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Phytoestrogens are a group of naturally occurring plant compounds with demonstrated estrogenic and/or antiestrogenic activity. They are present in many human foodstuffs including beans, sprouts, cabbage, spinach, soybeans, grains, and hops, and have been identified in a number of botanical dietary supplements. These substances hold great promise for development as botanical dietary supplements for postmenopausal women and can act as idealized selective estrogen response modifiers (SERM's) with the desirable properties of being anti-estrogenic in breast and uterine tissue, but being pro-estrogenic in bone and brain, and in lipid metabolism. This ideal set of properties would confer protection from heart disease, osteoporosis, and Alzheimer's disease without increasing the risk of hormone-dependent cancers of the breast and uterus.

Estrogen influences the growth, proliferation and regulated function of many tissues. Cells of living humans are exposed to a large number of estrogens and antiestrogens which originate both endogenously and from environmental sources. Exposure to exogenous compounds can be intentional or unintentional. Intentional exposure includes administration of antiestrogens and estrogens for treatment of various cancers, prescription of estrogens (along with progesterones) for hormone replacement in post menopausal women, and intentional ingestion of phytoestrogen-rich foodstuffs such as soy. Unintentional exposure includes exposure to industrial and agricultural compounds such as DDT and its derivatives and bisphenol A, and inadvertent ingestion of phytoestrogens in food.

Estrogen Replacement Therapy (ERT) has many demonstrated benefits, including decreases in bone loss, fractures and tooth loss; decreased risk of myocardial infarction, gastrointestinal cancer and colon cancer; delay of onset of Alzheimer's disease; and probable decrease in age-related macular degeneration and reversal of urogenital atrophy. Unfortunately, ERT is also associated with elevated risk of gallstones, deep vein thrombosis and endometrial cancer, and there is growing evidence that ERT may also be associated with a moderate increase in risk of breast cancer. Even a modest increase in cancer risk may be problematic, since long term ERT therapy may be required to achieve desired effects such as cardioprotection and prevention of osteoporosis.

Ideal hormone replacement therapy would confer the benefits of today's ERT, most notably preventing heart disease and osteoporosis, without elevating risk of cancer. Selective estrogen receptor modulators (SERMs) such as raloxifene were recently developed in an effort to duplicate the benefits of ERT without introducing the accompanying risks. However, while raloxifene use appears to be associated with reduced risk of breast cancer and decreased loss of bone the in the hip and spine, observed decreases in fractures are limited to the vertebrae, and there is an association with elevated risk of thrombosis. There are no data on cardioprotective effects, although the related compound tamoxifen does not significantly reduce cardiac mortality.

Estrogens appear to cause cancer of several reproductive organs, but also have demonstrated therapeutic benefit, most notably in the treatment of prostate cancer. Antiestrogens are potent therapeutic agents for treatment and possible prevention of numerous reproductive cancers. These findings are consistent with our understanding that estrogens regulate development and function of cell lineages of numerous reproductive tissues including breast, uterus, vagina, ovary, testis, epididymis, and prostate. It is therefore likely that a compound can have a protective effect on a certain cell types and stages, while having detrimental effects on others. While endogenous estrogen may rarely present such conflicts, exogenous estrogens and antiestrogens are administered systemically and thereby delivered to numerous cell populations


Epidemiologic evidence from other cultures and migrant populations strongly suggests that a diet rich in legumes, high fiber grains, fruits and vegetables is associated with reduced incidence of a number of cancers and other chronic diseases. To date, individual food types and components responsible for preventive effects have not been identified, but a large body of data supports the hypothesis that soy isoflavones are important in the observed associations. Dietary intervention studies suggest that soy protein isolate and isoflavones may reduce the risk of breast cancer and help to alleviate postmenopausal symptoms in women. Tentative evidence further suggests that phytoestrogens may have favorable effects on bone density, similar to those associated with the related pharmaceutical compound ipriflavone. Finally, soy appears to have beneficial effect on blood lipids, which may help reduce the risk of cardiovascular disease.

Until recently, there has been little data linking these beneficial effects of dietary soy to individual phytoestrogen constituents. Furthermore, there are conflicting reports as to whether phytoestrogens are estrogenic, weakly estrogenic, or anti-estrogenic in various experimental systems and in humans. In fact, some researchers have sounded the alarm that soy may increase the risk of breast cancer in postmenopausal women, based on studies conducted in ovarectomized animals implanted with human breast cancer cells derived from permanent cell lines or in human breast cancer cell cultures studies in the absence of estradiol. We believe these studies are flawed in that postmenopausal women have circulating estradiol produced through the action of aromatase in adipose tissue. Nonetheless, while soy protein is a high quality protein and an excellent addition to the diet, more evidence will be required before particular dietary practices or changes can be recommended to postmenopausal women who wish to reduce heart disease risk while preventing osteoporosis and breast cancer. There is an urgent need to clarify whether the soy isoflavones are indeed estrogenic in humans.








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