Phytoestrogens are a group of naturally occurring, plant-derived compounds that have either a weak estrogenic, or anti-estrogenic effect. They are often called “dietary estrogens”, and are used widely by women to treat the symptoms of menopause. Their popularity has increased after several large women’s health trials alluded to health risks in women taking hormone replacement therapy for menopausal symptoms.
Phytoestrogens can be divided into three groups:
Flavonoids, such as genistein, naringenin, and kaempferol
Coumestans, such as coumestrol
Lignans, such as enterodiol, and enterolactone.
The most widely known and studied phytoestrogens are the isoflavones found in red clover and soy: genistein, formononentin, biochanin, and daidzein.
Urologists have known, or rather assumed, that diets high in soy, such as in Asia, have a protective effect on men against development of prostate cancer. However, in women there has been conflicting evidence. Some studies show a protective effect against breast cancer, while some in vitro studies differ on whether they hinder or potentiate tumor cell growth. Some phytoestrogens are weakly estrogenic and bind the estrogen receptor, but are approximately 1,000 times weaker than estradiol. Other phytoestrogens exhibit a blocking effect on the estrogen receptor. The isoflavones in soy show mainly an agonist effect, namely, a weak estrogen effect.
Does this mean that soy compounds can lead to “side effects” such as endometrial hyperplasia or cancer? This of course is not known.
More intrigue: genistein antagonizes the inhibitory effect of tamoxifen on breast cancer cell growth in vivo. This raises more questions than answers.
Recently, a group of researchers from Austria set out to clarify the safely profile of phytoestrogens by analyzing all known studies published in English. One hundred seventy four randomized controlled trials comparing phytoestrogens to placebos were identified, however in 82, no side effects were discussed. Mean treatment duration was short at approximately six months.
Various categories of side effects were studied: gastrointestinal, gynecological, urinary, neurological, musculoskeletal, etc. The most common side effects seen among the women were GI complaints such as nausea, vomiting, heartburn, gastric irritation or pain. Women older than 55 had a higher rate of these GI symptoms. Studies in the U.S. and Europe were less likely to report GI side effects. The length of the study, such as six months versus 24 months did not lead to a higher incidence of side effects. Actually, fewer side effects were observed the longer women were taking phytoestrogens. Other side effects noted were muscle pain and sleepiness.
Of potential gynecological side effects, the side effects of vaginal spotting, nipple discharge, breast pain/enlargement, breast cancer, endometrial hyperplasia, and pelvic pain were reviewed. One study showed a higher rate of endometrial hyperplasia with atypia after five years of phytoestrogen supplementation. However there was no observed increased risk of endometrial cancer or breast cancer in any individual study or meta-analysis. There was no indication of other side effects that can occur with hormone replacement such as stroke, blood clots, heart attack and breast cancer.
The authors were cautious but did conclude that based on the available data, phytoestrogens can be used over a two year period. However, they did not comment on their efficacy in controlled menopausal symptoms. Overall, only GI upset was seen to be the category of significant side effects, while over a two year period, no endometrial or breast cancer was observed. This comprehensive review that these researchers took highlights the recurrent theme that when treating oneself with medication or “natural products," when it involves hormone manipulation we may not know the true long term (more than five years) effect. We have also learned that they may be safe in the short term, there is sometimes conflicting data, and they should be taken in moderation. Just because compounds occur in nature doesn’t confer on them an automatic sense of “safety” or “health”. And certainly, eating a soy burger may have less fat than a regular burger, but only eating soy burgers is not going to make you live to 100 (without hot flashes).