1. RESEARCH POSTER PRESENTATION DESIGN © 2011 www.PosterPresentations.com QUICK DESIGN GUIDE (--THIS SECTION DOES NOT PRINT--) This PowerPoint 2007 template produces a 100cm x 140cm professional poster. It will save you valuable time placing titles, subtitles, text, and graphics. Use it to create your presentation. Then send it to PosterPresentations.com for premium quality, same day affordable printing. We provide a series of online tutorials that will guide you through the poster design process and answer your poster production questions. View our online tutorials at: http://bit.ly/Poster_creation_help (copy and paste the link into your web browser). For assistance and to order your printed poster call PosterPresentations.com at 1.866.649.3004 Object Placeholders Use the placeholders provided below to add new elements to your poster: Drag a placeholder onto the poster area, size it, and click it to edit. Section Header placeholder Move this preformatted section header placeholder to the poster area to add another section header. Use section headers to separate topics or concepts within your presentation. Text placeholder Move this preformatted text placeholder to the poster to add a new body of text. Picture placeholder Move this graphic placeholder onto your poster, size it first, and then click it to add a picture to the poster. Student discounts are available on our Facebook page. Go to PosterPresentations.com and click on the FB icon. QUICK TIPS (--THIS SECTION DOES NOT PRINT--) This PowerPoint template requires basic PowerPoint (version 2007 or newer) skills. Below is a list of commonly asked questions specific to this template. If you are using an older version of PowerPoint some template features may not work properly. Using the template Verifying the quality of your graphics Go to the VIEW menu and click on ZOOM to set your preferred magnification. This template is at 100% the size of the final poster. All text and graphics will be printed at 100% their size. To see what your poster will look like when printed, set the zoom to 100% and evaluate the quality of all your graphics before you submit your poster for printing. Using the placeholders To add text to this template click inside a placeholder and type in or paste your text. To move a placeholder, click on it once (to select it), place your cursor on its frame and your cursor will change to this symbol: Then, click once and drag it to its new location where you can resize it as needed. Additional placeholders can be found on the left side of this template. Modifying the layout This template has four different column layouts. Right-click your mouse on the background and click on “Layout” to see the layout options. The columns in the provided layouts are fixed and cannot be moved but advanced users can modify any layout by going to VIEW and then SLIDE MASTER. Importing text and graphics from external sources TEXT: Paste or type your text into a pre-existing placeholder or drag in a new placeholder from the left side of the template. Move it anywhere as needed. PHOTOS: Drag in a picture placeholder, size it first, click in it and insert a photo from the menu. TABLES: You can copy and paste a table from an external document onto this poster template. To adjust the way the text fits within the cells of a table that has been pasted, right-click on the table, click FORMAT SHAPE then click on TEXT BOX and change the INTERNAL MARGIN values to 0.25 Modifying the color scheme To change the color scheme of this template go to the “Design” menu and click on “Colors”. You can choose from the provide color combinations or you can create your own. © 2011 PosterPresentations.com 2117 Fourth Street, Unit C Berkeley CA 94710 posterpresenter@gmail.com Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and Applications Britta Engert & Yiota Panayiotis Introduction What Are Phytoestrogens and What Do They Do? Mechanism of Phytoestrogen Action on Estrogen Receptors and Gene Activation 20 Excretion Gene Activation Phytoestrogen IsoflavonesGenisteinDaidzeinCoumestansCoumestrolLignansEnterodiolEnterolactone Phytoestrogen Categories Phytoestrogens are plant-derived compounds that share a similar structure to estradiol, the predominant oestrogen that is found in menstruating women. Because of this similarity, phytoestrogens have been found to have both oestrogenic and anti-oestrogenic effects inside the human body, through their ability to bind to estrogen receptors (ER). ERs are protein molecules found in cells that are targets for oestrogen action, for example, ERs can be found in breast tissue, ovarian cells, endometrial tissue and the hypothalamus. There are two types of ERs, namely, ER-  and ER-  and phytoestrogens appear to have a higher affinity for ER- , but can bind to both. 16 By binding to ER sites, phytoestrogens have been shown to have an effect on the levels of endogenous oestrogen in various ways. Firstly they can act as ligands that are agonists, that is, once bound to ERs they can activate an oestrogenic response that influences cell DNA, but the effect on cell DNA of a phytoestrogen would be much weaker than estradiol. Secondly, they can act as antagonists, in that they bind to an ER but produce no oestrogenic response. In both instances phytoestrogens compete with endogenous oestrogen but in an antagonist reaction they deactivate ERs through there binding. How it is determined whether a phytoestrogen acts as an agonist or antagonist is unclear, but it is thought to be either dependant on the source of the phytoestrogen, or, through their ability to act as adaptogens, modulating homeostatic response according to the body’s needs. 16 Regardless as to whether the phytoestrogen acts as agonist or antagonist, the body will respond to endogenous oestrogen in various ways as a result. The very binding of phytoestrogens to ERs will result in an excess of endogenous oestrogens in circulation, these are then metabolised by the liver through a process called glucoronidation where they are prepared for excretion from the body through the bowel or the urinary system. It is important to note at this stage that effective excretion of oestrogens through the bowel is largely dependent on the presence of healthy intestinal bacterial flora and liver metabolism, otherwise there is a high risk of oestrogen reabsorption. 16 Although the main way that phytoestrogens are synthesised are through this mechanism of ER binding, more recent research has also shown that they have the ability to inhibit enzymes (such as aromatase) 17,18 that are involved in conversion of other steroids into oestradiol. Phytoestrogens are also found to inhibit cell signalling pathways that influence cell proliferation (PI3-K/Akt pathways). 19 As interest in the practise of Chinese Herbal Medicine (CHM) grows in the United Kingdom and Europe, it has naturally come under the scrutiny of the western biomedical model and the political, legislative and cultural context within which it finds itself. It has therefore become necessary for the profession as a whole to adapt the traditional approach and application of Chinese herbs in order to better suit the western mind; with scientific research being at the forefront of this movement. One such exploration first began quite independently to Chinese medicine as epimediological studies in the eighties found lower incidences of breast cancer in the East comparative to the West. 1 It was suggested at the time that a higher consumption of phytoestrogens in the Eastern diet were the reason for this, and so differences were attributed to lifestyle factors rather than genetics. Thirty years on, there has been continued and growing interest in phytoestrogens and whether they can help or exacerbate oestrogen senstive disorders, particularly certain types of cancer, endometriosis and menopausal symptoms. More recently, studies have also focused on the natural sources of these phytoestrogens, some of which are the herbs that are familiar to CHM. 2-15 As the theoretical concerns have remained largely inconclusive scientifically, it raises the question of safety to the clinical application and use of certain herbs that are known for their high phytoestrogen content. The aim here is to explore the issues that come up in recent research, so that the profession can continue to develop its own knowledge base and understanding. On this basis, safe and responsible practice can continue and dialogue with our biomedical colleagues encouraged, as it is only here that the integrity of our own tradition can continue to evolve. Estrogen Molecule Estrogen Receptor DNA Molecule Deactivated ER Oestrogen Sensitive Disease Breast Cancer Uterine Cancer Prostrate Cancer Ovarian Cysts Endometriosis Menopausal Symptoms

2. RESEARCH POSTER PRESENTATION DESIGN © 2011 www.PosterPresentations.com QUICK DESIGN GUIDE (--THIS SECTION DOES NOT PRINT--) This PowerPoint 2007 template produces a 100cm x 140cm professional poster. It will save you valuable time placing titles, subtitles, text, and graphics. Use it to create your presentation. Then send it to PosterPresentations.com for premium quality, same day affordable printing. We provide a series of online tutorials that will guide you through the poster design process and answer your poster production questions. View our online tutorials at: http://bit.ly/Poster_creation_help (copy and paste the link into your web browser). For assistance and to order your printed poster call PosterPresentations.com at 1.866.649.3004 Object Placeholders Use the placeholders provided below to add new elements to your poster: Drag a placeholder onto the poster area, size it, and click it to edit. Section Header placeholder Move this preformatted section header placeholder to the poster area to add another section header. Use section headers to separate topics or concepts within your presentation. Text placeholder Move this preformatted text placeholder to the poster to add a new body of text. Picture placeholder Move this graphic placeholder onto your poster, size it first, and then click it to add a picture to the poster. Student discounts are available on our Facebook page. Go to PosterPresentations.com and click on the FB icon. QUICK TIPS (--THIS SECTION DOES NOT PRINT--) This PowerPoint template requires basic PowerPoint (version 2007 or newer) skills. Below is a list of commonly asked questions specific to this template. If you are using an older version of PowerPoint some template features may not work properly. Using the template Verifying the quality of your graphics Go to the VIEW menu and click on ZOOM to set your preferred magnification. This template is at 100% the size of the final poster. All text and graphics will be printed at 100% their size. To see what your poster will look like when printed, set the zoom to 100% and evaluate the quality of all your graphics before you submit your poster for printing. Using the placeholders To add text to this template click inside a placeholder and type in or paste your text. To move a placeholder, click on it once (to select it), place your cursor on its frame and your cursor will change to this symbol: Then, click once and drag it to its new location where you can resize it as needed. Additional placeholders can be found on the left side of this template. Modifying the layout This template has four different column layouts. Right-click your mouse on the background and click on “Layout” to see the layout options. The columns in the provided layouts are fixed and cannot be moved but advanced users can modify any layout by going to VIEW and then SLIDE MASTER. Importing text and graphics from external sources TEXT: Paste or type your text into a pre-existing placeholder or drag in a new placeholder from the left side of the template. Move it anywhere as needed. PHOTOS: Drag in a picture placeholder, size it first, click in it and insert a photo from the menu. TABLES: You can copy and paste a table from an external document onto this poster template. To adjust the way the text fits within the cells of a table that has been pasted, right-click on the table, click FORMAT SHAPE then click on TEXT BOX and change the INTERNAL MARGIN values to 0.25 Modifying the color scheme To change the color scheme of this template go to the “Design” menu and click on “Colors”. You can choose from the provide color combinations or you can create your own. © 2011 PosterPresentations.com 2117 Fourth Street, Unit C Berkeley CA 94710 posterpresenter@gmail.com Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and Applications Britta Engert & Yiota Panayiotis Phytoestrogenic Components of Chinese Herbs 21-23 In Vivo Studies Dan Dou Chi Semen sojae preparatum IsoflavonesCoumestans Dang Gui Angelica sinensis radix IsoflavonesCoumestansLignans Gan Cao Gycyrhizzae radix IsoflavonesCoumestansSaponins Gan Jiang Zingiberis rhizoma Beta-Sitosterol Sheng Ma Cimicifuga racemosa IsoflavonesCoumestansLignans Ge Gen Puerariae radix IsoflavonesCoumestans Huang Qi Astragalus membranacus Beta-SitoSterolSaponins Ren Shen Ginseng radix Beta-SitosterolSaponins Shao Yao Paeonia lactiflora Beta-Sitosterol Ku Shen Sophorae flavenscentis radix Isoflavones Mo Yao Commiphora myrrha Beta-Sitosterol Pu Gong Ying Taraxacum officinale Beta-Sitosterol Huai Hua Sophorae flos Isoflavones Xi Yang Shen Panax quinquefolium Beta-SitosterolSaponins Sheng Di Huang Rehmannia radix Beta-Sitosterol Study name Study Design InterventionsParticipant Study Length Outcome Measures ResultsHirata et al, 1997 2 Double- blind, randomized, placebo-controlled Dang gui vs placebo 71 Post- menopausal women 24 weeks 1)Endometrial thickness 2) Vaginal cell maturation 3) Vasomotor flushes No difference between treatment and placebo group Quella et al, 2000 3 Double- blind, randomized, placebo- controlled Soy tablets vs placebo 177 Breast cancer survivors 4 weeksHot flashes Soy not more effective than placebo Davis et al, 2001 4 Double- blind, randomized, placebo-controlled CHM vs placebo 55 postmenopausal Australian women 12 weeksVasomotor symptomsCHM was no more effective than placebo Ziegler, 2004 24 Epidemiological Study Intake of phytoestrogens (lignans and isoflavones ) 15000 Dutch women 8 Years 1) Phyto-estrogen intake 2) Breast cancer rate No association between phyto-estrogen intake and breast cancer Newton et al, 2006 5 Double- blind, randomized, placebo-controlled Black cohosh vs black cohosh + multi botanical vs multi- Botanical + soy vs estrogens vs placebo 351 peri- or post- menopausal women 12 monthVasomotor symptoms1) Herbal intervention not different from placebo 2) Hormone therapy superior to placebo Kwee et al. 2007 6 Double- blind, randomised placebo- controlled CHM vs HRT vs placebo 31 Dutch women 16 weeksVasomotor symptoms1) HRT most effective 2) CHM more effective than placebo Rotem and Kaplan, 2007 7 Double- blind, randomized, placebo-controlled Phyto-Complex (black cohosh, dang gui, milk thistle, red clover, American ginseng, chaste-tree berry) vs placebo 50 pre and postmenopausal women, aged 44–65 years 3 monthMenopausal symptomsPhyto-Complex significantly higher reduction in menopausal symptoms to placebo D’Anna, 2009 25 Double- blind, randomized, placebo-controlled Genistein vs placebo n=38924 months Hot flushes Endometrial thickness 1) Genistein reduces hot flushes 2) No difference in endometrial thickness Lipovac, 2011 8 Double- blind, randomized, placebo-controlled cross over Red clover Vs placebo Post- menopausal women 187 daysMucosal status Libido Tiredness Moods Subjective improvement of all symptoms with Red clover extract Deng et al, 2012 9 Multicenter follow-up study Fufang vs placebo 194 postmenopausal women (47– 70 years old) 5 yearsPotential adverse events and fracture incidence Fracture incidence 2.4 fold lower in the treatment group than placebo Summary of Results Clinical research into the use of herbs with phytoestrogen components in patients at risk of, or with, oestrogen sensitive cancers is limited. Current evidence, which is mostly epidemiological, would not support any effect of phytoestrogens, neither positive nor negative. However, only reports in the English language have been reviewed. There may be a significant body of research reported in Chinese or Japanese language, which could not be accessed. Research into the use of CHM with phytoestrogens for menopause related symptoms would suggest good safety and efficacy for herbs in the treatment of mild symptoms, however for moderate or severe cases classic HRT is clearly more effective. 5,6,7,8,9,25 The design of almost all clinical studies does not take into account the theory and practice of classical CHM, but applies them in isolation from their usual formulas, sometimes even only using components of single herbs, for short time frames, and outside the classical CHM diagnostic framework (pattern discrimination).

3. RESEARCH POSTER PRESENTATION DESIGN © 2011 www.PosterPresentations.com QUICK DESIGN GUIDE (--THIS SECTION DOES NOT PRINT--) This PowerPoint 2007 template produces a 100cm x 140cm professional poster. It will save you valuable time placing titles, subtitles, text, and graphics. Use it to create your presentation. Then send it to PosterPresentations.com for premium quality, same day affordable printing. We provide a series of online tutorials that will guide you through the poster design process and answer your poster production questions. View our online tutorials at: http://bit.ly/Poster_creation_help (copy and paste the link into your web browser). For assistance and to order your printed poster call PosterPresentations.com at 1.866.649.3004 Object Placeholders Use the placeholders provided below to add new elements to your poster: Drag a placeholder onto the poster area, size it, and click it to edit. Section Header placeholder Move this preformatted section header placeholder to the poster area to add another section header. Use section headers to separate topics or concepts within your presentation. Text placeholder Move this preformatted text placeholder to the poster to add a new body of text. Picture placeholder Move this graphic placeholder onto your poster, size it first, and then click it to add a picture to the poster. Student discounts are available on our Facebook page. Go to PosterPresentations.com and click on the FB icon. QUICK TIPS (--THIS SECTION DOES NOT PRINT--) This PowerPoint template requires basic PowerPoint (version 2007 or newer) skills. Below is a list of commonly asked questions specific to this template. If you are using an older version of PowerPoint some template features may not work properly. Using the template Verifying the quality of your graphics Go to the VIEW menu and click on ZOOM to set your preferred magnification. This template is at 100% the size of the final poster. All text and graphics will be printed at 100% their size. To see what your poster will look like when printed, set the zoom to 100% and evaluate the quality of all your graphics before you submit your poster for printing. Using the placeholders To add text to this template click inside a placeholder and type in or paste your text. To move a placeholder, click on it once (to select it), place your cursor on its frame and your cursor will change to this symbol: Then, click once and drag it to its new location where you can resize it as needed. Additional placeholders can be found on the left side of this template. Modifying the layout This template has four different column layouts. Right-click your mouse on the background and click on “Layout” to see the layout options. The columns in the provided layouts are fixed and cannot be moved but advanced users can modify any layout by going to VIEW and then SLIDE MASTER. Importing text and graphics from external sources TEXT: Paste or type your text into a pre-existing placeholder or drag in a new placeholder from the left side of the template. Move it anywhere as needed. PHOTOS: Drag in a picture placeholder, size it first, click in it and insert a photo from the menu. TABLES: You can copy and paste a table from an external document onto this poster template. To adjust the way the text fits within the cells of a table that has been pasted, right-click on the table, click FORMAT SHAPE then click on TEXT BOX and change the INTERNAL MARGIN values to 0.25 Modifying the color scheme To change the color scheme of this template go to the “Design” menu and click on “Colors”. You can choose from the provide color combinations or you can create your own. © 2011 PosterPresentations.com 2117 Fourth Street, Unit C Berkeley CA 94710 posterpresenter@gmail.com Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and Applications Britta Engert & Yiota Panayiotis Conclusion References and Bibliography In Vitro Studies Study Name Study Design Intervention Outcome Measure Results DiPaola et al, 1998 10 1998 10 1) Yeast assay 2) Menopause mouse model 3) Male patients with prostate cancer PC-SPES (chrysanthemum, isatis, licorice, Ganoderma lucidum, Panax pseudo- ginseng, Rabdosia rubescens, saw palmetto, scutellaria) 1) Yeast proliferation rate 2) Mouse uterus size 3) Human PSA and Testosterone level Marked oestrogenic effect in vitro and in vivo Santell et al, 2000 26 Mice inoculated with MDA-MB-231 cells (breast cancer cells) Genistein diet1) Genistein concentration required to inhibit tumor growth in vitro 2) Genistein plasma concentration in relation to diet 3) Tumor growth with Genistein diet 1) Genistein concentration required to inhibit tumor growth can not be achieved with Soy diet 2) In vivo tumor growth not inhibited by Genistein Bodinet and Freudenstein, 2002 11 Cell PreparationBlack cohosh (Cimicifuga racemosa [CR]), on estrogen-dependent mammary cancers 1) CR-extract inhibited MCF- 7 cell (cancer cell) proliferation 2) CR-extract inhibited estrogen-induced proliferation of MCF-7 cells 3) Proliferation-inhibiting effect of tamoxifen was further enhanced by the CR-extract 1) Non-estrogenic, or estrogen-antagonistic effect of CR on human breast cancer cells 2) Breast cancer treatment with CR – extract is safe Wang et al, 2003 12 2003 12 Osteoporotic mouse model Puerariae radix dietfemoral bone mineral density Puerariae radix prevented osteoporosis Bodinet and Freudenstein, 2004 13 2004 13 In vitro: MCF 7 and HeLa cell line Proliferation and toxicity assay using Black cohosh, Soy, Red clover Cell toxicity and proliferation 1) Black cohosh, Soy: no cytotoxic effect Red clover: cytotoxic at high concentration 2) Soy and Red clover enhance MCF 7 proliferation, Black cohosh doesn’t Xu et al, 2011 14 2011 14 Menopause mouse model Tiáo-Gēng-Tāng(TG) Vs Estrogen Estradiol, LH, FSH levels, Estrogen Receptor (ER) expression TG less effective than estrogen in balancing female hormones, but stronger upregulation of ER Martínez- Montemayor et al, 2011 15 In vitro: inflammatory breast cancer cells SUM-149 Ganoderma lucidum (Reishi) 1) apoptosis rate 2) cell invasion assay 3) Gene expression profile 1) Increased apoptosis, 2) Reduced invasivenes, 3) Downregualation of cell cycle progression Cell culture studies suggest that some phytoestrogens may increase oestrogen sensitive cancers. This is in sharp contrast to early epidemiological studies which suggest a reduced breast cancer rate in Asian women, possibly phytoestrogen diet related. 1 Most carcinogenic effects of phytoestrogens were only observed at non- physiological serum levels, which can not be achieved through oral intake. Often results from pre-clinical studies (cell culture, animal) can not be translated into positive results in (human) clinical studies. 16 Current research into Chinese medicinal herbs with phytoestrogenic components is driven by theoretical concerns around safety and potential commercial exploitation, such as, breast cancer risks and HRT replacements that promise treatment without the oestrogen side effects. However, it is difficult to justify such concerns given the evidence. Firstly, concerns around cancer and cell proliferation from the use of CHM with phytoestrogenic components have not been confirmed by clinical data and it appears that phytoestrogenic components are safe and efficient to treat mild menopausal symptoms. Overall, research is largely inconclusive. As Carreau et al 27(p183) state from their own inconclusive findings: ‘This suggests that the estrogenic and/or anti-estrogenic activity of structurally diverse natural phytoestrogens is complex, which is consistent with published data that often give contradictory results for these compounds.’ Also, one can see from both the in vivo and in vitro studies, that the scientific methods applied do not account for CHM theory and the diagnosis of an individual patients syndromes. Typically research aims to find new biomedical components for exploitation in orthodox medicine, rather than aiming to show clinical efficacy of a CHM formula. Herbs are only considered in isolation and based on their active phytoestrogenic ingredients. In contrast, classical CHM uses herbs within polypharmacy formulas, leading to enhancement and buffer effects, and an overall more balanced treatment. 28 Most current research forces CHM into a western medical framework, removing all the core CHM concepts, and consequently developing conclusions of limited value to CHM practice, both from an efficacy and safety point of view. The long track record of CHM has shown good empirical efficacy for menopausal symptoms with no obvious associated cancer risk. Clinical research applying current scientific methods (randomised control trials) is necessary to further consolidate this knowledge and secure the survival of CHM in the modern world. However, this research must take into account the classical CHM diagnostic framework and prescribing methods. CHM practitioners should lead the way and promote clinical settings that facilitate modern research and move away from a mostly historical approach. Ideally, CHM hospitals need to be established and, in collaboration with individual practitioners, become centres of clinical research. 1. Peeters PHM, Keinan-Boker L, van der Schouw YT, Grobbee DE. Phytoestrogens and Breast Cancer Risk. Breast Cancer Research and Treatment 2003;77: 171-183. http://igitur-archive.library.uu.nl/med/2006- 0803-200546/Peeters_03_Phytoestrogensandbreastcancerrisk.pdf (accessed 26 October 2012). 2. Hirata JD, Swiersz LM, Zell B, Small R, Ettinger B. Does Dong Quai Have Estrogenic Effects in Post-menopausal Women? A Double-Blind, Placebo-Controlled Trial..Fertility and Sterility 1997;68(6): 981-6. http://www.ncbi.nlm.nih.gov/pubmed/9418683 (accessed 26 October 2012). 3. Quella SK, Loprinzi CL, Barton DL, Knost JA, Sloan JA, La Vasseur BL, Swan D, Krupp KR, Miller KD, Novotny PJ. Evaluation of Soy Phytoestrogens for the Treatment of Hot Flashes in Breast Cancer Survivors: A North Central Cancer Treatment Group Trial. Journal of Clinical Oncology 2000;18(5): 1068-74. http://www.ncbi.nlm.nih.gov/pubmed/10694559 (accessed 26 October 2012). 4. Davis SR, Briganti EM, Chen RQ, Dalais FS, Bailey M, Burger HG. The Effects of Chinese Medicinal Herbs on Post-Menopausal Vasomotor Symptoms of Australian Women. The Medical Journal of Australia 2001;174(2): 68-71. http://www.ncbi.nlm.nih.gov/pubmed/11245505 (accessed 26 October 2012). 5. Newton KM, Reed SD, LaCroix Z, Grothaus LC, Ehrlich K, Guiltinan J. Treatment of Vasomotor Symptoms of Menopause with Black Cohosh, Multibotanicals, Soy, Hormone Therapy or Placebo: A Randomized Trial. Annals of Internal Medicine 2006;145(12): 869-79. http://www.ncbi.nlm.nih.gov/pubmed/17179056 (accessed 26 October 2012). 6. Kwee SH, Tan HH, Marsman A, Wauters C. The Effect of Chinese Herbal Medicines (CHM) on Menopausal Symptoms Compared to Hormonal Replacement Therapy (HRT) and Placebo. Maturitas 2007;58(1): 83-90. http://www.ncbi.nlm.nih.gov/pubmed/17689896 (accessed 26 October 2012). 7. Rotem C, Kaplan B. Phyto-Female Complex for the Relief of Hot Flushes, Night Sweats and Quality of Sleep: Randomized, Controlled, Double-Blind Pilot Study. Gynaecological Endocrinology 2007;23(2): 117- 22. http://www.ncbi.nlm.nih.gov/pubmed/17454163 (accessed 26 October 2012). 8. Lipovac M, Gruenhut C, Gocan A, Kurz C, Benedikt N, Imhof M. Effect of Red Clover Isoflavones Over Skin, Appendages and Mucosal Status in Post-Menopausal Women. Obstetrics and Gynecology International 2011;949302: 10. http://www.ncbi.nlm.nih.gov/pubmed/22135679 (accessed 26 October 2012). 9. Deng WM, Zhang P, Huang H, Shen YG, Yang QH, Cui WL, He YS, Wei S, Ye Z, Liu F, Qin L. Five Year Follow-Up Study of a Kidney Tonifying Herbal FuFang for Prevention of Post-Menopausal Osteoporosis and Fragility Fractures. Journal of Bone and Mineral Metabolism 2012;30(5):517-24. http://www.ncbi.nlm.nih.gov/pubmed/22722637 (accessed 26 october 2012). 10. DiPaola RS, Zhang H, Lambert GH, Meeker R, Licitra E, Rafi MM, Zhu BT, Spaulding H, Goodin S, Toledano MB, Hait WN, Gallo MA. Clinical and Biologic Activity of an Estrogenic Herbal Combination (PC- SPES) in Prostrate Cancer. The New England Journal of Medicine 1998;339(12): 785-91. http://www.ncbi.nlm.nih.gov/pubmed/9738085 (accessed 26 October 2012). 11. Bodinet C, Fraudenstein J. Influence of Cimicifuga Racemosa on the Proliferation of Estrogen Receptor-Positive Human Breast Cancer Cells. Breast Cancer Research and Treatment 2002;76(1): 1-10. http://www.ncbi.nlm.nih.gov/pubmed/12408370 (accessed 26 October 2012). 12. Wang X, Wu J, Chiba H, Umegaki K, Yamada K, Ishimi Y. Puerariae radix Prevents Bone Loss in Ovariectomized Mice. Journal of Bone and Mineral Metabolism 2003;21(5): 268-75. http://www.ncbi.nlm.nih.gov/pubmed/12928827 (accessed on 26 october 2012). 13. Bodinet C, Fraudenstein J. Influence of Marketed Herbal Menopause Preparations on MCF-7 Cell Proliferation. The Journal of the North American Menopause Society 2004;11(3): 281-289. http://www.ncbi.nlm.nih.gov/pubmed/15167307 (accessed 26 October 2012). 14. Xu LW, Kluwe L, Zhang TT, Li SN, Mou YY, Ma J, Sun ZJ. Chinese Herb Mix Tiao-Geng-Tang Possesses Antiaging and Antioxidative effects and Upregulates Expression of Estrogen Receptors Alpha and Beta in Ovariectomized Rats. BMC Complementary and Alternative Medicine 2011;11: 137. http://www.ncbi.nlm.nih.gov/pubmed/22206438 (accessed 26 October 2012). 15. Martinez-Montemayor M, Acevedo RR, Otero-Franqui E, Cubano LA, Dharmawadhane SF. Ganoderma lucidum (Reishi) Inhibits Cancer Cell Growth and Expression of Key Molecules in Inflammatory Breast Cancer. Nutrition and Cancer 2011;63(7): 1085-94. http://www.ncbi.nlm.nih.gov/pubmed/21888505 (accessed 26 october 2012). 16. Rice S, Whitehead SA. Phytoestrogens Oestrogen Synthesis and Breast Cancer. The Journal of Steroid Biochemistry and Molecular Biology 2008;108(3-5): 186-95. http://www.ncbi.nlm.nih.gov/pubmed/17936616 (accessed 26 October 2012). 17. Aldercreutz H, Bannwart C, Wahala K, Makela T, Brunow G, Hase T, Arosemena PJ, Kellis JT, Vickery LE. Inhibition of Human Aromatase by Mammalian Lignans and Isoflavoid Phytoestrogens. The Journal of Steroid Biochemistry and Molecular Biology 1993;44(2): 147-53. http://www.ncbi.nlm.nih.gov/pubmed/8382517 (accessed 26 October 2012). 18. Chen S, Kao YC, Laughton CA. Binding Characteristics of aromatase Inhibitors and Phytoestrogens to Human Aromatase. 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