Estrogenic and Antiestrogenic Effects

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A number of natural compounds can produce estro-genic and antiestrogenic effects. These compounds, which include isoflavonoids, flavones, and flavonols, as well as stilbenes like resveratrol and mammalian lignans like those produced after flaxseed ingestion, are referred to as phytoestrogens. (Resveratrol and flaxseed are discussed in Chapter 20.)

The factors that dictate what response a phytoestrogen will produce are actually complex, but in general, phy-toestrogens possess weak estrogenic activity as compared to estrogen, and they compete with estrogen for estrogen receptors in a cell's nucleus. In addition, they can occur at much higher plasma concentrations than estrogen. Therefore, when estrogen levels are low (as in postmenopausal women), they have the potential to produce estrogenic effects. At least one human study using moderate isoflavone doses (140 milligrams per day, from soy concentrate) noted a slight but significant es-trogenic effect in postmenopausal women.

a A fifth study was indexed in MEDLINE, but it was in Polish and had no abstract.

Using the same reasoning, when estrogen levels are high (as in premenopausal women), we would expect genistein or other phytoestrogens to produce antiestro-genic effects. The effects of genistein on premenopausal women, however, are still uncertain. Mild estrogenic effects from genistein have been reported in some human studies, and two studies have noted that soy intake (at 38 to 60 grams per day) had a stimulatory effect on the breast tissue of healthy premenopausal women.39-42 In another study, a high (60 gram) soy diet for two weeks produced estrogenic effects in the healthy breast tissue of premenopausal women, but these effects were weak.43

Based on the above, we conclude that genistein is likely to produce estrogenic effects in postmenopausal women and may or may not produce them in premeno-pausal women. Some readers aware of the epidemi-ologic studies may be surprised at this conclusion; such studies have reported, for example, that the risk of developing breast and endometrial cancers is reduced 5 to 10-fold in women who regularly consume soy.44,45,46, a On the surface, these results suggest that genistein does not produce estrogenic effects in women. The results are not consistent, however, and the role of isoflavon-oids in risk reduction is still uncertain. Importantly, there is some recent evidence that a protective effect, at least for breast cancer, may be due to early-life exposure to genistein as opposed to current exposure.47,48,49 Furthermore, other soy components besides isoflavones may be involved in any protective effects.

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