HORMONAL RESPONSES TO A LOW FAT HIGH FIBER AND SOY DIET

目的.我们的主要目标是量化低脂肪高纤维的影响， （LFHF）饮食和/或大豆补充剂对与以下相关的激素模式的影响 乳腺癌（BC）风险。 第二个目的是评估 和使用日常唾液样本测量卵巢类固醇的精确性 整个月经周期。 背景/意义。假设过度累积暴露于 雌二醇（E2）和孕酮（PG）在绝经前妇女增加 发展BC的风险提供了一个统一的解释， 流行病学和实验室结果。第二个假设，将BC与 支持16 α相对于2-羟基化E2代谢产物的过量产生 越来越多的证据LFHF饮食与减少 绝经前妇女的E2水平和16 α-羟基化水平降低，但 证据稀少且不一致。一项大型随机试验， 具有最小干预比较组，更长的随访时间， 更可靠的测量骑自行车的妇女的激素水平可以有助于 通过激素控制BC风险的饮食有价值的证据 机制等含有高水平植物雌激素的大豆食品也可能 对荷尔蒙有很好的影响。植物雌激素的摄入量 与SHBG的肝脏产生增加有关， 减少游离E2。我们提出了一项随机安慰剂对照试验， 大豆补充剂，以评估其单独和与 LFHF饮食。唾液中E2和PG的测量提供了以下可能性： 更丰富、更敏感的数据集，用于研究饮食对健康的影响。 生物可利用激素水平随时间变化的因素，但从未 在干预环境中进行了评估。 方法. 200名女性（非肥胖，定期，年龄30-45）将遵循 常规或LFHF饮食，并将在 基线（B）、4和12个月。在12个月时，两组中的女性将被重新- 随机接受大豆补充剂或安慰剂，最后的随访将 发生在16个月。（有关饮食干预的详细信息，请参见 IRPG提案）除了写月经日记，140名女性还将 在B、4、12和16个月提供：i）一份用于E2、PG的黄体中期血液样品 和SHBG水平，和ii）用于16 α和2-OHE 1测定的黄体中期尿。一 60名女性的频繁样本（FS）亚组将提供上述加， iii）在第7天和从第14天到下一次月经的每3天的血液样品 开始（6-7个样品/周期），和iv）完整周期的每日唾液样品 在B、4、12和16个月时。主要分析将比较 各饮食组的血清E2、PG和SHBG以及尿16 α：2 OHE 1比率。 在FS亚组中，我们将使用唾液PG来选择最佳时间 用于黄体中期分析的血液，并比较累积的唾液E2和PG 在不同的饮食组中。血液、尿液、乳腺液和乳房X线照片（女性 年龄超过40岁）的数字化实质密度读数将被储存， 单独供资的分析。

Purpose. Our main goal is to quantify the impact of a low-fat high-fiber (LFHF) diet and/or a soy supplement on hormonal patterns associated with breast cancer (BC) risk. A secondary purpose is to assess the convenience and precision of using daily saliva samples to measure ovarian steroids throughout the menstrual cycle. Background/Significance. The hypothesis that excess cumulative exposure to estradiol (E2) and progesterone (PG) in premenopausal women increases the risk of developing BC offers a unifying explanation for diverse epidemiologic and laboratory findings. A second hypothesis, relating BC to overproduction of 16alpha vs. 2-hydroxylated E2 metabolites, is supported by a growing body of evidence. The LFHF diet has been linked with reduced E2 levels and decreased 16alpha-hydroxylation in premenopausal women, but the evidence is sparse and inconsistent. A large randomized trial, featuring a minimal intervention comparison group, longer follow-up, and more reliable measures of hormone levels in cycling women can contribute valuable evidence on dietary control of BC risk through hormonal mechanisms. Soy foods containing high levels of phytoestrogens might also have a favorable effect on hormone profiles. Phytoestrogen intake has been linked to an increase in hepatic production of SHBG and a resultant decrease in free E2. We propose a randomized placebo-controlled trial of soy supplement to evaluate its effects both alone and in combination with the LFHF diet. Salivary measurements of E2 and PG offer the possibility of far richer and more sensitive datasets for studying the impact of dietary factors on time-varying levels of bioavailable hormone, but have never been evaluated in an intervention setting. Methods. 200 women (non-obese, regular periods, aged 30-45) will follow either usual or LFHF diet and will provide hormonal and other data at baseline (B), 4 and 12 mos. At 12 mos, women in both groups will be re- randomized to either soy supplement or placebo and a final follow-up will occur at 16 mos. (Details of the diet intervention in the accompanying IRPG proposal.) In addition to keeping menstrual diaries, 140 women will provide at B, 4, 12 and 16 mos.: i) one midluteal blood sample for E2, PG and SHBG levels, and ii) midluteal urine for l6alpha and 2-OHE1 assays. A Frequent Sample (FS) subgroup of 60 women will provide the above plus, iii) blood samples on day 7 and every 3rd day from day 14 to next menses onset (6-7 samples/cycle), and iv) daily saliva samples for a full cycle at B, 4, 12 and l6mos. The main analysis will compare mean changes in serum E2, PG and SHBG and urine l6alpha:2OHE1 ratios across diet groups. In the FS subgroup, we will use salivary PG to select the best-timed bloods for midluteal analysis and compare cumulative salivary E2 and PG across diet groups. Blood, urine, breast fluid and mammograms (in women over age 40) for digitized parenchymal density readings will be banked for separately funded analyses.