WOmen-Oxidative Stress, Estrogens, and Exercise (WOOSEE)

以乳腺癌诊断为主要结局进行随机对照运动干预试验是不可行的。因此，确定运动是否会改变与乳腺癌发病率相关的生理结果是有意义的，包括氧化应激、雌激素、雌激素代谢和代谢因素，如体脂、空腹胰岛素升高、胰岛素抵抗、IGF轴蛋白血浆水平的改变。我们建议在一项随机对照试验中检查有氧运动训练对年轻（18-30岁）绝经前正常女性的上述机制的影响。要检验的主要假设是运动是否会改变氧化应激， 通过F2-异前列烷。这项资助的创新源于癌症生物标志物的同步测量，这将使我们能够探索这些生理参数变化之间的关系，这些生理参数可能在运动-癌症联系中发挥重要作用。令人信服的初步数据表明，为促进健康和预防慢性疾病而推荐的运动量（每周5次，每次30分钟的中等强度有氧运动）可能会以与降低癌症风险一致的方式改变这些风险因素。我们将招募400名女性，预计脱落率为20%，最终样本为320名女性（每组n=160）。将在随机化前受试者月经周期的第7 - 10天和基线周期后的第5个月经周期进行测量。与会者还将使用 排卵试剂盒，以确定是否运动改变黄体期长度或排卵状态。测量将包括氧化应激（F2-异前列腺素）、雌激素代谢产物、身体组成（双能X射线吸收测定法）、胰岛素、葡萄糖和胰岛素抵抗（HOMA指数）、胰岛素样生长因子轴蛋白（IGF-1、IGFBP-1、-2和-3）、次最大适应度、问卷（损伤/疾病、人口统计学）和饮食（通过食物频率问卷）。

It is not feasible to conduct randomized controlled exercise intervention trials with breast cancer diagnosis as the primary outcome. Therefore, it is of interest to determine whether exercise will alter physiologic outcomes associated with breast cancer incidence, including oxidative stress, estrogens, estrogen metabolism, and metabolic factors such as body fat, elevated fasting insulin, insulin resistance, alterations in plasma levels of IGF-axis proteins. We propose to examine the effects of aerobic exercise training on each of these mechanisms among young (18-30 years), pre-menopausal, eumenohrreic women in a randomized controlled trial. The primary hypothesis to be tested is whether exercise alters oxidative stress as measured by F2-lsoprostanes. The innovation of this grant stems from the concurrent measurement of cancer biomarkers, which will enable us to explore relationships between changes in these physiologic parameters that may have an important role in the exercise - cancer link. Compelling preliminary data indicate that the amount of exercise recommended for health promotion and chronic disease prevention (5 weekly 30 min sessions of moderate intensity aerobic exercise) may alter these risk factors in a manner consistent with reduced cancer risk. We will recruit 400 women and anticipate a dropout rate of 20%, for a final sample of 320 women (n=160 per group). Measurements will be made from days 7 to 10 of the participants menstrual cycle prior to randomization and at the 5th menstrual cycle after the baseline cycle. Participants will also use ovulation kits to determine whether exercise alters luteal phase length or ovulatory status. Measurements will include oxidative stress (F2-isoprostanes), estrogen metabolites, body composition (dual energy x-ray absorptiometry), insulin, glucose, and insulin resistance (HOMA index), insulin-like growth factor axis proteins (IGF-1, IGFBP-1, -2, and -3), submaximal fitness, questionnaires (injury/illness, demographics), and diet (by food frequency questionnaire).