Endometrial cancer

Human estrogen estradiol is known to stimulate the growth of cancer cells. Since soy isoflavones have both estrogenic and antiestrogenic properties, they have been the subject of many cancer studies to determine their overall effect. Uterine fibroids are the most common tumors originating in the smooth muscle wall of the uterus and are the major cause of hysterectomy. Although in vitro studies confirm growth-stimulatory effect of isoflavones on endometrial cancer cells, human studies indicate that isoflavones may actually offer protection from cancer. Epidemiological evidence also shows that Asian women, who consume more isoflavones than Western women, have lower incidence of endometrial cancer.

Study results

But what do these in-vitro studies tell us? A study by the National Institutes of Health, USA, found that low concentrations of genistein stimulated the growth of uterine fibroids in vitro [1]. The researchers found that estrogen receptor alpha was involved in the genistein activation of uterine receptors for insulin-like growth factor-I. Another study by the Yale University School of Medicine, USA, also found that isoflavones induced growth of endometrial cancer cells, but only when dosed at high levels and in the absence of estradiol [2]. When cancer cells were also treated with estradiol, the isoflavones acted protectively by reducing the estrogenic activity of estradiol.

Most animal studies using ovariectomized or estrogen receptor-alpha deficient rodents show that high levels of isoflavones have estrogenic effects, whereas others demonstrate a protective action of isoflavones [3]. For example, on study found that daidzein and genistein prevented estrogen-induced endometrial cancer in mice. It should be noted that results of animal studies using such experimental models cannot reliably be applied to humans.

As demonstrated by epidemiological and clinical studies, there is little evidence that soy isoflavones can cause endometrial cancer [3]. Soy intake may even offer protection against endometrial cancer in premenopausal women, due to anti-estrogenic effects of isoflavones. A meta study by the Korean National Cancer Center investigated the associations between soy food intake and the risk of endometrial cancer and ovarian cancer [4]. They found that women consuming most soy had 30% fewer cases of endometrial cancer than those counsuming less soy. They concluded that their results showed protective effects of soy intake on the risk for endocrine-related gynaecological cancers. Mahady wrote in Nutritional Reviews that clinical and epidemiological data does not link isoflavones intake with risk of endometrial cancer when used at normal therapeutic levels (40 to 80 mg isoflavones per day) [5].

Lead author Ollberding wrote in Journal of the National Cancer Institute that intake of isoflavone-containing foods may be associated with a reduced risk of endometrial cancer [6]. Ollberding and co-workers came to this conclusion after conducted a prospective analysis of more than 46 thousand nonhysterectomized postmenopausal women, 489 of which developed endometrial cancer. They obtained dietary information at baseline and found a reduced risk of endometrial cancer with higher isoflavone intake.

Conclusion

In conclusion, most evidence from human studies points in the direction of soy reducing the risk of endometrial cancer.

References

[1] Di et al. Hum Reprod. A low concentration of genistein induces estrogen receptor-alpha and insulin-like growth factor-I receptor interactions and proliferation in uterine leiomyoma cells. 2008 Aug;23(8):1873-83.
[2] Kayisli et al. Estrogenicity of isoflavones on human endometrial stromal and glandular cells. J Clin Endocrinol Metab. 2002 Dec;87(12):5539-44.
[3] Andres et al. Crit Rev Toxicol. Risks and benefits of dietary isoflavones for cancer.
2011 Jul;41(6):463-506.
[4] Myung et al. BJOG. Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis. 2009 Dec;116(13):1697-705.
[5] Mahady. Do soy isoflavones cause endometrial hyperplasia? Nutr Rev. 2005 Nov;63(11):392-7.
[6] Legume, Soy, Tofu, and Isoflavone Intake and Endometrial Cancer Risk in Postmenopausal Women in the Multiethnic Cohort Study. J Natl Cancer Inst. 2011 Dec 12