DESCRIPTION (Taken from the application): Because of the significantly higher rate of anterior cruciate ligament injuries in females, it is necessary to identify and control gender related injury risk factors. Previous studies indicate potential gender differences in a variety of musculoskeletal stability factors, which dictate the maximal load that the knee can withstand during sport activity. Musculoskeletal stability factors found to differ between males and females include both passive (ligament compliance and laxity), and active (muscle stiffness, reflex behavior, and recruitment patterns) factors. Thus, when exposed to similar sport-induced mechanical loading conditions, this evidence suggests females may have less joint stability, thus a lower tolerance to joint load and associated higher risk of ligament injury. While research suggests female sex hormones may have a profound effect on collagen properties, their influence on passive and active musculoskeletal stability factors and ACL injury risk has yet to be adequately studied. This study represents Phase I of a comprehensive research agenda to evaluate the influence of gender and cyclic hormones on musculoskeletal stability and ACL injury risk. The proposed research aims to demonstrate the influence of gender and sex specific hormones on passive ligament behavior across one complete menstrual cycle. To measure ligament behavior, graded ligament stress testing will be performed at incremental forces from 0-190 Newtons to determine joint displacement (forward translation of the tibia on the femur) relative to applied force. Blood will be drawn at the same time as ligament testing to determine estrogen, progesterone, and testosterone concentrations. Female subjects (N=20) will be tested on a daily basis across one complete menstrual cycle, while male subjects(N=20) will be tested once every 7 days over a period of 28 days. Specific objectives are to 1) comprehensively quantify gender differences in anterior cruciate ligament compliance, 2) compare and quantify daily changes in ligament compliance as a function of cycling levels of estrogen and progesterone across one complete menstrual cycle, and 3) relate gender differences in ligament compliance to cycling hormone levels during the course of the menstrual cycle. Once the relationship between gender, hormone concentrations and ligament compliance is established, the consequence of increased ligament compliance on proprioception and reactive neuromuscular control of joint stability will be evaluated. Parallel research efforts will explore the influence of gender and sex specific hormones on muscular stiffness and reflex muscle behavior. Understanding the combined impact of changes in ligament and muscle compliance on knee stability with sudden joint loading will make an important contribution to our understanding of ACL injury risk factors and our efforts to develop effective injury prevention strategies.