Effects Of Soy Isoflavones Research Articles

Soy and Its Isoflavones: The Truth Behind the Science in Breast Cancer

Epidemiological and migratory evidence suggests that dietary soy consumption can lower the risk for breast cancer. The role of soy isoflavones in cancer prevention and promotion is somewhat unclear. There are two views in terms of soy isoflavones and breast cancer. One line of evidence suggests that soy and its isoflavones have exhibited cancer-preventive properties including lengthening the menstrual cycle, altering estrogen metabolism away from cancerous compounds, and demonstrating anti-proliferative properties in vivo. On the contrary, isoflavones found in soy products are suggested to behave as weak estrogens and as such, much speculation surrounds the influence of soy and/or its isoflavones on hormone-receptor-positive cancers. The objective of this review is to present the latest knowledge regarding the role of soy and its isoflavones with the development and advancement of breast cancer, the safety of soy isoflavones for breast cancer survivors, and a comparison of the carcinogenic effects in animal models following soy isoflavone and estrogen administration. This review compares and contrasts literature in terms of the anti-cancer and cancer-promoting effects of soy isoflavones and estrogen in humans and animal models. In conclusion, current human and animal data provide evidence for several anticancer properties of soy and/or its isoflavones. Although the specific quantities and constituents responsible for the observed anti-cancer effects have not been elucidated, it appears that soy isoflavones do not function as an estrogen, but rather exhibit anti-estrogenic properties. However, their metabolism differs between humans and animals and therefore the outcomes of animal studies may not be applicable to humans. The majority of breast cancer cases are hormone-receptor-positive; therefore, soy isoflavones should be considered a potential anti-cancer therapeutic agent and warrant further investigation.

Phytoestrogens and bone health at different reproductive stages

Background: Isoflavones are an alternative to hormonal therapy for the relief of menopausal symptoms. Since isoflavones interact with estrogen receptors it has been hypothesized that such substances may have an effect on bone health.Objective: To clarify the effect of isoflavones on bone at experimental and clinical level, and to identify areas that require further clarification and research.Method: A systematic review of studies involving isoflavones and bone health was performed, and a specific search on isoflavone’s mechanism of action and the importance of equol production was made based on Internet search engines, MEDLINE (1966–October 2012) and the Cochrane Controlled Clinical Trials Register. This search was supplemented by a handsearch of reference lists of selected papers.Results: In vitro and animal studies show a positive effect of isoflavones on bone which has not been clearly confirmed by long-term human trials. Equol producers seem to present a more positive response to isoflavone intervention. Isoflavone rich diets could help maintain peak bone mass in premenopausal women. The effect of isoflavones in perimenopausal women is insufficiently studied but it seems to attenuate bone loss in the menopausal transition. In postmenopause, isoflavones may present a modest benefit but its clinical relevance in preventing osteoporotic fractures remains to be determined.Conclusions: The present review suggests that isoflavone increase bone mineral density and decrease the bone turnover resorption markers. The effect of soy isoflavones on BMD is mediated by equol production, reproductive status, supplement type, isoflavone dose and intervention duration.

Soy isoflavone: The multipurpose phytochemical (Review)

Soy isoflavones are compounds found in soybean and soybean products. They have been reported to possess numerous physiological properties, such as antitumor, anti-menopausal (female) osteoporosis and anti-aging. They have also been reported to improve learning and memory skills in menopausal women and aid in the prevention and treatment of heart disease, diabetes and Kawasaki disease (KD). In this review, the effects of soy isoflavones on various diseases were analyzed. Based on the analysis, it was hypothesized that the function of soybean isoflavones in the prevention and treatment of various diseases results from their phytoestrogen and antioxidant properties. However, due to their phytoestrogen properties, it is recommended that the risks of soy isoflavone intake as food and/or medical treatment be further evaluated.

Soy extracts suppressed iodine uptake and stimulated the production of autoimmunogen in rat thyrocytes

Soy consumption is associated with thyroid disorders such as hypothyroidism, goiter, and autoimmune thyroid disease (ATD) as well as increased iodine requirement in certain cases. However, the anti-thyroid component(s) in soy are yet to be identified and the molecular mechanism(s) involved remain unclear. This study examined the effects of soy isoflavones (ISF) on iodide uptake and expression of thyroglobulin (Tg) and sodium/iodide symporter (NIS) in thyrocytes. Fischer rat thyroid cells (FRTL) were treated with Novasoy (a soy alcohol extract containing 30% ISF) or major ISF aglycones or glycosides for 24 h. Iodide uptake was measured by a colorimetric assay. The protein level of Tg and NIS was measured by Western blotting. Cytotoxicity of tested compounds was determined by the MTT cell proliferation assay. Iodide uptake in FRTL cells was dose-dependently suppressed by Novasoy added into the cell culture (10, 25, or 50 µg/mL, P < 0.05). However, neither the major ISF aglycones nor glycosides alone or in combination had similar effects. Novasoy (up to 200 µg/mL) had no cytotoxic effect. Novasoy (1, 10, and 50 µg/mL) and genistein (1 and 10 µM) markedly increased the protein content of a 40 kDa Tg fragment (P40, a known autoimmunogen) and non-glycosylated NIS in the FRTL cells (P < 0.05). Overall, this study demonstrated that the alcohol soluble component(s) other than the major ISF in soy remarkably inhibited iodide uptake in the FRTL cells. Soy ISF, particularly genistein, induced the production of P40, which might be responsible for the higher incidence of ATD reported in soy infant formula-fed children.

Abstract LB-358: Soy improves radiotherapy for lung tumors and mitigates radiation-induced injury to lung tissue.

Abstract Radiotherapy of locally-advanced non-small cell lung cancer (NSCLC) is limited by pneumonitis and fibrosis caused by radiation-induced injury to normal lung tissue. We have investigated the effect of a high thoracic dose of radiation combined with soy isoflavones in a pre-clinical model of orthotopic A549 human lung carcinoma xenografts in nude mice. Mice bearing established lung tumors (&amp;gt;300µm) were pretreated with soy for 3 days starting day 15 after A549 cell injection, and then received 10 Gy irradiation administered to the whole lung. Soy treatment, given orally at 1mg/day (50mg/kg) was continued for 5 days per week for 4 more weeks, then lungs were perfused with formalin and processed for histology. The effect of the therapy on the tumor cells, the surrounding tumor microenvironment and lung tissue structures was further analyzed using novel immunostaining and quantitative techniques. Compared to large invasive lung tumor nodules (up to 1-2 x 106 µm2) in untreated mice, the combined therapy caused a significant inhibition of tumor progression in lungs resulting in few residual small tumor nodules (0.02-0.07 x 106 µm2, p&amp;lt;0.05) with a low index of proliferation (mean of 16 positive nuclei for Ki-67 compared to 147 in control tumors, p&amp;lt;0.001). Pneumonitis was evaluated by morphometric measurements of the thickness of alveolar septa on H&amp;E stained lung tissue sections. Soy isoflavones reduced the extent of pneumonitis induced by radiation resulting in 30% of the lung tissue with thickened septa compared to 45% observed in lungs treated with radiation only. Fibrosis staining using Masson's Trichrome revealed that radiation caused a dramatic increase in collagen fibers supporting the vessel and bronchiole walls and this effect was mitigated by soy isoflavones. Triple immunofluorescent staining of lung vessel walls was performed on lung tissue sections using antibodies specific to endothelial cells (anti-CD31), pericytes (anti-SMA) and collagen (anti-collagen IV). This technique revealed that soy isoflavones combined with radiation decreased the fraction of vessels with damaged basement membrane to 25% down from 42% in radiation-alone treated lungs. Thus, these studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while acting as radioprotectors for the surrounding lung tissue. Soy isoflavones reduced pneumonitis and fibrosis, and preserved the integrity of lung structures including alveolar septa, bronchioles and vessels, probably by mitigation of the inflammatory response induced by radiation. Complementing cancer radiotherapy with soy isoflavones has the potential to improve its effectiveness on the tumor target and reduce dose-limiting radiotoxicity to the normal lung and could be applied in the treatment of advanced stage NSCLC. Citation Format: Gilda Gali Hillman, Vinita Singh-Gupta, David J. Hoogstra, Lisa Abernathy, Joseph Rakowski, Christopher Yunker, Fazlul H. Sarkar, Andre A. Konski, Fulvio Lonardo, Michael C. Joiner. Soy improves radiotherapy for lung tumors and mitigates radiation-induced injury to lung tissue. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-358. doi:10.1158/1538-7445.AM2013-LB-358

Increased protein synthesis of IRES containing mRNAs, that induce cell survival and proliferation, by the daidzein metabolite equol may contribute to breast cancer malignancy.

The effects of soy isoflavones on established breast cancer remain to be understood. We recently reported that dietary daidzein increased primary mammary tumor growth and metastasis, and upregulated eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E. The increased eIF expression in tumor extracts of mice after daidzein diets was associated with protein expression of mRNAs with internal ribosome entry sites (IRES). Results with metastatic cancer cell lines show that the effects of daidzein in vivo can be recapitulated by its metabolite equol. Equol increased metastatic cancer cell viability and up‐regulated gene and protein expression of the transcription factor c‐Myc. In vitro, equol, but not daidzein, up‐regulated eIF4G without affecting eIF4E or its regulator, 4E‐BP, levels. This elevated eIF4G was not associated with eIF4E or 4E‐BP in cap affinity chromatography assays or co‐immunoprecipitations. In dual luciferase assays, IRES‐dependent protein synthesis was increased by equol. As shown by western blotting and polysomal associations, equol specifically increased the expression of IRES‐containing mRNAs of cancer promoting molecules. Therefore, upregulation of eIF4G by equol may result in increased translation of pro‐cancer mRNAs with IRESs and, thus, promote cancer malignancy. Supported by US Army/BCRP W81XWH‐11–1‐0199 to CD and NIH/NIGMS SC3GM084824 to SD.

Effects of soy isoflavones and mechanical vibration on rat bone tissue

Objective To investigate the effects of soy isoflavones (Iso) and mechanical vibration treatments alone or combined on bone extracellular matrix constituents of ovariectomized rats.Methods Forty female Wistar rats at the age of 6 months were ovariectomized (Ovx) and ten were sham-operated (sham). After 3 months, the animals were divided into five groups: GI (sham); GII (Ovx); GIII, ovariectomized and orally treated with isoflavones (200 mg/kg) for 90 consecutive days; GIV, ovariectomized and submitted to vibration for 90 days (5 days/week); GV, ovariectomized and treated with isoflavones plus vibration. After treatments, the rats were euthanized, and their femurs were removed for histological routine and biochemical study. Histological sections were stained with hematoxylin–eosin, picrosirius red and alcian blue. Shaft of femurs were submitted to biochemical assay and tibias were subjected to biophysical and biomechanical tests.Results Treatments did not have significant effects on the trabecular bone volume, but the combined treatments showed trophic effects on the cortical bone width and area. Bone density and the content of organic material of the tibias were higher in the GIV and GV groups. The GV group showed the highest presence of mature collagen fibers and content of total glycosaminoglycans, while the highest contents of chondroitin sulfate and other sulfated glycosaminoglycans were seen in the GIV group.Conclusion The mechanical vibration treatment is more efficient than soy isoflavones in improving bone quality by increasing the bone density, the content of sulfated glycosaminoglycans and the presence of mature collagen fibers. In addition, the combined interventions have partial trophic and synergistic effects that are bone site-specific in ovariectomized rats.

The effects of soy isoflavone on bone density in north region of climacteric Chinese women

Only a few investigations were based on limb bone density. This study evaluated the efficacy of soy isoflavone in the treatment of the principal menopausal disorders, limb bone density and the role of pathway. The research protocol involved the random subdivision of the enrolled sample into two groups of 40 women, who were to receive treatment for 6 months with isoflavone (90 mg/day) and with placebo. All of the patients were asked to fill in a questionnaire concerning their complaints. BMD of the radius and tibia were measured using quantitative ultrasound. Bone metabolism indexes calcium, phosphorus and alkaline phosphatase (ALP) were examined regularly. Serum cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) examined by ELISA. The results of the score of Kupperman table showed that the isoflavone can lead to a significant reduction in some of the disorders. Compared with placebo, the tibia bone density in isoflavone group increased obviously against the base value before trail. Isoflavone led to a stronger descent of the concentration of ALP and a decrease of IL-6 and TNF-α level than placebo. For climacteric women, soy isoflavone in the dose of 90 mg/day could improve some menopausal syndromes and was effective on increasing limb bone density, which maybe had the relationship with the levels of IL-6, TNF-α and ALP in serum.

A Comparative Analysis of the Photo-Protective Effects of Soy Isoflavones in Their Aglycone and Glucoside Forms

Isoflavones exist in nature predominantly as glucosides such as daidzin or genistin and are rarely found in their corresponding aglycone forms daidzein and genistein. The metabolism and absorption of isoflavones ingested with food is well documented, but little is known about their use as topical photo-protective agents. The aim of this study was to investigate in a comparative analysis the photo-protective effects of isoflavones in both their aglycone and glucoside forms. In human skin fibroblasts irradiated with 60 mJ/cm2 ultraviolet B (UVB), we measured the expression levels of COX-2 and Gadd45, which are involved in inflammation and DNA repair, respectively. We also determined the cellular response to UVB-induced DNA damage using the comet assay. Our findings suggest that both the isoflavone glucosides at a specific concentration and combination with an aglycone mixture exerted an anti-inflammatory and photo-protective effect that prevented 41% and 71% of UVB-induced DNA damage, respectively. The advantages of using either isoflavone glucosides or an aglycone mixture in applications in the field of dermatology will depend on their properties and their different potential uses.

Effects of Soy Isoflavone and Endogenous Oestrogen on Breast Cancer in MMTV-erbB2 Transgenic Mice

Soy isoflavone is associated with modification of breast cancer risk. Effects of dietary isoflavone on breast tissue carcinogenesis under varying endogenous oestrogen contexts were investigated. Five-week-old mouse mammary tumour virus (MMTV)-erbB2 female transgenic mice (n = 180) were divided into three equal groups: low-, normal- and high-oestrogen groups. Each group was then subdivided into an experimental group (given soybean feed) and a control group (given control feed). In the high-oestrogen environment, breast cancer incidence was significantly lower in the experimental versus the control group, whereas in the low-oestrogen environment, breast cancer incidence was significantly higher in the experimental versus the control group. There were no between-group differences in mean breast tumour latency, mean largest tumour diameter and breast tumour tissue vascular endothelial growth factor levels. Dietary soy isoflavones promote breast cancer at low oestrogen levels but inhibit breast cancer at high oestrogen levels. This effect may only occur during the initiation stage of breast cancer.

Vitamin D interactions with soy isoflavones on bone after menopause: a review.

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.

Radioprotective Effects of Soy Isoflavones on Normal Lung Tissue Could Translate to Improve Radiation Therapy Outcome of Lung Cancer

Radioprotective Effects of Soy Isoflavones on Normal Lung Tissue Could Translate to Improve Radiation Therapy Outcome of Lung Cancer

Endogenous and Exogenous Equol Are Antiestrogenic in Reproductive Tissues of Apolipoprotein E-Null Mice1–3

Equol is an isoflavone (IF) metabolite produced by intestinal microbiota in a subset of people consuming dietary soy. Equol producers may show different responses to soy foods and phenotypes related to cancer risk. Here, we assessed the effects of soy IF, endogenous microbial equol production, and dietary racemic equol in a 3 × 2 × 2 factorial experiment using gnotobiotic apoE-null mice ( n = 9–11/group/sex). At age 3–6 wk, equol-producing microbiota were introduced to one-half of the colony ( n = 122). At age 6 wk, mice were randomized to receive a diet that contained 1 of 3 protein sources: casein and lactalbumin, alcohol-washed soy protein (low IF), and intact soy protein (high IF), with total IF amounts of 0, 42, and 566 mg/kg diet, respectively. One-half of each diet group also received racemic equol (291 mg/kg diet). After 16 wk of dietary treatment, serum isoflavonoid profiles varied with sex, soy IF amount, and intestinal microbiota status. There were no treatment effects on tissues of male mice. In females, reproductive tissue phenotypes differed by equol-producing ability (i.e., microbiota status) but not dietary equol or IF content. Equol producers had lower uterine weight, vaginal epithelial thickness, total uterine area, endometrial area, and endometrial luminal epithelial height compared with nonproducers ( P < 0.05 for all), with an association between microbiota status and estrous cycle ( P> chi-square = 0.03). Exogenous equol reduced expression of progesterone receptor (PGR) and the proliferation marker Ki67 ( P< 0.0001) in vaginal epithelium and endometrium; for endogenous equol, only PGR was reduced ( P <0.0005). Our findings indicate that equol diminishes estrogen-dependent tissue responses in apoE-null mice.

Soy isoflavones modulate adipokines and myokines to regulate lipid metabolism in adipose tissue, skeletal muscle and liver of male Huanjiang mini-pigs

Although a growing body of evidence suggests that soy isoflavones help regulate lipid metabolism, the underlying mechanism has not yet been thoroughly clarified. The present study was undertaken to determine the effects of soy isoflavones on the expression of genes involved in lipid metabolism in different adipose tissue depots, skeletal muscle and liver of male Huanjiang mini-pigs, as well as the expression of adipokines and myokines. A total of 36 male Huanjiang mini-pigs were fed basal diet (control, Con), low-dose soy isoflavones (LSI) and high-dose soy isoflavones (HSI). The results showed that LSI and HSI regulated the expression of genes involved in the anabolism and catabolism of fatty acids in dorsal subcutaneous (DSA), abdominal subcutaneous (ASA) and perirenal (PRA) adipose tissue depots, as well as longissimus dorsi muscle (LDM) and liver. LSI and HSI also regulated the expression of adipokines in DSA, ASA and PRA, and the expression of myokines in LDM in male Huanjiang mini-pigs. In addition, soy isoflavones regulated plasma glucose, leptin and adiponectin contents after treatment for two months. Our results indicate that soy isoflavones, by regulating the expression of adipokines and myokines, may regulate the metabolism of lipids and could have potential therapeutic applications in lipid abnormalities.

Soy isoflavones (daidzein & genistein) inhibit 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cutaneous inflammation via modulation of COX-2 and NF-κB in Swiss albino mice

It is well established that aberrant production of inflammatory mediators has been associated with most the toxic manifestations and the genesis of different chronic diseases including cancer. The basic aim of the present study is to investigate the effects of soy isoflavones (SIF) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cutaneous inflammatory responses and to explore the underlying molecular mechanisms. We have studied the protective effects of SIF against TPA induced oxidative stress, pro-inflammatory cytokines level, activation of NF-κB, expression of COX-2 and ki-67 in mouse skin. Animals were divided into five groups I–V (n=6). Groups II, III and IV received topical application of TPA at the dose of 10nmol/0.2ml of acetone/animal/day, for 2 days. Animals of the groups III and IV were pre-treated with SIF 1.0μg (D1) and 2.0μg (D2) topically 30min prior to each TPA administration, while groups I and V were given acetone (0.2ml) and SIF (D2), respectively. We have found that SIF pretreatment significantly inhibited TPA induced oxidative stress, proinflammatory cytokines production and activation of NF-κB. SIF also inhibited the expression of COX-2 and ki-67. Histological findings further supported the protective effects of SIF against TPA-induced cutaneous damage. Thus, our results suggest that inhibitory effect of SIF on TPA-induced cutaneous inflammation includes inhibition of proinflammatory cytokines, attenuation of oxidative stress, activation of NF-κB and expression of COX-2.

Combined effect of soy isoflavones and vitamin D3 on bone loss in ovariectomized rats

ObjectiveSeveral studies have shown that soy isoflavones have estrogen-like activities and might constitute an alternative to hormone replacement treatment. The present study investigated the effects of soy isoflavones alone and combined with vitamin D3 on prevention of bone loss. MethodsSprague-Dawley rats were sham-operated (n = 8) or ovariectomized (OVX; n = 40), and then the OVX rats were randomly assigned to five groups that were untreated or treated for 14 wk with vitamin D3, 17β-estradiol, soy isoflavone extract (SIE), or vitamin D3 plus SIE. The effects of the isoflavones and 1α,25(OH)2D3 on cultured osteoblasts and osteoclasts also were investigated. ResultsIn OVX rats, the bone mineral density and trabecular bone volume loss were improved by 17β-estradiol, SIE, or SIE plus vitamin D3 treatment. SIE treatment was more effective than vitamin D3 or 17β-estradiol in inhibiting increases in serum tumor necrosis factor-α levels and osteoblast osteoprotegerin expression. SIE plus vitamin D3 was more effective in increasing osterix expression than each alone. Bone cell cultures showed that the isoflavones induced preosteoblasts to differentiate into osteoblasts and increased osteoblast mineralization. Isoflavones inhibited preosteoclasts and osteoclast proliferation and decreased osteoclast resorption. The combination of isoflavones plus 1α,25(OH)2D3 showed additive effects on the increase in cell proliferation of cultured preosteoblasts. ConclusionTreatment with soy isoflavones might be an alternative to hormone replacement therapy in decreasing bone loss from postmenopausal estrogen deficiency. In addition, there are further effects on increasing transcription factor osterix expression and preosteoblast proliferation when these were combined with vitamin D3.

Abstract 4298: In-utero, but not pubertal, soy exposure suppresses estrogen-regulated gene expression in non-human primate breast

Abstract Background: Cynomolgus macaques (nonhuman primates, NHP) are highly similar to humans in their genetics, reproductive physiology, and anatomy. More importantly, they undergo a similar mammary gland development process and develop spontaneous breast cancers. Epidemiological studies of humans show that high soy intake is associated with lower breast cancer risk. Since nutrition and/or environmental exposure during youth are critical factors to disease risk in adulthood, timing of intervention may determine soy protective effect to breast cancer. Studies in NHP allow interrogation of developmental effects on the primate breast to a degree not possible in human subjects. We report here novel in-utero developmental effects of soy isoflavones (IF) on the NHP breast. Method: Soy IF were detected in amniotic fluid (255.5 + 93.3 nM) and milk (266.3 nM), which confirmed that soy exposure occurred in-utero and via nursing. We assessed the effects of in-utero and pre-pubertal soy exposure on the breast of NHP during puberty with a focus on changes related to estrogen exposure. We utilized mammary tissues from animals that were exposed to soy beginning in-utero (n=5 for soy and casein/control groups) or before puberty (n=12-17 for soy and casein groups). Animals were fed a diet modeled on a typical North American diet (35% calories from fat) with soy dose approximated at 120-180 mg IF/person/day. We assessed nipple length, mammary gland morphology, markers of mammary gland differentiation, proliferation, and estrogen receptor activity, and concentrations of serum estradiol and progesterone. Results: Regardless of dietary treatment, gene expression of estrogen-responsive markers in the breast was highest during pre-puberty and decreased across the pubertal transition (P&amp;lt;0.0001 for time effect on ESR1, PGR, GREB1, and TFF1). This pattern coincided with a decrease of terminal end bud structures and an increase of lobular differentiation and glandular area. Although an effect of dietary soy was not observed in pre-pubertally exposed animals, in-utero exposed animals showed lower expression of TFF1 (0.03-fold; P&amp;lt;0.05), a classic marker of estrogen receptor alpha (ER) activity. Serum estradiol level was not different with dietary treatment, nor did IF alter mRNA expression of estrogen-metabolizing enzymes in the breast. Conclusions and Future Directions: Our data suggest that timing of exposure may influence the effects of dietary soy on the breast; in-utero soy exposure resulted in modestly lower expression of a gene marker of ER activity, while pre-pubertal exposure had negligible effects on mammary gland outcomes. A follow-up study is currently underway to further examine potential effects of in-utero soy exposure on estrogen responsiveness and pubertal development, and whether epigenetic modulation is the underlying mechanism behind the differential expression of estrogen-related genes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4298. doi:1538-7445.AM2012-4298

Alternative and complementary therapies for the menopause

Despite a re-evaluation of risks in recent years, hormone replacement therapy is still surrounded by controversy. Almost 30% of women in a recent survey sought a natural approach to combat climacteric symptoms. Nevertheless, a large proportion of patients felt that they wanted a good safety profile and strong evidence base for treatment. This article seeks to review the evidence supporting non-hormonal approaches to treatment. There is only conflicting evidence at best to support alpha-2 agonists, e.g. clonidine and limited evidence for dihydroepiandrosterone and natural progesterones. There is limited randomized controlled trial data for gabapentin, selective norepinephrine re-uptake inhibitors (SNRIs) and selective serotonin re-uptake inhibitors (SSRIs), many of these studies being related to breast cancer patients. Of the herbal medicinal products, the largest evidence base rests with phytoestrogens. A Cochrane Database review looking at all types of phytoestrogens, e.g. red clover extracts, dietary soya and soya extracts concluded that there was no evidence to support improvement in climacteric symptoms and the meta-analysis of a 178 studies on soy products was inconsistent. Nevertheless, other studies disagree. Mammographic density is not affected by soy or phytoestrogen products and recent in vitro work shows only a weakly proliferative effect of soy isoflavone on breast cancer cells and evidence that soy isoflavone blocks the proliferative effect of estradiol on these cells. There are no studies looking at clinical outcome measures for cardiovascular disease but a number of studies looking at biochemical markers including arterial wall stiffness and apolipo protein B. Recent studies have also looked at the effects of red clover isoflavone on mood and depression, using specific depression rating scales. Finally, it is important to note that herbal medicinal products should not be used without caution. Some may produce quite marked side-effects in high doses and others can interact with pre-existing medication. A strategy for which patients are suitable for herbal medicinal products is reviewed.

Systematic review of soy isoflavone supplements on osteoporosis in women

ObjectiveTo clarify the effect of soy isoflavones on prevention of osteoporosis, and the effective dosage of soy isoflavones and its duration. MethodsRandom control trials that investigated the association of soy isoflavones and osteoporosis were included in the meta-analysis by researching MEDLINE, EMBASE and the Chinese Biomedical Database up to October 2011. The Rev Man software was used for all of the statistical analysis. ResultsThe present meta-analysis found that soy isoflavones significantly increased the bone mineral density by 54% and decreased the bone resorption marker urinary deoxypyridinoline (DPD) by 23% compared to baseline in women. Using random effects model, the effect of isoflavones on bone mineral density (BMD) regarding menopausal status and isoflavone dose revealed higher weighted mean difference changes were found in postmenopausal women and isoflavone dose above 75 mg/d. Subgroup analysis of trials with menopausal status, supplement type, isoflavone dose and intervention duration that used soy isoflavone extracts resulted in significant different overall effect of DPD using by random effects model. Sensitivity analysis indicated that the effect of soy isoflavones on BMD and DPD was robust. ConclusionsThe present meta-analysis reveals that soy isoflavone supplements significantly increase bone mineral density and decrease the bone resorption marker urinary DPD. It shows no significant effect on bone formation markers serum bone alkaline phosphatase. The significant effect of soy isoflavones on BMD and urinary DPD is relative to menopausal status, supplement type, isoflavone dose and intervention duration.

Urinary Estrogen Metabolites During a Randomized Soy Trial

One of the hypothesized protective mechanisms of soy against breast cancer involves changes in estrogen metabolism to 2-hydroxy (OH) and 16α-OH estrogens. The current analysis examined the effect of soy foods on the 2:16α-OH E1 ratio among premenopausal women during a randomized, crossover intervention study; women were stratified by equol producer status, a characteristic thought to enhance the protective effects of soy isoflavones. The study consisted of a high-soy diet with 2 soy food servings/day and a low-soy diet with <3 servings of soy/wk for 6 mo each; estrogen metabolites were measured in 3 overnight urines (baseline and at the end of the low- and high-soy diet) using gas chromatography mass spectrometry for the 82 women who completed the study. Urinary isoflavonoids were assessed by liquid chromatography mass spectrometry. When applying mixed models, the 2:16α-OH E1 ratio increased (P = 0.05) because of a nonsignificant decrease in 16α-OH E1 (P = 0.21) at the end of the high-soy diet. Similar nonsignificant increases in the 2:16α-OH E1 ratio were observed in equol producers (P = 0.13) and nonproducers (P = 0.23). These findings suggest a beneficial influence of soy foods on estrogen metabolism regardless of equol producer status.