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New studies suggest that eating large amounts of soy’s estrogen-mimicking compounds might reduce fertility in women, trigger early puberty and disrupt development of fetuses and children

Soy is ubiquitous in the American diet. Over a quarter of all infant formula sold is made with it, and the U.S. Food and Drug Administration promotes it in foods to reduce the risk of heart disease. School lunch programs across the country are even adding soy to hamburger patties.

Many of soy’s health benefits have been linked to isoflavones—plant compounds that mimic estrogen. But animal studies suggest that eating large amounts of those estrogenic compounds might reduce fertility in women, trigger premature puberty and disrupt development of fetuses and children.

Although most studies looking at the hormone-disrupting properties of genistein, the main isoflavone in soy, have been conducted in rodents, many scientists believe the findings may be relevant to humans as well.

“We know that too much genistein is not a good thing for a developing mouse; it may not be a good thing for a developing child,” said Retha Newbold, a developmental biologist at the National Institute of Environmental Health Sciences. More definitive answers, she said, may lay ahead in future long-term human studies.

Soy consumption in the U.S. has skyrocketed since the early 1990s, with soy food sales climbing from $300 million in 1992 to over $4 billion in 2008. Clinical studies have shown that eating soy can lower cholesterol as well as the risk for certain types of breast and prostate cancer.

But Newbold and other researchers are not convinced that eating more soy is healthy for everyone. Infants fed soy formula ingest six to 11 times more genistein on a bodyweight basis than the level known to cause hormonal effects in adults.

“Giving an infant or child estrogen is never a good thing,” said Newbold.

Though studies on the harmful effects of soy isoflavones in people have been limited and inconclusive, there’s strong evidence from animal studies that genistein alters reproduction and embryonic development, according to Newbold, a co-author of two of the new rodent studies.

In some lab studies, animals were fed doses similar to what people might get from a high-soy diet, which would be roughly 25 or more grams per day. Blood levels of genistein in people eating a lot of soy are generally in the range of one to five micromoles, or about one milligram of genistein circulating in the body of an average adult.

One study showed that genistein led to reduced fertility and abnormal embryo development in female mice. They were fed one to ten micromoles in their drinking water for four days. The highest doses were associated with fewer eggs that were successfully fertilized and increased cell death in developing embryos. Wen-Hsiung Chan at Chung Yuan Christian University in Taiwan conducted the study, which was published in July in the journal Reproductive Toxicology.

In another study, young female rats were fed high, medium, or low doses of genistein. Those fed the largest quantities from birth to weaning had reproductive effects later, including early puberty and irregular estrous cycles (similar to the menstrual cycle in humans). High doses also led to smaller litters.

The rats were tested before and during pregnancy, and then several generations of their offspring were examined. The study, by a team including Newbold and Barry Delclos of the National Center for Toxicological Research, was published in the journal in April.

In male rats, high doses led to abnormal growth of breast cells, but did not cause cancer or the feminization of reproductive organs, according to another study by Newbold and others published in November.

In those two studies, the rodents were fed at least five times more genistein than the amount that people would be exposed to through food, supplements or infant formula. Such a high dose was used because they wanted to test the effects of the maximum amount that could be ingested by the rats without severely limiting their ability to reproduce.

The growing body of research in recent years raises questions about possible risks to women trying to get pregnant, as well as to developing fetuses and infants who consume large amounts of genistein in formula, some researchers said.

The findings trouble Heather Patisaul, a developmental biologist at North Carolina State University, and others who study soy's impact on development.

“Our reproductive system and the rat reproductive system aren’t that different. The same hormones are involved," Patisaul said.

While any impacts on adult fertility are likely reversed by eating less soy, impacts on the reproductive tracts of infants could be permanent.

But to date, only one study has looked at the long-term effects of soy formula on reproductive development in people. It found that women fed soy formula as infants had slightly longer periods and more menstrual cramping than those who were not fed soy formula.

Brain development, which begins in the womb and continues through puberty, also may be altered by estrogen in soy, Patisaul said. It is controlled by a well-organized combination of genes and hormones. Introducing compounds that mimic estrogen could throw off the balance, with long-term impacts on behavior and brain chemistry.