The Impact of Oral Contraception on Anterior Cruciate

The Impact of Oral Contraception on Anterior Cruciate Ligament Injuries in Young Female Athletes Alexis Giovinazzo MPH (c), MMS (c) Faculty Advisor: Renee Langstaff, MSPAS, PA-C Department of Medical Science Abstract Anterior Cruciate Ligament (ACL) rupture is a significant knee injury which disproportionately affects young female athletes. The relationship of ACL injury and the timing of the menstrual cycle has been previously suggested, implicating the use of oral contraceptive pills (OCPs) as well. This review evaluates the relationship, suggesting the use of OCPs maintain steady serum hormone levels, promoting a more stable knee joint and less ACL rupture in young female athletes. Additional studies must entertain the prophylactic use of OCP, but an extensive cost benefit analysis is warranted. Introduction ACL injury is the most common ligamentous knee injury, and female athletes are 2 to 8 times more likely to be affected. The primary function of the ACL is to prevent anterior translation of the tibia. Injury most commonly is non- contact, and occurs after sudden change in direction or deceleration. The ACL tissue contains estrogen and progesterone receptors, making the tissue susceptible to fluctuations in hormone levels during the menstrual cycle. The mechanism of OCP is through maintaining steady hormone levels, thus, preventing ovulation. Previous studies support that ACL functionality is dependent upon the serum estradiol level which may have implications in the incidence of ACL injury. The purpose of this investigation is to determine if OCP users are more protected against ACL rupture than NOCP users in female athletes ages 15 to 24. Methods A literature search was conducted in November 2018 utilizing Google Scholar and Pub. Med. Six total studies were selected; case-control (2), randomized control trial (2), and systematic review (2). Inclusion criteria consisted of date of publication, study population, and direct comparison of OCP verse NOCP users. Results Discussion Table A: Comparison of Study Designs Study Design Total N Forcada et al (2017) SR 6 studies Gray et al (2016) CC 51, 276 Herzberg et al (2017) SR 21 studies 68, 758 subjects Lee et al (2013) RCT 19 Lee et al (2015) RCT 40 Rahr. Wagner et al (2014) CC 12, 225 Age (years) 15 -25 OCP Type Populations Outcome measurements OCP current use, OCP use, ACL ever use, Never OCP use injury, timing of cycle Monophasic, multiphasic, progestin only, combination 15 -39 Monophasic, multiphasic, progestin only, combination 15 -24 Estrogen containing OCP Control (NOCP), Case (long term >90 d), Case (short term <90 d) ACL injury (NOCP), ACL injury (follicular phase), ACL injury (ovulatory phase), ACL injury (Luteal phase) 18 -30 Low dose OCP Case (self reported OCP <50 mcg ethinyl user for >6 months), estradiol control (NMP) 18 -30 OCP (30 -50 mcg Case (>1 year OCP use), ethinyl estradiol) Control (never user) OCP use, OCP type, OCP duration, ACL injury OCP use, ACL laxity, ACL injury, timing of cycle OCP use, ACL elasticity, FFK, KFEH Subjective pain scale, ACL laxity, timing of cycle. Case (current user), ACL injury, OCP Case (past 5 year user), exposure duration control (never user) 15 -40 Low dose OCP (<35 mcg estrogen) OCP=oral contraceptive pills; NOCP= non oral contraceptive pills; RCT = Randomized Control Trial; CC = Case Control; MA = Meta Analysis; SR= Systematic Review; NMP: normal menstrual period; FFK= force to flex the knee; KFEH= knee flexion-extension hysteresis Table B: Summary of Results Study OCP Duration OCP Type Timing of Cycle ACL Laxity Total Forcada et al (2017) Gray et al (2016) NS NA S S NS S NA S Herzberg et al (2017) NS NS S Lee et al (2013) S NA S S NS Lee et al (2015) S NA S S NS Rahr- Wagner et al (2014) S NS NA NA S Key: S= significant; NS= not significant; NA= results not applicable Based on this review there appears to be significant support that OCPs maintain steady hormone levels leading to a more stable knee joint, less knee laxity, and ultimately less ACL injury. Specifically, three main outcomes were supported. First, participants on OCPs had less knee laxity than NOCP users. Second, ACL tears occur most often during the preovulatory phase. Third, there were less ACL ruptures in OCP users compared to those not using OCP. The support for the aforementioned claims is rooted primarily in the relationship between serum estradiol levels and the subsequent effect on the ACL tissue. The strengths of this review includes the diversity of study designs, similar variable measures, and statistically significant results reported with a p value <0. 05 in all studies. Limitations include small sample size in the RCTs, risk of error during measurements, and recall bias for OCP compliance. Additionally, no studies initiated OCPs for prophylaxis of ACL injury and side effects or resulting complications of the medication were not included in the studies. Conclusion While OCPs are proposed to be protective against knee injury in young female athletes, there are no current studies evaluating the prophylactic use of OCPs in this population. Considerations regarding the anticipated side effects or complications of putting young female athletes on OCPs must be investigated for this capacity. In addition, the population evaluated is typically otherwise healthy, and initiating a OCPs for prophylaxis alone may be putting young females at risk for complications. References Rahr-Wagner L, Thillemann T, Mehnert F, Pedersen A, & Lind M. Is the Use of Oral Contraceptives Associated with operatively Treated Anterior Cruciate Ligament Injury? A Case-Control Study From the Danish Knee Ligament Reconstruction Registry. The American Journal of Sports Medicine. 2014; 42(12) 2897 -2905. Doi: 10. 1177/0363546514557240 Forcada C, Pons A, Seijas R, et al. 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The Effect of Menstrual Cycle and Contraceptives on ACL Injuries and Laxity: A systematic Review and Meta-analysis. The Orthopedic Journal of Sports Medicine. 2017; 5(7) doi: 10. 1177/23259671177187