The company Pascoe advertises its new dietary supplement MENOFLAVON with headlines such as "Red Clover - Phytohormone without Side Effects", "How to Outwit the Aging Process" or "Red Clover Isoflavones may have Cancer Preventive Effects". Red clover extract is supposed to be effective against menopausal problems, osteoporosis, myocardial infarction, memory dysfunction and allegedly even prevents cancer. (1)
Isoflavones are considered to be the most effective among the so-called phytoestrogens. Phytoestrogens are plant derived products with chemical structures similar to estrogens and with effects comparable to weak estrogens or anti-estrogens. The most commonly investigated isoflavones, are genistein and daidzein which are affluent in soybeans but also in red clover and other plants. (2) Another important group of phytoestrogens consists of lignans found in high concentrations in flaxseed as well as grains, vegetables and fruits. The estrogenic components of cimicifuga extract (REMIFEMIN; a-t 1999; No. 1: 18 and 2000; 31: 55-6) are thought to be triterpenoid glycosids und isoflavones. (3)
Evidence of the alleged benefit of phytoestrogens during or after menopause is predominantly epidemiological. For example, the fact that menopausal symptoms are rare and the risk of breast cancer is relatively low in Japanese women is attributed, among other factors, to the high quantity of soy in Asian diet. In addition, a lower risk of cardiovascular diseases is thought to be related to this kind of diet. (4) Whether there is in fact a causal connection or whether use of soy represents no more than a marker of a more healthy lifestyle, remains open.
At this time, no relevant influence of phytoestrogens on hot flashes during menopause can be deduced from published randomized studies which mostly report negative results. (4,5) Also, there are no convincing arguments for a cardioprotective effect. A meta-analysis of controlled studies revealed that a diet rich in soy proteins lowers both the serum cholesterol and triglyceride levels. (6) However, whether these effects are due to the isoflavone component of soy has not been shown conclusively. (5) Studies with clinical end points are not available. The surrogate parameter of serum lipid levels is also influenced by estrogens. Nevertheless, there is no evidence from randomized trials that hormone replacement therapy prevents cardiovascular diseases in postmenopausal women, it may actually promote them (a-t 1998; No. 9: 83; 2001; 32: 83-4).
Published data do not support any protective effect against the development of osteoporosis. Two randomized short term studies with isoflavone containing soy products do not show any effects on bone density. (7,8) A third study shows an increase of bone density under a daily isoflavone dosage of 90 mg, yet no improvement with 56 mg per day. (9) A fracture preventing effect has not been studied.
Contrary to what the cited epidemiological data suggest, there are considerable concerns against the use of phytoestrogens in women with a history of breast cancer: The isoflavones genistein and daidzein stimulate growth of hormone dependent breast cancers both in vitro and animal studies. In addition, both substances antagonize the anti-proliferative effects of tamoxifen (e.g. NOLVADEX). (10) A concentration dependent biphasic effect has been shown for genistein. High concentrations of genistein inhibit in vitro tumor growth and amplify the effects of Tamoxifen. (10) However, the concentration required for these effects cannot be achieved in vivo even under high dosages.
Studies with premenopausal women showed that the intake of isoflavone containing soy products increased the proliferation rate of epithelial breast cells and secretions of breast fluids. In almost 30% of cases, hyperplastic epithelial cells were detected in the breast fluid. (11,12)
Summary: A clinical benefit of phytoestrogens has not been proven. Published data do not support the use of phytoestrogens in order to treat menopausal symptoms or to prevent osteoporosis or cardiovascular diseases. In breast cancer, phytoestrogens may even increase risk and are therefore contraindicated. The isoflavonones genistein and daidzein stimulate tumor growth both in vitro and animal studies and counteract the effects of the anti-estrogen tamoxifen (e.g. NOLVADEX). Women with breast cancer are strongly advised against taking them.