EMRSHN: Exploring the modulatory role of sex hormones along the neuromechanical axis in females

肌肉骨骼损伤的发生率在男性和女性之间有很大差异， 女性运动员的交叉韧带（ACL）损伤高达9倍。这些损伤会造成短暂或长期的- 长期健康问题，包括从学校或工作中损失的时间，心理困扰和受伤后的关节 骨关节炎性激素可能对这种伤害差异做出重大贡献： 这种差异在青春期之前并不明显，而且损伤不成比例地发生在月经的前半段。 周期虽然大多数研究都集中在肌肉骨骼系统的被动成分，认为， 女性波动的激素浓度可能会改变韧带本身的机械性能，这是一个直接的影响。 韧带松弛和ACL损伤之间的联系尚未得到证实。这项提案的目的是测试我们的 一种中心假设，认为性激素浓度的变化会导致运动基本要素的变化 控制-在多个层次，从肌肉肌腱单位的运动控制电路。在我们的初步调查中 数据，在肌肉水平，我们已经表明，肌肉反射反应最低时，雌二醇 浓度最高，膝前松弛无变化。在脊髓回路水平，我们已经表明， 虽然激素浓度的日常变化不调节脊髓运动神经元的兴奋性， 服用口服避孕药的妇女总体兴奋水平较低。最后，在大脑层面， 我们已经表明，当雌二醇 浓度最高。在我们提案的目标1和2中，日常测试将允许前所未有的详细 评估激素浓度与肌肉变化之间的时间特异性关系， 在放松和活动状态下的脊柱水平。在目标3中，每日激素浓度将具体 确定每个受试者的测试日，指导有针对性的评估波动激素的作用， 浓度对皮质兴奋性的影响在目标1中，我们将确定性激素波动对 主动和被动状态下的肌肉牵张反射，以及激素浓度 变化和反射反应。我们将使用技术上简单的评估，可以在 领域在目标2中，我们将确定性激素波动对脊髓运动神经元兴奋性的影响 使用H-反射作为探针，同时使用肌肉抽搐反应来改变肌肉力学。 目标1和2将包括注重口服避孕药的不同作用。在目标3中，我们将使用成对脉冲 主动收缩期间经颅磁刺激以确定性激素的影响 自然骑车女性大脑皮层兴奋性的波动。我们的研究结果有可能指导未来 研究伤害预防策略，包括有针对性的神经肌肉训练。这些知识将 使临床医生能够教育女性患者在高血压期间性激素对神经肌肉的影响 波动，包括青春期，怀孕和更年期。

The rate of musculoskeletal injury differs substantially between men and women, with the incidence of anterior cruciate ligament (ACL) injuries up to 9 times higher in female athletes. These injuries cause short- and long- term health problems, including time lost from school or work, psychological distress, and post-injury joint osteoarthritis. Sex hormones may make a significant contribution to this injury disparity: injury rate differences are not evident until puberty, and injuries occur disproportionately in the first half of the menstrual cycle. While most research has focused on passive components of the musculoskeletal system, arguing that female fluctuating hormone concentrations may change mechanical properties of the ligament itself, a direct link between ligament laxity and ACL injury has not been proven. The goal of this proposal is to test our central hypothesis that changes in sex hormone concentration result in changes to the basic elements of motor control – at multiple levels, from the musculotendinous unit to motor control circuitry. In our preliminary data, at the muscle level, we have shown that the muscle reflex response is lowest when estradiol concentrations are highest, with no change in anterior knee laxity. At the spinal circuitry level, we have shown that while day-to-day changes in hormone concentration do not modulate spinal motor neuronal excitability, a lower overall level of excitability exists in women who take oral contraceptives. Finally, at the level of the brain, we have shown the excitability of intra-cortical interneuronal circuits is increased when estradiol concentrations are highest. In Aims 1 & 2 of our proposal, daily testing will allow, as never-before, a detailed assessment of the time-specific relationship between hormone concentration and changes at the muscle and spinal level during both relaxed and active states. In Aim 3, daily hormone concentrations will specifically determine each subject's testing day, guiding targeted assessments into the role of fluctuating hormone concentrations on cortical excitability. In Aim 1 we will determine the influence of sex hormone fluctuations on the muscle stretch reflex during active and passive states, and the time-lag between hormone concentration changes and the reflex response. We will use a technically simple assessment that could be implemented in the field. In Aim 2 we will determine the influence of sex hormone fluctuations on spinal motor neuron excitability using H-reflex as a probe and the simultaneous change in the muscle mechanics using muscle twitch response. Aims 1 & 2 will include a focus on the differential role of oral contraceptives. In Aim 3 we will use paired-pulse transcranial magnetic stimulation during active contraction to determine the influence of sex hormone fluctuations on cortical excitability in naturally cycling women. Our findings have the potential to guide future research in injury prevention strategies, including targeted neuromuscular training. This knowledge will enable clinicians to educate female patients on neuromuscular effects of sex hormones during times of high fluctuations, including puberty, pregnancy, and menopause.