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Phytoestrogens & Your Baby

Don't doubt it - phytoestrogens are bad for your baby.

Why expose your baby?

Many parents that fed soy formulas in the 1960's did so after receiving the advice that they were 'better than breast milk'.  Had they known that these products contained phytoestrogens, compounds that are now known to cause thyroid disorders, behavioural and developmental disorders and cancer they would not have even contemplated the use of what was, in hindsight, an experimental product.

Most parents feeding soy formulas still have absolutely no idea that they contain these potent endocrine disrupting compounds, and by not disclosing the presence of phytoestrogens in their products, soy formula manufacturers are in violation of the WHO code of marketing breast-milk substitutes.  For a review on the health concerns raised about soy infant formula, read the Food Commission Briefing Paper written by Dr Mike Fitzpatrick and Sue Dibb.

The message from Soy Online Service is simple.   Breast is best, everything else is greatly inferior.  If your child is lactose intolerant or allergic to dairy protein, there are alternatives to soy.  Soy Online Service advice is do not feed a soy formula under any circumstances.  Why?   Despite knowing for years about the toxic effects of phytoestrogens, soy formula manufacturers have not acted to remove them from their products.  Infants fed soy formulas are still being exposed to unacceptably high levels of phytoestrogens.

Why are we so sure that phytoestrogens are bad for your baby? 

And why, when the evidence is plain are regulators not doing more to reduce the risk of exposing developing infants to these potent endocrine disruptors?

The American Academy of Pediatrics (AAP) has recently stated that a number of studies are currently addressing the soy-formula/phytoestrogen issue. But this gives precious little direction or peace of mind to those that are currently feeding, or have been fed, a soy formula. So when and how is the phytoestrogen issue likely to be resolved? In reality it could be years before science provides the answers, and perhaps those answers will never come. But if bodies such as the AAP don't know what to make of phytoestrogens, and a real risk is recognised, then the only decision that can be made is a precautionary one.

This is the essence of the ‘precautionary principle', that is, a bona fide risk of harm that lacks some degree of scientific certainty should not prevent regulators from acting to protect those who are at risk of that harm.

In this instance the precautionary principle would dictate that:

• until phytoestrogens are proven to be safe for infants they should be removed from soy formulas.
• soy formula manufacturers should bear the burden of proving the safety of phytoestrogens.

The fact is that there is strong evidence of real harm being caused to soy formula fed infants by phytoestrogens leaves little room for debate on whether the precautionary principle should apply in this case.

The only ones likely to strongly disagree with the precautionary approach are soy formula manufacturers. In February 1998 the Infant Formula Council issued a statement on phytoestrogens. Like previous statements from infant formula manufacturers, their release was notable for its dismissal of any possible concern and its total failure to address the real issues.

The Infant Formula Council argument began by announcing that studies on infants fed soy formulas ‘have not indicated any evidence of harmful effect'. This statement is nonsense because there have been no studies that have specifically investigated the potential harmful effects that phytoestrogens might have on infants.

This statement is also incorrect. Although there have been no direct investigations of the potential harmful effects of phytoestrogens on infants, other studies provide strong evidence that phytoestrogens in soy formulas do harm infants.

Firstly, the consumption of soy-based formulas was associated with an increased occurrence of premature thelarche in Puerto Rico. In 1982 Pediatric endocrinologists in Puerto Rico reported on an increase in the incidence of breast development in girls younger than eight years of age. Of the 552 diagnosed cases reported between 1978 and 1982, a representative group of 130 were studied in an attempt to identify possible factors that might have contributed to what was considered an epidemic of premature thelarche.

Approximately 68 percent of the cases (85 out of 130) studied experienced the onset of thelarche before they were 18 months old. In these most overt cases, the investigators found a positive statistical association between premature thelarche and the consumption of soy formulas (22 cases), various meat products (10 cases) and a maternal history of ovarian cysts (16 cases).

Despite the probability that phytoestrogens in soy formulas were culpable in the Puerto Rico outbreak and the fact that mounting evidence that the early onset of puberty is increasing in the US (at the same time as soy formula sales reach record levels), there have been no studies to further investigate the link between soy formulas and premature thelarche.

What are the long term risks associated with premature thelarche? There is still debate over whether or not premature thelarche progresses to precocious puberty, but there is evidence from several studies that shows that it does increase the chance of early menarche. A higher incidence of ovarian cysts has also been found in girls that develop breasts at an early age. The earlier the onset of menarche, the greater the lifetime risk of breast cancer, and the early incidence of ovarian cysts is an established risk factor in the later development of ovarian cancer. One can only wonder why the Infant Formula Council don't consider the Puerto Rico cases of premature thelarche as evidence of harm.

Secondly, like many endocrine disruptors, the soy phytoestrogens can cause thyroid dysfunction in humans. Reports from the late 1950s and early 1960s found that infants fed soy-flour formulas developed goitre, although the goitrogenic factors were not isolated at that time. More recent reports have further identified the actual toxicity of soy to the thyroid and mechanistic investigations have determined that the anti-thyroid factors in soy are the phytoestrogens.

Little doubt can remain that the goitre in infants fed soy formulas was caused by the phytoestrogens. Claims that phytoestrogens have had no effect on the infant endocrine system just don't wash, unless of course the thyroid is no longer part of the endocrine system. If further evidence is needed that there is genuine cause for concern then it should be noted that malignant goitre has also occurred in experimental animals fed soy even when iodine is present in their diets and there is clear potential for soy isoflavones to cause a range of thyroid disorders in iodine sufficient humans.

It is possible, but unlikely, that the Infant Formula Council are not aware that phytoestrogens cause goitre. The soy industry has known that soy contains goitrogenic agents for over 60 years and for more than 40 years it has been known that these agents are also present in soy formulas. The cases of goitre that were reported in soy formula fed infants in the late 1950's ceased when manufacturers added more iodine to their products. But is the simple addition of more iodine to soy formulas an appropriate way in which to counteract the goitrogenic and anti-thyroid effects of the phytoestrogens?

To answer that question one must understand how the soy phytoestrogens (isoflavones) act on the thyroid. Isoflavonoid, and the related flavonoid, compounds are well known goitrogens and anti-thyroid agents. They typically act against the thyroid by inhibition of thyroid peroxidase (TPO). The soy isoflavones are no exception. They are potent inhibitors of TPO, in fact they are more potent than either of the anti-thyroid drugs PTU or MMI. What is food for thought is that in vitro the isoflavones inhibit TPO catalysed reactions at concentrations that are comparable to those found in the plasma of human infants fed soy formulas.

The fact is that soy formula fed infants appear to be at real risk of long term thyroid damage. If you want to be sure your child will not be at risk of such harm then the message is simple; avoid soy formulas. And just in case you're told that there is no evidence that thyroid soy formulas increase the risk of thyroid disease, consider the fact that a preliminary report has found a significant association between feeding soy formulas and the development of autoimmune thyroid disease (ATD). Although the mechanism by which ATD may occur in infants fed soy formulas was not discussed by the authors, ATD is associated with exposure to estrogens.

So far the only government agency to publicly acknowledge the potential of soy formulas to damage your baby's thyroid is the New Zealand Ministry of Health.  Why not write to your health agencies and ask them to warn parents of the dangers of soy formulas?

Why you shouldn't believe soy formulas manufacturers?

They're just plain dishonest.   Take, for example IDFA (Infant and Dietetic Foods Association) in the UK.  In their 1 September 1999 letter to Jilly Rosser, Editor of Practising Midwife, IDFA's Executive Secretary, Sarah Jacobs, wrote:

"The accusation that soya-based infant formulas have been part of a 'large, uncontrolled and basically unmonitored infant experiment' is untrue.  Soya infant formulas have a long history of use and there is considerable body of evidence based on human research studies and clinical trials to show that they are safe and that infants thrive well on them".

In truth there is no evidence that soy formulas are safe, but Dr Dan Sheehan's statement that infant formula feed has been a 'large, uncontrolled and basically unmonitored infant experiment' is accurate.

IDFA have been guilty of telling porkies about soy formulas previously.  In their 10 January 1995 Press Release 'Phytoestrogens and Soya Infant Formulas' IDFA reported that:

The first two points are outright lies.  The latter point contains an element of truth.  The breast milk of women eating soy products does contain phytoestrogens but the levels are more than 1000 times lower than the levels in soy formulas.  IDFA's attempt to dupe consumers into thinking that infants exposed to soy formulas are only receiving low levels of phytoestrogens, comparable with those found in breast milk is viewed by Soy Online Service in the same light as the "better than breast milk" line that infant formula manufacturers sold consumers in the 1960's.  And all this in the name of infant nutrition!   When will the deliberate deception end?

Contact us

If you are concerned that soy formulas may be responsible for a thyroid problem or some other developmental disorder in your baby contact our medical expert; you may also receive free legal advice from Soy Online Service.  Contact:

webmaster@soyonlineservice.co.nz

Useful references:

Bisphenol A in infant formula at 'dangerous' levels, says group, 12/6/2007 by Ahmed ElAmin. Bisphenol A (BPA), known as the 'gender bender' chemical, leaches into liquid baby formula from the linings of cans at levels dangerous to infant health, according to new research published yesterday by a US environmental group. The Environmental Working Group (EWG) said the research reveals that Bisphenol-A, used to line nearly all infant formula cans, was found in at levels "far higher" in the product than those that leach from plastic bottles under normal use. EWG had previously estimated that one out of every 16 infants fed ready-to-eat liquid formula are exposed to BPA at doses exceeding those that caused increased aggression and significant changes in testosterone levels in laboratory animals. Read more here

Soya Formula for Infants Should Only Be Administered on Doctor's Advice, Says German Consumer Safety Watchdog, 19-11-07: Infant formula and follow-up formula based on cow's milk protein or soy protein is for sale in the European Union. Soy formula should only be administered to infants over a longer period when this is necessary on medical grounds. If a mother is unable to breastfeed her baby, she can fall back on infant formula from the drug store or supermarket. Products made from soybean protein and from cow's milk are on sale. Soybeans contain high concentrations of isoflavones. They should, therefore, only be given to infants over longer periods in exceptional, justified cases. Isoflavones are similar to the female hormone oestrogen; however, they have a far weaker effect. Furthermore, soybeans may also contain higher amounts of the plant component, phytate. Professor Dr. Dr. Andreas Hensel, President of the Federal Institute for Risk Assessment (BfR), comments, "Infant formula and follow-up formula made from soy protein should only be administered on medical grounds and then only under medical supervision." Read more here

POSSIBLE EFFECTS OF PHYTOESTROGENS IN SOY INFANT FORMULA Soy formula, which contains phytoestrogens, genistein and daidzein (also called isoflavones) is given to approximately 25% of those US children fed formula. It is estimated that an infant exclusively fed soy formula receives the estrogenic equivalent of at least five birth control pills per day. By contrast, almost no phytoestrogens have been detected in dairy-based infant formula or in human milk, even when the mother consumes soy products. A recent study found that babies fed soy-based formula had 13,000 to 22,000 times more isoflavones in their blood than babies fed milk-based formula. Scientists have known for years that isoflavones in soy products can depress thyroid function, causing autoimmune thyroid disease and even cancer of the thyroid. But what are the effects of soy products on the hormonal development of the infant, both male and female? Read the full article here.

Endocrine disrupters and female reproductive health. McLachlan JA, Simpson E, Martin M.
Department of Pharmacology, Tulane University School of Medicine, and Environmental Endocrinology Laboratory, Center for Bioenvironmental Research, Tulane and Xavier Universities, New Orleans, LA 70118, USA. john.mclachlan@tulane.edu There is growing evidence of the impact of estrogenic contaminants in the environment. Studies have shown that male fish in detergent-contaminated water express female characteristics, turtles are sex-reversed by polychlorinated biphenyls (PCBs), male frogs exposed to a common herbicide form multiple ovaries, pseudohermaphroditic offspring are produced by polar bears, and seals in contaminated water have an excess of uterine fibroids. Read more here

News from Soyatech.com - A substance found in soy-based infant formula and over-the-counter dietary supplements affects the development of ovaries and eggs in female infant mice, according to a study conducted by researchers at the National Institutes of Health (NIH) and Syracuse University. Read the article here.

GM: New study shows unborn babies could be harmed - Mortality rate for new-born rats six times higher when mother was fed on a diet of modified soya. Women who eat GM foods while pregnant risk endangering their unborn babies, startling new research suggests. The study - carried out by a leading scientist at the Russian Academy of Sciences - found that more than half of the offspring of rats fed on modified soya died in the first three weeks of life, six times as many as those born to mothers with normal diets. Six times as many were also severely underweight.

Healthy Alternatives to Conventional Infant Formula - go here for cow mik, goat-milk, liver, fortified commercial formula, egg yolk and whey-based formula alternatives suggested by Dr Mercola.

Manganese Content of Soy or Rice Beverages is High in Comparison to Infant Formulas - read about the effects of Manganese in our Soy Toxins section.

Soy Products and Infant Leukemia

Artificial baby milks: how safe is soya?

"Two separate studies -- one in animals and the other in humans -- that considered together suggest that a diet high in soybeans and other legumes during pregnancy and breastfeeding may have a subtle but long-term impact on the development of children." writes Dr Mercola. Read the full article here

Read the British Dietetic Associations position on the use of soya protein for infants Here.

New guidelines on infant feeding in the first 12 months of life by Judy More, Royal London Hospital, London. Read More Here

The United Kingdom Chief Medical Officer has warned all doctors that soy-based infant formulas should be used  only in exceptional circumstances, because of a risk to long term Reproductive Health.  Full information on the UK Expert Committee's findings are Here

In their Paediatric Policy, the Royal Australasian College of Physicians Health Policy Unit outlines their policy on the Use of Soy Protein Formula.

The Insider's Guide to Natural Medicine" is also alarmed at the harm soy does to baby's thyroid.  Read their opinion Here.

An article published in Scientific American (2002) suggests soy infant formula may impair the developing immune system.  Read More Here

Natural Life Magazine #68 - Soy Infant Formula Dangerous to Babies, Say Groups

Soy and children's health: a formula for trouble.  Follow this Link to an article published in Environmental Health Perspectives.

The literature is replete with numerous studies showing deleterious effects on multiple organ systems - including the immune system.  For example this letter from the American Journal of Clinical Nutrition.

"For the males, decreased sperm count and enlarged prostates. The treatment altered virtually every aspect of the reproductive system. The place next to the testes, the duct system called the epididymis where the sperm are stored prior to being ejaculated -- it was abnormally small, which could account also for lowered sperm count in the ejaculate. But we know also the testis is making fewer sperm. We see changes in growth rate as well. One of the interesting things is that these very low doses of estrogen increase rates of growth. The animals were actually growing larger than they would have normally. It was really quite a dramatic effect. The females went into puberty early. And we saw changes in behavior, changes in reactivity to the presence of other animals in the environment. Essentially the animals looked to be somewhat hyper-reactive to stimuli. We have, in other words, effects on brain and behavior. We're also seeing changes in liver enzyme activity which determines the way we respond to external chemicals, how fast we clear drugs, how we metabolize drugs.

In other words, in every aspect of physiology that we look for, we see effects. And they're permanent. And the important thing about what I'm talking about is we are only exposing babies to these chemicals for very, very short periods of time in development and the consequences are for the rest of the life of that individual. Once you change the development of an organ there is no way to undo that effect. It's a life sentence -- that's a lifetime consequence. Medical science can't undo the development of organs."  Fredrick Vom Saal, Professor of Biological Sciences, University of Missouri in an interview on estrogenic chemicals in the environment conducted in February 1998 by Doug Hamilton, producer of FRONTLINE's "Fooling With Nature."  Full interview can be found here

For further information on soy protein intolerance, follow this link to eMedicine.com

Canadian Health Coalition say Health Canada are exposing babies to serious risk and recommend that the routine use of soy-based infant formulas must be stopped.

It is already known to medical researchers that thyroid dysfunction in a mother increases the risk of her baby having subnormal thyroid and brain functions.  This report of research at John Hopkins University supports the potential link between isoflavone consumption during pregnancy, thyroid harm and birth defects

There are  links between high soy diets during pregnancy and nursing and eventual developmental changes in children.  Congenital abnormalities of the genital tract are also increasing, and once again soy phytoestrogens may be implicated, according to a study that found a higher incidence of birth defects in male offspring of vegetarian, soy-consuming mothers.

"Excess consumption of soy or other phytoestrogens also might contribute to pseudopuberty."  Soy has been linked as a potential clinical factor in the early onset of puberty termed "Precocious Puberty".  Read more from eMedicine.com.

Read more about the potential effects of soy on Male Reproductive Health published in Endocrinology journal.

Soyonlineservice receives questions about whether soy formulas are causing scoliosis in children. As far as we know there has been no direct research on an association between soy formulas and childhood scoliosis, presumably because the industry has never admitted that it leaves this chemical in its products.  Howerver, the levels of phytic acid in soy protein can run as high as 3% of the volume, and soy protein is 19% of soy formulas. Therefore it is feasible and entirely possible for its depletion to the later onset of scoliosis to result.  Read more about Other Soy Toxins Here.

Lactational transfer of the soy isoflavone, genistein, in Sprague-Dawley rats consuming dietary genistein.

Doerge DR, Twaddle NC, Churchwell MI, Newbold RR, Delclos KB.

Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, AR 72079, USA.

Exposures of Sprague-Dawley rats to the soy isoflavone, genistein, throughout the entire lifespan have produced a number of effects on reproductive tissues, immune function, neuroendocrine function and behavior. Our previous studies investigated pharmacokinetics and disposition of genistein during adult and fetal periods and this study describes the internal exposures of post-natal day 10 (PND10) rat pups due to lactational transfer of genistein. Conjugated and aglycone forms of genistein were measured by using LC/MS/MS in serum (PND10) and milk (PND7) from lactating dams consuming a genistein-fortified soy-free diet, and in serum from their pups at a time when milk was the only food source (PND10). This study shows that limited lactational transfer of genistein to rat pups occurs and that internal exposures to the active aglycone form of genistein are generally lower than those measured previously in the fetal period. These results suggest that developmental effects attributable to genistein exposure in our chronic and multi-generation studies are more likely to result from fetal exposures because of the higher levels of the active estrogenic aglycone form of genistein in utero, although the possibility of neonatal responses cannot be excluded.

Prof Kenneth Setchell:

Prof Cliff Irvine:

The potential adverse effects of soybean phytoestrogens in infant feeding [letter].
Irvine C, Fitzpatrick M, Robertson I, Woodhams D.  N Z Med J 1995 May 24 108:1000 208-9.
Download letter.

Dr Dan Sheehan:

Isoflavone content of breast milk and soy formulas: benefits and risks [letter]
Sheehan DM.  Clin Chem 1997 May 43:5 850.

Other work:

Effects of lactational exposure to soy isoflavones on reproductive system in neonatal female rats.
Liu Z, Zhang X, Li L, Zhang W, Cui W, Song Y, Wang W, Jia X, Li N, Yan W, Basic Clin Pharmacol Toxicol. 2008 Mar;102(3):317-24.

Lactational exposure to isoflavones could result in oestrogen-like actions on the reproductive system of neonate female rats, which mechanisms may be, at least, involved with modifications of hormone production and steroid receptor transcription in the reproductive system.

Full Abstract Here

Genistein at a concentration present in soy infant formula inhibits Caco-2BBe cell proliferation by causing G2/M cell cycle arrest.
Chen AC, Donovan SM. J Nutr. 2004 Jun;134(6):1303-8.

Thus, a biphasic effect of genistein was seen with a low dose stimulating intestinal cell proliferation through the estrogen receptor, whereas a high dose of genistein inhibited intestinal cell proliferation and altered cell cycle dynamics. A high dose of genistein may potentially compromise intestinal growth.

Full Abstract Here

Manipulation of prenatal hormones and dietary phytoestrogens during adulthood alter the sexually dimorphic expression of visual spatial memory.
Lund TD, Lephart ED. BMC Neurosci. 2001;2(1):21. Epub 2001 Dec 18.

Full Abstract Here

Hypocalcemic tetany in 'alternative' soy milk nutrition in the first months of life
Anil M, Demirakca S, Dotsch J, Kiess W. Klin Padiatr. 1996 Nov-Dec;208(6):323-6.

A 14 weeks old infant was admitted to the intensive care unit with life-threatening hypocalcemic-hyperphosphatemic spasms. Hypocalcemia-hyperphosphatemia was found to have been caused by feeding a high phosphate/ low calcium soy milk. The daily uptake of calcium was calculated to have been 3.3-6 mmol that of phosphate 30 mmol. The parents strongly believed that soy milk formulas were equivalent to breast milk and cow's milk formulas and lived on a strictly vegetarian diet.

 Vegetarian feeding had led to life-threatening hypocalcemic hyperphosphatemic spasms in the infant. We conclude that malnutrition and false nutritional beliefs have to be included as a potential cause of early hypocalcemia in infants.

Full Abstract Here

Read more on milk alternative issues on our Chicken Roost page

The phenotype of the aromatase knockout mouse reveals dietary phytoestrogens impact significantly on testis function.
Robertson KM, O'Donnell L, Simpson ER, Jones ME. Endocrinology 2002 Aug;143(8):2913-21

Our study highlights the importance of estrogen in spermatogenesis and shows that relatively low levels of dietary phytoestrogens have a biological effect in the testis.

Full Abstract Here

Estrogen and spermatogenesis.
O'Donnell L, Robertson KM, Jones ME, Simpson ER. Endocr Rev 2001 Jun;22(3):289-318

This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

Full Abstract Here

Premature thelarche in Puerto Rico. A search for environmental factors.
Freni-Titulaer LW, Cordero JF, Haddock L, Lebrón G, Martínez R, Mills JL. Am J Dis Child 1986 Dec 140:12 1263-7.
Abstract
Pediatric endocrinologists in Puerto Rico reported a threefold increase in the number of patients with
premature thelarche seen between 1978 and 1981. A matched-pairs case-control study was conducted to evaluate associations with potential environmental exposures to substances with estrogenic activity, as well as with familial factors. Analysis was performed on 120 pairs, the case subjects of which were selected from those diagnosed between 1978 and 1982. In subjects 2 years of age or older at the onset of thelarche, no significant associations were found. In subjects with onset before 2 years of age, significant positive associations were found with a maternal history of ovarian cysts, consumption of soy-based formula, and consumption of various meat products. A statistically significant negative association was found with consumption of corn products. These statistical associations are probably not sufficient to explain the reported increase because in over 50% of the case subjects there was no exposure to any of the risk factors for which statistical associations were found. Exposure to other substances with possible estrogenic effect, such as waste products from pharmaceutical factories and pesticides, was also excluded as a possible cause. These findings suggest that better diagnosis and reporting, or conceivably the presence of entirely new, unsuspected factors, could account for the reported increase.

Developmental effects of dietary phytoestrogens in Sprague-Dawley rats and interactions of genistein and daidzein with rat estrogen receptors alpha and beta in vitro.
Casanova M, You L, Gaido KW, Archibeque-Engle S, Janszen DB, Heck HA. Toxicol Sci 1999 Oct;51(2):236-44

...effects of dietary genistein included a decreased rate of body-weight gain, a markedly increased (2.3-fold) uterine/body weight (U/BW) ratio on postnatal day (pnd) 21, a significant acceleration of puberty among females...

Full Abstract Here

Soy isoflavone supplements antagonize reproductive behavior and estrogen receptor alpha- and beta-dependent gene expression in the brain.
Patisaul HB, Dindo M, Whitten PL, Young LJ. Endocrinology 2001 Jul;142(7):2946-52

Supplement treatment also resulted in a significant decrease in receptive behavior in estrogen- and progesterone-primed females. The observed disruption of sexual receptivity by the isoflavone supplement is probably due to antiestrogenic effects observed in the brain.

Full Abstract Here

Effect of estradiol and soy phytoestrogens on choline acetyltransferase and nerve growth factor mRNAs in the frontal cortex and hippocampus of female rats.
Pan Y, Anthony M, Clarkson TB.  Proc Soc Exp Biol Med 1999 Jun;221(2):118-25

Our data suggest that soy phytoestrogens may function as estrogen agonists in regulating ChAT and NGF mRNAs in the brain of female rats.

Full Abstract Here

Influence of perinatal genistein exposure on the development of MNU-induced mammary carcinoma in female Sprague-Dawley rats.
Yang J, Nakagawa H, Tsuta K, Tsubura A. Cancer Lett 2000 Feb 28;149(1-2):171-9

Genistein treatment during the perinatal period resulted in lower body weight and lower relative uterine-ovarian weight at 35 days, and a prolonged estrus cycle with a long estrus phase at 12-16 weeks.

Thus, perinatal genistein is an endocrine disrupter and increases the multiplicity of MNU-induced mammary carcinoma in rats.

Full Abstract Here

Neurobehavioral actions of coumestrol and related isoflavonoids in rodents.
Whitten PL, Patisaul HB, Young LJ. Neurotoxicol Teratol 2002 Jan-Feb;24(1):47-54

Treatment of rat dams with a 100-ppm coumestrol diet from birth to postnatal day (PND) 21 induced premature anovulation in female offspring, and treatment from birth to PND 10 suppressed sexual behavior in male offspring.

Full Abstract Here

Cross-species and interassay comparisons of phytoestrogen action.
Whitten PL, Patisaul HB. Environ Health Perspect 2001 Mar;109 Suppl 1:5-20

In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses.

Full Abstract Here

Placental transfer of the soy isoflavone genistein following dietary and gavage administration to Sprague Dawley rats.
Doerge DR, Churchwell MI, Chang HC, Newbold RR, Delclos KB. Reprod Toxicol 2001 Mar-Apr;15(2):105-10

These studies show that genistein aglycone crosses the rat placenta and can reach fetal brain from maternal serum genistein levels that are relevant to those observed in humans.

Full Abstract Here

Mass spectrometric determination of Genistein tissue distribution in diet-exposed Sprague-Dawley rats.
Chang HC, Churchwell MI, Delclos KB, Newbold RR, Doerge DR. J Nutr 2000 Aug;130(8):1963-70

Endocrine-responsive tissues including brain, liver, mammary, ovary, prostate, testis, thyroid and uterus showed significant dose-dependent increases in total genistein concentration.

Full Abstract Here

Genistein exerts estrogen-like effects in male mouse reproductive tract.
Strauss L, Makela S, Joshi S, Huhtaniemi I, Santti R. Mol Cell Endocrinol 1998 Sep 25;144(1-2):83-93

...genistein (2.5 mg s.c./kg of body weight/day for 9 days) reduced testicular and serum testosterone concentrations, pituitary LH-content and prostate weight.

These results suggest that in adult males, genistein induces the typical estrogenic effects in doses comparable to those present in soy-based diets.

Full Abstract Here

Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring.

Hilakivi-Clarke L, Cho E, Onojafe I, Raygada M, Clarke R. Oncol Rep 1999 Sep-Oct;6(5):1089-95

A high estrogenic environment in utero may increase subsequent breast cancer risk.

Our results suggest that a maternal exposure to subcutaneous administration of genistein can increase mammary tumorigenesis in the offspring, mimicking the effects of in utero estrogenic exposures. Further, increased ER protein levels and reduced PKC activity in the mammary gland may be involved in increasing susceptibility to carcinogen-induced mammary tumorigenesis in rats exposed to genistein in utero.

Full Abstract Here

Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats.
Delclos KB, Bucci TJ, Lomax LG, Latendresse JR, Warbritton A, Weis CC, Newbold RR. Reprod Toxicol 2001 Nov;15(6):647-63

Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements.

Body weight and feed consumption of the treated dams prior to parturition showed a decreasing trend with a significant reduction at the highest dose. Litter birth weight was depressed in the 1250 ppm dose group, and pups of both sexes in that dose group had significantly decreased body weights relative to controls at the time of sacrifice. The most pronounced organ weight effects in the pups were decreased ventral prostate weight in males at the 1250 ppm dose and a trend toward higher pituitary gland to body weight ratios in both sexes. Histopathologic examination of female pups revealed ductal/alveolar hyperplasia of the mammary glands at 250 to 1250 ppm. Ductal/alveolar hyperplasia and hypertrophy also occurred in males, with significant effects seen at 25 ppm and above. Abnormal cellular maturation in the vagina was observed at 625 and 1250 ppm, and abnormal ovarian antral follicles were observed at 1250 ppm. In males, aberrant or delayed spermatogenesis in the seminiferous tubules relative to controls was observed at 1250 ppm. There was a deficit of sperm in the epididymis at 625 and 1250 ppm relative to controls, although testicular spermatid head counts and epididymal spermatozoa counts did not show significant differences from controls at these doses. Both sexes showed an increase in the incidence and/or severity of renal tubal mineralization at doses of 250 ppm and above.

Dietary genistein thus produced effects in multiple estrogen-sensitive tissues in males and females that are generally consistent with its estrogenic activity. These effects occurred within exposure ranges achievable in humans.

Full Abstract Here

Use of soy-based infant formulas and soy/isoflavone supplements has aroused concern because of potential estrogenic effects of the soy isoflavones genistein and daidzein.

...genistein produced suppression of humoral immunity.

Genistein injected at 8 mg/kg per day produced serum genistein levels comparable to those reported in soy-fed human infants, and this dose caused significant thymic and immune changes in mice.

Critically, dietary genistein at concentrations that produced serum genistein levels substantially less than those in soy-fed infants produced marked thymic atrophy. These results raise the possibility that serum genistein concentrations found in soy-fed infants may be capable of producing thymic and immune abnormalities, as suggested by previous reports of immune impairments in soy-fed human infants.

Full Abstract Here