Anterior Cruciate Ligament Injuries: Sex-Based Differences

Introduction and Epidemiology

In spite of years of research and evolving techniques, rupture of the anterior cruciate ligament (ACL) continues to represent one of the most common traumatic injuries in competitive sports. Female athletes have been noted to be at particular risk for ACL tears, with injury rates as high as two to eight times as those experienced by males, especially in sports requiring quick or repetitive lateral movement. In addition to being at increased risk for primary rupture, females are more likely to sustain a contralateral injury or undergo revision surgery, experiencing rates of secondary ACL sequela as high as 34%.

Interestingly, several well-designed studies have failed to identify female gender as an independent risk factor for ACL injury on multivariate regression analysis. This has led to the suggestion that the observed increase in risk for female ACL injury is a mere reflection of increasing sports participation. However, this theory has been largely discredited by multiple surveillance studies, which failed to find an increase in ACL injury risk when expressed as a percentage of active female athletes. In one such study, performed by the National Collegiate Athletic Association, no significant change in the rate of ACL injury was noted over a 15-year period, in spite of increased female sports participation rates.

Given these findings, the increased propensity for female ACL injury is likely multifactorial, attributed to factors such as variations in anatomic size and morphology, hormonal levels, and alterations in neuromuscular control. Accordingly, this chapter reviews the current understanding of the female ACL, summarizing potential contributing causes for increased risk, while also discussing strategies for injury prevention, surgical reconstruction, and rehabilitation.

Anterior Cruciate Ligament Anatomy and Function

The ACL is the primary contributor of anteroposterior and rotatory stability to the knee, especially in lower flexion angles. It is composed of two distinct segments, the anteromedial and posterolateral bundles, which are named based on their respective insertion sites on the tibia. The native ACL is covered by synovial tissue, with the deeper areas being largely avascular, minimizing healing potential. Limited vascularity is supplied to the femoral insertion via the posterior soft tissues, with the tibial insertion site receiving a small vascular contribution from the anterior horn of lateral meniscus. The ACL is also rich in mechanoreceptors, functioning to provide proprioceptive feedback while initiating protective muscular reflexes.

The ACL’s femoral insertion site is oval in shape and smaller in size than the ligament’s broad tibial insertion. The isthmus of ACL exists at mid-substance, with a cross-sectional area of less than half of the tibial or femoral insertions. The intra-articular portion of the ACL is quite dynamic, demonstrating its shortest length at 90 degrees of knee flexion and increasing to its maximal size in full extension.

When viewed arthroscopically, the ACL can be readily appreciated originating from the posterior aspect of the lateral femoral condyle, coursing in an anteromedial direction to insert at the interspinous area of the tibia. This intra-articular course is located within the ‘femoral notch,’ composed of the area between the medial and lateral condyles of the femur. Femoral notch size and the shape often play an important role in ACL injury, with several gender-specific differences noted. Notch size can also affect intraoperative visualization, complicating the creation of anatomic tunnels, one of the most impactful metric on return-to-play outcomes.

Gender-Based Anatomic Differences

The size of the ACL itself has been postulated to contribute to gender-based differences in ACL injury patterns. When compared with their male counterparts, ACLs in females tend to be smaller in overall volume, while also possessing less tensile resistance, demonstrating decreased elongation distances to failure. Such mechanical differences have also been noted clinically, with females’ knees exhibiting less resistance to rotation and anterior translation as measured on KT-1000.

Females also possess a larger quadriceps angle or ‘Q-angle’, resulting from a wider and shorter pelvis. The Q-angle is formed via the composite of two lines, originating from the anterior superior iliac spine and tibial tubercle, that course through the center of the patella. Increases in the Q-angle result in a more laterally based quadriceps force vector, placing the knee in increased valgus, thus predisposing to ACL rupture with athletic activity. ,

In a 2020 systematic review, Bayer et al. examined the morphologic risk factors for ACL injury. Of all the factors considered, an A-shaped notch, sometimes referred to as ‘notch stenosis,’ was the most commonly cited cause for increased risk of ACL injury. This finding seems to correlate with increased injury risk, , as a review of patients undergoing ACL reconstruction noted a greater percentage of A-shaped notches in females than males. Other authors have reported similar findings, noting a decreased notch size in females.

Several morphologic factors have also been demonstrated to contribute to increased risk for ACL injury based on condylar anatomy. In one study, ACL-injured females were noted to demonstrate an increased condylar offset ratio, defined as the difference between the anatomic and transcondylar axes of the femur. A second study reported a lateral femoral condylar offset of >63% to similarly correlate with increased ACL injury. With regard to tibial morphology, multiple authors have reported an increased tibial slope to correlate with increased injury risk. , In one such study, small variations seemed predictive, with a mean lateral tibial slope of 6.3 degrees noted in individuals experiencing ACL injury, compared to just 4.1 degrees in their uninjured counterparts.

In an examination of risk factors for subsequent injury to the contralateral anterior cruciate ligament (CACL), Davey et al. noted a rate of 20% for CACL injury following an index ACL tear. In this cohort of 61 female athletes, at a mean follow-up of 45 months, younger females with increased hip anteversion and increased contralateral knee laxity were noted to be at the greatest risk for CACL rupture. Interestingly, while younger patients were at higher risk of CACL pathology, increased sports participation was somewhat protective, with prior competitive play associated with decreased overall injury risk.

Menstrual Hormones and Oral Contraception

The effects of menstrual hormones and oral contraceptive (OCP) use represent an oft debated risk factor for female ACL injury. Indeed, over the past decade, the amount of research dedicated to hormonal effects on ACL injury has more than doubled, allowing for an increasingly evidence-based approach to an often controversial topic.

With regard to specific menstrual hormones, estradiol has been demonstrated to result in a dose-dependent reduction of fibroblast and collagen production. The resulting increase in ligamentous laxity has been correlated with increased risks for female ACL injury, especially in the preovulatory phase of the menstrual cycle. Conversely, progestins have been found to inhibit such increases in laxity, , suggesting a decreased risk for ACL injury during the luteal phase ( Fig. 3.1 ).

Fig. 3.1

Hormonal fluctuations during the menstrual cycle. FSH , follicle-stimulating hormone; LH , luteinizing hormone.

Modified from Senanayake and Potts, 2008.

In examining several high-quality studies investigating knee laxity during phases of the menstrual cycle, a significant increase in laxity was noted in the ovulatory phase compared with the follicular phases. Further supporting this assertion, several studies have found ligamentous laxity to be the highest with increasing levels of estradiol. However, a similar reduction in laxity was not noted during the luteal phase, calling into question the overall importance of laxity in ACL injury and suggesting that the potential increases in risk are likely multifactorial.

The suppression of follicular development and ovulation with OCP use has been postulated to mitigate this cyclic increase in laxity, possibly resulting in a lower rate of ACL injury. However, the ability to demonstrate the protective effect of OCP use is complicated by the need to compare large numbers of female athletes of similar demographics, with readily available data regarding OCP usage. To date, two large, high-quality studies exist that have demonstrated a similar risk reduction of around 20%. ,

The first study, a Danish registry-based study, drew information from the country’s knee ligament register as well as a prescription drug registry. Through this anonymized information, 4497 females undergoing ACL reconstruction surgery were compared to 8858 age-matched controls. Analysis of this data demonstrated an 18% risk reduction for ACL injury with OCP use. In a second US-based study, 12,819 ACL injuries were compared to 38,457 matched controls by using a commercial insurance database. Analysis of this cohort demonstrated a near 20% risk reduction for eventual ACL reconstruction in females on regular OCP use.

Also of recent interest has been the potential effect of hormones on muscle activation and knee alignment. In this regard, several studies have investigated the role of female hormonal fluctuation on neuromuscular activity. Specifically, electromyographic studies have demonstrated differences in muscle activation in the quadriceps and hamstrings (HSs) throughout the menstrual cycle. In one study, alterations to the lateral HSs were found to be most pronounced during the follicular phase. In a second similar investigation, Khowailed et al. noted ovulatory phase alterations to medial quadriceps activation that placed the knee in a position of risk for increased ACL loads.

Importantly, it must be mentioned that a 2017 systematic review noted overall evidence to be ‘very low’ utilizing the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to analyze the effect size of the aforementioned studies ( ). Thus in spite of substantial increase in the amount of recent literature, concrete ramifications of menstrual hormones on ACL injury will likely remain controversial for the foreseeable future.

Gender Differences in Knee Kinematics

Aside from downstream hormonal effects, it has long been postulated that one contributor to the overall increase in risk for female ACL injury stems from variations in neuromuscular control between genders. Females have been noted to be ‘quadriceps dominant,’ possessing a relatively larger percent of their lower extremity mass in the quadriceps muscles when compared to the HSs. Such imbalances can result in athletes landing in a more upright position, with females demonstrating relatively increased knee extension, thus placing increased strain on the ACL upon impact.

Females have also been demonstrated to exhibit differences in the mechanics of athletic movements such as sidestep cutting. Indeed, in an investigation of female soccer athletes with and without the presence of a defender, the defended condition resulted in increased medial ground reaction forces. The defended position was also noted to result in increases in flexion and abduction of the hip and knee, potentially predisposing for ACL injury. Similar results were noted in a subsequent study of stop-jump kinetics, with females’ knees demonstrating increased anterior tibial shear force as well as valgus and extension during landing.

In an attempt to mitigate such inherent risk factors, Hewett et al. prospectively analyzed two cohorts of female soccer, basketball, and volleyball athletes. The first group received neuromuscular preventative training before and throughout their seasons, while the second group was left to coach-led participation alone. When compared with females in a neuromuscular prevention program, untrained females were 3.6 times more likely to sustain a traumatic ACL event, with smaller but significant reductions in the rate of noncontact ACL injuries also noted between the groups. Such imbalances are of particular concern in the setting of fatigue, which may compromise the ability to alter muscle activation patterns due to the inhibition of rapid neuromuscular feedback. ,

In a biomechanical study employing three-dimensional motion analysis during vertical jumping, male and female landing kinematics was compared. Female athletes were found to land with greater total knee valgus and overall lower extremity valgus angles than their male counterparts. Females were also found to demonstrate significantly greater muscle activation differences between the dominant and nondominant extremities. Based on these findings, the authors postulated that females were at increased risk for ACL injury owing to the lack of dynamic knee stability.

In an analysis of gender differences during a single-leg squat maneuver, alterations to ankle, hip, and trunk mechanics demonstrated females to have tendency toward a valgus position during increasing lower extremity loads. Specifically, the authors identified females to demonstrate increased ankle dorsiflexion and pronation, increased hip adduction and external rotation, and decreased lateral trunk flexion compared to males. Taken together, these differences were found to result in a decreased ability to maintain a varus knee position, potentially increasing anterior forces on the ACL.

In a seminal paper, Hewett et al. was able to identify the aforementioned alterations to knee mechanics in a clinical setting. In a study of 205 high-risk female athletes, the authors performed three-dimensional analysis of knee kinetics and kinematics during simulated jump landings. Athletes were then followed up throughout their respective competitive seasons. Compared to their uninjured colleagues, those who went on to sustain an eventual ACL injury were noted to share several distinct alterations to drop landing joint angles and forces. These included a decreased stance phase and an almost 10-degree difference increase in abduction angle. Furthermore, those with ACL injury demonstrated 2.5 times greater abduction moments and increase in ground reaction forces of 20%. The authors further identified abduction moments to be highly predictive of ACL injury, with a sensitivity of 73% and sensitivity of 78%. Dynamic valgus also demonstrated a strong correlation coefficient, with a noted r 2 of 0.88 for eventual ACL pathology.

Taken together with other factors predictive of risk, such as age, morphologic characteristics, and increased level of competition, the abovementioned biomechanical data provide a framework for ever-increasing strategies for ACL injury prevention and rehabilitation. Consideration of the many factors introduced earlier also plays an important role in the operative approach to reconstruct the female ACL.


With the complexity of anatomic and knee kinematic differences in the female knee, an ACL prevention program must be multifactorial in nature. Three meta-analyses indicate that, in females, exercise-based injury prevention programs are effective in reducing the risk of all ACL injuries. The injury prevention programs are found to be most effective when they incorporate multiple exercise components, such as trunk/core strengthening, plyometrics, strengthening, stretching, and proprioception. Programs including only one exercise component did not show a significant reduction of injuries. Additionally, feedback on form during tasks including drop jumps and single-leg squat maneuvers was found to be effective in reducing injury. The feedback provided to athletes allows for addressing the changes in knee kinematics discussed earlier. Interestingly, programs without a balance training component were found effective in preventing ACL injuries in females. In fact, one study found an inverse relationship between the time spent performing balance activities and the protective effect of the program.

Time to return to sport (RTS) postoperatively is a highly studied aspect of ACL rehab, but equally important can be the appropriate time to implement a prevention program. When compared with females over 18 years of age, two meta-analyses found that females under the age of 18 years have a greater reduction in ACL injuries when completing exercise-based ACL prevention programs. A meta-regression by Sugimoto et al. found a 17% lower risk of ACL injury in athletes aged 14–18 years compared with their 18+-year-aged peers when completing a prevention program.

Implementation of a prevention program has become more commonplace in the preseason, but preseason training alone was not effective in reducing ACL injuries. Exercise-based prevention programs that began in the preseason, continued throughout the season, and consisted of greater than 20 min of duration multiple times per week have been shown to be most effective in reducing ACL injuries. , , Compliance of athletes to their exercise program during that time has a potential inverse dose-response relationship, with the incidence of ACL injury in adolescent female athletes, according to Sugimoto et al. With a compliance percentage of >66.6%, athletes demonstrated an 82% lower ACL injury incidence than their less compliant counterparts.

A gold standard for exercise-based ACL prevention programs has not been established, but two programs have shown to be very effective in the female adolescent population. The Knakontroll program was implemented with over 4500 female soccer players aged 12–17 years. The intervention group saw a 64% reduction in ACL injuries and 30% reduction in severe knee injuries. The PEP (Prevent injury and Enhance Performance) program was studied by Mandelbaum et al. in females aged 14–18 years and found an 89% decrease in ACL injuries in the first season of implementation and a 74% decrease in the second season. Similar nonsignificant decreases in ACL injuries were found by Gilchrist et al. in college-aged females.

Operative Considerations

Perhaps the single largest preoperative consideration in surgical reconstruction of the female ACL is the choice of graft selection. In a large, multicenter study examining outcomes at 6 years, the Moon (Multicenter Orthopaedic Outcomes Network) Knee Group identified three independent risk factors for ACL revision and contralateral injury. These included a high-grade preoperative pivot shift, young age, and choice of autograft. While gender was not identified as a risk factor, the choice of graft did impart a significant impact, with patients receiving a HS autograft demonstrating an odds ratio of 2.1 for reinjury compared to those reconstructed with a bone-patellar tendon-bone (BTB).

Salem et al. noted a similar finding in an examination of outcomes in 256 athletes, with the authors limiting their investigation to females between the ages of 15 and 20 years. In this cohort, the authors noted a significantly lower rate of rerupture between the BTB (6.4%) and HS (17.5%) groups. However, BTB grafts were associated with a much higher rate of prolonged kneeling pain (12%) when compared with HS grafts (2%). Given these findings, the current literature does suggest an advantage to graft survivability when electing for a BTB-based over an HS-based reconstruction.

More recently, quadriceps tendon (QT) ACL reconstruction has gained increased attention due to the readily available access to a larger sized graft, , with the quadriceps also noted to possess a larger cross-sectional area and increased load to failure compared to a patellar tendon graft. A second potential advantage to QT grafts is that similar clinical outcomes can be achieved utilizing partial- and full-thickness grafts, in contrast to BTB grafts, which require harvesting of full tendon depth. In an examination of postoperative extension strength, Hunnicutt et al. reported similar quadriceps function between BTB and QT groups at 8 months following ACL reconstruction. The authors also noted no difference in patient-reported outcomes between the two groups, a finding that was again verified by a subsequent prospective study, this time at 2-year follow-up. In a second systematic review and meta-analysis, QT ACL reconstruction demonstrated similar survivability to HS- and BTB-based procedures. Several findings were also reported favoring QT ACL reconstruction, including decreased donor-site pain and increased Lysholm scoring at final follow-up.

Surgical Technique

As previously mentioned, several authors have noted females to be more likely to possess a narrowed or ‘A’-shaped intercondylar notch. Therefore a surgical approach that allows for consistent, anatomic ACL reconstruction in the setting of a narrowed intra-articular working space should be preferentially chosen to optimize outcomes. Notably, we would caution against routine reliance on a ‘notchplasty’, as it is our preference to preserve as much native anatomy as possible. Ultimately, whichever method allows for the most repeatable creation of anatomic tibial and femoral tunnels should be elected, as improper tunnel placement has been identified as the most common surgical risk factor for suboptimal patient outcomes, and highly predictive of the need for revision.

It is our preference to perform knee arthroscopy with a standard two portal approach, modifying the medial portal to allow for both meniscal work while maintaining an appropriate trajectory for separate, anteromedial drilling. A second accessory medial portal can also be utilized; however, in our experience, this is rarely necessary if medial portal placement is appropriately planned employing outside-in localization techniques.

While we hesitate to make concrete recommendations with regard to routine graft choice, several key points warrant emphasis in the decision-making process. First, in the absence of complicating factors, allograft use in the young female athlete should be avoided to mitigate the risk of graft failure, , while avoiding the increased cost associated with allograft use. Second, practitioners should be confident in their abilities to obtain an autograft of appropriate size with their preferred autograft, as sizes of less than 8 mm are associated with higher failure rates.

Our preference is to elect for either a BPTB- or a QT-based reconstruction, noting the benefits of faster incorporation and bone to bone healing with patellar tendon, with potentially easier access to a larger graft size employing a QT. Furthermore, it is our tendency to avoid HS reconstruction as a primary choice; although admittedly, the choice of autograft remains nuanced and highly controversial. Finally, multiple studies of graft fixation methods have failed to identify any one method to exhibit clear superiority ; however, a more recent study did note larger metal screws to act as a potential risk factor for revision. The most common methods of fixation include aperture-based methods in the form of screws and cross-pins versus suspensory fixation with a button-based device.

Aside from the restoration of ACL’s integrity, special attention should also be paid to address secondary pathology encountered at the time of reconstruction, such as meniscal tears, compromise of collateral stabilizers, or cartilaginous lesions. Indeed, multiple authors have demonstrated the presence of meniscal injury to negatively impact outcomes following ACL reconstruction, with tears identified later on more likely to be complex and associated with degenerative progression. We do caution against the routine use of lateral tenodesis procedures, as the need for extra-articular augmentation can often be mitigated by emphasizing an anatomic reconstruction, while minimizing the risk for potential overconstraint. However, benefits in such extra-articular stability procedures have been demonstrated in select at-risk groups, such as younger individuals undergoing revision surgery, a grade III pivot shift, or those exhibiting signs of advanced ligamentous laxity.

Return to Sport

RTS after ACL reconstruction is a highly debated topic, with time frames ranging anywhere from 6 months to 2 years. Adolescent athletes can find themselves under pressure to return quickly after ACL reconstruction, including external pressure from coaches, parents, and teammates as well as internal pressure. Hewett and Nagelli postulate that after the 2-year mark in the adolescent population, the risk of repeat ACL injury is significantly decreased. This reduction is likely due to resolution of a multitude of risk factors including bone bruises, decreased proprioception, ligamentization, and decreased knee strength. Delaying for 2 years in adolescents comes at a potential separate cost of decreased social/team engagement and scholarship potential, and certainly, further study is needed. Grindem articulated that for each month the RTS was delayed until 9 months, the reinjury rate was significantly reduced by 51% for each month.

Perhaps even more important is the use of a criterion-based RTS battery of tests to reduce the risk of reinjury. Kyritsis et al. defined a set of RTS criteria as follows:

  • zero to trace effusion on stroke test,

  • one-repetition maximum quadriceps limb symmetry index (LSI) >90% on knee extension,

  • one-repetition maximum HSs LSI >90% on HS curl,

  • good neuromotor control with no increased pain/effusion with sports-specific activities,

  • functional hop testing >90% LSI for all four tests with good neuromotor control,

  • running t-test <11 s.

Two studies have shown that if an athlete does not pass all the RTS criteria, they are at a four times greater risk of ACL reinjury. , In a prospective 2-year cohort study, Grindem et al. reported a 38.2% ACL reinjury rate for level I sport athletes who failed the RTS criteria. In contrast, athletes who passed the RTS testing demonstrated a 5.6% reinjury rate. In this same study, postoperative quadriceps strength was shown to be directly related to reinjury risk. For every 1% increase in quadriceps LSI, there was a resultant 3% decrease in reinjury risk. Examining quadriceps strength as an individual RTS criterion shows a 33.3% reinjury risk for LSI <90% versus a 12.5% reinjury risk for those with LSI >90%. The current gold standard of knee extension isokinetic testing is oftentimes unavailable to clinicians outside the research setting. Thus knee extension one-repetition maximum testing is more commonly used.

In 2017, Wellsandt proposed that LSI was underestimating the true strength required postoperatively. Due to the bilateral resultant atrophy that occurs postoperatively, Wellsandt recommended utilizing an Estimated Preinjury Capacity (EPIC) value in place of LSI. EPIC utilized an uninvolved limb quadriceps strength measurement taken preoperatively. The resultant value required a higher involved limb quadriceps strength to meet the 90% RTS criteria and did show lower reinjury rates compared to LSI testing. Thus far, further study is required on EPIC, as LSI remains the commonplace testing strategy.

Neuromotor deficits are linked to a risk of reinjury, and thus it is essential to complete neuromuscular training prior to RTS. Neuromuscular training targets deficient muscles, utilizes muscle coactivation patterns associated with sports, and helps modify preexisting mechanics shown to increase injury risk. It is important to include bilateral training to address mechanical faults that may exist, as well as trunk proprioception to decrease external knee abduction loads. Progression should be form-dependent on the correct execution of each task and will vary greatly between athletes.


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Aug 21, 2021 | Posted by in SPORT MEDICINE | Comments Off on Anterior Cruciate Ligament Injuries: Sex-Based Differences

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