Soy has been a dietary supplement of interest for decreasing menopausal symptoms and breast cancer for some time. The interest comes primarily from association studies of a high-soy diet and decreased breast cancer/menopausal symptoms in Asia. Soy is an isoflavone, which is part of a much larger class of plant compounds called flavonoids. Three types of isoflavones are found in soy products:
Isoflavones are often referred to as phytoestrogens or plant-based estrogens because they have been shown, in cell line and animal studies, to have the ability to bind with the estrogen receptor.
There is confusion about the safety of these plant-based estrogens because these agents can have properties that can cause estrogen-like effects in some cells, causing them to proliferate (divide and grow); while in other cells, isoflavones can stop or block estrogen effects, causing unwanted cells to not grow or even die. There is continuing debate about the following questions:
- What doses and types of soy inhibit estrogen as a growth factor?
- Under what circumstances does soy inhibit estrogen as a growth factor?
- In what doses or circumstances does soy promote estrogen-related growth?
Definitive answers to these questions are not known, but phytoestrogens continue to be investigated for chemopreventive properties. On the other hand, soy has been well studied in numerous randomized, placebo-controlled trials for its effects on reducing hot flashes.[63,64,65,66,67][Level of evidence: I] Most of those trials show that soy is no better than a placebo in reducing hot flashes.[Level of evidence: I]; Currently, there are no compelling data that would inspire the use of soy for hot flash management.
Similarly, trials of black cohosh that have been well designed with a randomized, placebo-controlled arm have also found that black cohosh is no better than a placebo in reducing hot flashes.[67,70,71][Level of evidence: I] Black cohosh used to be thought of as having estrogenic properties, but it is now known that it acts on serotonin receptors, as discussed at the Workshop on the Safety of Black Cohosh in Clinical Studies. One study evaluated black cohosh, red clover, estrogen and progesterone, and placebo in a randomized, double-blind trial.[Level of evidence: I] Each treatment arm was small (n = 22); however, over 12 months, hot flashes were reduced 34% by black cohosh, 57% by red clover, 63% by placebo, and 94% by hormone therapy. Of note, adherence rates were reported to be about 89% over the four groups during this long-term study. At 12 months, physiologic markers such as endometrial thickness, estradiol, estrone, follicle-stimulating hormone, sex hormone–binding globulin, and liver function tests were not statistically different for those on either red clover or black cohosh, compared with those on placebo. However, because these groups were small, the power for this secondary analysis was not reported, and it was likely underpowered to detect important differences.