Could Regulating Female Hormones Reduce ACL Injury Risk?

Girls and women are 2x-6x more likely to have an anterior cruciate ligament (ACL) tear than men in similar sports.

Why?

One cause, say two studies, one from the University of Texas and another from Aarhus University in Denmark may be the level of female hormones. Both studies found that women who took birth control pills reduced their risk of ACL surgery by almost 20%.

The University of Texas study, “Effects of Oral Contraceptive Use on Anterior Cruciate Ligament Injury Epidemiology,” used national claims data from 2002 to 2012 to measure exposure to oral contraceptives and their effect on ACL injury risk. According to their data, published in Medicine & Science in Sports & Exercise, women age 15-19 years old undergoing surgical repair of the anterior cruciate ligament were 18% less likely to use oral contraceptives than matched controls (p < 0.0001).

In the Danish study, “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 researchers also studied women who were operatively treated for ACL injury. This time they measured oral contraceptive exposure at the time of the ACL injury as well as in the 5 years previous. They too found that oral contraceptive users had a reduced risk for ACL injury. The study was published in The American Journal of Sports Medicine.

Need to Establish Protective Effect

Subsequent reviews of these studies, however, pointing to the fact that they were limited by the information in the patients’ records. Another limiting factor was that they only included women who underwent surgery and not those who chose nonsurgical solutions.

The reviewers in one review from Brown University argued that a protective effect was not established. They wrote, “A better understanding of the relationship between oral contraceptive pill use and ACL injury is warranted.”

A recent study in the Physician and Sportsmedicine, “Oral contraceptives provide protection against anterior cruciate ligament tears: a national database study of 165,748 female patients,” however offers more evidence that oral contraceptives do have a protective effect on ACL tear, especially in the 15-19 age group. That study reported that the athletes they studied who used oral contraceptives experienced a 63% reduction in the rate of tear.

The researchers used the PearlDiver Technologies, Inc. database to collect data on all oral contraceptive female users between the ages of 15 and 49. They compared a group of females who were undergoing surgery for an ACL injury who were on oral contraceptives to a group of females having the surgery who were not on birth control.

According to the data collected from 82,874 patients, those who did not take oral contraceptives had 569 (0.69%) ACL reconstructions vs. 465 (0.56%) in the oral contraceptive group (p < 0.001).

Of those patients aged 15 to 19 who took oral contraceptives, 13.33% underwent ACL reconstruction while 29.35% of that group who did not take oral contraceptives underwent ACL reconstruction.

The researchers wrote, “Future prospective studies should be aimed at determining the number needed to treat to truly experience a protective effect. While there are potential risks of oral contraceptives (thromboembolism, weight gain, etc.), those at high risk for ACL tear could potentially benefit from their use.”

They added, “This leads us to conclude that female athletes, specifically in the 15- to 19 year-old age group should be screened for current [oral contraceptive] usage, and that discussion should be had toward potentially beginning [oral contraceptive] usage in female populations at higher risk for injury (soccer players, basketball players, etc.).”

When asked if this is enough data to recommend oral contraceptives to prevent ACL injuries, Steven F. DeFroda, M.D., M.E., Orthopaedic Trauma Fellow at Brown University/Rhode Island Hospital and lead researcher on the study told OTW, “It’s important to stress that we aren’t explicitly ‘recommending’ the use of oral contraceptives for the prevention of ACL injuries. As our study was retrospective in nature, it is subject to certain limitations, however our findings did support a trend within literature that regulating estrogen and progesterone levels could lead to a decrease risk of ACL injury (although the jury is certainly still out as to the optimal formulation) and if this is a causative effect or just a confounder within these groups.

“At this time the data we have suggests that it is a potential side benefit, and this should warrant a discussion point for both active patients and their primary care doctors in the event that patients are already considering oral contraceptives.”

He added that there are side effects to taking oral contraceptives—weight gain and blood clots—so they wouldn’t recommend it for the sole purpose of ACL preventions, but would encourage a female patient to discuss the pros and cons of this medication with their prescribing physician.

“We are currently interested in examining which formulations of oral contraceptives may best offer the protective effect. We have ongoing research examining low versus high estrogen medications and low versus high progesterone medications (also retrospective in nature),” he said.

What about sex differences in other injuries?

When asked if the risk for other orthopedic injuries could also be linked to a woman’s menstrual cycle, he said that this question was of great interest to him and his colleagues.

He said, “Relaxin is a hormone that also circulates at higher levels in females. We mention that this hormone does seem to align with risk of ACL injury. Our sports injury research team has examined the effects of this hormone on shoulder instability and was unable to find a similar association, so the short answer is the jury is still out!”

“It has obviously been well documented that elderly females are at a higher risk of osteoporosis and fragility fracture due to decreasing bone mineral density once estrogen levels drop following menopause, and there are well documented links regarding the ‘female athlete triad’ (now being referred to as Relative Energy Deficiency in Sports Syndrome RED-S Syndrome by some) commonly effecting endurance females and consisting of amenorrhea, some form of eating disorder or energy deficient state and stress fracture, but to our knowledge nothing explicitly related to the menstrual cycle, at least nothing as widely studied as the ACL.”

More Work to Do

These results are tantalizing, but more work is required.

Aside from hormonal levels, current research is also pointing to differences in landing biomechanics and neuromuscular control. Women have a greater valgus angle in their knees. And, female athletes commonly land after a jump with the knee in a straight position putting a lot of force on the knee joint. Male athletes, on the other hand, commonly land with their knees bent.

Additionally, when it comes to neuromuscular control, women have difficulty keeping their knees in a stiff position because of increased anterior tibial laxity.

And then of course there is the 2018 Duke University study “Determination of the Position of the Knee at the Time of an Anterior Cruciate Ligament Rupture for Male Versus Female Patients by an Analysis of Bone Bruises,” published in the American Journal of Sports Medicine which suggests that there are actually no gender differences at all in how ACL injuries occur.

The Duke researchers used MRI scans from within a month of the injury to study bone bruises on the knees. They then with the help of 3-D modeling recreated the position of the knee at the time of the injury. Their results showed that knee position was similar in both the male and female athletes.

So, more work to do, for sure.