Evaluating the Safety of Soy

By Dónal P. O'Mathúna, PhD. Dr. O'Mathúna is Senior Lecturer in Ethics, Decision- Making & Evidence, School of Nursing, Dublin City University, Ireland; he reports no financial relationship to this field of study.

Source: Chandrareddy A, et al. Adverse effects of phytoestrogens on reproductive health: A report of three cases. Complement Ther Clin Pract 2008;14:132-135.

Phytoestrogens have been thought to have favorable effects on women's health and perhaps in offsetting cancers. The possible adverse effects of phyto-estrogens have not been evaluated.

Abnormal uterine bleeding with endometrial pathology in three women was found to be related to a high intake of soy products. The first woman had postmenopausal bleeding with uterine polyp, proliferative endometrium, and a growing leiomyoma. The second woman presented with severe dysmenorrhea, abnormal uterine bleeding, endometriosis, and uterine leiomyoma not responding to treatment. The third woman had severe dysmenorrhea, abnormal uterine bleeding, endometriosis, and uterine leiomyomata, and presented with secondary infertility. All three women improved after withdrawal of soy from their diet.

Additional information on phytoestrogens is necessary to ascertain their safety before they can be routinely used as supplements.

Commentary

Phytoestrogens are compounds that act in similar ways to estrogen and are found in plants (phyto means "having to do with plants"). Soybeans are probably the best-known natural source of phytoestrogens. The type found in soy is called isoflavones, with genistein and daidzein being the most abundant members of the group. Soy flour and soy milk retain the phytoestrogens, while soy sauce and soybean oil contain very small quantities of phytoestrogens. Much interest has developed around the use of phytoestrogens as a natural form of estrogen replacement therapy. Many phytoestrogen products are available as dietary supplements and soy is sometimes consumed as a source of estrogen. However, a 2007 Cochrane Review concluded that there was no evidence that phytoestrogens alleviate vasomotor menopausal symptoms such as hot flushes and night sweats.1

With the widespread use of phytoestrogens, safety has been a concern. The article reviewed here presents findings from three cases in which an association between phytoestrogen and abnormal uterine bleeding is proposed. Being case studies, care must be taken to avoid suggesting causation where only correlation is warranted. However, concerns have been raised for several years that careful evaluation of potential adverse effects of phytoestrogen is necessary before their use can be widely recommended. These three cases possess important similarities that warrant further investigation.

The three women were of varying ages (ages 56, 43, and 35 years). They presented with varying degrees of abnormal uterine bleeding and other endometrial abnormalities. Various diagnostic and treatment protocols were undertaken with little improvement in symptoms. Dietary evaluation revealed that all three women had been consuming large quantities of soy for a number of years. Unfortunately, the precise quantities were reported for only one of the women. Such details are important to include in case reports and their omission here is a significant limitation. The first woman was reported to have been consuming enough soy milk to provide 40 g of isoflavones per day, which seems like an extraordinarily large amount. Usually, about 40 g of soy or 50 mg of isoflavones per day is recommended. The two other women were reported as consuming extremely large amounts of soy in various forms.

What is probably most notable about these cases is that all three women's symptoms were resolved relatively quickly after soy intake was stopped. This occurred after other medical treatments had been ineffective.

Although some studies have been conducted on phytoestrogens, much remains uncertain about their adverse effects. The Cochrane Review of phytoestrogens for menopausal symptoms found that most studies did not collect data on adverse effects to the endometrium or vagina.1 On this basis, the reviewers concluded there was no evidence of phytoestrogens causing estrogenic stimulation of the endometrium (an adverse effect) when used for up to two years.

However, an earlier study had found that women taking 150 mg soy isoflavones per day for five years had higher levels of endometrial hyperplasia.2 Other studies have not found increased rates of these effects, but they have been conducted for shorter durations. The study which found adverse endothelial effects is the longest randomized controlled trial conducted to date. The women in the three case studies had been consuming large quantities of soy for three, five, and 21 years, respectively. The discussion following the three case studies reviewed a small number of in vitro studies that lend support to claims that phytoestrogens can stimulate the endometrium in similar ways to estrogen.

While these case studies should not be taken to demonstrate causation, they point to the importance of clinical vigilance and further research in this area. Clinicians caring for women with abnormal bleeding should ask about dietary supplement use, and soy intake in particular. The amount and duration of intake should be specifically inquired about. Ethical problems would arise with conducting randomized controlled trials to test for adverse effects of extremely high soy intake, but case-control and cohort trials are warranted. The first step is to determine whether the patterns noted in these case studies are more widespread.

References

1. Lethaby AE, et al. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007;(4):CD001395.

2. Unfer V, et al. Endometrial effects of long-term treatment with phytoestrogens: A randomized, double-blinded, placebo-controlled study. Fertil Steril 2004;82:145-148.