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

男性和女性之间肌肉骨骼损伤的发生率存在显着差异，前部损伤的发生率 女性运动员的十字韧带 (ACL) 损伤高达 9 倍。这些伤害会导致短期和长期 短期健康问题，包括耽误学校或工作时间、心理困扰和关节受伤后 骨关节炎。性激素可能对这种伤害差异做出了重大贡献：伤害率 直到青春期，这种差异才明显，并且伤害发生在月经前半段的比例不成比例。 循环。虽然大多数研究都集中在肌肉骨骼系统的被动组件上，但认为 女性激素浓度的波动可能会改变韧带本身的机械性能，这是一个直接的影响 韧带松弛与 ACL 损伤之间的联系尚未得到证实。该提案的目的是测试我们的 中心假设是性激素浓度的变化会导致运动基本要素的变化 控制——从肌腱单元到运动控制电路的多个级别。在我们的初步 数据，在肌肉水平上，我们已经表明，当雌二醇时，肌肉反射反应最低 浓度最高，膝关节前部松弛度没有变化。在脊髓回路水平上，我们已经证明 虽然激素浓度的日常变化不会调节脊髓运动神经元的兴奋性， 服用口服避孕药的女性总体兴奋性水平较低。最后，在大脑层面， 我们已经表明，当雌二醇时，皮质内神经元回路的兴奋性会增加 浓度最高。在我们提案的目标 1 和 2 中，日常测试将前所未有地提供详细的信息 评估激素浓度和肌肉变化之间的时间特定关系 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期，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，以及激素浓度之间的时间滞后 变化和反射反应。我们将使用技术上简单的评估，可以在 场。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，并使用肌肉抽搐反应同时改变肌肉力学。 目标 1 和 2 将重点关注口服避孕药的不同作用。在目标 3 中，我们将使用配对脉冲 主动收缩时经颅磁刺激以确定性激素的影响 自然骑行女性皮质兴奋性的波动。我们的研究结果有可能指导未来 伤害预防策略的研究，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性激素高时对神经肌肉的影响 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.