Oral Contraceptive Use | Does Estrogen cause or prevent ACL injury?

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

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. This article will look further at oral contraceptive use and knee instability.

ACL Injury in Women, a growing mountain of research

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.

  • Oral contraceptive pill users had more pain than non-oral contraceptive pill users after heavy exercise.
  • Health professionals working with young female adults should recognize that oral contraceptive pill users may be at higher risk for having knee injuries.2

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:

  • Hormones have been reported to affect ligament laxity in different studies. However the underlying mechanism is debatable. Some studies believed that the changes in estrogen levels influenced knee laxity variation throughout the menstrual cycle but others deny this explanation.
  • Studies show that ACL laxity was the lowest in the post-ovulatory (luteal) phase of the menstrual cycle and highest in the pre-ovulatory phase.
  • Besides endogenous steroid hormones, oral contraceptive pills consumption may have a role to play in knee laxity. However the exact mechanism is not well known.
  • The controversial effect of oral contraceptive pills may raise from different hormonal composition, pill cycle, different ligaments or tendons tissues, its influence on structure or mechanical properties or does not.
  • Female athletes on containing high doses estrogen and progesterone have greater ACL laxity than athletes not on oral contraceptive pills. The mechanisms underlying oestrogen and progesterone effect are currently not fully understood, however estrogen has been reported to stimulate collagenase enzyme responsible for collagen breakdown.
  • Estrogen and progesterone have been shown to up-regulate the expression of relaxin and that may explain the increased laxity under the influence of both hormones.
    • Note on Relaxin: During pregnancy, a woman’s body secretes a hormone called relaxin which causes ligaments to loosen in preparation for birth. Ligament laxity is normal during pregnancy. Relaxin’s effects include the production and remodeling of collagen, increasing the elasticity and relaxation of muscles, tendons, and ligaments. Relaxin is secreted by all females, the highest levels being during the middle of the luteal phase (ovulation) of the menstrual cycle (days 20-23). According to this study relaxin might not play an important direct role as its role as a “ligament relaxer,” is being played parallel by Estrogen and progesterone. However, the interchange of chemical messages between all three hormones can be seen at the ACL, hamstring tendons, and patellar tendons where laxity occurs at the specific times in the menstrual cycle.
    • Both estrogen and progesterone have also been shown to inhibit the collagen synthesis in the tendon and skeletal muscles which might also contribute towards a decrease in knee laxity. Therefore, variation of the reported effect of estrogen and progesterone maybe related to interaction between these two hormones.3

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 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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