Estrogenicity Of Soy Formula

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，但喂食大豆配方奶粉的婴儿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中是否具有临床可检测到的雌激素活性，每公斤接触量最高的一组，在临床上是重要的；此外，这可能是对实验室雌激素活性测量预测人类实际内分泌反应能力的关键测试。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。 在波士顿儿童S医院，我们在儿科超声领域的合作伙伴开发并评估了乳房、子宫、卵巢、睾丸、前列腺、肾上腺和甲状腺检查的评分员间和评分员内的可靠性。使用NIEHS制定的方案和资格标准，到2004年秋季，他们将检查96名女孩和60名男孩，女孩的年龄从不到48小时到一岁不等，男孩的年龄从不到48小时到6个月不等。我们发现，这些方法是可靠的，即子宫和卵巢的体积随着时间的推移而变化，但子宫内膜条纹不随时间变化。乳房组织和伴随的脂肪很容易被成像。 在费城S儿童医院，我们的合作者正在对84名年龄不到48小时到6个月的男女儿童的乳房和生殖器进行体检。这项检查是对著名的Ballard胎龄分级标准的修改，该标准使用乳房和生殖器对雌激素的反应程度。雌激素化的程度与胎龄密切相关，因此可以使用这种检查来估计孩子在子宫内的周数。我们发现，乳房组织随着时间的推移而变化，脂肪和腺体是可以区分的。我们还发现，阴道壁细胞很容易收集，而且它们似乎对雌激素有反应。在第一年收集的尿样中，服用大豆配方奶粉的儿童的异黄酮浓度要高出3-5个数量级。Equol不存在。我们还在这个地点收集了样本，用于分析各种激素，但仍在开发方法。 我们现在正在分析体检、超声波和异黄酮类数据，并开始计划下一步的研究。

Genistein and daidzein are estrogenic isoflavones found in soybeans. Although they are about 1/10,000 as potent as estradiol, infants fed soy formula have serum concentrations that are up to 4 orders of magnitude higher than estradiol. 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 actual endocrine response 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. At the Boston Children?s Hospital, our collaborators in pediatric ultrasound have developed and assessed inter- and intra- rater reliability for examinations of the breast, uterus, ovaries, testes, prostate, adrenals, and thyroid. Using a protocol and eligibility criteria developed at NIEHS, by fall 2004 they will have examined 96 girls, ranging in age from less than 48 hours to one year, and 60 boys, ranging in age from less than 48 hours to 6 months. We find that the methods are reliable, ans that uterine and ovarian volume changes over time but that the endometrial stripe does not. Breast tissue and accompanying fat is readily imaged. At the Children?s Hospital in Philadelphia, our collaborators are doing physical examinations of the breasts and genitalia of 84 children total of both sexes ages from less than 48 hours to 6 months. This examination is a modification of the well-known Ballard scale for gestational age, which uses the degree of estrogen response by the breasts and genitals. The degree of estrogenization is so strongly related to gestational age that the weeks in utero for the child can be estimated using this examination. We find that breast tissue varies over time, and that fat is distinguishable from gland. We also find that vaginal wall cells are easy to collect, and that they appear to be estrogen responsive. In urine samples collected over the first year, isoflavone concentrations ar 3-5 orders of magnitude higher in children fed soy formula. Equol is not present. We have also collected samples at this site for analysis of a variety of hormones but are still developing methods. We are analyzing the physical examination, ultrasound, and isoflavone data now, and are beginning to plan the next study.