ASSOCIATION BETWEEN THE MENSTRUAL CYCLE AND ACL INJURIES IN FEMALE ATHLETES: A VALIDATION STUDY

Participants: E. M. Wojtys, L. J. Huston, M. L. Greenfield, T. Hewett, T. Lindenfeld, K. Spindler

Keywords: knee, ACL, menstrual cycle, female

Introduction

The prevalence rate of knee injuries has been documented to be 4 to 8 times higher in females compared with males in the same sport. Possible explanations include gender related differences in physiological and physical factors, i.e., anatomy, ligament size, hormones, muscle strength, endurance, coordination, training, neuromuscular, and muscle fiber composition. An area that has received very little attention is the role of hormonal differences in predisposing female athletes to injury of the anterior cruciate ligament. It has been recently shown that estrogen and progesterone receptor sites exist in the cells of the human anterior cruciate ligament, thereby suggesting that the female sex hormones have an effect on its structure and composition. The objective of this study is to determine if an association exists between the fluctuating hormonal levels of the menstrual cycle and the increased rate of ACL injuries in female athletes.

Materials and Methods

This multi-center study is being conducted at the University of Michigan, in collaboration with the Cincinnati Sportsmedicine Center (director: Frank Noyes, M.D.), and Vanderbilt Medical Center (director: Kurt Spindler, M.D.). Athletic trainers, emergency room physicians, and primary care physicians from these institutions will help identify female athletes who have suffered an acute ACL tear (less than 24 hours). Sixty female volunteers sustaining an acute ACL injury will be asked to participate. Each subject will be asked to provide two urine samples: one within 24 hours of injury and the second within 24 hours of the first day of menses (control). Since urinary excretion of hormones typically is delayed by 12 or more hours, collection within 24 hours should permit identification of the reproductive hormonal status of the patient at the time of injury and at the onset of menses with considerable accuracy.

Subjects: Women with acute (less than 24 hours) ACL injury will be recruited for this study through local high schools and colleges. All participants and their parents (if they are under 18 years) in the study will be provided information and informed consent for participation will be obtained. The protocols have been reviewed and approved by the Institutional Review Board for use on human subjects. Women with a history of either irregular (defined as greater than three days variation between cycle period length) or missed menstrual cycles will be excluded from the study. Only non-contact ACL injuries will be analyzed.

Urine Samples: Each subject will be asked to provide two urine samples: one within 24 hours of injury and the second sample within 24 hours of the first day of her menstrual period. The urine samples will be kept frozen until time of analysis. Estrogen (E1G), progesterone (PDG), and lutenizing hormone (LH) metabolites will be assayed by the University of Michigan’s Reproductive Sciences Program CLASS laboratory (director: Rees Midgley, M.D.). Hormone concentrations will be normalized by creatinine excretion to correct for differences in urinary dilution.

Questionnaire: Each participant will be asked to complete a questionnaire administered by one female staff member at each institution. This questionnaire was validated in our last study for test/re-test reliability and shown to be reproducible via a kappa statistic. This questionnaire was also evaluated by an adolescent medicine specialist and found to be appropriate. Subjects will be asked to provide the date and mechanism of injury, including the number of minutes played before the injury occurred, the nature of the ACL injury (i.e. contact or non-contact, jumping, landing, or pivoting mechanism). In addition, each woman will be asked to provide a detailed history of her menstrual cycle, including frequency and regularity, date of last menstrual period, average length of cycle, premenstrual symptoms, oral contraceptive use or hormone replacement use, and frequency of athletic participation during the month.

Significance

The etiologic factors of the higher than expected ACL injury in the athletic female remain unknown, giving impetus to this research. Complex interrelationships between the hormonal and musculoskeletal systems exist that may contribute to injuries of this nature. It is the goal of this study is to determine if an association exists between the fluctuating hormonal levels of the menstrual cycle and the increased rate of ACL injuries in female athletes.

Progress

We are currently collecting data from all institutions. Data analysis is underway.