Evista® (raloxifene), Hot Flashes and Soy Phytoestrogens
Frederick R. Jelovsek MD
"Do you have information regarding interactions between the hormone Evista, and use of soy or other non-pharmaceutical products for relief of hot flashes during menopause?"
I am 53, and have been taking Evista® (raloxifene) for almost four months as hormone replacement therapy; I also take vitamin supplements and 1200 mg of calcium daily. I have been suffering from hot flashes numerous times daily and at night. ". Anonymous
Raloxifene (Evista ®) is in a category of an anti-estrogen similar to tamoxifen which is used to treat breast cancer. Tamoxifen was somewhat more effective than raloxifene in treating breast cancer so raloxifene fell by the wayside. Then it was found that raloxifene helped prevent the bone loss osteoporosis. Although it did not prevent bone loss as well as estrogens after menopause, it was marketed as an osteoporosis preventative in women who cannot or do not wish to take estrogen as hormone replacement.
Broadly speaking, both raloxifene and tamoxifen are called selective estrogen receptor modulators (SERMs). This means that they react with estrogen receptors in the body but they may not produce the same cellular effects in the breast, uterus, bone, heart and vaginal tract as estrogens do. As it turns out, these SERMs have variable effects on the different tissues. Both raloxifene and tamoxifen have a negative breast effect. Tamoxifen stimulates endometrium just as estrogen does while raloxifene has no endometrial stimulation effects. On the other hand, both tamoxifen and raloxifene help prevent bone loss, but they also seem to make hot flashes worse.
Does raloxifene (Evista ®) cause hot flashes?
Any woman taking raloxifene may be at risk for hot flashes. The real question is are the hot flashes worse or more frequent than if no medicine were being taken at all? There have been several randomized trials including placebo medications using raloxifene to help prevent bone loss. These were summarized in a study that found raloxifene slightly increases the history of hot flashes versus placebo (no active medicine) 28% vs 21% (1). Thus raloxifene makes menopause slightly worse as measured by hot flashes.
Will soy or other phytoestrogens help decrease hot flashes?
In general, phytoestrogens help decrease hot flashes (1). The rule-of-thumb is that they decrease hot flashes about 50% as well as pharmaceutical estrogens.
As far as other positive estrogen effects manifest by phytoestrogens, isoflavones (40 mg/day) have a significant positive vascular effect like estrogens but they do not improve the lipid profile as do pharmaceutical estrogens. Also they do not lower blood pressure in hypertensive patients. They can contribute positively to the prevention of bone loss and sometimes they increase bone density but not to the extent that estrogen does.
Will taking raloxifene (an anti-estrogen) nullify benefits of soy or phytoestrogens
This is an excellent question without a certain answer. We can only guess at the interaction between soy and an anti-estrogen and their effect on hot flashes. One study looked at use of soy in women who were under treatment for breast cancer. Presumably most of them were on tamoxifen. They found that soy did not reduce the incidence of hot flashes versus placebo. This would suggest that raloxifene and soy together may not have any adverse effects, but there may not be any reduction of hot flashes by adding the soy while taking raloxifene (Evista ®).
What would happen if a woman took raloxifene and estrogen together?
Both raloxifene and estrogen would compete for the same estrogen receptors. It is not clear which would win out but studies are starting to appear in which both estrogens and anti-estrogens have been given. One such study of women with breast cancer receiving tamoxifen were given estrogen replacement also. That study found that estrogen was still efficacious even though it was given along with tamoxifen.
What remains to be seen is whether there is any real benefit in taking both an estrogen and an anti-estrogen together. In theory, perhaps a woman could take a low estrogen dose and a low raloxifene dose and get most of the positive benefits on bone, heart, brain and colon cancer without any increased risk of breast cancer. We know that there would probably be a reduction in hot flashes with such a regimen and net positive effects on other systems, but until a study comes along testing this hypothesis, we will not know whether the combination can decrease breast cancer and at the same time deliver all of the other long term estrogen benefits.
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