Phytoestrogens in health and disease.Recent Prog Horm Res 1999; 54:185-210; discussion 210-1RP
Phytoestrogens are compounds found in a wide variety of plant foods that historically are said to exhibit estrogen-like activity and, more recently, have been reported to display both estrogenic and anti-estrogenic effects. Population-based studies have been interpreted to suggest that consumption of a phytoestrogen-rich diet is protective against breast, prostate, and bowel cancer and cardiovascular disease and ameliorates estrogen-deficiency symptoms in postmenopausal women. Consequently, there is a global movement towards increased consumption of phytoestrogen-rich foods and tabletized concentrated isoflavone extracts are being heavily promoted. Evaluating the effects and hence the potential benefits and risks of phytoestrogens is a complex task. The interindividual diversity and complexity in dietary phytoestrogen absorption and metabolism make the bioactivity of these compounds unpredictable. Epidemiological studies of relationships between phytoestrogens and cancer and cardiovascular disease that take into account confounding factors are scarce. Results of many of the in vitro and in vivo studies are conflicting and confusing. These compounds do not simply mimic the effects of human steroidal estrogen but rather demonstrate both similar and divergent actions. The ultimate actions of these compounds in specific cells are determined by many factors, including the relative levels of estrogen receptor (ER) alpha and ER beta and the diverse cocktail of co-activators and co-repressors present in any given cell type. Therefore, effects vary according to the phytoestrogen studied, cell line, tissue, species, and response being evaluated. Overall, it is naive to assume that exposure to these compounds is always good; inappropriate or excessive exposure may be detrimental. Extensive documentation of the specific intracellular effects of the various phytoestrogens in different tissues, the relationships between timing and duration of exposure and disease, and results from prospective randomized studies in humans of their clinical effects and potential side effects are essential. Only then can widespread recommendations regarding the dietary and pharmacological intake of these compounds be made.