An Exploratory Assessment of Associations Between Serum Estrogen to Progesterone Ratio and Anterior Cruciate Ligament Size, Biomechanics, and T2* Relaxation Time in the Porcine Model

Adolescent females are at a higher risk of anterior cruciate ligament (ACL) injury than males. While prior studies have associated injury timing and menstrual cycle phase, these data are limited by indirect cycle tracking and lack of analysis on ACL structure, mechanics, or composition. Additionally, little is known about how female sex hormones influence the distinct ACL bundles. This exploratory study investigated associations between serum sex hormone concentrations and size, mechanics, and composition of the ACL and its bundles in a female adolescent pig model. Serum from nine adolescent female Yorkshire crossbreed pigs was collected pre-euthanasia and analyzed for levels of estradiol, progesterone, and testosterone. The ACL and its bundles were assessed for size via MRI, mechanics via robotic testing, and composition via biochemical and histological analyses. While individual hormone levels and the estradiol-to-progesterone (E/P) ratio had no association with most metrics, the E/P ratio was significantly associated with ACL size and T2* relaxation time. Higher E/P ratios were negatively associated with AM bundle cross-sectional area (CSA) (R2=0.44) and overall ACL volume (R2=0.49) and positively associated with PL bundle T2* relaxation time (R2=0.69, p < 0.05). Serum E/P ratio was also positively associated with normalized ACL stiffness, but there were no associations observed for tissue composition. The results of this exploratory study indicate that the ACL may be responsive to exposure to the relative concentration of female sex hormone in a bundle-specific manner.