Soy and Fertility in Women

In this post (part 1) I will summarize the research on soy and phytoestrogens on female fertility and in my next post I will discuss male fertility (part 2). Soy has been researched quite extensively for its benefits on cancer and heart disease prevention, but there is plenty of conflicting information regarding soy and fertility. Firstly I want to say that research on this is still in the making, and many more studies will need to be done on more adult women in order to come to any real conclusions.

Soy Formula and Newborns

Many studies on soy and fertility are related to newborn intake of soy. There has been much concern with feeding newborns soy formula as a substitute for dairy formula or breast milk (around 25% of infants are fed soy formula). The concern is that there may be permanent reproductive effects of soy in newborns as opposed to temporary effects of soy in adults. The reproductive system is in a very sensitive time of development in the newborn. Most studies in this area have been done on animals, specifically rats and there are very large differences in estrogen metabolism between rats and humans which I will discuss below. There is very scarce research on adult women and soy.

Study on Women exposed to Soy Formula as Infants

A study published in the Journal of the American Medical Association on young adults fed soy based formula in infancy showed the following results for women: No significant changes in pregnancy outcomes in women who were fed soy formula, although they did have increased length of menstrual cycle and of discomfort with the menses (which could be related to newborn exposure to high levels of phytoestrogens in formula). This study did not go into details asking women about length of time to conceive and use of reproductive technology to conceive, so it is lacking some information for our purposes. Also, this study did not account for current intake of soy products.

Studies : Soy Formula Given to Infants Show Differing Outcomes in Hormonal Response

A study on infants fed soy formula for 6 months concluded that long-term feeding of soy formula in infants did not produce estrogen-like hormonal effects. They suggested that their findings confirm the theory that phytoestrogens have a low affinity for estrogen receptors and therefore produce only weak biologic effects. Another study, however, found that infants who were fed soy formula had early onset of thelarche (breast development) compared to children who were not. It appears then, that there is much conflicting information on soy formula in infants and their later fertility, but what we do know is that breast milk is always best. Support for breastfeeding can help to ensure healthy reproductive capacity for future generations.

Soy Intake and Effects on Fertility

pregnancy testFor the purpose of fertility patients, we are looking more at the consumption of soy in the diet, and sadly, there is little human data on this subject in females.

Phytoestrogen Intake in Japanese Women and changes in Estrogen levels

In a study on Japanese women they found that of those who consumed the highest dietary amounts, there was a lower estradiol level on day 11 and 22 of the cycle. The study concluded that this would therefore lead to lower risk for breast cancer. Since this study did not evaluate reproduction specifically, we can’t say that this change would have any effect on fertility, however it does show that high soy intake can modify hormone balance in premenopausal women.

Animal Studies
There is little information on soy and reproduction in adult females, but we can look to some animal studies for more information:

Soy administration to Rhesus Monkeys – No Negative Reproductive Outcome

A study done on rhesus monkeys at the age of puberty showed that monkeys fed soy protein with isoflavones had lower risks of cardiovascular disease and no changes in reproductive markers(in neither hormone levels nor reproductive organs) compared to those not given isoflavones.

Mice given Genistein as Newborns have Impaired Implantation as Adults

For mice given 50 mg/kg genistein(a fairly high dose) as newborns, it was found that there were changes in the uterus/endometrium of the mice when they became adults which impaired implantation of embryos. Again, this is on newborn exposure and does not apply so much to adult women taking soy, because effects of phytoestrogens on adults tend to be temporary whereas when they are on newborn animals they tend to affect development.

Administration of High Doses of Phytoestrogens in Adult Mice

Long term administration of a phytoestrogenic herb Pueraria merifica in mice found that taking a low dose(10 mg/kg) of phytoestrogen had no impact on hypothalamic-pituitary-ovarian-uterine axis, and that taking a high dose of 100 mg/kg had adverse effects on mating efficiency and reproduction. The higher dose could be correlated to taking a high potency phytoestrogen/soy protein formula, and the lower dose could be correlated to a small dietary quantity.
Criticisms of this study according to our purposes are that this study did not involve soy, but another plant phytoestrogen.

Problems in Comparing Humans to Monkeys and Rodents in Studies on Soy and Reproduction

I would like to make a very important point here. Rodents and monkeys in general are very potent intestinal producers of an estrogen called equol. A study in the American Journal of Clinical Nutrition found that equol accounted for 71-90% of the summed isoflavones in rat serum and 54% of isoflavones in chimpanzee serum. Equol is a byproduct of intestinal bacteria as they break down phytoestrogens such as soy. It has been found though, that only around 20-50% the adult human population make equol after ingesting soy foods and most of the human population does not produce equol at all. Equol production is correlated to greater health benefits of soy such as prevention of hormonally mediated cancers and has a much more potent effect than genistein (an isoflavone from soy). Studies show that equol producing individuals show stronger responses to high isoflavone diets. This may also indicate that in certain women, soy may have a more pronounced effect on fertility but for the majority, it may have a much lower impact than what is seen in rats/mice/monkeys. This implies that much more research will need to be conducted on humans and that we should not jump to any conclusions based on animal studies. Something else very important to consider here, is that human infants do not make equol until they are over 4 months old. This makes it difficult to correlate studies done on newborn mice/rats who are given soy with infants given soy formula.

Adult women and soy – Equol production and Effects on Estrogen Levels

A study done on Irish women given a soy beverage investigated the differences in human metabolism of soy. Most of the women after drinking the soy, had a moderate drop in their salivary estrogen levels. In 34% of the group, estradiol levels raised significantly.

The group who had the rise in estrogen levels a) had significantly less children b) had lower isoflavone excretion in urine (c) were more likely to be equol producers (67% compared to 41.7%), and (d) more likely to be to be first-degree relatives of breast cancer patients. It was also found that the patients who had higher body mass index were more likely to be first degree relatives of breast cancer patients. This study indicates that the gut has a large role to play in the effect of soy on hormones and also, especially that if body mass index is high, the effects of estrogen are disruptive. We also know that from other studies that obesity negatively impacts fertility and causes risk for estrogen positive diseases such as breast cancer and fibroids.

Study on Soy and IVF Cycles – Soy improves outcome of IVF

There is one placebo controlled trial using 1500 mg of isoflavones from soy with progesterone injection in the luteal phase, compared to groups given placebo and progesterone injection.  274 cycles were investigated in this study.  Results indicated that implantation rate, clinical pregnancy rate, and ongoing pregnancy/delivered rate were significantly higher in the group given the soy phytoestrogens.  This study included only women under age 40, and who had been given downregulation prior to their cycle.  This indicates that the phytoestrogens from soy may actually prove to be therapeutic in IVF cycles, particularly where there was downregulation given (medication which shuts down the natural menstrual cycle prior to the IVF cycle).  Since this is just one study, and since not all ivf cycle are downregulated this this treatment method would require more research, but it may prove to be promising.

What about Soy and the Fertility of the Asian Population?

Many patients also ask about soy and the Asian population. In Asia since soy consumption is very common, if soy had a negative impact on fertility it might be quite evident.  In Asia, obesity is not nearly as prevalent as it is in North America. Estrogen is produced in fat cells from conversion of androgens. Therefore, if you are considering the average North American (63% of whom are overweight or obese) we can’t really compare the two groups. There have been correlations made between men of higher body mass index and effects of soy on fertility. for more complete analysis of this subject we would also have to consider the gut production of equol.

Summary

According to the research we currently have available and also taking into account traditional dietary intake, the following points should be considered:

1) body mass index is of utmost importance, if you keep your weight healthy, you will increase your fertility and reduce risk for disease. Follow the traditional Asian or Mediterranean plant-based diet and keep your bmi in the healthy range. This will do you far more good than entirely eliminating soy and continuing along the path of the typical North American diet low in fibre and filled with unhealthy fats, sugar and empty carbohydrates. A major study out of Harvard shows that a diet high in plant foods and whole grains, and low in empty carbohydrates, sugars and low quality fats had a 69% lower risk for having ovulatory disorders related to infertility.

2) moderation is the key. avoid using large amounts of soy products and protein, particularly around ovulation and implantation (around 7-10 days after ovulation). Small amounts of soy in the diet should cause no problem according to what we currently know and it may have many other health benefits. In North America we have the tendency to isolate soy proteins and isoflavones, the result of this on reproduction is quite unknown. I would suggest whole foods and moderate consumption.

3) if you are having longstanding fertility concerns, and are a consumer of large amounts of soy, you may consider eliminating it for some time, especially if you are overweight.

4) millions of women have consumed soy products and become pregnant, so it is not something to worry excessively about. Stress can have much more profound effects on your fertility than a small amount of soy.

5) genetic modification has not been considered in these studies. If you do choose to include soy in your diet, use non GMO. Soy can also be sprayed with pesticides which often have estrogenic effects, so choose organic soy.

References

Anthony et al. Soybean isoflavones improve cardiovascular risk factors without affecting the reproductive system of peripubertal rhesus monkeys. J Nutr. 1996 Jan;126(1):43-50.Burton, J and Wells, M. The effect of phytoestrogens on the female genital tract. J Clin Pathol. 2002 June; 55(6): 401–407.Chavarro et al. Diet and Lifestyle in the Prevention of Ovulatory Disorder Infertility. Obstetrics & Gynecology: November 2007 – Volume 110 – Issue 5. pp 1050-1058

Freni-Titualer et al. Premature thelarche in Puerto Rico. A search for environmental factors. Am J Dis Child. 1986 Dec;140(12):1263-7.

Giampietro et al. Soy protein formulas in children: no hormonal effects in long-term feeding. J Pediatr Endocrinol Metab. 2004 Feb;17(2):191-6.

Gu et al. Metabolic Phenotype of Isoflavones Differ among Female Rats, Pigs, Monkeys, and Women. J. Nutr. 2006 136: 1215-1221

Hall et al. Equol producer status, salivary estradiol profile and urinary excretion of isoflavones in Irish Caucasian women, following ingestion of soymilk. Steroids. 2007 Jan;72(1):64-70.

Jefferson et al. Neonatal Exposure to Genistein Disrupts Ability of Female Mouse Reproductive Tract to Support Preimplantation Embryo Development and Implantation. Biol Reprod. 2009 Mar;80(3):425-31

Nagata et al. Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women. Nutr Cancer. 1997;29(3):228-33.

Rozman et al. NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Soy Formula. Birth Defects Res B Dev Reprod Toxicol. 2006 August; 77(4): 280–397.

Setchell et al. S-Equol, a potent ligand for estrogen receptor {beta}, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. Am J Clin Nutr 2005 81: 1072-1079

Strom et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA. 2001 Aug 15;286(7):807-14.

Sukanya et al. Assessment of Fertility and Reproductive Toxicity in Adult Female Mice after Long-Term Exposure to Pueraria mirifica Herb. J. Reprod. Dev. Vol. 53, 995-1005 (2007)

Vittorio Unfer, Maria Luisa Casini, Sandro Gerli, Loredana Costabile, Marcella Mignosa, Gian Carlo Di Renzo Fertility and Sterility – December 2004 Vol. 82, Issue 6, Pages 1509-1513

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Soy and Fertility Part 1- Phytoestrogens and Fertility in Women by Dr. Fiona McCulloch ND is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.5 Canada License.
Based on a work at drfionamcculloch.wordpress.com.
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