2001 WHRG Grant Program

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Sex Hormone Binding
Globulin ACL Stiffness

William A. Romani, PhD, PT
School of Medicine, University of Maryland, Baltimore

Anterior cruciate ligament (ACL) injuries occur more frequently in women than in men who participate in similar activities. Several theories regarding the potential causes of these differences have been proposed. Fluctuating levels of sex hormones on the structure of the ACL has been proposed as a potential contributor to this difference in injury rates. ACL tissue exposed to estrogen showed a decrease in collagen synthesis in vitro and a decreased load to failure in vivo when compared to unexposed tissue. In humans ACL laxity was higher during ovulation and the luteal phase of the menstrual cycle when estradiol concentrations are usually higher than at the onset of menses. Moveover, previous studies in our laboratory have identified a moderate negative correlation between serum estradiol concentrations and ACL stiffness and a high negative correlation between changes in serum estradiol concentrations and changes in ACL stiffness between the onset of menses and ovulation. If the ACL loses stiffness during periods of high estradiol concentration, the ligament will be less able to tolerate high loads and be more susceptible to injury.

Estradiol is only one of several hormones, proteins, and second messengers that may have an effect on the remodeling and structure of the ACL. Sex hormone binding globulin (SHBG) recognizes a specific receptor on estrogen sensitive tissue. The interactions between SHBG, estradiol, and the SHBG binding site are part of a signal transduction pathway that modulates the estrogenic effects on estrogen sensitive target tissues. In estrogen sensitive tissue the effects of estrogen are mitigated by the presence of SHBG through the induction of cyclic AMP and protein kinase A. It is possible that this decreased effect of estrogen may also exist in estrogen sensitive ligamentous tissue. If this is the case then a rise in SHBG concentration should decrease estradiol's effect on reducing fibroblast proliferation and collagen formation and lead to an increase in ACL stiffness.

This study will investigate healthy, active women between 18 and 40 years old who have regular menstrual cycles and who are not using oral contraception. Women will report to our laboratory for testing at three times during the course of one menstrual cycle; onset of menses, ovulation, and during the luteal phase. Subjects will have the stiffness of their ACL tested with the KT-2000 knee arthrometer and have 10 ml of blood drawn at each session. Statistical analysis will determine if there are differences in cycle and if a correlation exists between the serum concentration of SHBG and ACL stiffness. We hope to use the results of this study to help us to determine if there are increases in ACL stiffness when serum SHBG concentrations are higher and better understand the potential hormonal causes of the higher number of ACL injuries in women than in men.