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Soy and Menopausal HealthIn the Spotlight: Isoflavones
More than 600 scientific papers are now published on isoflavones annually, compared with just 12 for the entire year of 1985. The US government is very interested in the health effects of isoflavones. For example, the National Cancer Institute (NCI) has been investigating the anticancer effects of soy, especially isoflavones, since 1991.(8) In 1999, the US Department of Agriculture (USDA), in conjunction with Iowa State University, created an online database on the isoflavone content of foods, and in that same year, the National Institute of Aging (NIA) and the National Institute of Health (NIH) convened a three-day workshop on isoflavones.(9)
As the chemical structure of isoflavones is similar to that of estrogen, it is not surprising that isoflavones can mimic estrogen's effect on the human body in many ways(10)(11)(12)(13) — but not all. This may be a good thing because estrogen has positive effects on some parts and systems of the body and negative effects on others. The ideal estrogen substitute would have estrogen-like effects on the coronary vessels, skeletal system and brain but anti-estrogenic effects on the breast and uterus lining. It appears that the isoflavones found in soy foods may do just that. Estrogen, for instance, increases endometrial cell proliferation(14) and serum triglyceride levels(15) — bad things from the point of view of disease risk — whereas isoflavone-rich soy protein — bad things from the point of view of disease risk — whereas isoflavone-rich soy protein(16)(17) and isolated isoflavones(18)(19) have no effect on endometrial cell proliferation in the uterus and little or no effect on serum triglyceride levels.(20)(21)(22)(23) HERS I/II and WHI: HRT versus Soy
Breast Cancer
The WHI and HERS II studies indicated that breast cancer risk would be two to three times higher in lifetime HRT users. Several epidemiological studies have also found increases of this magnitude.(24)(25)
It seems, however, that it is the combination of estrogen and progestin, not estrogen alone, that increases breast cancer risk.(26)(27)(28)(29)(30) Supporting this are several epidemiological studies which found that estrogen alone only slightly increases breast cancer risk, whereas the combination of the two hormones markedly increases risk. It is very important that, unlike the combination estrogen/progestin arm of the study referred to above, the estrogen-only arm of WHI was not discontinued and that, thus far, no increase in breast cancer risk has been reported. Likely Effects of Soy
The first research on soy and breast cancer was undertaken not only because breast cancer mortality rates are generally low in Asia(31) but also because weak estrogen-like compounds such as isoflavones, have been known for decades to exert anti-estrogenic effects under some experimental conditions(32) In fact, the first study demonstrating the anti-estrogenic effects of genistein in rodents was published in 1966.(33) Isoflavones can exert anti-estrogenic effects in several ways,(34) although we have little direct evidence of these effects in humans. Overall, the evidence that soy intake by adults reduces breast cancer risk is not certain but an exciting hypothesis, based on studies of Japanese immigrants,(35) as well as on animal(36) and epidemiological studies involving soy(37) is that soy consumption early in life markedly reduces adult breast cancer risk.
Despite the mounting evidence for the anticancer effects of soy, some researchers are concerned that the estrogen-like properties of isoflavones might increase breast cancer risk in certain high-risk women. However, although controversial, increasingly the available evidence suggests that neither soy nor isoflavones are a concern because the real culprit now appears to be the combination of estrogen and progestin, rather than estrogen alone.(38) Clinical research also suggests soy is safe. In one study, isoflavone supplements had no effect on breast tissue density — increased breast density can be a precursor of breast cancer — in premenopausal women,(106) whereas in another, isoflavones decreased breast tissue density in women 56-65 years of age.(39) These effects are not only opposite to those of HRT, but suggest that soy either has no effect on or decreases breast cancer risk.(40) The bottom line is that soy, unlike HRT, does not appear to increase breast cancer risk. Venous Thromboembolic Disease
The WHI study found that HRT, and estrogen in particular, raises the risk of increased blood clotting, something that can cause diseases such as deep vein thrombosis and pulmonary embolism.(41)(42)
Likely Effects of Soy
Isoflavone-rich soy protein and isoflavones either reduce or have no effect on blood clotting.(43)(44)(45) Animal research even suggests that soy and isoflavones may actually inhibit unhealthy blood clotting.(46)(47) Overall, there is no evidence to suggest that like estrogen, isoflavones, or soy, increase the risk of deep vein thrombosis or pulmonary embolism.
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