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Med J Aust 2000; 173 Suppl 6 November: S97-S98

Phytoestrogens are compounds derived from plants, which, after being metabolised in the gut, may exert oestrogenic and anti-oestrogenic effects.¹ Epidemiological studies comparing Asian and Western populations suggest that consuming a phytoestrogen-rich diet ameliorates symptoms of oestrogen deficiency in postmenopausal women,² and may protect against breast cancer, bone loss and cardiovascular disease.^3,4 However, the findings of recent intervention studies do not support a role for phytoestrogens as an alternative to conventional hormone replacement therapy (HRT) in postmenopausal women.

The first study to show that certain dietary phytoestrogens can exert mild oestrogenic effects in postmenopausal women was published in 1990, and revealed an increase in vaginal-cell maturation index (an indicator of oestrogen activity).⁵ Subsequently, reports of effects of phytoestrogen supplementation on postmenopausal vasomotor symptoms have not been consistent. There are considerable differences between studies, with no clear correlation between oestrogenic changes in vaginal cells and effects on vasomotor symptoms.⁶ An Australian study of the effects of soy versus wheat flour supplementation on hot flushes and vaginal cells in postmenopausal women showed no benefit with soy compared with wheat after 12 weeks.⁷ The reduction in the rate of hot flushes after 12 weeks was greatest in the wheat diet phase, which was associated with very low urine isoflavone levels. Another study reported a small reduction in hot flushes in postmenopausal women whose diet was supplemented with soy versus placebo, but the effects were not dramatic.⁸

Two studies have investigated the effects of a tablet preparation of isoflavones extracted from red clover (Promensil; Novogen) versus placebo in postmenopausal women.^9,10 Doses of both 40mg and 160mg per day had the same effect as placebo in reducing hot flushes, and did not alter vaginal cytology or serum concentrations of sex hormone binding globulin, follicle-stimulating hormone or total cholesterol.^9,10 Similarly, another study showed no significant benefit of concentrated phytoestrogens in tablet form over placebo at 12 weeks.¹¹ Phytoestrogens do not appear to relieve other symptoms that characterise the menopausal transition, such as anxiety, arthralgia, myalgia and headaches.^9,10

Phytoestrogens have been reported to have anticarcinogenic properties,^1,12 and some epidemiological studies have suggested an association between high phytoestrogen intake and reduced breast cancer risk.^13,14 A study of urinary phytoestrogen excretion in Australian women immediately after diagnosis of breast cancer reported lower isoflavone excretion in women with breast cancer compared with controls, despite similar dietary patterns.¹⁵

A study in postmenopausal women in Singapore did not observe a beneficial relationship between soy intake and breast cancer,¹⁶ while a Chinese study found no association between soy and breast cancer, but rather an inverse correlation between intake of fibre and other nutrients and breast cancer rates.¹⁷ This is consistent with a progressive reduction in the relative risk of breast cancer with each quintile of increasing fibre intake for women.¹⁸ Most recently, lower levels of oestrogen receptor (ER) alpha gene expression have been shown in normal breast tissue in Japanese women compared with white Australian women and this may contribute to ethnic differences in breast cancer rates.¹⁹

Isoflavones have been shown to have protective effects in animal studies of experimentally induced breast cancer, measured by tumour number, incidence, metastases and latency.^20,22 However, studies in breast cancer cell lines have shown that, at low concentrations (equivalent to levels measured in humans consuming 40mg of phytoestrogen supplement daily), phytoestrogens stimulate ER-positive cells with no effect on ER-negative cells.^23-25 Consistent with these findings, daily soy supplementation stimulates oestrogen-sensitive markers²⁶ and increases the rate of breast epithelium proliferation in premenopausal women.²⁷ At very high concentrations phytoestrogens inhibit the growth of both ER-positive and ER-negative cell lines.^20,25,28 The role of phytoestrogens in cardiovascular disease, as well as their emerging role in bone health, is addressed elsewhere.

Thus, most randomised controlled trials show no benefit of phytoestrogen supplementation for vasomotor symptoms in postmenopausal women. Phytoestrogens have oestrogenic effects on the breast, and large, longer term studies examining the effects of phytoestrogen supplements on the breast in premenopausal and postmenopausal women are required before concentrated supplements can be safely recommended. In the interim, concurrent use of high-dose phytoestrogen supplements and tamoxifen in women with breast cancer should also be discouraged until further information is available, because of the potential for isoflavones to antagonise the desired anti-oestrogenic effects of tamoxifen.²⁹

Foods such as legumes, grains, vegetables and cereals are not only rich in phytoestrogens but are also excellent sources of protein, iron and fibre. Maximising the consumption of these foods, rather than just soy products, should be encouraged.

Summary Most randomised placebo-controlled trials show no benefit of phytoestrogens in managing menopausal vasomotor symptoms. Concentrated phytoestrogen supplements appear to have oestrogenic actions in the breast and may interfere with the therapeutic use of tamoxifen. Unlike concentrated supplements, foods rich in phytoestrogens, such as vegetables, grains and legumes, are also excellent sources of fibre, unsaturated protein, vitamins and minerals and their consumption should be encouraged.

References

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