Does Estrogen cause or prevent ACL injuries in women?

Danielle R. Steilen-Matias, MMS, PA-C

One of the more controversial discussions surrounding women and ACL injuries is hormonal involvement, specifically hormonal involvement surrounding the menstrual cycle.

In a recent study, doctors say that hormones such as estradiol have an effect on human connective tissue, making women more susceptible to knee injuries. In another recent study, doctors say oral contraceptives do not put 15-19 year old women at greater risk for ACL injury, in fact the oral contraceptives may prevent it.

Though males and females have the same musculoskeletal structures, there are some unique differences that actually make female athletes more prone to injury. In regard to skeletal differences, males usually have wide shoulders and narrow hips, whereas a female generally has a wide pelvis in relation to the width of her shoulders. This wider pelvis is necessary for childbirth. This wider pelvis is stabilized by the sacroiliac ligaments in the back and the pubic symphysis and pubic ligaments in the front. (Please see our article Pelvic Floor Disorders, Pelvic Girdle Pain, and Symphysis Pubis Dysfunction following sports injury for a more detailed discussion). It is these ligament structures that are stressed and account for the significant back pain that occurs in 50 percent of women who are pregnant.

This wider pelvis in females leads to an increased inward slant of the thigh and, therefore, an increased Q-angle of the knee. The Q-angle, a measurement of the angle created by the line from the anterior superior iliac spine and the patella, and the line from the patella to the tibial tubercle, is normally less than 12 degrees. An increased Q-angle produces excessive lateral forces on the quadricep’s mechanism and abnormal tracking of the patella. This is one of the reasons why chondromalacia patella or patellofemoral syndrome is more common in women.

The problem of the Q-Angle has been recognized for some time, noted in studies more than twenty years ago. (1,2). More recently and building on this research was a March 2021 study (3) which documented in young (average age 23) division one women soccer players in Spain that  that Anterior cruciate ligament (ACL) and meniscus injuries occurred in totality in non-contact circumstance.

As stated above, a female’s thighs tend to slant inward towards the knees more than a male’s. This puts additional strain on a woman’s hips and their ligamentous support. This is one of the reasons that the majority of the 120,000 hip replacements done each year are in women. Females also have a wider carrying angle of the elbows. This is similar to the Q-angle of the knee. This wider angle places additional stress on the medial elbow stabilizers, namely the ulnar collateral ligaments, which are usually the culprits when a female athlete has medial elbow pain.

Body composition is also different between males and females. The average body fat content of the female is approximately 26 per-cent, compared with that of the male at 14 percent. The female has a lower lean body mass indicating less muscle mass. The greater muscle mass in males is due to the predominant effect of the androgen hormones, whereas estrogen, predominant in females, results in increased body fat. As it turns out, this difference in hormones is key to understanding why female athletes are more easily injured and repair more slowly than their male counterparts. Testosterone stimulates fibroblastic proliferation, whereas estrogens, especially estradiol, inhibits it.

British, American, and Brazilian researchers writing in October 2021 in the BMJ open sport & exercise medicine (4) announced a new study to understand hormones : “Exercising women report three to six times more ACL tears than men, which happen, in the majority of cases, with a non-contact mechanism. This sex disparity has, in part, been attributed to the differences in reproductive hormone profiles between men and women. Many studies have shown that anterior knee laxity and the rate of non-contact ACL injuries vary across the menstrual cycle, but these data are inconsistent. Similarly, several studies have investigated the potential protective effect of hormonal contraceptives on non-contact ACL injuries, but their conclusions are also variable.”

The controversy continues.

ACL Injury in Women, oral contraceptives

July 2017 research in the Orthopaedic journal of sports medicine, led by Seattle Pacific University and Oregon Health & Science University doctors examined studies suggesting an association between hormonal fluctuations and ACL injury in women athletes.

They cite that recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury.

In fact recent research on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting this type of  analysis for the first time.

However, the overall strength of this evidence that oral contraceptives may offer reduction in risk of injury is low.

BUT, it needs to be studied: “Promising potential directions for future research include long-term observational studies with ongoing hormonal assays and large interventional trials of follicular suppression, including newer hormonal methods.”1

In other words – research for or against oral contraceptives protective or non-protective role in ACL injury can be called controversial.

Here is research highlights from a recent study by doctors at the Physical Therapy Department, College of Health Science, Gachon University published in The Tohoku journal of experimental medicine.

The researchers looked for an answer as to why women have a greater risk for non-contact injuries of anterior cruciate ligament (ACL) compared to men when participating in the same sports.

The study examined the difference in ACL laxity after an eccentric (resistance) exercise in the lower limbs in young healthy women between oral contraceptive pill (OCP) users and non-OCP users to see the effect of  oral contraceptive pill on ACL laxity.

Forty young healthy women participated in the experiments (25 with normal menstrual cycle and 15 with taking Oral Contraceptives).

ACL laxity and a visual analog pain scale (0-10) were measured before and after squatting exercises.

One important aspect of healing chronic pain with Prolotherapy is to ensure that a patient’s lifestyle habits and factors are pro-healing. While this may sound obvious, many patients are surprised to learn that certain lifestyle factors are harmful to joint health. One such factor is toral contraceptive.

Some women who take the birth control pill are at a disadvantage when it comes to healing an injury because estradiol inhibits healing. It is important to stress some women as recent research seeks to understand which women are more likely to be at greater risk as we will see in research below.

Estrogen, the female hormone, dramatically inhibits fibroblasts. These fibroblasts are what make the collagen that makes up the ligaments and tendons, which are injured during sports or other chronic pain injuries. The more estrogen some women have, the more inhibition may occur.

For many decades the effect of high and low levels of estrogen on injury susceptibility in female athletes have been studied.

Doctors at the University of Tehran published their findings on the role of estrogen through the menopausal cycle, here are the summary bullet point findings:

Some women at risk for ACL injury from oral contraceptive, some may be protected by oral contraceptive use

In a study from the University of Texas, doctors examined the connection between oral contraceptives, elevated estrogen levels, and anterior cruciate ligament injuries. What they examined was that elevated estrogen levels are likely increase the risk for injury and that this risk may be partially or fully lessened by the use of oral contraceptives.

The purpose of this study was to determine if women undergoing anterior cruciate ligament surgical reconstruction were less likely to use oral contraceptives than matched non-injured population. (In other words, did the use oral contraceptive use put these women at greater risk for ACL injury).

The doctors looked at women 15-39 years old. Exposure to oral contraceptives was defined as the presence of any prescription fill for oral contraceptives during the previous 12 months to index date.

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
ACL injury requiring reconstruction cases among two older age groups, 25-29 and 30-34 year olds, were more likely to use oral contraceptives than controls.

So what does this mean? Doctors found that 15-19 year old female athletes use less oral contraceptives than 15-19 year old non-athletes, and that their data suggests that women ages 15-19 yr undergoing anterior cruciate ligament reconstruction used oral contraceptives at a lower rate than the general population.4

Do you have a question about knee injury? Get help and information from our Caring Medical staff

1 Hutchinson, M. Knee injuries in female athletes. Sports Medicine. 1995; 19:288-302. [Google Scholar]
2 Bergstrøm K, Brandseth K, Fretheim S, Tvilde K, Ekeland A. Activity-related knee injuries and pain in athletic adolescents. Knee Surgery, Sports Traumatology, Arthroscopy. 2001 May;9(3):146-50. [Google Scholar]
3 Agustín MS, Medina-Mirapeix F, Esteban-Catalán A, Escriche-Escuder A, Sánchez-Barbadora M, Benítez-Martínez JC. Epidemiology of injuries in first division Spanish women’s soccer players. International journal of environmental research and public health. 2021 Jan;18(6):3009. [Google Scholar]

1 Herzberg SD, Motu’apuaka ML, Lambert W, Fu R, Brady J, Guise JM. The effect of menstrual cycle and contraceptives on ACL injuries and laxity: a systematic review and meta-analysis. Orthopaedic journal of sports medicine. 2017 Jul 19;5(7):2325967117718781. [Pubmed] [Google Scholar]

2 Lee H, Petrofsky JS, Yim J. Do Oral Contraceptives Alter Knee Ligament Damage with Heavy Exercise? Tohoku J Exp Med. 2015;237(1):51-6. doi: 10.1620/tjem.237.51. [Pubmed] [Google Scholar]

3 Dehghan F, Soori R, Dehghan P, et al. Changes in Knee Laxity and Relaxin Receptor Isoforms Expression (RXFP1/RXFP2) in the Knee throughout Estrous Cycle Phases in Rodents. Vaudry H, ed. PLoS ONE. 2016;11(8):e0160984. doi:10.1371/journal.pone.0160984. [Pubmed] [Google Scholar]

4 Gray AM, Gugala Z, Baillargeon JG. Effects of oral contraceptive use on anterior cruciate ligament injury epidemiology. Medicine & Science in Sports & Exercise. 2016 Apr 1;48(4):648-54. [Pubmed] [Google Scholar]

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