Estrogenicity Of Soy Formula

我们正在对新生儿对雌激素暴露的解剖学、超声和生化反应进行初步研究，以计划进行一项临床研究，比较富含植物雌激素的大豆配方奶与牛奶配方奶和人奶的雌激素效应。可能的影响包括1)雌激素活性的解剖学表达：乳房芽、唇部大小、外阴解剖、阴囊皱纹，以及超声检查显示的小卵巢囊肿和可能的前列腺体积；2)活性的生化证据：促性腺激素减少，雌酮/雌二醇合成减少。这些研究始于2003年夏天。 染料木素和大豆苷元是在大豆中发现的雌激素异黄酮类化合物。尽管它们的效力约为雌二醇的万分之一，但在喂食大豆配方奶粉的婴儿中，它们的血清浓度比雌二醇高出4个数量级。临床试验数据显示，与人奶或牛奶配方奶粉相比，服用大豆配方奶粉的婴儿胆固醇合成增加，与雌激素效应一致，对脊髓灰质炎疫苗的反应降低，这可能是也可能不是雌激素效应。在喂食大豆的婴儿中，还没有找到雌激素暴露的解剖学、超声和其他生化证据。无论这种广泛使用的产品在婴儿身上是否具有临床上可检测到的雌激素活性，每公斤接触量最高的一组，在临床上都是重要的；此外，这可能是对实验室雌激素活性测量方法预测人类内分泌干扰能力的关键考验。我们已经开始了初步研究，以检查新生儿雌激素反应生理学的自然历史，并将利用这些结果来开发一项关于大豆配方奶粉对婴儿可能的雌激素效应的纵向研究。 这两个临床站点于2003年夏天开始招收儿童，招收时间为6个月。植物雌激素分析将由FDA和CDC进行。激素分析将由NICHD进行，数据处理和分析将直接在NIEHS进行。

We are doing pilot studies of the anatomical, ultrasonagraphic, and biochemical responses of newborns to estrogen exposure, in order to plan a clinical study comparing the estrogenic effects of soy formula, which is high in phytoestrogens, with cow milk based formula and human milk. Plausible effects include 1) anatomic expression of estrogen activity: breast buds, labial size, vulval anatomy, scrotal rugae, and, by ultrasound, small ovarian cysts and possibly prostate volume and 2) biochemical evidence of activity: decrease in gonadotropins, decrease in estrone/estradiol synthesis. These studies began in Summer, 2003. Genistein and daidzein are estrogenic isoflavones found in soybeans. Although they are about 1/10,000 as potent as estradiol, serum concentrations are up to 4 orders of magnitude higher than estradiol in infants fed soy formula. Clinical trial data show increases in cholesterol synthesis consistent with an estrogen effect in infants fed soy formula vs. human milk or cow milk formula, and lowered response to polio vaccination, which might or might not be an estrogen effect. Anatomic, sonographic, and other biochemical evidence of estrogen exposure has not been looked for in infants fed soy. Whether such widely used products do or do not have clinically detectable estrogenic activity in infants, the group with the highest exposure per kilo, is important clinically; in addition, it may be a crucial test of the ability of laboratory measures of estrogenicity to predict "endocrine disruption" in humans. We have begun pilot studies to examine the natural history of estrogen responsive physiology in the newborn, and will use the results to develop a longitudinal study of the possible estrogenic effects of soy formula on infants. The two clinical sites began enrolling children in summer, 2003, and will enroll for 6 months. Phytoestrogen analyses will be done by FDA and CDC. Hormone analysis will be done by NICHD, and data handling and analysis will be directed at NIEHS.