Introduction

1. Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and ApplicationsBritta 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 Phytoestrogen Categories 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 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-aand ER-band phytoestrogens appear to have a higher affinity for ER-b, 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)17,18that 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

2. Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and ApplicationsBritta Engert & Yiota Panayiotis Phytoestrogenic Components of Chinese Herbs 21-23 In Vivo Studies Summary of Results

3. Phytoestrogens: Theoretical Concerns Versus Clinical Knowledge and ApplicationsBritta Engert & Yiota Panayiotis Conclusion References and Bibliography In Vitro Studies 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 al27(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. 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