Despite being widely commercially available for decades and having been used by as many as 20 million Americans during infancy, the advantages and disadvantages of soy infant formula (SIF) have been debated for 25 years. This debate exists despite the U.S. National Toxicology Program twice concluding there is little evidence to suggest SIF isn’t safe, a conclusion consistent with the position of the American Academy of Pediatrics.1
In 2001, a landmark study by Strom et al.2 concluded that “exposure to soy formula does not appear to lead to different general health or reproductive outcomes than exposure to cow milk formula.” This retrospective study examined a wide variety of health outcomes among 248 adults who were fed SIF and 563 adults who were fed cow milk formula during infancy.
You would think this study would have helped to alleviate concerns, but despite this conclusion, this study has been cited as support by those raising alarm about the safety of SIF. This may seem surprising, but Strom et al.2 did recommend that the few statistically significant findings from their research should be explored in future studies. One of the significant findings was that women who had been fed SIF as infants reported slightly longer duration of menstrual bleeding and greater discomfort with menstruation. As discussed below, 17 years later, this finding was investigated by Upson et al.3 in a paper published in “Human Reproduction.”
The research by Strom et al.2 is considered a landmark study for at least two reasons. One, it is a retrospective study that provides insight into the possible health effects of soyfoods as long as 34 years after consumption. Critics of SIF often suggest that potential harm may not be immediately obvious. To this way of thinking, the many relatively short-term feeding studies (<1 year) that have demonstrated normal growth and development in response to SIF, aren’t enough to fully address safety issues. However, the study by Strom et al.2 addresses the limitation of the short-term studies. Reason number two: infants were enrolled in the study before the age of 9 days and were studied through 16 weeks of age. Thus, this study avoided having to rely upon the memory of adults for information about formula feeding habits.
The Strom et al.2 study found that, among women who were fed SIF, menstrual bleeding was 0.37 days longer (95% confidence interval [CI], 0.06, 0.68), but there was no difference in the severity of menstrual flow. The clinical significance of slightly longer menstrual bleeding, if any, is unclear. Women were also 77% (95% CI: 1.04, 3.00) more likely to report greater discomfort with menstruation (extreme discomfort vs no or mild pain), but no difference was noted in cramps with menses. In addition, women fed SIF were no more likely to seek medical attention to evaluate symptoms of pain associated with menstrual periods. Furthermore, as noted by the authors, neither of the two above statistically significant findings would have remained so if the results had been adjusted for the multiple comparisons tested in this study.
As noted, a study was published this year that followed up on the menstrual findings by Strom et al.2 The data for this study by Upson et al.,3 come from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of African-American women ages 23-35 years at enrollment. Data on SIF feeding was ascertained by self-administered questionnaire for 1553 participants, with 89% of participants receiving assistance from their mothers. Information on menstrual pain indicators was collected by web- and telephone-interview. Of the women in this study, only 198 (12.7%) were fed SIF.
Overall, there was no association between SIF feeding and ever or current medication use for menstrual pain. There was an increased likelihood of women reporting moderate/severe menstrual discomfort/pain with “most periods,” but not “every period,” or “occasional periods” during early adulthood (ages 18-22 when not using hormonal contraception). Finally, there was an increased risk of use of hormonal contraception for menstrual pain within the first 5 years after the onset of menses (adjusted relative risk; 1.7; 95% CI: 1.0, 2.7), but not at least 5 years after the onset of menses. It is notable that despite the statistical significance, only 19 women fell into the category of hormonal contraception use during the first 5 years after the onset of menses and use of SIF.
This analysis from the SELF study is well done, but considering all the comparisons made, it is not surprising that some findings resulted in statistical significance. Also, relying upon the memory of study participants and their mothers about the use of SIF is of questionable reliability. Finally, since this study, like the study by Strom et al.2 is an observational study, no causal relationship between SIF and the reported health outcomes in these studies can be established. It is not inconceivable that unidentified factors associated with the maternal decision to choose SIF could influence reports about menstrual pain later in life.
At this point it would be premature to conclude that SIF causes pain during menstruation and for this reason, it is premature for mothers to factor this outcome into their decision about which formula to use for their daughters. Unfortunately, it will be difficult to generate data that can provide meaningful insight into the question at hand. Thus, the position of the American Academy of Pediatrics (AAP) on the use of SIF remains operative. The AAP concluded that in term infants, SIF provides nutrition for normal growth and development, although there are few medical indications for its use in place of cow’s milk formula.
- McCarver G, Bhatia J, Chambers C, et al. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Birth Defects Res B Dev Reprod Toxicol. 2011;92(5):421-68.
- Strom BL, Schinnar R, Ziegler EE, et al. Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA. 2001;286(7):807-14.
- Upson K, Adgent MA, Wegienka G, et al. Soy-based infant formula feeding and menstrual pain in a cohort of women aged 23-35 years. Hum Reprod. 2018.