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Chapter: Modern Pharmacology with Clinical Applications: Herbal Medicine

Herbal Preparations: Soy and Other Phytoestrogens

Soybeans (Glycine max) are protein-rich legumes widely grown around the world as a food crop.

Soy and Other Phytoestrogens


Soybeans (Glycine max) are protein-rich legumes widely grown around the world as a food crop. They are the major dietary source of isoflavones, which are bro-ken down in the intestine into the phytoestrogens genis- tein and daidzein. It is believed that the lower risk of breast cancer, cardiovascular disease, and osteoporosis in Asian women is partly due to their high soy diet, since these benefits are lost when they adopt Western dietary habits. Flaxseed, from flax (Linum usitatissimum), is the source of another type of phytoestrogen, lignan, as well as linolenic acid and omega-3 fatty acids. Red clover (Trifolium pratense) contains isoflavones as well as coumarin and produces effects somewhat similar to those of diethylstilbestrol. The negative effect of red clover on sheep fertility threatened the economy in New Zealand at one time.


Perhaps the most marketed herbal phytoestrogen is black cohosh, or black snakeroot (Cimicifuga race-mosa), a tall woodland perennial with white torchlike flowers native to eastern North America. The rhizome contains triterpene glycosides and many other ingredi-ents that appear to have phytoestrogenic effects. Other traditional herbs sometimes promoted as phytoestro-gens, such as dong quai (Angelica sinensis), have little medical evidence to support their use.



Mechanism of Action


Soy isoflavones appear to act as selective estrogen recep-tor modulators in that they can occupy and block the - estrogen receptor. In premenopausal women with nor-mal estrogen levels, soy therefore would have an overall antiestrogen (estrogen blocking) effect, whereas in postmenopausal women lacking estrogen, a weak estro-genic effect would be observed. Soy may also increase the excretion of bile acids and lower cholesterol.


The mechanism of black cohosh’s phytoestrogen ef-fect is unclear, although it may also inhibit estradiol binding to estrogen receptors. It does not appear to con-tain isoflavones like soy, and there are conflicting find-ings on its estrogenic activity. Early reports of luteiniz-ing hormone suppression have been contradicted by more recent research showing no change in go-nadotropins or estradiol. There appears to be no stimu-latory effect on estrogen receptor–positive breast can-cer cells.





Soy is possibly effective in reducing menopausal symp-toms, such as hot flashes, although it is much less effective than estrogens for this purpose. Higher isoflavone doses than are typically achieved in the U. S. diet are necessary to protect against osteoporosis. High isoflavone soy pro-tein intake outperformed lower isoflavone supplements in this regard. Ipriflavone, a semisynthetic isoflavone, is effective in the treatment and prevention of osteoporosis and is used for this purpose in Europe and Japan. In the United States, the FDA has approved the use of soy in conjunction with a low-fat diet for cholesterol reduction. There also is evidence that diets high in soy protein re-duce the likelihood of prostate cancer. There is much less evidence available regarding the effectiveness of red clover and flaxseed; however, they too appear to hold some promise for menopausal symptoms, lipid reduction, and prostate cancer.


Black cohosh (Remifemin preparation) appears mod-estly effective in menopausal symptom relief, according to several German studies of up to 6 months’ duration; however, more research is necessary before it can be rec-ommended as an estrogen alternative. Black cohosh is less effective than estrogen for symptom reduction and is not known to have any effect against osteoporosis.


Adverse Reactions, Contraindications, and Interactions


While soy is generally considered safe, it may induce nausea, bloating, and allergic reactions (itchy rashes or even asthma if inhaled as dust) in some people. One study suggested that high midlife soy (tofu) consump-tion may be associated with cognitive decline in later life. However, educational and social differences be-tween the high- and low-tofu groups may also account for some of these findings. Research findings in regard to the safety of soy in breast cancer patients conflict, with an in vitro study suggesting possible stimulation of estrogen-dependent breast cell cultures.


Black cohosh may cause nausea, vomiting, hypoten-sion, and even miscarriage. It is absolutely contraindi-cated in pregnancy. Red clover contains coumarins and should therefore be avoided with anticoagulants. Diets high in red clover isoflavones have reduced livestock fertility and theoretically could do the same in humans. Flaxseed may cause nausea, diarrhea, and flatulence. Cyanogenic nitrates in flax (especially in immature seed pods) have produced toxic reactions.




Soy protein doses of 20 to 60 g daily are used to reduce hot flashes and to lower elevated cholesterol. Higher doses of isoflavones (2.25 mg/g soy protein) or more than 60 g soy protein may help prevent osteoporosis.


Black cohosh root doses vary widely, with up to 2000 mg/day of root being taken several times daily. Remifemin is the best-studied brand, and tablets con-taining 40 mg of black cohosh extract with 1 mg of triterpenes are given as one or two tablets twice daily.




Soy appears to have weak estrogenic activity when taken after menopause but may block the effects of more potent estrogens (thereby reducing breast cancer risk) when used before menopause. It can reduce menopausal symptoms but is less effective than estro-gen in this regard. Although long-term high soy diets may help prevent osteoporosis, it is likely that most U. S. women will not consume enough to be adequate for osteoporosis treatment. Semisynthetic or concentrated isoflavone preparations may play a role in the future.


Black cohosh may reduce menopausal symptoms, and it appears safe and well tolerated for at least a 6- month period. It lacks the other proven benefits of es-trogen, however. There is less information to recom-mend red clover and flaxseed, although they remain widely used for this purpose.


A listing of other popular herbs and their proposed actions is given in Table 69.4.



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