Since the recent well-founded anxiety about the long-term effects of hormone replacement therapy (HRT), many women have sought alternatives to estrogen. The sudden decline in estrogen after menopause is linked to decreased bone mineral density (and thus an increased risk of osteoporosis), increased total and LDL cholesterol levels, and some reduction in mental functioning.

The isoflavones are estrogen-like compounds that occur naturally in plant foods, and they have found favor with women wanting to try a possibly safer alternative to HRT. Soy protein supplementation has been shown in some studies to reduce cholesterol levels by about 10%. But a study reported in the Journal of the American Medical Association now finds no obvious benefits of soy supplements on bone mineral density (BMD), cholesterol levels, or mental functioning.

This study was done in Utrecht, Netherlands. Women aged 60 to 75 were invited by mail to participate, if they were suitable for receiving estrogen therapy. After baseline screening, they were assigned at random to receive either 25.6 g (about an ounce) of isoflavone-rich soy protein powder that could be mixed with food or beverages, or a matching 'placebo' - 25.6 g of total milk protein powder. Both powders contained extra vitamins and minerals. One dose of powder was to be taken daily for 12 months. The study was 'double-blind', meaning that neither the women nor the investigators knew which supplement each subject was taking, until after the study was finished.

BMD measurements in the femur and lumbar spine were done at baseline and after 12 months. Plasma lipids were also measured before and at the end of the study. Mental ability ('cognitive function') was assessed using the Mini-Mental State Exam, a verbal learning test of memory, recall tests, complex attention tasks, and verbal skills; these tests were also carried out at baseline and at the end of the 12 months. A blood test for a soy component was done at 12 months to test for compliance with the regime.

Of 300-plus women willing to participate, 100 had to be turned down, for medical (75) or non-medical (25) reasons. This left 102 women in the placebo group, and 100 in the soy group. The blood tests for genistein - the soy component - showed that the women in the soy group stuck the regime.

A total of 175 women completed the baseline and 12-month tests. Their mean age was 67. There were no differences between the two groups after one year with respect to cognitive function test results and plasma lipid levels. In the BMD analyses there was a slight increase in one of 13 different measurements with the women from the soy group, but the other 12 measurements showed no differences between the groups.

There were no differences between the groups with respect to complaints of 'side effects' - the pattern and frequency of such complaints were the same in each group.

Most of the promising results with soy as an estrogen-substitute have been obtained in animal studies. The authors suggest that there may be a species-difference in the tissues' response to isoflavones.

It's also possible that the disappointing results are because this study was done in older women (60-75) who were, on average, 18 years post-menopausal; perhaps one year of soy treatment was too little, too late. The recent Women's Health Initiative Memory Study report, while failing to show a benefit of estrogen on mental functioning, pointed out that the subjects studied were also age 65-79, and the lack of response might be due to their relatively advanced age.

This study clearly does not support the view that isoflavones from soy protein have beneficial effects on BMD, mental functioning, or blood lipid levels. However, before proclaiming that many thousands of women must be wrong, further studies are warranted, that start earlier, last longer, and use a variety of isoflavone preparations.