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高纤维 (LFHF)饮食和/或大豆补充剂对激素模式的影响 乳腺癌(BC)风险。第二个目的是评估其便利性 使用每日唾液样本测量卵巢类固醇的精确度 在整个月经周期中。 背景/意义。假设过量的累积暴露于 绝经前妇女雌激素(E_2)和孕酮(PG)增加 开发BC的风险为多样化提供了统一的解释 流行病学和实验室检查结果。第二个假设，与公元前 支持过量生产16α与2-羟基化的E2代谢物 越来越多的证据。LFHF的饮食被认为与减少 绝经前妇女的E2水平和16a-羟化水平降低，但 证据很少，而且前后不一致。一项大型随机试验， 具有最低限度的干预对照组、更长的随访时间和 对骑自行车的女性进行更可靠的荷尔蒙水平测量可能会有所贡献 通过荷尔蒙控制饮食对患BC风险的有价值的证据 机械装置。含有高水平植物雌激素的大豆食品也可能 对荷尔蒙水平有很好的影响。植物雌激素的摄入量 与肝脏SHBG产量的增加有关，以及由此产生的 游离雌二醇量下降。我们建议进行一项随机安慰剂对照试验。 大豆补充剂，以评估其单独和联合使用效果 LFHF饮食。唾液中雌二醇和前列腺素的测定提供了一种可能性 更丰富、更敏感的数据集，用于研究饮食的影响 影响生物可利用荷尔蒙水平的因素，但从来没有 在干预环境中进行了评估。 方法：研究方法。200名女性(非肥胖、经期规律、年龄30-45岁)将紧随其后 通常或LFHF饮食，将提供荷尔蒙和其他数据在 基线(B)、4和12个月。在12个月，两组中的女性都将被重新 随机服用大豆补充剂或安慰剂，最后一次随访将 发生在16个月。(饮食干预的细节请参阅随附的 IRPG提案。)除了记录月经日记，140名女性还将 提供B、4、12和16个月：i)一份黄体中期血样，用于E2、PG 和SHBG水平，以及ii)黄体中期尿液用于16α和2-OHE1测定。一个 由60名女性组成的频繁样本(FS)小组将提供上述加分， 三)第7天和第14天至下一次月经的每3天的血样 起病(6-7个样本/周期)，以及iv)一个完整周期的每日唾液样本 在B、4、12和16个月。主要分析将比较 不同饮食组血E2、PG、SHBG和尿液16α/2 OHE1比值。 在FS亚组中，我们将使用唾液PG来选择最佳时机 用于黄体中期分析的血样和比较累积唾液雌二醇和孕酮 不同的节食组。血液、尿液、乳房积液和乳房X光检查(女性 40岁以上)对于数字化的实质密度读数将被存储为 单独资助的分析。

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.