestrogens genistein and daidzein in trophoblast cells. We found a significant decrease of hCG production in genistein- and daidzein-treated trophoblast cells that was concentration-dependent. Compared with daidzein, genistein seems to be a more efficient inhibitor of the production of hCG. CONCLUSION: The phytoestrogens genistein and daidzein can reduce hCG production in human term trophoblasts. Both phytoestrogens belong to the group of isoflavones, which are enriched in soy-containing foods and are widely consumed by humans for putative beneficial health effects. Because both phytoestrogens have inhibitory effects on hCG production during pregnancy, exposure to these estrogen-like compounds during sensitive periods of development may have the capacity to alter the function of the reproductive system and thereby influence fertility.     

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.     

Consensus: soy isoflavones as a first-line approach to the treatment of menopausal vasomotor complaints

The association between an increased uptake of isoflavones and a reduced frequency of menopausal hot flushes was first described in 1992, based on a lower incidence of hot flushes in countries with a high consumption of soy. Since then, numerous clinical trials with various sources of isoflavones including soy and red clover have been presented, with practically all of the studies with adequate design delivering an outcome in favour of isoflavone supplementation. An in-depth risk assessment (EFSA 2015) concludes that the amply available human data does not indicate any suspected harmful effects from a potential interaction of isoflavones with hormone-sensitive tissues in the mammary gland, the uterus and the thyroid gland. Safety was ascertained with long-term intake of up to 150?mg isoflavones per day ingested for the duration of at least 3 years. Moreover, high isoflavone intake was found to have preventive effects with respect to breast cancer. Clinical findings indicate potential benefits of isoflavone exposure even during breast cancer treatment with tamoxifen or anastrozole.     

Homeopathy: A State of the Science Review With Recommendations for Practical Therapies in Midwifery Practice

A substantial proportion of adults and children in the United States use complementary and alternative health practices, including homeopathy. Many homeopathic therapies are readily available over the counter, and many individuals access and self-administer these therapies with little or no guidance from health care practitioners. In addition, patients and health care providers are often confused by terminologies associated with complementary practices and may be unable to distinguish homeopathy from naturopathy, herbalism, holistic medicine, Ayurveda, traditional Chinese medicine, or other forms of health care. Compared with European and Asian countries, education in the United States about complementary and alternative health practices is not typically found within traditional nursing, midwifery, or medical education curricula. Given this lack of education and the broad acceptance and popularity of homeopathy, it is necessary for health care practitioners to improve their knowledge regarding similarities and differences among therapies so they can fully inform and make appropriate recommendations to patients. The intent of this article is therefore to examine the state of existing science of homeopathy, distinguish it from other complementary methods, and provide midwives and women's health care providers with an introduction to common homeopathic therapies that may be recommended and safely used by persons seeking midwifery care. This review also presents the evidence base, pharmacology, manufacturing, and regulation of homeopathic therapies. We also consider controversies and misunderstandings regarding safety and efficacy of homeopathic remedies relevant to women and birthing persons. Examples of practical applications of homeopathic therapies for use in midwifery practice are introduced. Implications for practice and sample guidelines are included.     

Endometrial effects of long-term treatment with phytoestrogens: a randomized, double-blind, placebo-controlled study

Objective

To determine the effects of 5 years of treatment with soy phytoestrogens on histological characteristics of endometrium in postmenopausal women.

Design

Randomized, double-blind, placebo-controlled study.

Setting

Centre of Perinatal and Reproductive Medicine, Department of Gynecological, Obstetrical, and Pediatric Sciences, University of Perugia, Italy.

Patient(s)

Three hundred seventy-six postmenopausal healthy women, all with intact uterus.

Intervention(s)

Women were distributed in two different groups using randomized criteria: group A (n = 179) patients received soy tablets (150 mg of isoflavones per day) for 5 years; group B (n = 197) patients received identical appearing placebo tablets for 5 years.

Main outcome measure(s)

Results of endometrial histology from biopsies obtained at baseline, 30 months, and 5 years after the beginning of the treatment.

Result(s)

Two hundred ninety-eight women completed the 5-year treatment. No cases of malignancy were detected during biopsy. Seventy percent of women undergoing treatment with soy phytoestrogens had an endometrium classified as atrophic or nonassessable versus 81% receiving placebo. The occurrence of endometrial hyperplasia was significantly higher in group A (3.37% vs. 0%).

Conclusion(s)

Long-term treatment (up to 5 years) with soy phytoestrogens was associated with an increased occurrence of endometrial hyperplasia. These findings call into question the long-term safety of phytoestrogens with regard to the endometrium.     

Ureteral mullerian carcinosarcoma (mixed mullerian tumor) associated with endometriosis occurring in a patient with a concentrated soy isoflavones supplementation

Malignant transformation and particularly malignant mixed mullerian tumor arising in extragenital endometriosis is extremely rare and occurs in the majority of cases after estrogen replacement therapy. We present a case of a 75-year-old woman who developed a ureteral malignant mullerian carcinosarcoma in a context of florid endometriosis. The patient had a history of total hysterectomy with bilateral salpingo-oophorectomy 30 years earlier for extensive endometriosis. Since 5 years, the patient has been on phytoestrogen supplementation consisting of 72 mg/day of superconcentrated soy isoflavones. This is the first case of ureteral mullerian carcinosarcoma arising in endometriosis foci after extensive phytoestrogen supplementation. Our data suggest that phytoestrogens at least in concentrated form may play a role not only in maintenance of endometriosis but also in its malignant transformation. Given the extraordinary popularity and availability of these dietary supplements, several studies are indispensable regarding their safety particularly in women with extensive endometriosis.