Touted as the 'natural cure' for menopause, the high dose plant supplements may have strong oestrogenic effects on the body, with all the dangers of large doses of ordinary oestrogens.
As bad news about HRT keeps rolling in, conventional and alternative practitioners have found themselves scrambling around for something to give women complaining of menopausal symptoms. So far, phytoestrogens have fitted the bill marvellously. Depending on whose research you read, phytoestrogens have either no oestrogenic effect or only a weak one. They work, we're told, by modifying the sensitivity of cells to physiological oestrogens as well as by modifying their production and metabolism. The result of this action on a given tissue can be either proestrogenic or antioestrogenic. Much attention has been focused on the antioestrogenic effect, which proponents say is protective. Phytoestrogens supposedly bind with oestrogen receptors in the body, preventing stronger and potentially more harmful oestrogens (both human and environmental) from taking hold and potentially causing cancer.
However, emerging evidence shows that phytoestrogens may not be all that weak. In sufficient quantities, they may cause all the same responses as physiological oestrogens (Endocrinology, 1998; 139: 4252-63).
The example of diethylstilbestrol (DES), an oestrogen given to women in the 1950s to prevent miscarriage, may be helpful. DES was considered a weak oestrogen in the sense that it did not compete with natural oestrogens for oestrogen receptors. Today, we are only beginning to understand the devastating generational effects of taking DES-research shows that even the granddaughters of women who took this hormone are at a higher risk of ovarian cancer.
Oestriol (an oestrogen metabolised from plant sources) is considered a weak oestrogen by some measures but a strong one by others. It is 'weak' because, when you compare equal amounts of natural oestrogen and oestriol, the latter has less of an effect on the body. However, animal data suggest that oestriol actually binds more strongly to receptors than DES does (J Steroid Biochem, 1977; 8: 151-5).
At the same time, oestriol can be considered 'strong' because, in large doses, it can produce quite profound effects. Again, we have mainly animal data to guide us but, in one human study, when 5 mg of oestriol was given to women intravaginally, this very large dose suppressed luteinising hormone (LH) production within two hours and suppressed follicle stimulating hormone (FSH) in five hours. A larger dose of 8 mg given orally had similar effects on LH and FSH after 30 days, and also had an oestrogenic effect on the vaginal epithelium (Fertil Steril, 1978; 30: 278-82).
Coumoestrol, found in high doses in red clover, is unique among phytoestrogens in that it has been shown to have a powerful oestrogenic effect six times that of regular iso flavones (Proc Soc Exp Biol Med, 1995; 208: 44-50).
Years ago, agricultural research showed that red clover could cause permanent infertility in sheep that consumed it (J Dept Agric West Aust, 1946; 23: 1-12). This effect was similar to that observed in animals exposed neonatally to oestrogens (J Reprod Fertil, 1981; Suppl 30: 223-30) and the strong oestrogenic effect of red clover has been confirmed in other studies (Proc Soc Exp Biol Med, 1995; 208: 92-7).
Another indication of the strength of an oestrogen is its ability to cause the uterus to enlarge. In terms of milligrams required to cause a certain rate of uterine enlargement, oestriol is slightly weaker than oestradiol (Gynecol Endocrinol, 1977; 11: 175-85). But given enough of the stuff, uterine enlargement will occur. When added to a long term culture of human breast cancer cells, oestriol stimulated their growth and overcame the antioestrogenic effect of tamoxifen (Cancer Res, 1977; 37: 1901-7). This has also been noted in laboratory studies.
The competition for oestrogen receptor sites is complex and not accomplished by the independent action of any single hormone. Whether a hormone binds to a particular site is likely to be the result of the sum total of biological (and increasingly today, non biological) hormones in the body.
We are only just beginning to understand that the body produces different types of oestrogens. For example, 2-hy droxyoestrone, which exerts a protective effect on the body, is considered a 'good' oestrogen whereas 16-alpha hydroxyoestrone, which can predispose the body to diseases such as cancer, is considered 'bad'. The same factors that influence the total amount of oestrogen in the body including diet, lifestyle, medications and use of other exogenous sources of oestrogen also influence the production of good and bad oestrogens.
In his book, The Breast Cancer Prevention Program (New York: Macmillan, 1977), Dr Samuel Epstein comments that among the risk factors for the development of breast cancer are the amount of oestrogens natural, synthetic, pseudo and phytoestrogens and the length of time a woman is exposed to them.
According to one reviewer, as far back as the 1940s, a Dr Alexander Lipshuts demonstrated that a continuous, weak oestrogenic stimulus was very effective in producing first fibromas and then cancer in one organ after another, and that the effect was not limited to the reproductive system (Townsend Lett Docs, 1997; 162: 53-7).
It is interesting that nobody has ever asked what happens to those 'other' oestrogens while the phytoestrogens are busy binding with oestrogen receptors.
There are many different oestrogen receptors in the body, located in the brain, breast, liver, skin, uterus, vagina, bone and bladder as well as several other sites. Throughout a woman's reproductive life, the number of these receptor sites can increase (up regulate) or decrease (down regulate), depending on the total amount of oestrogen circulating in the body. While this may have a positive effect on some tissues, for example, strengthening bones, it may create problems in others, for instance, in the breast, where an excess of oestrogens can lead to the development and proliferation of cancer cells.
Proponents of phytoestrogens say that excess oestrogen is simply excreted in urine, but this view is based on short term studies. In fact, the significance of the urinary excretion of hormones is not fully understood. Some argue that high excretion of the oestrogenic byproducts of phytonutrients shows that the body takes what it needs and discards the rest. Others argue that high urinary excretion of these substances is a clear indication of their hormonal activity and advise caution. There is evidence that, over the longer term, urinary excretion of phytoestrogens can decrease over time in women (Nutr Cancer, 1996; 26: 289-302; Am J Clin Nutr, 1998; 68 (6 Suppl): 1500S-4S).
What happens to these non excreted phytoestrogens is unknown. They may be broken down into non steroidal metabolites or they may have other fates, the long term effect of which we do not know. One laboratory study, for example, has shown that the flavonoids coumoestrol, genistein and daidzein have the potential to induce chromosomal abnormalities in human blood cells (Arch Toxicol, 1999; 73: 50-4).
What has been established is that there are considerable variations in the ways in which individuals metabolise phytoestrogens (Proc Soc Exp Biol Med, 1995; 208: 40-3). Metabolism is different between the sexes; it's also highly dependent on lifestyle. For example, to metabolise phytoestrogens effectively, the gut must be populated with beneficial microflora (J Nutr, 1995; 125: 2307-15).
Many things can negatively affect gut microflora, including a high fat diet (Nutr Cancer, 2000; 36: 27-32). A high fibre diet, on the other hand, promotes the metabolism of phytoestrogens (Proc Soc Exp Biol Med, 1998; 217: 335-9). Fermentation of soya also appears to increase the bioavailability of its iso flavones (J Am Diet Assoc, 1995; 95: 545-51; Am J Clin Nutr, 1998; 68 (6 Suppl): 1492S-5S).
While phytoestrogens are generally promoted as preventing cancer, laboratory studies the only controlled studies we have show mixed results, with some concluding that soya isoflavones inhibit tumour growth and others showing that they can promote it.
One review of 21 studies in vitro and in vivo involving 26 different cancer sites did show that soya isoflavones might provide protection for several types of cancer (Nutr Cancer, 1994; 21: 113-31). However, the majority of human evidence for cancer protection still comes from population studies, where it is almost impossible to account for all the variables which influence health and disease (Lancet, 1997; 350: 990-4).
Phytoestrogens may inhibit the growth and spread of cancer in diseased breasts. However, there is little real evidence that they can protect a normal healthy breast.
In fact, there is some evidence that a high intake of dietary soya for just 14 days can significantly stimulate the proliferation rate of breast skin cells, although the implications of this over the long term are anyone's guess (Am J Clin Nutr, 1998; 68 (6 Suppl): 1431S-5S.
What's more, in a recent study of the effects of different phytoestrogens on oestrogen receptor positive breast cancer cells in vitro, red clover had the same effect on cell growth as oestradiol (Proc Soc Exp Biol Med, 1998; 217: 369-78).
Other menopausal symptoms
Phytoestrogens are also purported to prevent osteoporosis, though much of the evidence is epidemiological (Menopause, 1999; 6: 233-41; Proc Soc Exp Biol Med, 1998; 217: 386-92) and animal (J Nutr, 1996; 126: 161-7). In human studies, improvements in bone health have been small and limited to the lumbar (lower back) vertebrae (Baillieres Clin Endocrinol Metab, 1998, 12: 543-57).
Studies of the ability of phytoestrogens to relieve menopausal symptoms are equally mixed (Obstet Gynecol, 1999; 94: 229-31). In a recent crossover study of breast cancer survivors, 150 mg of soya oestrogens per day gave less relief from hot flushes than placebo (J Clin Oncol, 2000; 18: 1068-74).
Two placebo controlled trials (sponsored by a major red clover supplement manufacturer) have shown no adverse or intolerance effects to standardised red clover extract which is rich in several isoflavones but also no real effectiveness in dealing with menopausal symptoms such as hot flushes. In one study comparing women given either a placebo or an isoflavone extract of red clover containing either 40 mg or 160 mg of total isoflavones. The study took place over a period of 12 weeks. Flushing activity decreased in all the groups, with no differences between the active and placebo groups (Climacteric, 1999; 2: 79-84).
In another study, 51 postmenopausal women received either placebo or a 40-mg standardised red clover supplement over a three month period, and then switched places. Once again, hot flushes decreased in both groups with no significant differences between them (Climacteric, 1999; 2: 85-92).
Phytotherapy vs phytonutrition
Some scientists specialising in environmental oestrogens make only a small distinction between man made oestrogens, such as those found in pesticides, and those which occur naturally in foods such as soybeans, flaxseed, fruits, vegetables and animal fat. Both, they say, are potential endocrine disrupters (Toxicol Lett, 1998; 102-3: 349-54).
Unlike their man made counterparts, these naturally occurring endocrine disrupters do not appear to be stored in the body for long. When taken as nutrients in the diet, some may even exert a protective effect. But several questions remain unanswered. For instance, what happens when we begin to deliberately bombard the body with these phytoestrogens either through high dietary intake or in supplement form?
One current trend is to eat more soya, and many women are introducing this product into their diet late in life (unlike Oriental women who may have been eating it all their lives) in quantities that are far and above what would be consumed by traditional cultures. Many more are ingesting soya without realising it since soya flour is used in many processed foods. Recent moves in the US to fortify even more foods with soya may further increase exposure to this product.
Far from being a miracle food, soya has some adverse consequences when consumed in high quantities. It can lower the bioavailability of vitamins A, B, C and E. It can also reduce iron levels, which may be why Oriental women balance soya intake with iron rich seaweed.
In support of the use of phytoestrogens, many alternative practitioners cite the experience of Asian women who, research tells us, live longer, have lower rates of heart disease and breast cancer, and do not suffer from menopausal symptoms to the same degree that Western women do (J Hong Kong Med Assoc, 1993; 45: 249-54; Maturitas, 1994; 19: 157-76). This, they say, is because of the high intake of phytoestrogens in this culture.
But women in Asian cultures take in plant oestrogens as phytonutrients. In the West, we take them primarily as supplements, or phytotherapy, with no optimal dosages established.
It is likely that the influence of concentrated phytoestrogens on the body's physiological systems may be quite different from those observed with the lower levels available through food. A typical phytoestrogen supplement in the UK or US may contain as much as 250 mg of phytoestrogens.
Compare this to Germany, where the recommended dose is 40 mg and women are advised not to take it for more than six months because of the lack of long term studies.
Natural foods contain literally hundred of different phytochemicals in a delicate synergy. Purified concentrates, on the other hand, are made to increase the dose of a specific known active ingredient while downgrading or eliminating others.
Much of what women are told about the actions of phytoestrogens is intelligent guesswork. In reality, we have no idea what will happen when we begin to dramatically change the ratios of exogenous to endogenous hormones in the body.
No one particularly wants to burst the bubble founded on an all natural 'cure' for the menopause.
However, in our rush to embrace an alternative to HRT, we may also be threatening the health of women in ways we cannot yet foresee the ultimate deception from a profession that promises 'safer alternatives'.