Why women are more likely to tear their ACLs

Effects of Hormones on ACL Injury Risk.

The anterior cruciate ligament (ACL) is frequently injured. Of the 120,000 significant ACL injuries that occur each year, they happen more often to females, and among athletic populations (Kaeding, Lager-St-Jean, & Magnussen, 2017). Female athletes are 2-8 times more likely to experience ACL tears due to a combination of anatomical factors and hormonal factors, neuromuscular factors, and different levels of hormones affecting ligament stiffness than male athletes. Anatomical sex differences between females and males include the structure of the surrounding areas and the properties of the ACL.

ACL Anatomical Overview.

The ACL is an important ligament in the knee joint complex. The ACL and the posterior cruciate ligament (PCL) criss-cross each other and maintain contact with the femur and tibia’s articular surfaces during knee flexion. The ACL is the weaker of the two ligaments, arising from the anterior intercondylar area of the tibia, just posterior to the attachment of the medial meniscus. It extends superiorly, posteriorly, and laterally to attach to the posterior part of the medial side of the lateral condyle of the femur (Moore, Dalley, & Agur, 2014). The ACL is shaped like an hour glass and is made up of two bundles, the anteromedial bundle and the posterolateral bundle (Irarrazzaval, Albers, Chao, & Fu, 2017). The fibers of the ligament are primarily composed of type I and type III collagen, which provides it with ability to withstand tensile load (Irarrazzaval et al., 2017). The role of the ACL is to limit excess motion and is an internal stabilizer of the knee joint. The ACL limits posterior rolling of the femoral condyles in the tibial plateau during knee flexion, and prevents the femur from becoming displaced from the tibia during hyperextension of the knee (Moore at al., 2014).

Mechanisms of Injury

Since the ACL works to limit flexion and extension, it makes sense that most ACL tears come from overly forceful or excessive hyperflexion and hyperextension. Some biomechanical causes of ACL tears include cutting movements with quick changes of direction with rapid deceleration, jump landing with the knee in total extension, and pivoting with the knee in full extension and a planted foot (Alentorn-Geli et al., 2009). Too much stress on the ACL causes the fibers to tear, causing instability in the knee joint, swelling and pain.

According to Weiss and Whatman (2015), several biomechanical factors contribute to ACL tears. Increased dynamic knee abduction increases tensile strain on the ligament and is a result of weak hip musculature, which indicates an inability of the hip musculature to properly absorb impact, forcing the knee to bear most of the stress (Weiss & Whatman, 2015). Excessive knee abduction loading is usually a chronic process in the cause of ACL injury. A decrease in the amount of knee flexion during landing movements, decreases the stability of the knee and may contribute to an ACL tear. Knee flexion of less than 30° creates a great load from the quadriceps to strain the ACL, and leads to the pathomechanics of anterior tibial displacement, knee internal rotation, and knee abduction motions (Weiss & Whatman, 2015). Increased hip flexion may be a compensatory mechanism to alleviate knee pain by absorbing more force at the hip joint. This may contribute to injury by increasing quadriceps activation, due to decreased to decreased hamstring strength which in turn decreases knee flexion (Weiss & Whatman, 2015). Increases in hip abduction lead to injury by excessive ground reaction force acting on the lateral side of the knee causing tensile strain on the ACL. Lastly a decrease in plantar flexion decreases shock absorption at the ankle joint, forcing the knee to absorb the impact (Weiss & Whatman, 2015).

Overview of Anatomical Variations that Predispose Females to ACL Injury

During the aging process the tibia and femur get wider and longer, creating instability in the knee joint. Female athletes often do not develop the compensatory strength necessary to deal with this instability, which may predispose them to a tear (Giugliano & Solomon, 2007). Women often also have larger Q angles than men, which is the acute angle between the line that connects the anterior superior iliac spine to the midpoint of the patella and the line that connects the tibial tubercle to the same reference point on the patella. The bigger the Q angle, the greater the lateral pull of the quadriceps, which adds to medial stress on the ACL (Giugliano & Solomon, 2007). Femoral notch width also plays a factor. The smaller the femoral notch, the more likely the ACL will get irritated and tear. Women with a smaller femoral notch (<13mm) are 16.8 times more likely to get their ACL torn (Abate, Vanni, & Pantalone, 2013). The ACLs of women are not as stiff or strong as men’s and therefore more likely to be torn (Abate et al., 2013).

Effect of Hormones on Injury Risk

Estrogen and testosterone have been shown to have an influence on the risk of anterior cruciate ligament (ACL) injury in two distinct ways: through the hormonal influence on the formation of collagen, and the hormonal influence of muscular support for the knee joint. Estrogen is the primary female sex hormone produced in the ovaries, and has been determined to decrease the proliferation of fibroblasts and the synthesis of type 1 procollagen (Stijak et al., 2015b). Testosterone is the primary male sex hormone produced in the testes, and leads to greater regeneration capacity of knee ligaments (Stijak et al., 2015a).

The formation of the collagen in the ligament is initiated by the transcription of messenger RNA (mRNA) collagen which directs the conversion of procollagen to collagen in the extracellular matrix (Romani, Langenberg, & Belkoff, 2010). “Some in vitro studies have shown that estrogen decreases the synthesis of type 1 collagen, which affects the extension strength of the ligament” (Stijak et al., 2015b, p. 2743). Receptors for estrogen and testosterone have been isolated on the human ACL, and in vitro experiments have demonstrated that collagen components are negatively associated with estrogen and positively associated with testosterone (Cammarata & Dhaher, 2008, p. 938). A higher ratio of estrogen to testosterone circulating in the body reduces the activity of mRNA collagen expression, whereas a higher ratio of testosterone to estrogen has been associated with increase of T1C and T3C synthesis. A correlation between increased risk for ACL rupture in men was determined in an experiment by Stijak et al. (2015), who could distinguish significant effects of these sex hormones on ACL integrity. Men with ruptured ACL had significantly higher levels of testosterone than those without, and men with higher concentrations of estrogen displayed statistically greater hyperelasticity than men with intact ACL (Stijak et al., 2015a). In a similar experiment conducted by the Stijak et al. (2015b), the same hormones were observed in female participants with and without ACL rupture. A correlation was found between higher levels of estrogen and ACL ruptures. Although higher testosterone levels were observed in men with ACL ruptures, the mechanism of injury was perceived to be different than women with ACL rupture and higher estrogen levels. The common reason for ACL rupture for women with elevated estrogen levels was linked to greater ligamentous laxity, while the men suffered injury due to the increased muscular force which overwhelmed the ACL during high-risk activity (Stijak et al., 2015a). Although anthropometric gender differences factor into this discussion (Cammarata & Dhaher, 2008), the significant effects of sex hormones on collagen make up have been shown to alter the tensile strength of the ACL (Romani et al., 2010).

Receptors for estrogen and testosterone exist in skeletal muscle (Bell et al., 2012) therefore also have an indirect effect on the ACL by way of an influence on muscular stiffness and power (Stijak et al., 2015a). The hamstrings are the primary dynamic stabilizer of the knee that reduce ACL loading, thus providing protection from ACL injury. Bell et al. (2012), showed the influence of estrogen and testosterone on neuro-mechanical properties of the hamstring muscle. Estrogen had the effect of lowering values for hamstring musculotendinous stiffness (MTS) and the rate of force production (RFP), whereas testosterone had a positive effect on the MTS and RFP.

The effects of estrogen and testosterone on the ACL should not be overstated because gender differences in passive joint stiffness must consider variation in anthropometric and anatomical factors (Cammarata & Dhaher, 2008). However, current research continues to corroborate the association between estrogen and knee laxity, and between testosterone and knee stiffness.

Another hormone to consider for effects on the ACL is relaxin. “Relaxin-2 is a peptide hormone historically recognized for its role in ligament catabolism to facilitate parturition, but it may also make female athletes more susceptible to ACL injury” (Konopka, DeBaun, Chang, & Dragoo, 2016, p.2385). Female athletes have a greater circulating serum relaxin concentrations while having an ACL tear. Konopka at el. (2016) discovered that men do not have significant serum levels of relaxin. Therefore, it is plausible that chronic relaxin exposure decreases the integrity of the female ACL, contributing to the sex disparity in ACL injury prevalence. Relaxin-2 has exposed to transmit collagenolytic effects by acting on at least 3 intracellular pathways. One mechanism is increasing matrix metalloproteinase levels or decreasing levels of tissue inhibitors of matrix metalloproteinases (Konopka et al, 2016). Relaxin decreases the production of collagen as it hinders type I and type III collagen protein sequence appearance.

Influence of the Menstrual Cycle on ACL Injury Risk

Females also may be more at risk for ACL injury due to menstruation. ACL injuries can occur at various stages of the menstrual cycle, because of fluctuating hormonal levels the neuromuscular and biomechanical variables are altered. According to Abt et al. (2007), approximately 22–40% of ACL injuries were documented to have occurred between 2 days pre-menses and 1–4 days post-menses (21% of total days for 28 day cycle). The menstrual cycle and sex steroid hormones have been implicated as risk factors for the greater occurrence of non-contact ACL injuries observed in female athletes compared with male athletes (Vescovi, 2011).

Vescovi (2011) explained it is plausible there could be an immediate or slightly delayed effect on knee joint laxity and potential ACL injury risk, resulting from the regulation of specific proteins involved with collagen and matrix metabolism after large absolute changes in sex steroid concentrations across the menstrual cycle; or a chronic effect on the size, shape and quality of the ligament as a result of the accumulated exposure to sex steroid hormones on ligament remodeling. ACL ruptures in females have significantly lower concentrations of 17-β estradiolgesterone (estradiol progesterone) and testosterone. 17-β estradiolgesterone ascends in the blood prior to ovulation, and decreases the synthesis of type I collagen. The menstrual cycle is influenced by ovarian production of 2 steroid hormones: progesterone and estradiol. Estradiol secretion is biphasic with both follicular (preovulatory) and luteal (postovulatory) peaks (Beynnon et al., 2006). “As the concentrations of sex hormones are low in the pre-ovulatory phase, the question arises as to whether ACL injury can be attributed to the pre-ovulatory phase itself or to the low concentrations of sex hormones” (Stijak, 2015b, p.2746). Testosterone is chiefly a male sex hormone yet it performs a physiological role in both sexes. “In addition to secondary sexual characteristics, testosterone, in both sexes, also affects the quality of bone tissue, as well as the increase of muscle mass” (Stijak, 2015b, p.2748).

Conclusion The ACL plays a key role in knee stability, therefore understanding the mechanism of injury is important. Risk factors for ACL injury are both biomechanical and hormonal. The hormones estrogen and relaxin negatively affect ligament laxity, while higher testosterone is associated with stronger, stiffer ACLs. Women may be more susceptible to ACL injury because generally speaking, they have higher levels of estrogen and relaxin, and lower levels of serum testosterone than men. Current research has also provided a correlation between fluctuations in hormone levels during the menstrual cycle, and higher incidence of ACL injury among women. Hormones indirectly impact the ACL via their influence on anatomical and neuromuscular factors, which must also be included in the discussion of ACL injury risk factors.

References

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