phytoestrogens and Osteoporosis--Postmenopausal

Osteoporosis is a systemic bone disease characterized by reduced bone mass and the deterioration of bone microarchitecture leading to bone fragility and an increased risk of fractures. Conventional anti-osteoporotic pharmaceutics are effective in the treatment and prophylaxis of osteoporosis, however they are associated with various side effects that push many women into seeking botanicals as an alternative therapy. Traditional folk medicine is a rich source of bioactive compounds waiting for discovery and investigation that might be used in those patients, and therefore botanicals have recently received increasing attention. The aim of this review of literature is to present the comprehensive information about plant-derived compounds that might be used to maintain bone health in perimenopausal and postmenopausal females.

Topics: Animals; Bone and Bones; Bone Density; Botany; Female; Fractures, Bone; Herbal Medicine; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens

The menopausal transition, or perimenopause, is characterized by menstrual irregularities, vasomotor symptoms, sleep disturbances, mood symptoms, and urogenital tract atrophy. These changes can also affect the quality of life and one's self-esteem. Hormone replacement therapy (HRT) is considered the best option to achieve therapeutic relief of different menopausal symptoms but is usually restricted to moderate or severe symptoms. Moreover, many women refuse HRT for a variety of reasons concerning the fear of cancer and other adverse effects. According to these considerations, new topics are emerging: Dissatisfaction with drug costs and conventional healthcare, desire for personalized medicines, and the public perception that "natural is good". In this context, nonhormonal therapies are mostly evolving, and it is not unusual that women often request a "natural" approach for their symptoms. The aim of this study is to investigate nonhormonal therapies that have been identified to reduce the menopausal symptoms.

Topics: Contraindications, Drug; Dietary Supplements; Hormone Replacement Therapy; Hot Flashes; Humans; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Sleep Wake Disorders; Vitamins

Hop (

Topics: Antineoplastic Agents, Phytogenic; Female; Flavanones; Humans; Humulus; Menopause; Molecular Structure; Osteoporosis, Postmenopausal; Phytoestrogens

Osteoporosis, a bone disease resulting in the loss of bone density and microstructure quality, is often associated with fragility fractures, and the latter imposes a great burden on the patient and society. Although there are several different treatments available for osteoporosis such as hormone replacement therapy, bisphosphonates, Denosumab, and parathyroid hormone, some concerns have been raised regarding the inherent side effects of their long term use. It would be of great relevance to search for alternative natural compounds, which could complementarily overcome the limitations of the currently available therapy. Herein, we review current literature on natural compounds that might have therapeutic values for osteoporosis. Search terms included bone resorption, bone density, osteoporosis, postmenopausal, osteoporosis or bone density conservation agents, and any of the terms related to traditional, herbal, natural therapy, natural health, diet, or phytoestrogens. All the compounds and herbs included in the review are naturally bioactive or are used in folk herbal medicine and have been reported to be capable of attenuating osteopenia or osteoporosis in vivo or in vitro, through various mechanisms - estrogen-like activity, antioxidant and anti-inflammatory properties, or by modulating the key signaling pathways in the pathogenesis of osteoporosis. Through our assessment of the therapeutic potential and outlook of alternative medicine, we aim to provide an appealing perspective for the consideration of the application of a complementary anti-osteoporotic treatment option and prevention strategy for osteoporosis or osteolytic bone disorders.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biological Products; Complementary Therapies; Female; Humans; Osteoporosis, Postmenopausal; Phytoestrogens

In developed countries, women spend more than one-third of their life in the menopause and at least half of them experience vasomotor symptoms that impair their normal function and well-being. Long-term estrogen replacement therapy (HRT) with estrogen can suppress typical menopausal symptoms and prevents osteoporosis. When estrogen-only HRT is started within 10 years after the menopause, the prevalence of cardiovascular disease is reduced, mortality is lower, and the risk of breast cancer is not significantly increased. Postmenopausal genital and urinary problems with recurrent infections, incontinence, and dyspareunia can effectively be treated by vaginal application of estriol, which seems to be safe for women treated for breast cancer. HRT after the age of 60 years is associated with a lower number needed to treat than number needed to harm, implying that there would be one unfavorable side-effect for up to ten women experiencing a positive effect. However, further studies are needed regarding the risk-benefit ratio of HRT in women over 70 years. It is concluded that transdermal substitution therapy with estradiol may increase the number of quality-adjusted life years of postmenopausal women. The combination with nutriceutical food supplementation may add to this benefit, but complementary prospective trials are still needed.

Topics: Breast Neoplasms; Cardiovascular Diseases; Dietary Supplements; Dyspareunia; Estradiol; Estriol; Estrogen Replacement Therapy; Female; Humans; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Randomized Controlled Trials as Topic; Vagina

Effects of isoflavones on bone health in postmenopausal women are expected, since it shows weak estrogenic activity. In the observational study in Asia, association between intake of soy foods or isoflavone and bone mineral density and fracture prevention has been observed. In the meta-analysis of intervention trials of isoflavone in 60 years or less of postmenopausal women, 75 mg by day about 6 months to 1 year intervention of isoflavones induced suppression of significant decline of bone resorption markers in the urine was observed. On the other hand, intended for Westerners women in the study intervened isoflavones with calcium and vitamin D simultaneously, it is not observed effectiveness of isoflavones on the bone. Such a difference might be due to diversity in the individual metabolic capacity for isoflavones as well as the effects of presence or absence of other co-interventions nutrients.

Topics: Biomarkers; Bone and Bones; Bone Density; Bone Resorption; Cytokines; Female; Fractures, Spontaneous; Glycine max; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens

Phytoetrogens and vitamin D administered in a dose-dependent manner effectively prevents bone loss in postmenopausal women and reduces the incidence of fractures. Recently, genistein has been found to stimulate the production of osteoprotegerin by human paracrine osteoblasts, providing a further mechanism for the bone-sparing effects of isoflavones.

Topics: Bone and Bones; Female; Genistein; Humans; Osteoporosis, Postmenopausal; Phytoestrogens; Vitamin D

Women have always looked for non-hormonal options to alleviate menopausal vasomotor symptoms and prevent menopausal bone loss. The use of complementary and alternative medicine for these purposes has particularly increased after the publication of the Women's Health Initiative's results suggesting that there might be more risks than benefits with hormone replacement. Phytoestrogens are plant-derived estrogens that, although less potent than estradiol, bind to the estrogen receptor and can function as estrogen agonists or antagonists. Soy isoflavones extracted from soy are the phytoestrogens most commonly used by menopausal women. Because typical Western diets are low in phytoestrogens and taking into account the general difficulty in changing dietary habits, most clinical trials in Western women have used isoflavone-fortified foods or isoflavone tablets. Although some women might experience a reduction in the frequency or severity of hot flashes, most studies point towards the lack of effectiveness of isoflavones derived from soy or red clover, even in large doses, in the prevention of hot flashes and menopausal bone loss. This article is part of a Special Issue entitled 'Phytoestrogens'.

Topics: Animals; Diet; Estrogen Replacement Therapy; Female; Guidelines as Topic; Hot Flashes; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Randomized Controlled Trials as Topic; Soy Foods

Hop extract is a long used medicinal product and, regarding hormonal activities, in 1999 a number of prenylflavanones have been identified as its major constituents with 8-prenylnaringenin (8-PN) being the main active estrogenic compound. There have been several in vivo studies performed that demonstrate the potential of hop extract and the single compound 8-PN to alleviate climacteric symptoms like osteoporosis, vasomotoric complaints, and sexual motivation. On the other hand, only a few clinical studies have been performed so far, and these mainly focused on menopausal discomforts, especially hot flushes, yielding rather inconclusive results. Despite preferentially activating estrogen receptor α, 8-PN is only slightly uterotrophic, but it also elucidates estrogenic effects on the mammary gland. In conclusion, although hop extract and especially 8-PN are promising candidates as a relief for climacteric symptoms, data on the safety and efficacy is still scarce.

Topics: Estrogen Receptor alpha; Female; Flavanones; Hot Flashes; Humans; Humulus; Mammary Glands, Human; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Extracts; Sexual Dysfunctions, Psychological; Uterus

Increasingly natural products particularly flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. This study has reviewed previous studies on the two better known flavonoids, genistein and icariin, their structures, functions, action mechanisms, relative potency, and potential application in regulating bone remodeling and preventing bone loss. Genistein, an isoflavone abundant in soy, has dual functions on bone cells, able to inhibit bone resorption activity of osteoclasts and stimulate osteogenic differentiation and maturation of bone marrow stromal progenitor cells (BMSCs) and osteoblasts. Genistein is an estrogen receptor (ER)-selective binding phytoestrogen, with a greater affinity to ERβ. Genistein inhibits tyrosine kinases and inhibits DNA topoisomerases I and II, and may act as an antioxidant. Genistein enhances osteoblastic differentiation and maturation by activation of ER, p38MAPK-Runx2, and NO/cGMP pathways, and it inhibits osteoclast formation and bone resorption through inducing osteoclastogenic inhibitor osteoprotegerin (OPG) and blocking NF-κB signaling. Icariin, a prenylated flavonol glycoside isolated from Epimedium herb, stimulates osteogenic differentiation of BMSCs and inhibits bone resorption activity of osteoclasts. Icariin, whose metabolites include icariside I, icariside II, icaritin, and desmethylicaritin, has no estrogenic activity. However, icariin is more potent than genistein in promoting osteogenic differentiation and maturation of osteoblasts. The existence of a prenyl group on C-8 of icariin molecular structure has been suggested to be the reason why icariin is more potent than genistein in osteogenic activity. Thus, the prenylflavonoids may represent a class of flavonoids with a higher osteogenic activity.

Topics: Adipogenesis; Animals; Bone Remodeling; Cell Differentiation; Female; Flavonoids; Genistein; Humans; NF-kappa B; Osteoblasts; Osteogenesis; Osteoporosis, Postmenopausal; Phytoestrogens; PPAR gamma; Protein Kinase Inhibitors; Receptors, Estrogen; Signal Transduction; Structure-Activity Relationship

Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.

Topics: Absorption; Bone Density; Calcium; Drug Synergism; Female; Genistein; Glycine max; Hip Fractures; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Postmenopause; Risk Factors; Vitamin D

A high intake of fruits and vegetables is associated with a lower risk of cancer. In this context, considerable attention is paid to Asian populations who consume high amounts of soy and soy-derived isoflavones, and have a lower risk for several cancer types such as breast and prostate cancers than populations in Western countries. Hence, interest focuses on soyfoods, soy products, and soy ingredients such as isoflavones with regard to their possible beneficial effects that were observed in numerous experiments and studies. The outcomes of the studies are not always conclusive, are often contradictory depending on the experimental conditions, and are, therefore, difficult to interpret. Isoflavone research revealed not only beneficial but also adverse effects, for instance, on the reproductive system. This is also the case with tumor-promoting effects on, for example, breast tissue. Isoflavone extracts and supplements are often used for the treatment of menopausal symptoms and for the prevention of age-associated conditions such as cardiovascular diseases and osteoporosis in postmenopausal women. In relation to this, questions about the effectiveness and safety of isoflavones have to be clarified. Moreover, there are concerns about the maternal consumption of isoflavones due to the development of leukemia in infants. In contrast, men may benefit from the intake of isoflavones with regard to reducing the risk of prostate cancer. Therefore, this review examines the risks but also the benefits of isoflavones with regard to various kinds of cancer, which can be derived from animal and human studies as well as from in vitro experiments.

Topics: Animals; Anticarcinogenic Agents; Biological Availability; Carcinogenicity Tests; Carcinogens; Cardiovascular Diseases; Diet; Disease Models, Animal; Drug Combinations; Female; Glycine max; Hormone Replacement Therapy; Humans; Isoflavones; Male; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Extracts; Risk Assessment

Isoflavones are a subgroup of phytoestrogens, natural plant substances with structure similar to 17-beta-estradiol and capable of binding to estrogen receptors (ERs). Isoflavones possess higher affinity to ERbeta than to ERalpha and may have a potency to activate both genomic and non-genomic estrogen signaling pathways. In addition, isoflavones interact with the metabolism of steroid hormones. Therefore, the actions of isoflavones are rather complex and may be related to large number of factors, which are not satisfactorily identified yet. Recently, isoflavones have come into focus of interest due to several reports about their positive effect on human health, in particular prevention of hormone-dependent cancers, cardiovascular diseases, osteoporosis, adverse menopausal manifestations and age-related cognitive decline. Isoflavones may bring new insights into the mechanisms of physiological regulations and increase the possibilities of medical interventions.

Topics: Cardiovascular Diseases; Female; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Signal Transduction

The present review summarizes the results of epidemiological studies and clinical trials assessing the skeletal effects of soy foods and soy dietary supplements.. Results from epidemiological studies suggest a beneficial skeletal effect in Asian women consuming typical Asian diets, but clinical trials are conflictive regarding the effects of phytoestrogens on bone mineral density and bone turnover markers in premenopausal and postmenopausal women. Much of the controversy lies in differences in study design, reporting of results, participants' age and menopausal status, and type and dose of phytoestrogen used.. Although western women will likely continue to incorporate soy foods and soy supplements into their diets with the increased availability of these products, published data are inconsistent and do not support soy's protective effect against bone loss. This conflicting evidence should be taken into account when considering using isoflavones in the prevention of bone loss and consequently fractures.

Topics: Animals; Bone and Bones; Dietary Supplements; Female; Functional Food; Health Status; Humans; Isoflavones; Male; Osteoporosis, Postmenopausal; Phytoestrogens; Soy Foods

Side effects and contraindications connected with hormonal replacement therapy in climacterium resulted in search for new methods of softening menopausal symptoms. The aim of the following study was to evaluate, based on literature analysis, the effectiveness of phytohormonal therapy as an alternative method of relieving the symptoms of menopausal period and preventing the diseases connected with deficiency of estrogens after menopause. Phytoestrogens therapy reduces the number and strength of the vasomotor symptoms and improves serum lipid profile. Moreover phytoestrogens show beneficial effects on bone tissue metabolism, skin and mucous membranes condition and are applicable in chemoprevention. This therapy is an effective method, allowing to avoid further changes in blood and urogenital systems, which result from estrogen stimulation deficiency. Phytoestrogens administration is an efficient method of relieving postmenopausal symptoms, facilitating the difficult menopausal period and keeping good health condition.

Topics: Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Postmenopause; Women's Health

Topics: Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens

Due to their ability to mimic the actions of mammalian estrogens, soy phytoestrogens have been proposed as potential therapeutic agents to aid in preventing postmenopausal bone loss. In vitro, phytoestrogens promote osteoblastogenesis and inhibit osteoclastogenesis. Although a relatively large number of intervention studies have been undertaken in animals and humans, the efficacy of phytoestrogens as bone-protective agents in vivo remains unclear. Differences in the bioactivities of individual phytoestrogens, differences in phytoestrogen metabolism and bioavailability within different study populations, and imprecise reporting of the dose of phytoestrogens administered in intervention studies may have contributed to the disparity in study findings.

Topics: Animals; Bone and Bones; Bone Density Conservation Agents; Clinical Trials as Topic; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Glycine max; Humans; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens

Traditional soyfoods have been consumed for centuries throughout much of East Asia and, recently, these foods have also become popular in the West. Soyfoods and specific soybean components, such as the protein and isoflavones, have attracted attention for their possible health benefits. Isoflavones are classified as phytoestrogens and have been postulated to be natural alternatives to hormone therapy for menopausal women. To provide guidance on optimal soy intake, this article evaluates Asian soy consumption and both clinical and Asian epidemiologic studies that examined the relationship between soy intake and a variety of health outcomes. On the basis of these data and the standard principles of dietary practice the author suggests that optimal soy protein and isoflavone intakes are 15-20 g/day and 50-90 mg/day, respectively. In addition, an intake of 25 g/day soy protein can be specifically used as the recommendation for cholesterol reduction.

Topics: Dietary Supplements; Dose-Response Relationship, Drug; Female; Health Promotion; Hot Flashes; Humans; Isoflavones; Nutritional Physiological Phenomena; Osteoporosis, Postmenopausal; Phytoestrogens; Soybean Proteins; United States; United States Food and Drug Administration; Women's Health

As oestrogen deficiency is the main cause in the pathogenesis of osteoporosis hormone-replacement therapy remains the mainstay for prevention. However, prophylaxis by hormone-replacement therapy is limited. Phyto-oestrogens, which are weakly-oestrogenic compounds present in plants, deserve particular mention because emerging data support the suggestion that they may prevent bone loss associated with the menopause. In the past few years extensive research using animal models has provided convincing data to indicate a significant improvement in bone mass or other end points following feeding with soyabean. Moreover, observational studies relate the lower incidence of osteoporosis among women in the Eastern world to a diet rich in phyto-oestrogens. However, it is not valid to extrapolate to the Western situation. The varied clinical trials that have been published suggest that isoflavones reduce bone loss in women in the early period post menopause, but a definitive result requires more investigations of the effect of phyto-oestrogens on bone health that have substantial sample size and are of long duration. In addition, the clinical efficacy of soya foods in preventing osteopenia depends on their intestinal metabolism. Thus, phyto-oestrogens are a source for putative innovative dietary health intervention for post-menopausal women. However, more data are necessary, particularly in relation to their effect on the risk of fracture.

Topics: Animals; Bone and Bones; Evidence-Based Medicine; Female; Glycine max; Humans; Isoflavones; Models, Animal; Osteoporosis, Postmenopausal; Phytoestrogens; Treatment Outcome

Plant-derived phytoestrogens are considered to be an alternative therapy for the prevention and control of bone loss in postmenopausal women. However, there are contradictory findings among clinical studies in the efficacy of soy isoflavones on bone metabolism in postmenopausal women. Inter-individual differences in gut bacteria metabolism of isoflavones to produce equol (the equol-producing phenotype) might partly explain these discrepancies. Among several trials in this area of research, few studies took the equol-producing phenotype into consideration, and those studies support the importance of this phenotype in the effect of soy isoflavones on bone health among post-menopausal women. Greater consideration of the equol-producing phenotype in the design of studies investigating the effect of soy isoflavones on bone health of postmenopausal women may provide more useful information.

Topics: Bone Density; Equol; Female; Gastrointestinal Tract; Genistein; Glycine max; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phenotype; Phytoestrogens; Postmenopause

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Topics: Anticarcinogenic Agents; Breast Neoplasms; Cardiovascular Diseases; Female; Genistein; Glycine max; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Postmenopause; Randomized Controlled Trials as Topic

Numerous publications and research studies on isoflavones have prompted a nationwide increase in the consumption of soy-based foods and supplements in the United States. Isoflavones are natural endocrine active compounds generally considered to promote health and prevent or slow the onset of certain chronic diseases such as osteoporosis. The beneficial effects of soy isoflavones on bone may, however, be life-stage specific and dependent on the estrogen receptor number and endogenous hormone milieu. Perimenopausal and early menopausal women may therefore be more receptive to the therapeutic effects of isoflavones on bone loss prior to the diminution of estrogen receptors that occurs in the postmenopausal years, whereas laboratory studies in developmental age range animals have demonstrated the potential for adverse effects following exposure to high levels of soy isoflavones. Clinical studies in developing humans that either support or refute findings in animal studies are lacking. The effects of chronic consumption of high levels of soy isoflavones at each life stage to assess risk-benefit ratios should be a high priority of research.

Topics: Animals; Bone and Bones; Bone Diseases; Female; Health; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Rats; Receptors, Estrogen; Soy Foods; United States

Consumers are increasingly looking to natural health products to manage specific diseases such as osteoporosis. As a result, healthcare providers need evidence-based information on which to base recommendations regarding use and efficacy.. To identify natural health products (NHPs, ie, dietary supplements) advocated for the prevention and treatment of osteoporosis and systematically review the evidence from randomized controlled trials for the effect of NHPs on bone mineral density (BMD)/fracture rate in women.. MEDLINE, Natural Medicines Comprehensive Database, and the Internet were initially searched to identify NHPs advocated for prevention and treatment of osteoporosis. For NHPs having evidence to support their claim, the aforementioned sources, along with International Pharmaceutical Abstracts, the Cochrane Library, the International Bibliographic Information on Dietary Supplements, the Cumulative Index to Nursing & Allied Health, and HerbMed, were searched to locate randomized controlled trials published in English between 1966 and October 2004. Bibliographies of identified articles were also searched. Randomized controlled trials were selected if they evaluated the use of a single NHP in women, using BMD/fracture rate as the outcome measure. NHPs were excluded from further evaluation if a review had already been published. Data were extracted using predetermined criteria and studies appraised using the Jadad scale. Forty-five NHPs were identified that the authors claimed to be beneficial in prevention and treatment of osteoporosis, with 15 having evidence to support their claim. Calcium; copper; evening primrose oil; fish oils; fluoride; magnesium; manganese; strontium; vitamin D; and black, green, and oolong tea did not meet study criteria.. Results from randomized controlled trials evaluating dehydroepiandrosterone (DHEA), phytoestrogens, and vitamin K2 (menaquinone or menatetrenone) were promising; however, study limitations suggest the need for confirmatory evidence.. Although no definitive conclusions can be drawn, the relative safety of phytoestrogens, DHEA, and vitamin K2 at the studied doses, as well as preliminary positive results from randomized controlled trials, provides some initial support for the use of these NHPs in the prevention and treatment of osteoporosis in women.

Topics: Biological Products; Bone Density; Complementary Therapies; Dietary Supplements; Female; Fractures, Bone; Humans; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic

A variety of common complementary and alternative medicine therapies are now being examined for effectiveness in the management of osteoporosis. Short-term studies in postmenopausal women show beneficial effects of soy isoflavone supplementation on bone density, but its long-term effects require clarification. Prospective controlled trials have shown that physical training can increase bone density to varying degrees. Other therapies that have been examined include herbal formulae, essential fatty acids and vitamins A, C, and K, but few data regarding their effectiveness, mechanisms and safety have been published. Further randomized controlled trials are needed.

Topics: Bone Density; Complementary Therapies; Drugs, Chinese Herbal; Exercise; Fatty Acids, Omega-3; Female; Humans; Osteoporosis, Postmenopausal; Phytoestrogens; Vitamins

In the discussion of the risk-benefit relation of the hormone replacement therapy (HRT) for elder women phytochemicals with estrogenic activity received a great deal of attention. Phytoestrogens are naturally occurring compounds with structural similarity to 17beta-estradiol. Especially genistein, an isoflavone most abundant in soy, possess a high and selective binding-affinity to the mammalian estrogen receptors. It has been found, that genistein exert in humans both: weak estrogenic and anti-estrogenic effects, similar to the SERMs. Consequently, it was concluded, that genistein might provide an alternative to prevent postmenopausal bone-loss and ameliorate menopausal symptoms without side-effects similar to HRT. Pre-clinical experiments and results from clinical pilot studies with pure genistein confirmed its efficacy in these indications. Nevertheless, currently some open issues still exist to recommend its intake thoughtlessly. Bonistein, pure synthetic genistein developed by DSM Nutritional Products, was tested extensively in appropriate models for bone health. A battery of toxicological studies was conducted to determine safe intake levels. In the early clinical development pharmacokinetic studies were performed in healthy volunteers and in postmenopausal women. Now large-scale studies are in preparation to investigate Bonistein's efficacy in postmenopausal bone-loss and climacteric syndrome.

Topics: Animals; Dietary Supplements; Female; Genistein; Hot Flashes; Humans; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens

Topics: Alkaline Phosphatase; Animals; Biomarkers; Bone and Bones; Bone Resorption; Calcium; Female; Food Analysis; Humans; Isoflavones; Osteocalcin; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Soy Foods

Recent results put into question the risks/benefits ratio of hormone replacement therapy and emphasize the importance of precise knowledge of the effects of other treatments that exist for postmenopausal symptoms or diseases. Our aim is to analyze their effect.. A review of randomized trials or epidemiological studies was undertaken.. Bisphophonates, calcitonin, parathormone, strontium ranelate, calcium and vitamin D have specific effects on bone. The efficacy of bisphophonates for prevention and treatment of osteoporosis has been proven and parathormone and strontium ranelate seem promising. These treatments are useful for women at high risk of osteoporosis who do not suffer from menopausal symptoms. Tibolone, SERMs and phytoestrogens exert effects on various tissues. SERMs are very promising, but they do not improve climacteric symptoms and their long term effects are still unknown. Tibolone has beneficial effects on climacteric symptoms and on bone loss, but recent results concerning its effects on the risk of breast cancer call into question its interest. The beneficial effects of phytoestrogens on bone and on vasomotor symptoms need to be confirmed.. At this time, none of the existing treatments for postmenopausal symptoms or diseases is ideal. The existence of several options for treatments of symptoms or diseases of the postmenopause is helpful as it affords several choices for physicians and for women who sometimes need to be treated for many years. However several questions remain unanswered concerning the long term effects of these treatments.

Topics: Climacteric; Estrogen Replacement Therapy; Female; Humans; Isoflavones; Menopause; Norpregnenes; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic; Selective Estrogen Receptor Modulators

Chemicals known to disrupt the endocrine system of animal models are assessed for their potential impact on the health of menopausal and postmenopausal women. These "endocrine disrupters" consist of two groups of compounds - man-made and naturally occurring. There is some evidence to suggest that the naturally occurring phytoestrogens, derived from plant material, may have some beneficial effects on menopausal symptoms and the risk of breast cancer, cardiovascular disease and osteoporosis. Further studies are required to confirm these possibilities. Some man-made environmental pollutants appear to increase the risk of breast cancer, although again the evidence is inconclusive. Mechanistic experiments indicate that these chemicals interact with oestrogen receptors and alter metabolism in a number of different ways, some of which may be important in postmenopausal women. Further investigation of the differences in mode of action between the man-made and the natural endocrine disrupters may lead to important insights into their effects on women's health.

Topics: Aged; Animals; Breast Neoplasms; Coronary Disease; Endocrine System; Environmental Pollutants; Female; Humans; Menopause; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Assessment; Uterine Neoplasms; Women's Health

Due to its incidence and clinical consequences osteoporosis followed by vertebral, hip, and forearm fractures represents an outstanding problem of nowadays' health care. Because of its high mortality rate hip fractures are of special interest. The number of fractures caused by postmenopausal osteoporosis increases with age. Costs of examinations and treatment of women with postmenopausal osteoporosis and fractures are also increasing and represent a significant amount all over the world. Organization of Osteoporosis Centres in Hungary was founded in 1995 and has been since functioning, however, only the one-sixth of osteoporotic patients are treated. Several risk factors are known in the pathogenesis of osteoporosis, first of all the lack of sufficient calcium and vitamin D intake, age, genetic factors, and circumstances known to predispose falling. Estrogen deficiency is the most likely cause of postmenopausal osteoporosis. Osteodensitometry by DEXA is the most important method to evaluate osteoporosis, since decrease in bone mineral density strongly correlates with fracture incidence. Physical, radiologic, and laboratory examination are also required at the first visit and during follow-up. The quantity of bone can hardly be influenced after the 35th year of age, thus prevention of osteoporosis has special significance: appropriate calcium and vitamin D supplementation, weight-bearing sports and physical activity can prevent fractures. According to the results from studies fulfilling the criteria of evidence-based medicine, first choice treatment of osteoporosis involves hormone replacement therapy, bisphosphonates, the tissue specific tibolone, raloxifen and calcitonin. Calcium and vitamin D supplementation are always necessary to be added to any antiporotic treatment. Other combinations of different antiporotic drugs are useless and make the treatment more expensive. Other treatments like massage, physiotherapy, hip-protecting pants, etc. as well as rehabilitation have special clinical significance.

Topics: Absorptiometry, Photon; Anabolic Agents; Calcitonin; Calcium, Dietary; Diphosphonates; Estrogen Replacement Therapy; Female; Fractures, Bone; Humans; Isoflavones; Motor Activity; Norpregnenes; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators; Vitamin D; Weight-Bearing

Perimenopausal period is associated with the reduction of endogenous estrogens which might lead to many disorders of general health in women. Traditional hormone replacement therapy (HRT) is effective for controlling vasomotor symptoms and reducing the risk of cardiovascular disease and osteoporosis in postmenopausal women. However, according to the latest studies, many women are reluctant to initiate this therapy because of concerns regarding the benefits and risks considering contraindications and side effects of it. Therefore, a lot of studies were carried out to find the influence of phytoestrogens on menopausal symptoms. Phytoestrogens are defined as naturally occurring compounds, found in plants; they have a variety of activities: estrogenic and antiestrogenic. Could phytoestrogens be used as an alternative to hormonal therapies for the management of menopausal symptoms?

Topics: Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Poland; Women's Health

Approximately 50% of Americans use dietary supplements on a regular basis spending an estimated $20 billion on supplements in the year 2000. Soy contains genistein and daidzein, two phytoestrogens, which work through the estrogen receptor and cause alterations in serum lipids, bone metabolism, and possibly cognition. In this article, we review the issues regarding the interpretation with studies using soy-based isoflavones, discuss their mechanism of action, and review the literature on the effect of these bio-active compounds on lipid metabolism, osteoblasts and osteoclasts, bone markers, bone mineral density, and cognition.

Topics: Animals; Bone Density; Clinical Trials as Topic; Cognition; Dietary Supplements; Disease Models, Animal; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Extracts; Plant Preparations; Rats

Research on the bone effects of natural phyto-oestrogens after menopause is at a relatively early stage. Published studies are few, difficult to compare and often inconclusive, due in part to design weaknesses. Currently, many questions remain to be answered including to what extent a safe daily intake may prevent postmenopausal bone loss. These questions can only be addressed by conducting well-planned, randomised clinical trials that take into consideration present knowledge in the oestrogen, phyto-oestrogen and bone fields. This review is intended to provide hints for critical decision-making about the selection of subjects, type of intervention, suitable outcome measures and variables that need to be controlled.

Topics: Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic; Research Design; Treatment Outcome

Osteoporosis is a serious public health concern. Skeletal fragility, leading to spine and hip fractures, is a major source of morbidity and mortality. Adequate calcium intake from childhood to the end of life is critical for the formation and retention of a healthy skeleton. It is important to prevent bone loss from occurring, to identify potential risk factors, and to correct them. Many genetic and lifestyle factors influence the risk for osteoporosis. Among these, diet is believed to be one of the most important, especially the roles of calcium and vitamin D. Deficiency in other dietary factors--eg, protein, vitamin K, vitamin A, phytoestrogens, and other nutrients--might also contribute to the risk for osteoporosis. In this article, the roles of diet and nutritional supplementation in preventing and treating osteoporosis are reviewed.

Topics: Adolescent; Adult; Aged; Bone and Bones; Calcium, Dietary; Child; Child, Preschool; Diet; Dietary Supplements; Estrogens, Non-Steroidal; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Isoflavones; Life Style; Male; Middle Aged; Nutritional Requirements; Nutritional Status; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Quality of Life; Risk Factors; United States; Vitamin A; Vitamin A Deficiency; Vitamin D; Vitamin D Deficiency; Vitamin K; Vitamin K Deficiency

Interest in the physiological role of bioactive compounds present in plants has increased dramatically over the last decade. Of particular interest in relation to human health are the class of compounds known as the phytoestrogens, which embody several groups of non-steroidal oestrogens including isoflavones & lignans that are widely distributed within the plant kingdom. Data from animal and in vitro studies provide plausible mechanisms to explain how phytoestrogens may influence hormone dependent states, but although the clinical application of diets rich in these oestrogen mimics is in its infancy, data from preliminary studies suggest potential beneficial effects of importance to health. Phytoestrogens are strikingly similar in chemical structure to the mammalian oestrogen, oestradiol, and bind to oestrogen receptors (ER) with a preference for the more recently described ER beta. This suggests that these compounds may exert tissue specific effects. Numerous other biological effects independent of the ER (e.g. antioxidant capacity, antiproliferative and antiangiogenic effects) have been ascribed to these compounds. Whether phytoestrogens have any biological activity in humans, either hormonal or non hormonal is a contentious issue and there is currently a paucity of data on human exposure. Much of the available data on the absorption and metabolism of dietary phytoestrogens is of a qualitative nature; it is known that dietary phytoestrogens are metabolised by intestinal bacteria, absorbed, conjugated in the liver, circulated in plasma and excreted in urine. Recent studies have addressed quantitatively what happens to isoflavones following ingestion--with pure compound and stable isotope data to compliment recent pharmacokinetic data for soy foods. The limited studies conducted so far in humans clearly confirm that soya isoflavones can exert hormonal effects. These effects may be of benefit in the prevention of many of the common diseases observed in Western populations (such as breast cancer, prostate cancer, menopausal symptoms, osteoporosis) where the diet is typically devoid of these biologically active naturally occurring compounds. However since biological effects are dependent on many factors including dose, duration of use, protein binding affinity, individual metabolism and intrinsic oestrogenic state, further clinical studies are necessary to determine the potential health effects of these compounds in specific population groups. However we cur

Topics: Animals; Breast Neoplasms; Coronary Disease; Diet; Endometrial Neoplasms; Estrogens, Non-Steroidal; Female; Humans; Infant; Infant Food; Intestinal Absorption; Isoflavones; Lignans; Male; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Premenopause; Risk Factors

The indications for hormone therapy (HT) have changed markedly since the 1980s; they now include the treatment of menopausal symptoms and the prevention and treatment of osteoporosis in the short term. Long-term therapy is discouraged because of the small increase in risk of breast cancer after 5 years of therapy. Careful assessment of the midlife woman allows for individualized risk-benefit analysis with the formulation of a specific health management plan. Lifestyle advice and modification form the cornerstone of management-followed by therapeutic options if appropriate indications exist. In some industrialized countries alternative therapies are preferred despite little scientific evidence of their efficacy. The choices of hormonal products have increased, with the introduction of new formulations and routes of administration allowing for more optimal treatment of the menopause, especially in the presence of concurrent medical conditions, for example, diabetes, breast cancer or fibroids.

Topics: Complementary Therapies; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Hot Flashes; Humans; Isoflavones; Life Style; Menopause; Mood Disorders; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

Phyto-oestrogens are oestrogenic compounds found in plants and consist of isoflavones, lignans and coumestans. Epidemiological studies provide evidence for a protective role of isoflavones, and to a lesser extent lignans, against the development of numerous chronic diseases, including several cancers, cardiovascular disease and osteoporosis. The structural similarity of phyto-oestrogens to endogenous oestrogens has prompted the hypothesis that phyto-oestrogens exert hormonal or anti-hormonal effects relevant to the risk of hormone-dependent disease and/or their suitability as a dietary alternative to hormone replacement therapy. The many human studies that have evaluated the effects of isoflavones and lignans on various endpoints relating to risk of various diseases have greatly increased knowledge of how these compounds behave. At the same time, additional questions have been generated. For example, the increasing interest in extracting isoflavones from the soybean for incorporation into dietary supplements has raised important concerns regarding safety and efficacy. Overall, it is clear that phyto-oestrogens are an area of active and advancing research with great potential to continue to affect human health.

Topics: Animals; Anticarcinogenic Agents; Breast Neoplasms; Cardiovascular Diseases; Female; Humans; Isoflavones; Male; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Prostatic Neoplasms

The role of soy phytoestrogens in preserving bone health has to date not been studied in large randomised controlled studies. These bioactive naturally occurring compounds are viewed as potential selective oestrogen receptor modulators based on their structural similarity to oestradiol, in vitro mechanisms of action and hormonal effects in human subjects. Much of the evidence for a role in bone health has stemmed from animal data, as most of the available human studies are of short duration and have used either bone biomarkers or bone mineral density as end point measures. However, recent data from a long-term study suggest these compounds have a bone conserving effect in menopausal women but to accurately examine the relative importance of these compounds for bone health in postmenopausal women an assessment of consumption on fracture rates will be critical.

Topics: Clinical Trials as Topic; Dietary Supplements; Female; Glycine max; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations

Impressive data from the many studies on cultured bone cells and rat models of postmenopausal osteoporosis support a significant bone-sparing effect of the soy isoflavones genistein and daidzein. Translating this research to the clinic has been more challenging, and thus far only a few clinical studies have attempted to tease out the influence of phytoestrogens on bone from the many other components of the diet. Human studies have shown promising although variable results. Studies have been mostly of short duration and with relatively small sample sizes, making it difficult to observe significant and accurate changes in bone. Levels of intake of the soy protein and isoflavones are varied, and the optimal isoflavone intake for bone-sparing effects remains to be determined. Clinical studies thus far performed can be broadly divided into those that have assessed biochemical evidence of reduced bone turnover from measurement of surrogate markers of osteoblast and osteoclast activity, and those that have examined changes in bone mineral density. There are no studies examining effects on fracture rate. This review focuses specifically on the potential influence of phytoestrogens on bone by examining the evidence from 17 in vitro studies of cultured bone cells, 24 in vivo studies of animal models for postmenopausal osteoporosis, 15 human observational/epidemiologic studies, and 17 dietary intervention studies. On balance, the collective data suggest that diets rich in phytoestrogens have bone-sparing effects in the long term, although the magnitude of the effect and the exact mechanism(s) of action are presently elusive or speculative.

Topics: Animals; Biomarkers; Bone and Bones; Clinical Trials as Topic; Disease Models, Animal; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

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.

Topics: Anticarcinogenic Agents; Clinical Trials as Topic; Female; Genistein; Humans; Isoflavones; Lipids; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations

Topics: Aromatase Inhibitors; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

Topics: Chemistry, Pharmaceutical; Climacteric; Drug Combinations; Drug Compounding; Drug Monitoring; Estradiol; Estrogen Replacement Therapy; Estrogens, Conjugated (USP); Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Medroxyprogesterone Acetate; Menopause; Osteoporosis, Postmenopausal; Patient Care Planning; Phytoestrogens; Plant Preparations; Raloxifene Hydrochloride; Risk Factors; Selective Estrogen Receptor Modulators

The way of nutrition and particular components of the diet have substantial influence on the development of many diseases. It has been proven by large epidemiological studies dealing with the incidence of cardiovascular diseases and tumours. What is more, the diet may have also an important role in the secondary prevention of myocardial infarction. The role of a soy as a component of the diet with potentially favorable action on human health was discussed in this paper. Special attention was paid to mechanisms of action of soy phytoestrogens and their influence on development of ischaemic heart disease, tumours, osteoporosis and other symptoms related to menopause.

Topics: Breast Neoplasms; Cardiovascular Diseases; Climacteric; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Male; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Soybean Proteins

Women frequently chose alternatives to hormone replacement therapy (HRT) for treatment of menopause even though medical indications for estrogens may be present. Prior breast cancer or fear of breast cancer is a major consideration. This review of alternatives to estrogen discusses the evidence linking breast cancer to HRTs and compares potential risks and benefits of HRT to nonHRT alternatives for relief of vasomotor symptoms, vaginal atrophy, neurocognitive changes and prevention of heart disease and osteoporosis. Practical guidelines are suggested for use of alternatives for each problem.

Topics: Aged; Antidepressive Agents; Atrophy; Bone Density; Bone Resorption; Breast Neoplasms; Calcitonin; Calcium; Cardiovascular Agents; Cardiovascular Diseases; Clinical Trials as Topic; Contraindications; Diphosphonates; Double-Blind Method; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Fractures, Bone; Hot Flashes; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Life Style; Menopause; Mental Disorders; Meta-Analysis as Topic; Middle Aged; Multicenter Studies as Topic; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations; Randomized Controlled Trials as Topic; Risk; Safety; Selective Estrogen Receptor Modulators; Urothelium; Vagina

Estrogen replacement therapy (ERT) is recommended for postmenopausal women primarily for reduction of menopausal symptoms and prevention of osteoporosis and cardiovascular disease. However, only 35% to 40% of women ever start ERT, and many do not continue it. One of the reasons women are reluctant to receive postmenopausal ERT is that they perceive prescription estrogens as being "unnatural." Because of this, there is increasing interest in the use of plant-derived estrogens, also known as phytoestrogens. This article reviews the evidence for the potential of phytoestrogens, either in dietary or supplemental form, to replace traditional forms of ERT. A comprehensive search of the English-language literature identified more than 1000 articles published in the past 30 years about phytoestrogens. In total, 74 studies were selected for inclusion in this review based on relevance, inclusion of human subjects wherever possible, and study design. The studies examine phytoestrogens' inhibition of the growth of cancer cell lines in vitro and in animals. They also look at the role of phytoestrogens in the reduction of cholesterol levels, and the use of one phytoestrogen derivative, ipriflavone, in the prevention of osteoporosis. Some small studies examine the role of phytoestrogens in the prevention of menopausal symptoms. Evidence for the potential health benefits of phytoestrogens is increasing. However, the clinically proven health benefits of prescribed ERT far outweigh those of phytoestrogens. Therefore, there is insufficient evidence to recommend the use of phytoestrogens in place of traditional ERT, or to make recommendations to women about specific phytoestrogen products.

Topics: Breast Neoplasms; Cardiovascular Diseases; Cell Division; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Prognosis

Phytoestrogens, plant chemicals classified as isoflavones, coumestans and lignans, display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor beta. They are common components of food items such as grains, beans, fruits and nuts. Isoflavones are primarily found in soybeans and foods made from soy. In particular, significant therapeutic properties have been generally attributed to soy isoflavones, but most of the claims have been poorly, or not at all, confirmed by well designed clinical trials. Such is the case of the purported role of soy isoflavones in reducing plasma cholesterol levels. This link is now not supported by many authors or by appropriately designed clinical studies. The role of isoflavones in cancer prevention, particularly of tumours under endocrine control (breast, prostate and others) is again only supported by weak to nonexisting clinical evidence. A similarcase is that of the prevention/treatment of postmenopausal symptoms and osteoporosis. Disturbing data have been reported on potential negative effects of soy isoflavones on cognitive function in the aged, particularly relating to tofu intake. Recent studies have finally indicated a potential role for soy isoflavones in inducing chromosomal changes in cells exposed in vitro and potentiating chemical carcinogens. These findings may not, however, be extrapolated to clinical conditions. Available data do not appear to unequivocally support beneficial effects of soy isoflavones, and warn against their wide use, in the absence of satisfactory clinical findings.

Topics: Adult; Animals; Breast Neoplasms; Cardiovascular Diseases; Cholesterol; Climacteric; Cognition; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Soybean Proteins

Ovarian hormone deficiency is a major risk factor for osteoporosis in postmenopausal women. Hormone replacement therapy (HRT) is perhaps the most effective treatment, as it has been demonstrated to both reduce the rate of bone loss and risk of fracture, including hip fracture. However, not all women who may benefit from HRT are willing to initiate this treatment due to fear of cancer and contraindications. Other therapeutic agents currently available are also associated with certain adverse effects. As a result, postmenopausal women are more inclined to use natural remedies to alleviate postmenopausal symptoms and help reduce their risk for chronic diseases such as osteoporosis. Recent reports support the notion that certain bioactive constituents, e.g., phytoestrogens, in plants play a role in maintaining or improving skeletal health. The main consumable plant sources of phytoestrogens include isoflavones and lignans found mainly in soybeans and flaxseed, respectively. Although this paper primarily focuses on the effects of soy protein or its isoflavones on bone, additional statements regarding the role of flaxseed and dried plums, a rich source of polyphenols, with respect to bone will be made.

Topics: Animals; Bone Density; Complementary Therapies; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Flax; Glycine max; Humans; Isoflavones; Male; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Rats; Risk Factors; Seeds; Treatment Outcome

Topics: Adult; Bone Density; Caffeine; Calcium, Dietary; Energy Intake; Estrogens, Non-Steroidal; Family Practice; Female; Humans; Isoflavones; Life Style; Middle Aged; Nutritional Requirements; Nutritional Sciences; Osteoporosis, Postmenopausal; Patient Education as Topic; Phytoestrogens; Plant Preparations; Risk Factors; Sodium, Dietary; Vitamin D

Topics: Animals; Breast Neoplasms; Cardiovascular Diseases; Contraindications; Estrogens, Non-Steroidal; Female; Hormone Replacement Therapy; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Factors

Topics: Adult; Aged; Alzheimer Disease; Breast Neoplasms; Cardiovascular Diseases; Cohort Studies; Diet; Double-Blind Method; Embryonal Carcinoma Stem Cells; Estrogens; Estrogens, Non-Steroidal; Female; Follow-Up Studies; Gonadal Steroid Hormones; Hormone Replacement Therapy; Hot Flashes; Humans; Isoflavones; Longevity; Menopause; Menopause, Premature; Middle Aged; Neoplasm Recurrence, Local; Neoplasms, Hormone-Dependent; Neoplasms, Second Primary; Neoplastic Stem Cells; Obesity; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic; Safety; Selective Estrogen Receptor Modulators; Survivors; Weight Gain

Isoprene is the main component of steroid hormones. It is found in many plants and herbal compounds, e.g. the isoflavonoids are therefore slightly estrogenic. Since they are bound to the estradiol receptors, more active estrogens cannot induce a signal transduction. Hence phytoestrogens may be protective on breast tissue and other hormone dependent organs.

Topics: Aged; Anticarcinogenic Agents; Breast Neoplasms; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Genistein; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Receptors, Estrogen; Resveratrol; Selective Estrogen Receptor Modulators; Stilbenes

Epidemiological studies revealed that foodstuffs, in particular, soy foods containing isoflavonoid phytoestrogens may reduce the risk of some hormone-dependent disease such as not only postmenopausal symptoms but also certain(breast, prostate and colon) cancers and cardiovascular disease. This review introduces the metabolism of soybean isoflavonoids by human intestinal bacteria and the binding and gene-expression activity of the metabolites towards the human estrogen receptor(hER) alpha and beta. The dietary isoflavones(daidzin and genistin) in soybean were metabolized to equol and dihydrogenistein via daidzein and genistein, respectively. The metabolites bind more strongly to hER beta than hER alpha. The binding affinity of genistein is comparable that of 17 beta-estradiol. Equol induces transcription most strongly both with hER beta and hER alpha.

Topics: Bacteria; Chromans; Digestive System; Equol; Estrogens, Non-Steroidal; Female; Gene Expression; Genistein; Humans; Isoflavones; Myocardial Ischemia; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Receptors, Estrogen

Estrogen deficiency in the postmenopausal woman results in numerous symptomatic and asymptomatic manifestations, including vasomotor symptoms, osteoporosis, heart disease, bladder and vaginal symptoms, and cardiovascular disease. Estrogen replacement therapy is associated with amelioration of these problems but has attendant risks. A newer class of drugs, the selective estrogen receptor modulators, provides both estrogen agonist and antagonist properties, depending on the target tissue. This article discusses the mechanism by which selective estrogen receptor modulators may vary in their end-organ effects and reviews the clinical studies associated with these compounds. Phytoestrogens are widely used in the United States, but little information is available regarding their potential long-term effects.

Topics: Aged; Bone Density; Estrogen Antagonists; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Piperidines; Plant Preparations; Postmenopause; Raloxifene Hydrochloride; Receptors, Estrogen; Tamoxifen

Food phytestrogens and prevention of postmenopausal osteoporotic and cardiovascular disease. Phytestrogens are diphenolic compounds, widely found in plants and foods, with structural and biological estrogen-like similarities. Their anti-estrogenic effects are well known and studied due to the possibility to prevent some tumors such as breast and prostate cancer. In menopause they have an estrogenic-like action on lipidic and bone metabolism. Phytestrogens rich foods can positively affect the postmenopausal osteoporotic and cardiovascular pathology.

Topics: Aged; Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Food; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause

Topics: Cardiovascular Diseases; Complementary Therapies; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

Limited acceptable alternatives to hormone replacement therapy exist for use by postmenopausal women. This oversight within the biomedical community is of particular concern considering the increasing number of postmenopausal women and the current low use of hormone replacement therapy. In addition, contraindications to hormone replacement therapy and controversies regarding recommendations for use of hormone replacement therapy also exist. With the notable exception of the advances in prevention of osteoporosis, alternatives to estrogen for other aspects of the sequelae of hypoestrogenism or aging are limited. Furthermore, there is widespread use of complementary therapies among postmenopausal women despite a lack of data on efficacy or safety of such therapies. Increased research into alternatives to estrogen for menopausal women is of clinical, scientific, and health policy importance.

Topics: Antioxidants; Climacteric; Contraindications; Coronary Disease; Estrogen Replacement Therapy; Estrogens; Estrogens, Non-Steroidal; Female; Health Promotion; Humans; Isoflavones; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Progestins; Risk Factors; United States

Phyto-oestrogens have emerged from their esoteric role in animal husbandry following the hypothesis that the human Western diet is relatively deficient in these substances compared with societies where large amounts of plant foods and legumes are eaten. Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers, cardiovascular disease, brain function, alcohol abuse, osteoporosis and menopausal symptoms. Of the two main classes of these weak oestrogens, the isoflavones are under intensive investigation due to their high levels in soyabean. Like the 'anti-oestrogen' Tamoxifen, these seem to have oestrogenic effects in human subjects in the cardiovascular system and bone. Although previously only available from food, isoflavones are now being marketed in health-food supplements or drinks, and tablets may soon be available over the counter as 'natural' hormone-replacement therapy. In cancer, anti-oestrogenic effects are thought to be important, although genistein especially has been shown to induce wide-ranging anti-cancer effects in cell lines independent of any hormone-related influence. There are few indications of harmful effects at present, although possible proliferative effects have been reported. In infants, the effects of high levels in soya milk formulas are uncertain. The second group, lignans, have been less investigated despite their known antioestrogenic effects and more widespread occurrence in foods. Investigation of the possible benefits of phyto-oestrogens is hampered by lack of analytical standards and, hence, inadequate methods for the measurement of low levels in most foods. This problem may prove to be a major dilemma for regulatory authorities, clinicians and others wishing to advise the general public on whether these compounds really do have the health benefits attributed to them.

Topics: Coronary Disease; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Male; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Risk Factors

Calcium and vitamin D can significantly impact bone mineral and fracture risk in women. Unfortunately, calcium intakes in women are low and many elderly have poor vitamin D status. Supplementation with calcium (approximately 1000 mg) can reduce bone loss in premenopausal and late postmenopausal women, especially at sites that have a high cortical bone composition. Vitamin D supplementation slows bone loss and reduces fracture rates in late postmenopausal women. While an excess of nutrients such as sodium and protein potentially affect bone mineral through increased calcium excretion, phytoestrogens in soy foods may attenuate bone loss through estrogenlike activity. Weight-bearing physical activity may reduce the risk of osteoporosis in women by augmenting bone mineral during the early adult years and reducing the loss of bone following menopause. High-load activities, such as resistance training, appear to provide the best stimulus for enhancing bone mineral; however, repetitive activities, such as walking, may have a positive impact on bone mineral when performed at higher intensities. Irrespective of changes in bone mineral, physical activities that improve muscular strength, endurance, and balance may reduce fracture risk by reducing the risk of falling. The combined effect of physical activity and calcium supplementation on bone mineral needs further investigation.

Topics: Accidental Falls; Adult; Aged; Bone and Bones; Bone Density; Calcium; Calcium, Dietary; Dietary Proteins; Estrogens, Non-Steroidal; Exercise; Female; Fractures, Bone; Humans; Isoflavones; Minerals; Muscle Contraction; Nutritional Physiological Phenomena; Osteoporosis; Osteoporosis, Postmenopausal; Physical Endurance; Phytoestrogens; Plant Preparations; Plants; Postural Balance; Risk Factors; Sodium, Dietary; Vitamin D; Walking; Weight Lifting; Weight-Bearing

Epidemiological studies suggest that diets rich in phytoestrogens (plant estrogens), particularly soy and unrefined grain products, may be associated with low risk of breast and prostate cancer. It has also been proposed that dietary phytoestrogens could play a role in the prevention of other estrogen-related conditions, namely cardiovascular disease, menopausal symptoms and post-menopausal osteoporosis. However, there is no direct evidence for the beneficial effects of phytoestrogens in humans. All information is based on consumption of phytoestrogen-rich diets, and the causal relationship and the mechanisms of phytoestrogen action in humans still remain to be demonstrated. In addition, the possible adverse effects of phytoestrogens have not been evaluated. It is plausible that phytoestrogens, as any exogenous hormonally active agent, might also cause adverse effects in the endocrine system, i.e. act as endocrine disrupters.

Topics: Animals; Breast Neoplasms; Cardiovascular Diseases; Diet; Endocrine Glands; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Prostatic Neoplasms; Receptors, Estrogen

For most women, the menopause presents two sets of problems. First, most notice unpleasant symptoms such as hot flushes and vaginal dryness, but second, there are long-term sequelae arising from oestrogen deficiency. The main long-term problems are an increased risk of bone loss and cardiovascular disease. This chapter will focus on the role of phytoestrogens in alleviating menopausal symptoms. Studies to date would suggest that phytoestrogenic products may help around two-thirds of women to cope with menopausal symptoms such as hot flushes, but there is little evidence that these products will help with vaginal dryness. It seems probable that these products lower cholesterol and therefore cardiovascular risk; however, it is important that women who use such products to alleviate menopausal symptoms have a bone density performed every 2 or 3 years to assess their risk of osteoporosis.

Topics: Asia; Cardiovascular Diseases; Diet; Estrogens, Non-Steroidal; Female; Hot Flashes; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Randomized Controlled Trials as Topic

Phytoestrogens are defined as naturally occurring plant compounds that are structurally and functionally similar to 17 beta-estradiol or that produce estrogenic effects. The commonest sources are cereals, legumes and grasses. Isoflavones are the most highly investigated subgroup of phytoestrogens. They are attenuated estrogens and behave both in vivo and in vitro as agonists and antagonists. The highest concentrations are found in soy beans and legumes. The relative potencies of isoflavones as compared to estradiol are small but they can exhibit bioactivity when tested in high concentrations. A high dietary intake of phytoestrogens was first noted to be associated with a decreased incidence of certain diseases. This epidemiological information was obtained primarily from studying Asian populations. Soy consumption is highest in Japan, where urinary levels of phytoestrogen metabolites are extremely high, and where there are lower rates of so-called 'Western' diseases, namely breast, endometrial, colon and prostatic cancers as well as atherosclerotic disease. These observations have prompted extensive research, which has demonstrated the varying degrees of estrogenicity of these phytoestrogen compounds. This article provides an epidemiological background to phytoestrogens, a brief description of their composition and biochemistry, and an overview of the literature to date on phytoestrogens with an emphasis on relief of menopausal symptoms.

Topics: Cardiovascular Diseases; Edible Grain; Estrogens, Non-Steroidal; Fabaceae; Female; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Poaceae

Women are exposed to xenobiotic estrogens at least to the same extent as men. These estrogenic chemicals are either from plant material in the diet (phytoestrogens) or from industrial sources. Mainly industrially derived environmental estrogens may accumulate within the food chain and persist in human adipose tissue. In contrast, phytoestrogens do not bioaccumulate and are rapidly excreted in urine. The phytoestrogens probably represent the source of most extensive exposure for humans. Epidemiological evidence suggests that diets rich in phytoestrogens are associated with reduced incidences of cardiovascular disease, breast cancer, prostate cancer and osteoporosis. The numerous bioactivities (other than just estrogenicity) of phytoestrogens and related dietary compounds make it difficult to single out the mechanisms mediating such protective effects. The possibility that the newly discovered estrogen receptor beta may be an important modulator of phytoestrogen action is opening up new lines of research. While the evidence suggests that phytoestrogens may be of positive relevance to postmenopausal women, indications that exposure of women to industrially derived xenobiotic estrogens provides risks to health remain unproven. Further work is necessary to clarify the relative importance of 'xenobiotic' estrogens to human health, but it must be emphasized that the estrogenic potency of all the xenobiotic estrogens is very low compared with that of endogenous estrogens.

Topics: Breast Neoplasms; Cardiovascular Diseases; Diet; Environmental Exposure; Environmental Pollutants; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Receptors, Estrogen; Risk Factors

The evidence that natural isoflavones protect against several chronic diseases is both observational and experimental. In humans, epidemiologic findings clearly show a higher incidence of some common types of cancer (i.e., breast, prostate, and colon) and of coronary heart diseases in Western populations exposed to limited amounts of soybean isoflavones (i.e., genistein, daidzein) in the diet. Further evidence for cancer and cardiac protection and antiatherogenic effects resulting from soybean isoflavones administration has been noted in various experimental animal models. Isoflavones may also prevent postmenopausal bone loss and osteoporosis. In fact, genistein has been reported to be as active as estrogens in maintaining bone mass in ovariectomized rats. Moreover, the synthetic isoflavone derivative ipriflavone is able to reduce bone loss in various types of animal models of experimental osteoporosis providing a rationale on its use in the prevention and treatment of postmenopausal and senile osteoporosis in humans. The mechanism through which isoflavones may exert the above-mentioned effects seems to depend, at least in part, on their mixed estrogen agonist-antagonist properties. An alternative hypothetical mechanism could derive from other biochemical actions of isoflavones such as inhibition of enzymatic activity, in particular protein kinases, or activation of an "orphan" receptor distinct from the estrogen type I receptor.

Topics: Animals; Coronary Disease; Diet; Disease Models, Animal; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Receptors, Estrogen

To review the sources, metabolism, potencies, and clinical effects of phytoestrogens on humans.. The MEDLINE data base for the years 1980-1995 and reference lists of published articles were searched for relevant English-language articles concerning phytoestrogens, soy products, and diets with high-phytoestrogen content.. We identified 861 articles as being relevant. Human cell line studies, human epidemiologic studies (case-control or cohort), randomized trials, and review articles were included. Animal studies regarding phytoestrogens were included when no human data were available concerning an important clinical area.. Included were studies containing information considered pertinent to clinical practice in the areas of growth and development, menopause, cancer, and cardiovascular disease. When findings varied, those presented in this study reflect consensus. All studies concurred that phytoestrogens are biologically active in humans or animals. These compounds inhibit the growth of different cancer cell lines in cell culture and animal models. Human epidemiologic evidence supports the hypothesis that phytoestrogens inhibit cancer formation and growth in humans. Foods containing phytoestrogens reduce cholesterol levels in humans, and cell line, animal, and human data show benefit in treating osteoporosis.. This review suggests that phytoestrogens are among the dietary factors affording protection against cancer and heart disease in vegetarians. With this epidemiologic and cell line evidence, intervention studies are now an appropriate consideration to assess the clinical effects of phytoestrogens because of the potentially important health benefits associated with the consumption of foods containing these compounds.

Topics: Animals; Cardiovascular Diseases; Climacteric; Diet; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Lignans; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Tumor Cells, Cultured

The wide distribution of plant estrogens or 'phytoestrogens' in cereals, vegetables and medicinal plants raises questions concerning the possible health risks and benefits associated with their consumption. In this article, we provide a synopsis of the literature relating principally to the clinical effects of phytoestrogens on the diseases associated with ageing. The sources, metabolism and properties of the different phytoestrogens are also discussed. The studies included were primarily restricted to those with data pertinent to clinical practice. Our contention is that phytoestrogens are at least part of the reason why vegetarians and Asian populations have a low rate of cancer and heart disease.

Topics: Adult; Aged; Climacteric; Colorectal Neoplasms; Coronary Disease; Cross-Cultural Comparison; Diet, Vegetarian; Estrogens, Non-Steroidal; Feeding Behavior; Female; Glycine max; Humans; Isoflavones; Male; Middle Aged; Neoplasms; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations

Postmenopausal estrogen depletion is a major contributing factor to bone loss. Soy isoflavones have variable effects on the prevention of postmenopausal bone loss, which is possibly related to the specific isoflavone content or the variable equol-producing capacity of individuals.. We aimed to determine the effects of the content of isoflavones in a soy supplement and the equol-producing ability of the individual on postmenopausal bone calcium retention.. The study was a blinded, randomized, crossover intervention trial in 24 postmenopausal women who were prescreened for their ability to convert daidzein to equol. Women were equilibrated with (41)Ca before the intervention. Interventions were 5 soy isoflavone oral supplements (2 doses of a genistein-rich soy supplement and 3 doses of mixed isoflavones in various proportions) and a bisphosphonate (risedronate). Each intervention was given sequentially for 50 d followed by a 50-d washout period. The percentage of bone calcium retention was determined from the change in urinary (41)Ca:calcium.. Interventions that ranged from 52 to 220 mg total isoflavones/d increased bone calcium retention between 3.4% and 7.6% (P < 0.05), which was a moderate effect compared with that of risedronate at 15.3% (95% CI: 7.1%, 22.7%; P = 0.0014). The most-effective soy intervention delivered 105.23 mg total isoflavones/d as genistein, daidzein, and glycitein in their natural ratios and increased bone calcium retention by 7.6% (95% CI: 4.9%, 10.2%; P < 0.0001). Genistein, at 52.85 mg/d, increased bone calcium retention by 3.4% (95% CI: 0.5%, 6.2%; P = 0.029); but there was no benefit at higher amounts (113.52 mg/d). There was no difference (P = 0.5) in bone calcium retention between equol producers and nonproducers.. Soy isoflavones, although not as potent as risedronate, are effective bone-preserving agents in postmenopausal women regardless of their equol-producing status, and mixed isoflavones in their natural ratios are more effective than enriched genistein. This trial was registered at clinicaltrials.gov as NCT00244907.

Topics: Administration, Oral; Aged; Bone and Bones; Calcium; Cross-Over Studies; Dietary Supplements; Dose-Response Relationship, Drug; Equol; Female; Genistein; Glycine max; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Postmenopause; Risedronic Acid

The treatment of 300-mg/day isoflavones (aglycone equivalents) (172.5 mg genistein + 127.5 mg daidzein) for 2 years failed to prevent lumbar spine and total proximal femur bone mineral density (BMD) from declining as compared with the placebo group in a randomized, double-blind, two-arm designed study enrolling 431 postmenopausal women 45-65 years old.. This study evaluated the effects of soy isoflavones on bone metabolism in postmenopausal women.. Four hundred and thirty-one women, aged 45-65 years, orally consumed 300-mg/day isoflavones (aglycone equivalents) or a placebo for 2 years in a parallel group, randomized, double-blind, two-arm study. Each participant also ingested 600 mg of calcium and 125 IU of vitamin D(3) per day. The BMD of the lumbar spine and total proximal femur were measured using dual-energy X-ray absorptiometry at baseline and every half-year thereafter. Serum bone-specific alkaline phosphatase, urinary N-telopeptide of type 1 collagen/creatinine, and other safety assessments were examined regularly.. Two hundred out of 217 subjects in the isoflavone group and 199 out of 214 cases in placebo group completed the treatment. Serum concentrations of isoflavone metabolites, genistein and daidzein, of the intervention group were remarkably elevated following intake of isoflavones (p < 0.001). However, differences in the mean percentage changes of BMD throughout the treatment period were not statistically significant (lumbar spine, p = 0.42; total femur, p = 0.39) between the isoflavone and placebo groups, according to the generalized estimating equation (GEE) method. A significant time trend of bone loss was observed at both sites as assessed by the GEE method following repeated measurement of BMD (p < 0.001). Differences in bone marker levels were not significant between the two treatment groups.. Treatment with 300-mg/day isoflavones (aglycone equivalents) failed to prevent a decline in BMD in the lumbar spine or total femur compared with the placebo group.

Topics: Absorptiometry, Photon; Bone Density; Bone Density Conservation Agents; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Femur; Genistein; Humans; Isoflavones; Lumbar Vertebrae; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Placebos; Treatment Outcome

S-equol, a metabolite of the soy isoflavone daidzein, has been proposed as having potential for relief of menopausal symptoms. This study compared the efficacy of the natural S-equol supplement, SE5-OH, with isoflavones for relieving hot flashes and other menopausal symptoms.. An 8-week randomized, double-blind, active comparator trial with SE5-OH was conducted in postmenopausal women (aged 45-65 years), who experienced ≥5 hot flashes/day. Participants (n=102) were assigned to one of four treatment groups: 10 (n=24), 20 (n=27), or 40 (n=25) mg S-equol/day or soy isoflavones (n=26). Participants recorded their hot flash frequency and rated their menopause symptom severity.. Reductions in hot flash frequency at week 8 were similar for all treatment groups. However, based on analyses of the cumulative effect for the 8-week period, 40 mg/day S-equol had a greater reduction of hot flash frequency compared to isoflavones (p=0.021). A subgroup analysis further indicated that for subjects with >8 hot flashes/day at baseline, 20 and 40 mg/day S-equol were superior to isoflavones in reducing hot flash frequency (p=0.045 and p=0.001, respectively). In addition, 10 and 20 mg/day S-equol improved muscle and joint pain score compared with isoflavones (p=0.003 and p=0.005, respectively).. S-equol, 10 mg/day, appears to be as effective as soy isoflavones at reducing hot flash frequency and more effective for relieving muscle and joint pain in postmenopausal women. S-equol, ≥20 mg/day, alleviates hot flashes to a greater extent than soy isoflavones in those women who experience >8 hot flashes/day.

Topics: Aged; Dietary Supplements; Double-Blind Method; Female; Hot Flashes; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Postmenopause; Soybean Proteins; Treatment Outcome; United States

Concerns regarding the risk of estrogen replacement have resulted in a significant increase in the use of soy products by menopausal women who, despite the lack of evidence of the efficacy of such products, seek alternatives to menopausal hormone therapy. Our goal was to determine the efficacy of soy isoflavone tablets in preventing bone loss and menopausal symptoms.. The study design was a single-center, randomized, placebo-controlled, double-blind clinical trial conducted from July 1, 2004, through March 31, 2009. Women aged 45 to 60 years within 5 years of menopause and with a bone mineral density T score of -2.0 or higher in the lumbar spine or total hip were randomly assigned, in equal proportions, to receive daily soy isoflavone tablets, 200 mg, or placebo. The primary outcome was changes in bone mineral density in the lumbar spine, total hip, and femoral neck at the 2-year follow-up. Secondary outcomes included changes in menopausal symptoms, vaginal cytologic characteristics, N -telopeptide of type I bone collagen, lipids, and thyroid function.. After 2 years, no significant differences were found between the participants receiving soy tablets (n = 122) and those receiving placebo (n = 126) regarding changes in bone mineral density in the spine (-2.0% and -2.3%, respectively), the total hip (-1.2% and -1.4%, respectively), or the femoral neck (-2.2% and -2.1%, respectively). A significantly larger proportion of participants in the soy group experienced hot flashes and constipation compared with the control group. No significant differences were found between groups in other outcomes.. In this population, the daily administration of tablets containing 200 mg of soy isoflavones for 2 years did not prevent bone loss or menopausal symptoms.. clinicaltrials.gov Identifier: NCT00076050.

Topics: Dietary Supplements; Double-Blind Method; Estrogen Replacement Therapy; Female; Genistein; Glycine max; Hot Flashes; Humans; Isoflavones; Logistic Models; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy

To investigate the therapeutic effects of ipriflavone on postmenopausal syndrome and osteoporosis in women.. A randomized and double-blind study was conducted. Sixty postmenopausal women with osteoporosis were chosen and they were randomly divided into three groups: Treatment group I was given oral compound calcium acid chelate and Vitamin AD guttate; treatment group II was given oral compound calcium acid chelate, Vitamin AD guttate and ipriflavone; Control group was given placebo and compound calcium acid chelate. The postmenopausal syndrome, bone mineral density (BMD), and bone biochemical markers were assessed 6 and 12 months after the treatment.. In treatment group II, hot flush and ostalgia syndromes were dramatically relieved, BMD and serum calcium level increased markedly and alkaline phosphatase, parathyroid hormone and tartrate-resistant acid phosphatase decreased markedly, comparing with treatment group I and control group (p < 0.05).. Ipriflavone could inhibit bone resorption and promote bone formation. It is an effective drug for the prevention and treatment to menopausal syndrome and osteoporosis. Ipriflavone could be used as a supplement to estrogen replacement treatment.

Topics: Acid Phosphatase; Adult; Alanine Transaminase; Bone Density; Bone Remodeling; Calcium; Double-Blind Method; Female; Humans; Isoenzymes; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Parathyroid Hormone; Phosphorus; Phytoestrogens; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase

Reduction of ovarian estrogen secretion at menopause increases net bone resorption and leads to bone loss. Isoflavones have been reported to protect bone from estrogen deficiency, but their modest effects on bone resorption have been difficult to measure with traditional analytical methods.. In this randomized-order, crossover, blinded trial in 11 healthy postmenopausal women, we compared four commercial sources of isoflavones from soy cotyledon, soy germ, kudzu, and red clover and a positive control of oral 1 mg estradiol combined with 2.5 mg medroxyprogesterone or 5 mg/d oral risedronate (Actonel) for their antiresorptive effects on bone using novel (41)Ca methodology.. Risedronate and estrogen plus progesterone decreased net bone resorption measured by urinary (41)Ca by 22 and 24%, respectively (P < 0.0001). Despite serum isoflavone profiles indicating bioavailability of the phytoestrogens, only soy isoflavones from the cotyledon and germ significantly decreased net bone resorption by 9% (P = 0.0002) and 5% (P = 0.03), respectively. Calcium absorption and biochemical markers of bone turnover were not influenced by interventions.. Dietary supplements containing genistein-like isoflavones demonstrated a significant but modest ability to suppress net bone resorption in postmenopausal women at the doses supplied in this study over a 50-d intervention period.

Topics: Aged; Analysis of Variance; Bone Density Conservation Agents; Bone Resorption; Calcium; Calcium Radioisotopes; Cotyledon; Cross-Over Studies; Dietary Supplements; Estradiol; Etidronic Acid; Female; Genistein; Glycine max; Humans; Isoflavones; Linear Models; Medroxyprogesterone; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Pueraria; Risedronic Acid; Single-Blind Method; Treatment Outcome; Trifolium

Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain.. We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy.. The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year.. Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses.. Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers.. After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups.. After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.

Topics: Aged; Biomarkers; Bone Density; Bone Diseases, Metabolic; BRCA1 Protein; BRCA2 Protein; Breast Neoplasms; Double-Blind Method; Endometrium; Female; Genistein; Humans; Mammography; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; RNA, Messenger; Sister Chromatid Exchange

Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women.. This clinical trial of before-after type was carried out on 15 women 45-64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed.. Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant.. In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.

Topics: Alkaline Phosphatase; Amino Acids; Bone Remodeling; Collagen; Collagen Type I; Female; Glycine max; Humans; Insulin-Like Growth Factor Binding Protein 3; Iran; Menopause; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Peptides; Phytoestrogens; Soybean Proteins

High phytoestrogen intake among Asian women has been thought to explain the low risk of bone fractures in these populations. In a randomized placebo-controlled trial we studied the effects of isoflavonoids on urinary output of the N-terminal cross-linked telopeptide of type I collagen, pyridinoline (Pyr), and deoxypyridinoline (Dpyr) (bone resorption markers) and serum levels of bone-specific alkaline phosphatase and N-terminal and C-terminal procollagen type I (bone formation markers). Fifty-five postmenopausal women with a history of breast cancer used phytoestrogens (114 mg of isoflavonoids) or placebo tablets daily for 3 months; the treatment regimens were then crossed over after a 2-month washout period. The markers were measured before and on the last day of each treatment period. Bone resorption was reduced during phytoestrogen use, as reflected in falls in the urinary output of Pyr (9%; P = 0.001) and Dpyr (5%; P = 0.008). Compared with the placebo group, the fall in Dpyr was significant (P = 0.022) and the falls in Pyr (P = 0.084) and N-terminal cross-linked telopeptide of type I collagen (P = 0.082) showed a trend toward significance. Bone formation markers were not affected by this regimen. Thus, isoflavonoid-induced inhibition of bone resorption may contribute to the low risk of osteoporosis in Asian women.

Topics: Adult; Aged; Bone Remodeling; Breast Neoplasms; Cross-Over Studies; Female; Hot Flashes; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Risk Factors

To compare the effect of a soy rich diet and hormone replacement therapy (HRT) on the main biomarkers of bone turnover and bone mineral density (BMD) at postmenopausal age.. 187 healthy asymptomatic postmenopausal women, aged 39-60, were recruited and randomized into a soy rich diet group, a HRT group, and a control group. Bone biomarkers and BMD were evaluated at baseline and after 6 months at the end of the study.. Diet is not as effective as HRT in reducing the postmenopausal turnover; however diet stimulates bone osteoblastic activity, as evidenced by significant increase in osteocalcin concentrations. BMD decreases significantly only in the control group, but not in the intervention groups.. Our data suggest that soy products could be effective in reducing the risk of osteoporosis in asymptomatic postmenopausal women, but our findings should be confirmed before recommending the diet as a valid alternative to HRT.

Topics: Adult; Biomarkers; Bone Density; Bone Remodeling; Collagen; Collagen Type I; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Hydroxyproline; Isoflavones; Middle Aged; Osteocalcin; Osteoporosis, Postmenopausal; Peptides; Phytoestrogens; Phytotherapy; Plant Preparations

To assess the pattern of biochemical markers of bone metabolism and vertebral bone mineral density in early postmenopausal women treated with combined ipriflavone and low dose conjugated estrogens.. Bone biochemical markers and vertebral bone density were evaluated in a longitudinal, comparative, 2 year study conducted in postmenopausal women treated with sole calcium supplementation (500 mg/day), or with either ipriflavone (IP) at the standard dose (600 mg/day) plus the same calcium dose, low dose conjugated estrogens (CE) (0.3 mg/day) plus calcium, or low dose IP (400 mg/day) plus low dose CE (0.3 mg/day) plus calcium. The results were analyzed by repeated measures analysis of variance, as appropriate.. No modifications of both urinary excretion of hydroxyproline and plasma osteocalcin levels were observed in calcium and in CE-treated women, while vertebral bone density significantly decreased (P < 0.0001) in both groups. In IP or IP + CE-treated women, plasma osteocalcin did not show any modification, while urinary hydroxyproline showed a significant (P < 0.05) decrease, that paralleled a significant (P < 0.05) increase in vertebral bone density.. Postmenopausal IP administration, at the standard dose of 600 mg/day, can prevent the increase in bone turnover and the decrease in bone density that follow ovarian failure. The same effect can be obtained with the combined administration of low dose (400 mg/day) IP with low dose (0.3 mg/day) CE.

Topics: Administration, Oral; Adult; Bone Density; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Longitudinal Studies; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Time Factors

Estrogen deficiency is the leading cause of postmenopausal osteoporosis(PMOP) and phytoestrogens soy isoflavones (SI) have been shown to improve PMOP. Equol (Eq), an in vivo metabolite of phytoestrogens soy isoflavones (SI), has a more stable structure and stronger biological activity than its parent compound and has the greatest estrogenic activity. However, there are few studies on the therapeutic effect of Eq on PMOP.. To explore the therapeutic effect and mechanisms of Eq on POMP.. Osteoblast-like cells ROS1728 were cultured with different doses of Eq, estradiol (E2), separately. The effect of Eq on the proliferation, apoptosis, cell cycle of osteoblasts were detected by CCK-8 and flow cytometry, and the expression of OPG/RANK/RANKL signaling pathway of osteoblasts was detected by Quantitative real-time PCR (qRT-PCR) and Western blot (WB), and RNA silencing technology were carried out to explore the receptors through which Eq plays a role. Then PMOP rat model was established and treated by Eq or E2 to further verification of the effect and mechanism of Eq on PMOP.. Eq promoted the proliferation and inhibited the apoptosis of osteoblasts and increased the proportion of osteoblasts in the S phase and G2/M phase in a dose-dependent manner. Mechanistically, Eq treatment upregulated the expression of OPG and OPG/RANKL ratio in osteoblasts and this regulatory effect was mainly mediated through the ERβ receptor. Furthermore, in vivo study, Eq improved microstructure and BMD of the femur of PMOP rat model, which imitated the osteoprotective effect of E2. Moreover, the Eq or E2 treatment increased serum levels of Ca, 1,25(OH)2D3, bone Gla-protein(BGP), and Type I procollagen (PC1), and reduced serum levels of phosphorus (P), parathyroid hormone(PTH), pyridinol (PYD), tartrate-resistant acid phosphatase (TRAP) and urinary level of deoxypyridinoline (DPD) in the treatment OVX group compared with the untreated OVX group. Meanwhile, Eq or E2 markedly induced the mRNA and protein expression of OPG and OPG/RANKL ratio.. Eq can combine with ERβ and exert a protective effect on PMOP by upregulating OPG/RANKL pathway.

Topics: Animals; Equol; Estrogen Receptor beta; Female; Humans; Osteoblasts; Osteoporosis, Postmenopausal; Osteoprotegerin; Phytoestrogens; RANK Ligand; Rats

Black tea and Nonileaf are among the dietary compounds that can benefit patients with bone resorption disorders. Their bone regeneration effects and their mechanisms were studied in estrogen-deficient rats.. Noni leaves (three doses) and black tea water extracts were fed to ovariectomized rats for 4 mo, and their effects (analyzed via mechanical measurements, micro-computed tomography scan, and reverse transcriptase polymerase chain reaction mRNA) were compared with Remifemin (a commercial phytoestrogen product from black cohosh).. The water extracts (dose-dependently for noni leaves) increased bone regeneration biomarker (runt-related transcription factor 2, bone morphogenetic protein 2, osteoprotegerin, estrogen receptor 1 [ESR1], collagen type I alpha 1A) expressions and reduced the inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, nuclear factor [NF]-κB, and receptor activator of NF-κB ligand) mRNA expressions/levels in the rats. The extracts also improved bone physical and mechanical properties. The extracts demonstrated bone regeneration through improving bone size and structure, bone mechanical properties (strength and flexibility), and bone mineralization and density.. The catechin-rich extract favored bone regeneration and suppressed bone resorption. The mechanisms involved enhancing osteoblast generation and survival, inhibiting osteoclast growth and activities, suppressing inflammation, improving bone collagen synthesis and upregulating ESR1 expression to augment phytoestrogenic effects. Estrogen deficiency bone loss and all extracts studied (best effect from Morinda leaf at 300 mg/kg body weight) mitigated the loss, indicating benefits for the aged and menopausal women.

Topics: Animals; Biomarkers; Bone and Bones; Bone Density; Bone Regeneration; Bone Resorption; Camellia sinensis; Collagen; Estrogen Receptor alpha; Estrogens; Female; Humans; Inflammation; Morinda; Osteoblasts; Osteoclasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Plant Leaves; Rats, Sprague-Dawley; Tea

Recent studies have shown that immune system plays a major role in pathophysiology of postmenopausal osteoporosis. Previously we have shown that phytoestrogens like daidzein and medicarpin exhibit immunoprotective effects, by virtue of which they alleviate bone loss. With this background, methoxyisoflavones like formononetin (formo) and isoformononetin (isoformo) that have been studied for preventing bone loss in ovariectomized rats were tested for their immunomodulatory effects in estrogen-deficient bone loss mice model.. Adult Balb/c mice (N = 8/group) were given oral dose of formo and isoformo at 10 mg/kg body weight, post ovariectomy (Ovx) daily for 6 weeks. Animals were autopsied and long bones were harvested to study bone microarchitecture. Peripheral blood mononuclear cells were isolated for fluorescence-activated cell sorting and RNA analysis. Serum was collected for enzyme-linked immunosorbent assay.. It was observed that formo and isoformo treatment to Ovx mice led to significant restoration of Ovx-induced deterioration of trabecular microarchitecture. Pro-osteoclastogenic subset Th17 and B cells were decreased in formo/isoformo-treated Ovx mice in comparison with vehicle-treated Ovx group. Formo and isoformo treatment to Ovx mice also led to decreased expression of Th17 diffentiation factors and promoted T-regulatory cell differentiation. Formo was more effective in enhancing the FOXP3 expression compared with isoformo. IL-17A-induced osteoclastogenesis and inhibition of osteoblast apoptosis were also suppressed by formo and isoformo treatment, with formo having a more potent effect.. Our study demonstrates the immunomodulatory activity of methoxyisoflavones, formo, and isoformo, which translate into improved skeletal parameters, thereby preventing Ovx-induced bone loss.

Topics: Animals; Apoptosis; B-Lymphocytes; Cell Differentiation; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; Female; Humans; Isoflavones; Leukocytes, Mononuclear; Lymphopoiesis; Menopause; Mice; Mice, Inbred BALB C; Osteoblasts; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Th17 Cells

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms.

Topics: Animals; Animals, Outbred Strains; Anti-Obesity Agents; Biomarkers; Bone Density Conservation Agents; Dietary Supplements; Disease Models, Animal; Fatty Liver; Female; Fruit; Humans; Hyperlipidemias; Lipid Regulating Agents; Lythraceae; Mice; Obesity; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Extracts; Plant Leaves; Specific Pathogen-Free Organisms; Trifolium

Topics: Bone and Bones; Female; Humans; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens

Since the in vitro and in vivo anti-osteoporotic effects of Pueraria mirifica (PM) in rodents have been verified, its activity in menopausal monkeys was evaluated as required before it can be applicable for human use. In this study, postmenopausal osteoporotic monkeys were divided into two groups (five per group), and fed daily with standard diet alone (PMP0 group) or diet mixed with 1000 mg/kg body weight (BW) of PM powder (PMP1000 group) for 16 months. Every 2 months, the bone mineral density (BMD), bone mineral content (BMC) and bone geometry parameters (cortical area and thickness and periosteal and endosteal circumference) at the distal radius and proximal tibia were determined using peripheral quantitative computed tomography together with plasma and urinary bone markers. Compared with the baseline (month 0) values, the cortical, but not trabecular, BMDs and BMCs and the cortical area and thickness at the metaphysis and diaphysis of the radius and tibia of the PMP0 group continuously decreased during the 16-month study period. In contrast, PMP1000 treatment ameliorated the bone loss mainly at the cortical diaphysis by decreasing bone turnover, as indicated by the lowered plasma bone-specific alkaline phosphatase and osteocalcin levels. Generally, changes in the cortical bone geometry were in the opposite direction to the cortical bone mass after PMP1000 treatment. This study indicated that postmenopausal monkeys continuously lose their cortical bone compartment, and they have a higher possibility for long bone fractures. Oral PMP treatment could improve both the bone quantity (BMC and BMD) and quality (bone geometry).

Topics: Animals; Biomarkers; Bone and Bones; Bone Density; Bone Density Conservation Agents; Cortical Bone; Dietary Supplements; Estrogen Replacement Therapy; Female; Humans; Macaca fascicularis; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Extracts; Plant Tubers; Postmenopause; Pueraria; Random Allocation; Thailand

Obesity emerged as the major risk factor for metabolic syndrome. Postmenopausal women are more prone to develop obesity than premenopausal women. The absence of safe and effective conventional treatments for postmenopausal obesity has changed the focus to natural products as alternative remedy. We investigated the molecular basis of the effect of soy isoflavones (SIFs) on hypertriglyceridemia and hepatic steatosis in an animal model of postmenopausal obesity. Ovariectomized (OVX) and sham-operated Wistar rats were fed with high-fat diet (HFD) and normal diet for 8 weeks with and without SIF extract (150mg/kg body weight/day). Both OVX and HFD per se and when combined caused hypertriglyceridemia, hypercholesterolemia and atherogenic lipid profile. Proteomic studies revealed that both OVX and HFD caused overexpression of hepatic lipogenic proteins, such as LXR, SREBP1, PPARγ, ACC and FAS, in association with reduced expression of lipolytic proteins, such as FXR, PPARα, insig2 and SHP. Histological analysis showed fat accumulation and morphological abnormalities in the liver of OVX and HFD rats. All these metabolic derangements were further augmented when OVX was followed by HFD. In conclusion, these findings suggest that there was a synergism in the development of deranged lipid metabolism with the coexistence of postmenopausal state and the intake of fat-rich diet. SIF extract markedly alleviated the derangement of lipid metabolism suggesting the use of this natural phytoestrogen as a strategy for relieving dyslipidemia and hepatic steatosis associated with the postmenopausal women.

Topics: Animals; Biomarkers; Diet, High-Fat; Dietary Supplements; Disease Models, Animal; Dyslipidemias; Female; Humans; Hypertriglyceridemia; Isoflavones; Lipid Metabolism; Liver; Metabolic Syndrome; Non-alcoholic Fatty Liver Disease; Obesity; Organ Size; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Random Allocation; Rats, Wistar; Soy Foods

Post-menopausal osteoporosis has long been treated and prevented by estrogen replacement therapy (ERT). Despite its effectiveness, ERT is associated with serious adverse effects. Labisia pumila var. alata (LP) is a herb with potential as an alternative agent to ERT due to its phytoestrogenic, antioxidative and anti-inflammatory effects on bone. This study aimed to determine the effects of LP supplementation on bone biomechanical strength of postmenopausal osteoporosis rat model.. Ninety-six female Sprague-Dawley rats aged 4 to 5 months old were randomly divided into six groups; six rats in the baseline group (BL) and eighteen rats in each group of; Sham- operated (Sham), ovariectomised control (OVXC) and ovariectomised with daily oral gavages of Premarin at 64.5 μg/kg (ERT), LP at 20 mg/kg (LP20) and LP at 100 mg/kg (LP100) respectively. These groups were subdivided into three, six and nine weeks of treatment periods. Rats in BL group were euthanized before the start of the study, while other rats were euthanized after completion of their treatments. Femora were dissected out for biomechanical strength analysis using Instron Universal Model 5848 Micro Tester.. OVXC group showed deterioration in the bone biomechanical strength with time. Both ERT and LP supplemented rats showed improvements in bone strength parameters such as maximum load, displacement, stiffness, stress, and Young Modulus. The most improved bone strength was seen in rats given LP at the dose of 100 mg/kg for nine weeks.. LP supplementation at 100 mg/kg was more effective than ERT in reversing ovariectomy-induced bone biomechanical changes.

Topics: Animals; Biomechanical Phenomena; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Femur; Humans; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Phytotherapy; Plant Extracts; Primulaceae; Rats, Sprague-Dawley; Stress, Mechanical

several studies have investigated the relationship between the estrogen receptor (ER) gene polymorphisms and the efficacy of estrogen replacement therapy in postmenopausal osteoporosis. However, the association of ER polymorphisms with the effects of dietary phytoestrogens on bone metabolism has not yet been reported. This study explores the possibility that ER alpha subtype (ERα) gene polymorphisms are involved in the effects of dietary phytoestrogens on bone mineral density (BMD) in postmenopausal women.. a total of 301 postmenopausal southern Chinese women were enrolled. Dietary phytoestrogen intake was evaluated using a food frequency questionnaire. ERα polymorphisms were examined with restriction fragment length polymorphism at the polymorphic PvuII and XbaI sites within intron 1. Dual-energy X-ray absorptiometry scans were performed to determine the BMD of the lumbar spine and hip.. the positive association of the lumbar spine BMD with dietary phytoestrogen intake was maintained only in groups with pp or xx genotypes (p < 0.05) and disappeared in groups with other genotypes. A positive association of the hip BMD with dietary phytoestrogen intake was observed only in the xx genotype group (p < 0.05).. the association of the dietary phytoestrogen intake and BMD in southern Chinese postmenopausal women varied with ERα gene polymorphisms.

Topics: Absorptiometry, Photon; Aged; Alleles; Bone and Bones; Bone Density; Bone Density Conservation Agents; China; Cross-Sectional Studies; Diet; Estrogen Receptor alpha; Female; Genetic Association Studies; Hip; Humans; Introns; Middle Aged; Nutrition Surveys; Osteoporosis, Postmenopausal; Phytoestrogens; Polymorphism, Restriction Fragment Length

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-β1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

Topics: Animals; Antioxidants; Biomarkers; Bone Density; Bone Density Conservation Agents; Dietary Supplements; Disease Models, Animal; Endometrial Hyperplasia; Endometrium; Estrogen Replacement Therapy; Female; Femur; Humans; Osteoporosis, Postmenopausal; Osteoprotegerin; Phytoestrogens; Random Allocation; RANK Ligand; Rats; Rats, Wistar; Resveratrol; Stilbenes; Time Factors

In this study, we investigated the synergistic effects of daidzein (Dz) and kiwifruit on bone and equol production in ovariectomised (OVX) rats. Female Sprague-Dawley rats were randomly assigned to one of five groups: sham operated, OVX control, OVX fed 0.1% Dz-supplemented diet (OVX + Dz), OVX fed 0.1% Dz and green kiwifruit (GRK)-supplemented diet (OVX + Dz + GRK) and OVX fed 0.1% Dz and gold kiwifruit (GOK)-supplemented diet (OVX + Dz + GOK). There were no significant differences in whole body and femur bone mineral density (BMD) among groups at week 8. BMD in the OVX group significantly decreased at week 8; however, BMD in the OVX + Dz + GRK was not significantly different from baseline in the end of the study. However, supplementation with kiwifruit did not affect urinary equol concentrations, urinary ratios of equol to Dz and the composition of caecal microbiota. These results suggest that the combination of Dz and GRK may slightly reduce bone loss caused by oestrogen deficiency but does not affect equol production.

Topics: Actinidia; Animals; Bone Density; Cecum; Dietary Supplements; Drug Synergism; Equol; Female; Fruit; Humans; Isoflavones; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations; Rats; Rats, Sprague-Dawley

Estrogen deficiency in menopausal women is the main cause of osteoporosis. Phytoestrogen could be a suitable candidate for treatment of post-menopausal osteoporosis. Recent studies showed that S. chinensis contains several lignans, which may be phytoestrogen. In this study, we investigated the ameliorative effects of S. chinensis on post-menopausal osteoporosis. 30% ethanol extract of S. chinensis (SC) was administered orally for 6 weeks after 7 weeks of ovariectomized-induced osteoporosis. Bone mineral density was significantly increased following increased serum osteocalcin levels by SC treatment. Histological analysis showed that SC reduced the increased growth plate of the epiphyseal plate in femur. In addition, pores within bone marrow cells filling the lateral and medial epicondyle were decreased. Serum estradiol concentration was significantly increased in the SC-treated group. The expressions of estrogen receptor-α and -β were increased in uterus and MCF-7 breast cancer cells by SC treatment. And two transcriptions of proto-oncogenes, c-fos and c-Jun, were suppressed by treatment of SC. From these data, we propose that S. chinensis attenuates post-menopausal osteoporosis with its phytoestrogenic effects. S. chinensis may have the potential to be used as an alternative for treatment of osteoporosis.

Topics: Administration, Oral; Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Urea Nitrogen; Bone Density; Cell Survival; Creatinine; ERRalpha Estrogen-Related Receptor; Estradiol; Female; Femur; Humans; MCF-7 Cells; Mice, Inbred ICR; Organ Size; Osteocalcin; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-fos; Proto-Oncogene Proteins c-jun; Receptors, Estrogen; Schisandra; Uterus

Postmenopausal osteoporosis affects millions of women, being estrogen deficiency the key factor in the pathogenesis of involutional osteoporosis. Fracture prevention is one of the public health priorities worldwide. Different treatments for osteoporosis are available. The various options are aimed to maintain bone health and decrease the risk of fractures. The majority of these drugs are antiresorptive agents, i.e., drugs that lower bone turnover, inhibiting osteoclastic bone resorption. Dietary sources of calcium intake and vitamin D are ideal, while pharmachological supplements should be used if diet alone cannot provide the recommended daily intake. Bisphosphonates are first-line therapy for patients with established osteoporosis at high risk of fracture. Some serious, but rare, adverse events have been associated with their long-term administration. The monoclonal antibody to RANKL, named denosumab, administered as a 60-mg subcutaneous injection every 6 months, is a valuable option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, who are unable to take other osteoporosis treatments. Teriparatide (PTH 1-34) is the only available osteoanabolic drugs for osteoporosis treatment at present. Its use is limited to severe osteoporosis because of the high cost of the treatment. In climacteric women, in different stages of menopausal transition, and beyond, hormone replacement therapy at different doses (HRT) rapidly normalizes turnover, preventing and/or treating osteoporosis. HRT is able to preserve and even increase BMD at all skeletal sites, leading to a significant reduction in vertebral and non-vertebral fractures. Selective estrogen modulators (SERMs) as raloxifene and bazedoxifene reduce bone turnover and maintains or increases vertebral and femoral BMDs in comparison to placebo and reduces the risk of vertebral and new vertebral fractures, in high risk women. The combination of a SERM with an estrogen has been defined as tissue selective estrogen complex (TSEC). The bazedoxifene with conjugated estrogen is able to reduce climacteric symptoms, reducing bone turnover and preserving BMD. Studies investigating the actions of phytoestrogens on BMD or bone turnover are largely contradictory, making them inconclusive. At the present time, phytoestrogens cannot be recommended for postmenopausal osteoporosis. In conclusion, the use of HRT for osteoporosis prevention is based on biology, epidemiology, animal and p

Topics: Anabolic Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Bone Density; Bone Density Conservation Agents; Denosumab; Diphosphonates; Female; Hormone Replacement Therapy; Humans; Osteoporosis; Osteoporosis, Postmenopausal; Osteoporotic Fractures; Phytoestrogens; Radiography; Risk Factors; Selective Estrogen Receptor Modulators; Teriparatide; Thiophenes; Treatment Outcome

Phytoestrogens have been implicated in the prevention of bone loss in postmenopausal osteoporosis. Recently, an active phytoestrogen from Curcuma comosa Roxb, diarylheptanoid (DPHD), (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol, was found to strongly promote human osteoblast function in vitro. In the present study, we demonstrated the protective effect of DPHD on ovariectomy-induced bone loss (OVX) in adult female Sprague-Dawley rats with 17β-estradiol (E2, 10 µg/kg Bw) as a positive control. Treatment of OVX animals with DPHD at 25, 50, and 100 mg/kg Bw for 12 weeks markedly increased bone mineral density (BMD) of tibial metaphysis as measured by peripheral Quantitative Computed Tomography (pQCT). Histomorphometric analysis of bone structure indicated that DPHD treatment retarded the ovariectomy-induced deterioration of bone microstructure. Ovariectomy resulted in a marked decrease in trabecular bone volume, number and thickness and these changes were inhibited by DPHD treatment, similar to that seen with E2. Moreover, DPHD decreased markers of bone turnover, including osteocalcin and tartrate resistant acid phosphatase (TRAP) activity. These results suggest that DPHD has a bone sparing effect in ovariectomy-induced trabecular bone loss and prevents deterioration of bone microarchitecture by suppressing the rate of bone turnover. Therefore, DPHD appears to be a promising candidate for preserving bone mass and structure in the estrogen deficient women with a potential role in reducing postmenopausal osteoporosis.

Topics: Animals; Bone Density Conservation Agents; Curcuma; Diarylheptanoids; Estradiol; Female; Humans; Osteoblasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Rats; Rats, Sprague-Dawley

Postmenopausal estrogen deficiency often causes bone density loss and osteoporosis. This study evaluated the effects of an oral administration of oil palm leaf extract (OPL) on bone calcium content and structure, bone density, ash weights, and serum total alkaline phosphatase (T-ALP) of estrogen-deficient ovariectomized (OVX) rats.. Female Sprague-Dawley rats were divided into five experimental groups: 1) intact (normal control); 2) ovariectomized (OVX control), and OVX rats supplemented with 3) 2% (w/v) green tea (OVX + GT), 4) OPL 150 mg/kg of body weight, or 5) OPL 300 mg/kg of body weight in the drinking water.. After 3 mo, the OVX control rats had significantly decreased femur and tibia masses (-5% and -3%, respectively), ash (-15% and -10%), calcium content (-0.5% and -2.7%), and bone density and T-ALP concentrations (-40%) compared with intact rats. The catechin-rich OPL dose dependently increased the OVX bone density and structure, femur and tibia masses (by +8% and +12% respectively), ash (by +30% and +20% respectively), calcium (by +3% and +5%), and T-ALP concentrations (by +76%) compared with the OVX rats. The increases by OPL were higher than that in OVX + GT and control intact rats.. The catechin-rich OPL increased the bone mass in estrogen-deficient rats by increasing osteoblast activities to higher levels than in normal rats and those supplemented with GT. This was shown by the modulation of serum T-ALP levels, bone calcium content, total mineral content, and bone histologic structure. The OPL is a potential inexpensive ingredient for protection against osteoporosis and influences bone metabolism by encouraging bone formation.

Topics: Alkaline Phosphatase; Animals; Arecaceae; Biomarkers; Bone and Bones; Bone Density; Bone Density Conservation Agents; Calcium; Catechin; Dietary Supplements; Female; Humans; Malaysia; Osteoblasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Extracts; Plant Leaves; Random Allocation; Rats; Rats, Sprague-Dawley

Topics: Animals; Antioxidants; Bone and Bones; Catechin; Dietary Supplements; Estrogens; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens

Estrogen deficiency after menopause results in rapid bone loss, predisposing women to osteoporotic fractures. Genistein, a phytoestrogen present in high concentrations in soy, is an ingredient in dietary supplements aggressively marketed for bone health. However, in a recent long-duration clinical trial in postmenopausal women, the efficacy of soy extracts in reducing bone loss was disappointing. To better understand the failure of soy extracts to consistently induce a robust skeletal response in women, we investigated the long-term (5 mo) efficacy of genistein, administered as a daily oral supplement, (1) in preventing cancellous bone loss in skeletally mature virgin Long-Evans rats ovariectomized at 7 months of age and (2) in improving cancellous bone mass and architecture in aged retired-breeder rats ovariectomized at 16 or 22 months of age.. Rats within each age group were randomly assigned into one of three treatment groups (n = 7-12 rats/group): (1) vehicle control, (2) genistein 485 μg/day, or (3) genistein 970 μg/day, resulting in mean (SE) serum genistein levels of 0.18 (0.10), 0.76 (0.15), and 1.48 (0.31) μM, respectively. Total tibia bone mass and density were evaluated using dual-energy x-ray absorptiometry, whereas cancellous bone mass and architecture in the tibial metaphysis, as well as cortical bone mass and architecture in the tibial diaphysis, were evaluated by micro-CT.. Oral genistein administered as a dietary supplement did not influence the cumulative effects of ovariectomy, aging, and/or reproductive history on cancellous and cortical bone mass and architecture.. Serum levels of genistein similar to those in women consuming a high-soy diet are ineffective in preventing or treating bone loss in rat models for postmenopausal osteoporosis.

Topics: Aging; Animals; Bone Density; Dietary Supplements; Disease Models, Animal; Female; Genistein; Humans; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Rats; Rats, Long-Evans; Reproduction; Tibia

Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects.

Topics: Alkaline Phosphatase; Animals; Bone Density; Creatinine; Disease Models, Animal; Estriol; Female; Femur; Genistein; Humans; Kidney; Osteoporosis, Postmenopausal; Ovariectomy; Parathyroid Hormone; Phytoestrogens; Protective Agents; Quinestrol; Rats; Rats, Sprague-Dawley; Receptor, Parathyroid Hormone, Type 1; Tensile Strength

Phytoestrogens have attracted attention for their potential in the prevention of postmenopausal osteoporosis. Recently, phytoestrogen-rich herb Pueraria mirifica has been demonstrated to possess an osteogenic effect on bone in ovariectomized rats, but its underlying cellular mechanism was not known. Here, we investigated the effects of P. mirifica extract and its major isoflavone compound, puerarin, on cell viability, cell proliferation and the expression of differentiation markers in rat osteoblast-like UMR106 cells. After exposure to 17β-estradiol (E2), genistein, P. mirifica extract and puerarin, proliferation but not viability of UMR106 cells was markedly decreased. Quantitative real-time PCR revealed that P. mirifica extract and puerarin significantly increased the mRNA expression of alkaline phosphatase (ALP) and osteoprotegerin, but not Runx2, osterix or osteocalcin. Puerarin also decreased the mRNA expression of receptor activator of nuclear factor-κB ligand, an osteoclastogenic factor, suggesting that it could induce bone gain by enhancing osteoblast differentiation and suppressing osteoclast function. Furthermore, after an exposure to high affinity estrogen receptor (ER) antagonist (ICI182780), the E2-, genistein-, P. mirifica extract- and puerarin-induced upregulation of ALP expressions were completely abolished. It could be concluded that P. mirifica extract and puerarin induced osteoblast differentiation rather than osteoblast proliferation in an ER-dependent manner. The present findings, therefore, corroborated the potential benefit of P. mirifica extract and puerarin in the prevention and treatment of postmenopausal osteoporosis.

Topics: Animals; Biomarkers; Cell Differentiation; Cell Line; Cell Proliferation; Drug Evaluation, Preclinical; Estradiol; Genistein; Humans; Isoflavones; Osteoblasts; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Extracts; Pueraria; Rats; Receptors, Estrogen; RNA, Messenger; Up-Regulation

Our previous study demonstrated that 60 % ethanol crude extract of Sambucus williamsii HANCE (SWH) improved bone mass, bone strength and bone micro-structure in both ovariectomised (OVX) rats and mice. The present study aims to identify the bioactive fractions and ingredients in SWH that account for its osteoprotective effects. Bilateral sham-operated mice acted as controls. OVX C57BL/6J mice, aged 12 weeks, were orally administrated daily with vehicle or 17β-oestradiol (3·2 mg/kg), SWH (60 % ethanol crude extract; 1·0 g/kg), SWA (water eluate; 0·570 g/kg), SWB (30 % ethanol eluate; 0·128 g/kg) or SWC (50 and 95 % ethanol eluates; 0·189 g/kg) for 12 weeks. The effects of the different fractions on bone properties in the OVX mice model were studied. In addition, their effects on osteoblast proliferation and differentiation were evaluated in UMR 106 cells. SWC significantly restored bone mineral density and improved bone size and bone content parameters in the femur and tibia as well as increased biomechanical strength at the tibia diaphysis in OVX mice. Similarly, SWC was the most potent fraction in stimulating cell proliferation and differentiation in UMR 106 cells. Also, SWC did not alter uterus weight in OVX mice. Nine major peaks, seven lignans and two phenolic acids, in the HPLC fingerprint of the SWC fraction were identified, isolated and characterised. In conclusion, the present study demonstrated that SWC was the most potent fraction in SWH that exerted anti-osteoporotic effects. Furthermore, lignans might be the potential bioactive components in SWC.

Topics: Animals; Biomechanical Phenomena; Bone and Bones; Bone Density; Bone Density Conservation Agents; Bone Resorption; Cell Differentiation; Cell Line; Cell Proliferation; Drugs, Chinese Herbal; Female; Humans; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Osteoblasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Rats; Sambucus

Topics: Estrogen Replacement Therapy; Female; Glycine max; Hot Flashes; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy

An integrated approach can be employed when counselling women about menopausal management options, where lifestyle, complementary therapies and hormone replacement therapy (HRT) are discussed. Women might opt to use an alternative approach to HRT for a variety of reasons, e.g. fear of side-effects and risks or contraindications to HRT. There are many choices of dietary and herbal approaches for menopausal symptoms, which essentially divide into food supplements and herbal medicines. The choice can often be overwhelming and confusing for the woman. Of concern, the evidence for efficacy and safety of some of these complementary therapies can be extremely limited or non-existent. In order to enable women to make a fully informed choice, it is important that, when a recommendation is made regarding a specific complementary therapy, it should focus on preparations for which a significant dataset exists for efficacy and safety and in which there is ongoing research and development. One of the most extensively studied food supplements has been the phytoestrogenic preparation containing red clover isoflavones. There have been six randomized trials thus far studying the impact on vasomotor symptoms, three of which have shown a significant benefit compared to placebo. There are also data from small randomized and observational trials showing positive outcomes for surrogate markers of osteoporosis and cardiovascular disease. A recent study using validated depression scales has shown that women using red clover isoflavones may also derive psychological benefits. Safety data are reassuring for the endometrium and breast, although further studies would be welcome, particularly in women with significant medical risks.

Topics: Breast; Cardiovascular Diseases; Complementary Therapies; Dietary Supplements; Endometrium; Female; Hot Flashes; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Placebos; Randomized Controlled Trials as Topic; Trifolium

Topics: Estrogen Replacement Therapy; Female; Glycine max; Hot Flashes; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy

Genistein, a major phytoestrogen of soy, is considered a potential drug for prevention and treatment of postmenopausal osteoporosis. The aim of the present study was to compare the effects of genistein, estradiol and raloxifene on the skeletal system in vivo and in vitro. Genistein (5 mg/kg), estradiol (0.1 mg/kg) or raloxifene hydrochloride (5 mg/kg) were administered daily by a stomach tube to mature ovariectomized Wistar rats for 4 weeks. Bone mass, mineral and calcium content, macrometric parameters and mechanical properties were examined. Also the effects of genistein, estradiol and raloxifene (10(-9)-10(-7) M) on the formation of osteoclasts from neonatal mouse bone marrow cells and the activity of osteoblasts isolated from neonatal mouse calvariae were compared. In vivo, estrogen deficiency resulted in the impairment of bone mineralization and bone mechanical properties. Raloxifene but not estradiol or genistein improved bone mineralization. Estradiol fully normalized the bone mechanical properties, whereas genistein augmented the deleterious effect of estrogen-deficiency on bone strength. In vitro, genistein, estradiol and raloxifene inhibited osteoclast formation from mouse bone marrow cells, decreasing the ratio of RANKL mRNA to osteoprotegerin mRNA expression in osteoblasts. Genistein, but not estradiol or raloxifene, decreased the ratio of alkaline phosphatase mRNA to ectonucleotide pyrophosphatase phosphodiesterase 1 mRNA expression in osteoblasts. This difference may explain the lack of genistein effect on bone mineralization observed in ovariectomized rats in the in vivo study. Concluding, our experiments demonstrated profound differences between the activities of genistein, estradiol and raloxifene towards the osseous tissue in experimental conditions.

Topics: Animals; Body Weight; Bone and Bones; Bone Density; Bone Marrow Cells; Bone Resorption; Calcification, Physiologic; Calcium; Cell Count; Cells, Cultured; Disease Models, Animal; Drug Combinations; Estradiol; Estriol; Female; Gene Expression; Genistein; Humans; Mice; Mice, Inbred BALB C; Organ Size; Osteoblasts; Osteoclasts; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Raloxifene Hydrochloride; Rats; Rats, Wistar; RNA, Messenger; Selective Estrogen Receptor Modulators; Thymus Gland; Uterus

There are virtually no prospective cohort studies in Germany regarding the changes of menopausal hormone therapy (HT) use pattern and factors associated with HT discontinuation after the release of the Women's Health Initiative (WHI) trial results.. We assessed HT prevalence and use pattern as well as factors associated with HT discontinuation in a cohort of 903 women 40 years of age and older, who participated in two consecutive follow-up visits in a 20-year prospective health study from July 2000 to February and from August 2002 to December 2004.. Overall, the prevalence of HT users in the cohort declined significantly from 35.4% in 2000-2002 to 22.5% in 2002-2004. Adjusting for aging of the population, a statistically significant decrease in HT user prevalence was consistently observed across subgroups of HT users defined by type and duration of HT use. The decline was most pronounced with respect to women using combined estrogen-progestin regimens (-10.5%), higher-dose estrogens (-11.6%), oral preparations (-11.1%), as well as long-term HT users (-8.4%). The prevalence of women indicating HT use for climacteric symptoms decreased significantly (-12.4%), whereas the prevalence of women reporting use of HT for the prevention of osteoporosis increased (+1.8%) significantly. Irrespective of hysterectomy status, half of the women who continued HT changed their HT preparations and switched to lower estrogen doses (11.5%), topical estrogens (8.2%), or phytohormones (3.8%). We did not observe any significant differences between women who continued and discontinued HT regarding health-related characteristics of the study population as of 2000-2002. However, women seeing a gynecologist in the 12 months preceding the 2002-2004 visit were significantly less likely to discontinue HT use in bivariate and multivariate analyses.. Substantial declines in HT user prevalence as well as changes in HT use patterns to lower-dose estrogen preparations and non-oral routes of administration are likely to reflect effects of the publication of the WHI results. Consulting a gynecologist appeared to be relevant for a woman's decision to continue HT.

Topics: Administration, Cutaneous; Adult; Aged; Cohort Studies; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Hot Flashes; Humans; Hysterectomy; Longitudinal Studies; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Progestins; Prospective Studies; Selective Estrogen Receptor Modulators; Sweating; Women's Health

Topics: Breast Neoplasms; Climacteric; Complementary Therapies; Coronary Artery Disease; Female; Hormone Replacement Therapy; Hot Flashes; Humans; Life Style; Osteoporosis, Postmenopausal; Phytoestrogens; Risk Factors; Thrombosis

Topics: Age Factors; Bone Density; Female; Humans; Isoflavones; Male; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Randomized Controlled Trials as Topic; Risk Factors; Sex Factors; Soy Foods

Intestinal bacterial metabolize the soy isoflavone daidzein to O-desmethylangolensin (O-DMA) or equol. Some individuals do not excrete O-DMA or equol after soy consumption, suggesting they do not harbor bacteria capable of producing these metabolites. The aim of this study was to evaluate bone mineral density (BMD) in relation to presence of these urinary metabolites.. BMD, determined by whole-body dual X-ray absorptiometry scan, was age-adjusted and evaluated in relation to O-DMA-producer and equol-producer phenotypes in 92 postmenopausal women, aged 50-75 years. Women consumed supplemental soy foods (daidzein source) for 3 days and collected a first-void urine sample on the fourth day in order to determine metabolic phenotypes.. In O-DMA producers (n=76) compared to O-DMA non-producers (n=16), greater total, leg and head BMD (p<0.05) were observed. Total BMD among the O-DMA producers (geometric mean=1.04 g/cm2) was 6% greater than total BMD among the O-DMA non-producers (geometric mean=0.98 g/cm2). Total and site-specific BMD did not differ between equol producers (n=24) and non-producers (n=68) (p>0.05). In exploratory analyses, among regular soy consumers, spinal BMD was 20% lower among the equol producers than non-producers, whereas, among soy non-consumers, no such difference was observed (p-interaction<0.05). Among equol producers, circulating estrone and free estradiol concentrations were inversely or not associated with total BMD, whereas, among equol non-producers, these hormones were positively associated (p-interaction<0.05).. Our results provide evidence that intestinal bacterial composition may influence BMD in postmenopausal women. Further studies characterizing associations of intestinal bacterial profiles with BMD are warranted.

Topics: Absorptiometry, Photon; Aged; Biomarkers; Bone Density; Equol; Female; Humans; Intestines; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phenotype; Phytoestrogens; Postmenopause; Soybean Proteins

Plant secondary metabolites with estrogenic activity (phyto-estrogens) have been studied in the past as a potential alternative to classical hormone-replacement therapy (HRT) in menopausal women. No final verdict on the efficacy of soy or red clover based pharmaceutical preparations has been reached despite numerous clinical studies. We have studied the novel and most potent phyto-estrogen 8-prenylnaringenin (8-PN) in adult ovariectomized rats, an established animal model to mimic hormone dependent osteoporosis in menopausal women. Our results demonstrate that 8-PN can completely protect from ovariectomy induced bone-loss while exhibiting minimal, (dose independent) trophic effects on uterus and endometrium. It is estimated that at equivalent bone protective doses of 17beta-estradiol and 8-PN, the phyto-estrogen has a 10-fold lower stimulatory effect on uterus and endometrium. The bone tissue specific effect of 8-PN was confirmed in a transgenic reporter mouse model (ERE-Luc mice). Here we also found pronounced estrogenic activity in prostate. Present results add important aspects to the pharmacological profile of 8-PN and position this compound as an interesting alternative new candidate for treatment of peri- and postmenopausal symptoms.

Topics: Animals; Body Weight; Bone Density; Epithelium; Estradiol; Female; Flavanones; Humans; Male; Mice; Mice, Transgenic; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Prostate; Rats; Rats, Sprague-Dawley; Uterus

Topics: Adult; Aged; Breast Neoplasms; Clinical Trials as Topic; Complementary Therapies; Culture; Estrogens; Fear; Female; Heart Diseases; Hormone Replacement Therapy; Humans; Longevity; Menopause; Middle Aged; Osteoporosis, Postmenopausal; Perimenopause; Phytoestrogens; Phytotherapy; Progestins; Risk Assessment; Women's Health

There is evidence that diets which contain high levels of phytoestrogenic isoflavanoids are associated with a low incidence of osteoporosis and menopausal vasomotor symptoms. Plant extracts such as red clover, which contain high levels of isoflavanoids, have been used to reduce menopausal symptoms and have been shown to reduce bone loss in healthy women. A placebo-controlled clinical trial [ISRCTN42940165] of red clover is reported in this issue of Breast Cancer Research and shows that these phytoestrogens do not cause any oestrogenic increase in breast density, which would indicate that they are unlikely to cause an increased risk of breast cancer.

Topics: Anticarcinogenic Agents; Bone and Bones; Breast; Breast Neoplasms; Female; Hormone Replacement Therapy; Hot Flashes; Humans; Isoflavones; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Extracts; Plant Preparations; Selective Estrogen Receptor Modulators; Thromboembolism; Trifolium

Topics: Cimicifuga; Estrogen Replacement Therapy; Female; Humans; Menopause; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Extracts

Phytoestrogens exert different estrogen receptor-dependent and -independent pharmacological actions. They share with estrogens several structural features and show greater affinity for the newly described estrogen receptor-beta. Many hope that phytoestrogens can exert the cardioprotective, anti-osteoporotic and other beneficial effects of the estrogens used in hormone replacement therapy in postmenopausal women without adversely affecting the risk of thrombosis and the incidence of breast and uterine cancers. Although there are many positive indications that phytoestrogens can fulfil this role, it remains to be proven: controlled interventional studies are lacking, and many questions remain unanswered. This review analyzes, on the basis of available experimental and epidemiological studies, the pros and cons of phytoestrogen use and describes the potential tissue targets and mechanisms of action of phytoestrogens.

Topics: Animals; Anticarcinogenic Agents; Cardiovascular Diseases; Clinical Trials as Topic; Diet; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Receptors, Estrogen

Topics: Cathepsin K; Cathepsins; Clinical Trials as Topic; Estrogen Replacement Therapy; Female; Humans; Isoflavones; Osteoporosis, Postmenopausal; Peptide Fragments; Phytoestrogens; Plant Preparations; Receptors, Calcium-Sensing; Vitamin D

The proliferative effects of thirty Oriental medicinal herbs on MCF-7 (estrogen-sensitive breast cancer cell line) and ROS 17/2.8 osteoblast-like cells were determined using the MTT assay. Methanol extracts from several herbs was found to show proliferative activity on the above two cell lines in the range of 5 to 100 microg/mL. Among these active herbs, the methanol extract from the rhizomes of Drynaria fortunei showed the most potent proliferative activity, and the cell proliferations were significantly increase by 136 and 158% in the MCF-7 and ROS 17/2.8 cells, respectively, when treated with 100 microg/mL. Through a bioassay-guided separation, eight flavonoids, including four new flavan-3-ols and two propelargonidins, together with the known (-)-epiafzelechin and naringin, were isolated. Their chemical structures were characterized as (-)-epiafzelechin (1), (-)-epiafzelechin-3-O-beta-D-allopyranoside (2), (-)-epiafzelechin-3-O-(6"-O-acetyl)-beta-D-allopyranoside (3), 4beta-carboxymethyl-(-)-epiafzelechin methyl ester (4), 4beta-carboxymethyl-(-)-epiafzelechin sodium salt (5), naringin (6), (-)-epiafzelechin-(4beta-->8)-4beta-carboxymethylepiafzelechin methyl ester (7) and (-)epiafzelechin-(4beta-->8, 2beta-->O-->7)-epiafzelechin-(4beta-->8)-epiafzelechin (8) by extensive 1D and 2D NMR spectroscopy. Most of these flavonoids, in the range of 10(-15) to approximately 10(-6) M, accelerated the proliferation of MCF-7 cell, with compounds 7 and 8, in the range of 10(-15) to approximately 10(-12) M, showing especially potent proliferation effects. Meanwhile, seven flavonoids, with the exception of compound 4, stimulated the proliferation of ROS 17/2.8 cells in the range of 10(-15) to approximately 10(-6) M, with compounds 5-8 especially accelerating the proliferation, in dose-dependent manners (10(-15) to approximately 10(-9) M), and their proliferative effect was much stronger than that of E2 and genistein. These results suggest that propelargonidin dimers and trimers isolated from the rhizomes of Drynaria fortunei may be useful as potential phytoestrogens, which play important physiological roles in the prevention of postmenopausal osteoporosis.

Topics: Animals; Breast Neoplasms; Cell Division; Drugs, Chinese Herbal; Flavonoids; Humans; Isoflavones; Magnetic Resonance Spectroscopy; Molecular Structure; Osteoblastoma; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Polypodiaceae; Rats; Rhizome; Tumor Cells, Cultured

The putative skeletal effects of dietary soy phytoestrogens (SPE) were examined in comparison with those of conjugated equine estrogens (CEE; Premarin) in a 3-yr longitudinal study in ovariectomized female monkeys. Controls received alcohol-extracted soy protein with low phytoestrogen content, and treatment groups received either CEE (admixed into the control diet) or unextracted soy protein isolate containing SPE. The acknowledged bone protective effect of CEE was reflected by higher bone mass (by dual energy x-ray absorptiometry) and lower bone turnover marker levels. In contrast, control and SPE groups lost significant lumbar spine bone mineral content and density and whole body bone mineral content within the first year, resulting in reduced bone mass for both groups compared with CEE (P < 0.0005). No effect of SPE was observed for any bone mass measure (P > 0.44), although transient, estrogen-like effects of SPE on serum alkaline phosphatase, calcium, and C-terminal cross-link of type I collagen were observed at 3 months (P < 0.02). These results suggest that SPE may be poor substitutes for mammalian estrogens in protecting against bone loss resulting from estrogen deficiency.

Topics: Animals; Biomarkers; Body Weight; Bone and Bones; Bone Diseases, Metabolic; Densitometry; Diet; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Glycine max; Humans; Isoflavones; Macaca fascicularis; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations

We investigated the ability of genistein and daidzein, two soybean isoflavones, compared with that of 17 alpha-ethinylestradiol, to prevent bone loss in ovariectomized rats, a model for postmenopausal osteoporosis. Female Wistar rats (n = 65; 12 mo old) were either sham-operated (SH; n = 13) or ovariectomized (OVX; n = 52). On d 0, OVX rats were randomly assigned to groups as follows: 13 received genistein [G; 10 mcg/(g body weight. d)], 13 were treated with daidzein [D; 10 mcg/(g body weight. d)], 13 received 17 alpha-ethinylestradiol [E(2); 30 mcg/kg body weight. d)] and 13 were untreated (OVX). Compounds were mixed with a soy protein-free powdered semipurified diet and given orally for 3 mo. On d 90, the bone mineral density (BMD) in lumbar vertebrae, femur and its metaphyseal and diaphyseal zones (rich in cancellous and cortical bone, respectively) was lower in OVX than in SH (P < 0.01). In D or E(2), the four BMD were not different from SH, whereas in G, only the diaphyseal BMD was not different from SH. Image analysis performed in the distal femur metaphysis revealed that the cancellous bone area was lower in OVX than in SH (P < 0.01). Only the area in D was not different from that in SH. Finally, the bone turnover, which was higher in OVX than in SH (P < 0.005 and P < 0.05 for plasma osteocalcin concentration and urinary deoxypyridinoline excretion, respectively), was not different in G, D or E(2) compared with SH. Therefore, consumption of 17 alpha-ethinylestradiol or daidzein was more efficient than genistein in preventing ovariectomy-induced bone loss in rats.

Topics: Animals; Body Weight; Bone Density; Equidae; Estrogens, Non-Steroidal; Female; Genistein; Goats; Humans; Isoflavones; Osteocalcin; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations; Radioimmunoassay; Rats; Rats, Wistar

Dairy foods provide the major, readily absorbed sources of calcium. Women aged 40 years and over should consume 3-4 serves of low-fat dairy food per day. If calcium supplements are required, the best absorption rate is from a dose of 500-600 mg of calcium once or twice daily. Exercise, alone or in combination with other therapeutic interventions, is effective in preventing bone loss. Vitamin D supplements may be necessary for women with inadequate sun exposure. Salty foods and the addition of salt to food should be avoided. While there is emerging evidence for the role of phytoestrogens in bone health, more human trials are required to strengthen this evidence.

Topics: Adult; Calcium, Dietary; Diet; Estrogens, Non-Steroidal; Exercise; Female; Humans; Isoflavones; Middle Aged; Osteoporosis; Osteoporosis, Postmenopausal; Phytoestrogens; Phytotherapy; Plant Preparations; Plants; Women's Health

Genistein, an isoflavone abundantly present in soybeans, has structural similarity to estrogen, suggesting that genistein may act as a phytoestrogen. To examine the possible role of genistein in hemopoiesis and bone metabolism, female mice were either sham-operated or ovariectomized (OVX), and selected OVX mice were administered genistein for 2-4 weeks (0.1-0.7 mg/day) or 17beta-estradiol (E2; 0.01-0.1 microg/day) s.c., using a miniosmotic pump (Alza Corp., Palo Alto, CA). In OVX mice, uterine weight declined but was completely restored by E2 administration. In contrast, genistein did not demonstrate a reversal of the OVX-induced uterine atrophy. The number of bone marrow cells markedly increased, 2-4 weeks after OVX, and most of these were B220-weakly positive pre-B cells. The increased B-lymphopoiesis was completely restored, not only by E2 but also by genistein administration. In OVX mice, the trabecular bone volume of the femoral distal metaphysis, measured by microcomputed tomography scanning and dual-energy x-ray absorptiometry, was markedly reduced; and genistein restored this, as did E2. These results indicate that genistein exhibits estrogenic action in bone and bone marrow, to regulate B-lymphopoiesis and prevent bone loss, without exhibiting estrogenic action in the uterus. Phytoestrogens may be useful for preventing bone loss caused by estrogen deficiency in females.

Topics: Animals; B-Lymphocytes; Bone Density; Bone Marrow Cells; Estradiol; Estrogens; Estrogens, Non-Steroidal; Female; Genistein; Glycine max; Hematopoiesis; Humans; Isoflavones; Mice; Organ Size; Osteoporosis, Postmenopausal; Ovariectomy; Phytoestrogens; Plant Preparations; Uterus

Phytoestrogens (PEs) are natural compounds, with a biological activity like estrogen, which comprise isoflavones, lignans and coumestans. A traditional Asiatic phytoestrogen-rich diet is associated with a lower incidence of breast cancer and postmenopausal illness, and much evidence indicates that PEs prevent bone resorption, increase bone density and reduce cholesterol. The estrogenic effects of phytoestrogens can be useful in preventing postmenopausal osteoporosis and cardiovascular disease.

Topics: Cardiovascular Diseases; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Postmenopause

Topics: Bone Density; Bone Remodeling; Calcium Channel Blockers; Diphosphonates; Estrogen Receptor beta; Estrogens, Non-Steroidal; Etidronic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Isoflavones; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Receptors, Estrogen; Risedronic Acid

Topics: Animals; Breast Neoplasms; Cardiovascular Diseases; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Isoflavones; Male; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Plants; Prostatic Neoplasms

The hypothesis was tested that the rate of postmenopausal bone loss is inversely associated with long-term urinary excretion of phyto-oestrogens, as a marker of habitual dietary intake.. Secondary analysis of a 10-year follow-up study (1979 1989) among postmenopausal women in the Netherlands.. From the original population of 154 women, 32 women were selected with an annual rate of radial bone loss of < or = 0.5% over the first 5 years of the study and 35 women with a rate of > or = 2.5% per year.. The isoflavonoids genistein, daidzein and equol, and the lignan enterolactone were determined by gas chromatography mass spectrometry in aggregate samples from annually collected urine samples. Cortical bone density of the radius had previously been measured annually by single-photon absorptiometry.. Excretion of isoflavonoids did not differ between both groups, although in multivariate analysis equol excretion was weakly positively associated with rate of bone loss in the 5 years after the menopause. Enterolactone excretion was significantly higher in the group with high rate of bone loss. This positive association remained in multivariate linear regression analysis after adjustment for age, years since menopause, body mass index and intake of calcium, vegetable protein and dietary fibre.. Enterolactone excretion is likely to be an indicator of consumption of grains and legumes; it is not clear whether the observed positive association with rate of bone loss is a causal one. Our results do not support a preventive effect of low, unsupplemented dietary intake of phyto-oestrogens on postmenopausal cortical bone loss. However, no conclusions can be drawn about effects of higher doses of phyto-oestrogens.

Topics: 4-Butyrolactone; Aging; Bone Density; Chromans; Equol; Estrogens, Non-Steroidal; Female; Gas Chromatography-Mass Spectrometry; Genistein; Humans; Isoflavones; Lignans; Linear Models; Middle Aged; Osteoporosis, Postmenopausal; Phytoestrogens; Plant Preparations; Postmenopause; Prospective Studies; Time Factors