Title: Phytoestrogens - Natural HRT or not?
Keywords: soy, hormone replacement therapy, phytoestrogens, oestrogen, breast cancer, endocrine, pesticides, steroid hormones, pollutants, infertility, isoflavones, xenoestrogens, coumestans, lignans, soya, soybeans, lentils, beans, linseed, flaxseed, whole grain, miso, tempeh, gut microflora, premenstrual tension, menopause, genistein, natural, cholesterol, breast tissue,
Author: Saffron Whitehead
First published in 'Health and Ageing', 2002
Phytoestrogens - Natural HRT or not?
Soy is being heavily promoted as a natural alternative to hormone replacement therapy (HRT) because it contains high concentrations of phytoestrogens that can mimic the action of natural oestrogens produced by the body. But should women be dosing themselves up with dietary supplements of phytoestrogens when their potential harmful effects are not yet known? And how can the epidemiological evidence that high soy diets may protect against breast cancer be reconciled with soy as a natural HRT when the growth of up to 50% of breast cancers are oestrogen-dependent?
Phytoestrogens are found in a wide variety of plants and constitute one of the two major groups of endocrine disrupting chemicals. The other group is the xenoestrogens. These are the man made chemicals and include synthetic oestrogens, industrial chemicals and pesticides. Whether natural or man-made, all endocrine disrupting chemicals have one thing in common. Their chemical structure, which often resembles our natural steroid hormones, allows them to bind with oestrogen receptors and mimic the action of our own hormones, albeit at concentrations 1,000 to 10,000 times higher than those found in the body.
Their rise to notoriety began with increasing stories of the decline in certain wild-life populations of fish, birds, reptiles and mammals that had been exposed to polluted water. What was happening was that pollution was disrupting the normal development of offspring so that they and subsequent generations became infertile or sexually incompetent and unable to breed. Finally the connection was made. The industrial pollutants contained endocrine disrupting chemicals. And when several studies emerged indicating declining sperm counts in men, it didn’t take long to attribute this to our polluted environment. Whilst some scientists remained sceptical about the validity of these studies, the media had a field day. Before long both environmentalists and the government were truly concerned about endocrine disrupting chemicals.
The story of phytoestrogens as endocrine disrupting chemicals began in the l940’s when an epidemic of infertility hit flocks of sheep grazing in the rolling hills of Perth in western Australia. First there was a striking increase in still-born lambs, then ewes failed to go into labour and the lambs died, and finally even after repeated breeding with fertile rams, the ewes became completely infertile. After extensive detective work over several years the problem was finally put down to clover - a Mediterranean species that had been introduced into Australia to improve their natural pastures. Eventually the clover was shown to contain a phytoestrogen classed as an isoflavone.
Inevitably research has moved from enviornmental studies into the laboratory - into the test tube and into experimental animals treated with megadoses of endocrine disrupting chemicals. Here lies the dilemma. To what extent can we equate this work to our natural exposure to xenoestrogens and dietary phytoestrogens?
Most phytoestrogens found in our food come from three chemical classes – the isoflavones, coumestans and lignans. The isoflavones that have oestrogenic activity are almost exclusively found in legumes including soybeans, lentils and beans such as haricot, kidney, and broad beans. The major coumestan is coumestrol that is present in sprouts and fodder crops. The third group, the lignans, are widely distributed in cereals, fruit and vegetables. They occur in particularly high concentrations in flaxseed (linseed) and to a lesser extent in whole grain cereals. Alcohol is not excluded from this list because phytoestrogens are present in beer made from hops and bourbon made from rye. There is one other group of natural oestrogenic chemicals that are not strictly phytoestrogens because they are produced by moulds growing on crops and infected food. They are classed as mycotoxins.
In the human diet the highest concentrations of phytoestrogens are the isoflavones in soy products and the lignans in flaxseed. But with the exception of fermented soy products, such as miso and tempeh, these phytoestrogens are present in food as inactive conjugated compounds. They have to be broken down in the gut to release to the active free compound or are further metabolized to active substances by the gut microflora.
It is possible to measure the concentration of isoflavones and lignans in human serum, urine, faeces, semen, saliva and breast milk, but their concentrations show wide individual variation. This, of course, is partly related to a person’s diet, to drugs, such as antibiotics that kill off the gut bacteria and to other factors such as bowel disease. What we don’t know is the fate of these phytoestrogens once absorbed. For example only 20% of one of the major phytoestrogens in soy that is ingested appears in the urine. Is the rest metabolised in the body or does it accumulate in tissues? So little is known about the fate of ingested phytoestrogens, it may be may be premature to extrapolate their effects in a test tube to their effects in the human body.
Of all the phytoestrogens present in our foods, the claimed health benefits of soy are most widely known and publicized. Go to any soy web site and there one sees claims that it is beneficial for treating a variety of medical conditions ranging from hypothyroidism, premenstrual tension, breast and prostate cancer and menopausal symptoms, to name but a few. In the laboratory the major oestrogenic ingredients of soy, genistein and diadzein, have been widely investigated.
It was initially believed that phytoestrogens would be predominantly oestrogenic, acting either as mimics of oestrogen or blocking the action of oestrogen produced in our bodies. But over the last decade it has become apparent that phytoestrogens have a range of actions and that no single action can explain many of the effects seen in experimental animals or in the test tube.
Many women are now using soy supplements as a ‘natural’ alternative to HRT presumably because they believe that soy’s oestrogenic ingredients will replace the loss of their natural hormones. A small number of studies have shown that soy supplementation can reduce hot flushes by 40%, but this effect is equivalent to a placebo response. Oestrogenic effects of soy, which can be seen by changes in vaginal cytology or oestrogen-sensitive breast tissue, are generally absent. There is conflicting data on whether soy can reduce cholesterol levels and its effects on the cardiovascular system and on bone are currently under investigation.
The issue of breast cancer is a difficult one although it is generally accepted that life-time exposure to oestrogens plays a role in the induction or development of this serious disease. Women often take soy because of their fear that conventional HRT will increase their risk of breast cancer, but is there any evidence that the weak oestrogenic effects of soy may also promote cancer growth? Results from a few case-controlled human studies looking at the connection between eating soy products and breast cancer are conflicting, most being carried out with small numbers of Asian women. Only three studies have included more than 200 women. The largest uncontrolled studies are those showing that the incidence of breast cancer amongst Japanese and Chinese women, who consume high concentrations of dietary soy, is at least two thirds lower than that seen women living in the US and European countries. Differences in diet are thought to be the major underlying factor but we cannot make the assumption that it is simply soy or the phytoestrogens it contains.
In the laboratory, high doses of genistein can inhibit the growth of experimentally induced tumours but in human breast-cancer cell lines low doses of genistein (as would be achieved on a high soy diet) promote cell growth. In contrast, very high pharmacological doses stop growth and promote cell death. We just don’t know whether high soy diets protect Asian women against breast cancer (and indeed prostate cancer in men). Does their life-time exposure to soy alter the development of breast tissue making them less susceptible to this disease in later life? When men and women of the Pacific Rim emigrate to the US their risk of prostate or breast cancers rises. For men it is in the same generation though in women this change usually occurs in the next generation.
Phytoestrogens are not simply oestrogen mimics or antagonists and they have been shown to have a wide variety of effects including growth promotion of new blood vessels, inhibitors of cell signalling and can mop-up free radicals. Genistein, for example, can block the effects of growth factors and inhibit enzymes that produce biologically active steroids. Such actions could explain an anti-tumourogenic effect of this phytoestrogen, but how does it help the menopausal woman whose only source of oestrogen is from converting androgens secreted by her adrenal glands into oestrogens? This requires the very enzymes that genistein inhibits.
In humans (it is not true in wildlife) there are no scientifically proven examples of environmental chemicals that improve, worsen or indeed cause medical conditions as a result of their hormone-like activity. but perhaps there should be caution about taking high-dose dietary supplements of refined phytoestrogens. As Professor Richard Sharpe, an expert in environmental oestrogens, surmises, “The old adage ‘absence of evidence is not evidence of absence’ is a useful guiding principle.”
Dr Saffron Whitehead,
Reader in Reproductive Physiology