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.

Research Highlights

A January 2024 study in Physical Therapy in Sport (1) looked to see if females were more susceptible to lower extremities injuries on different days of their menstruation cycles. In this study, samples of 18 healthy women with regular menstrual cycles were compared two times in their cycles, first in the peak of estrogen (mid-cycle) and second in the peak of progesterone (one week later). The researchers found no significant difference between days with estrogen and progesterone peaks and that there is the same risk for lower extremities injuries in estradiol and progesterone peak days of normal menstruating women. 

An October 2023 paper in the Orthopaedic Journal of Sports Medicine (2) found that female patients prescribed systemic contraceptives containing estrogen or progesterone had an increased rate of the need for reconstruction knee procedures for patellar instability.

A December 2023  study in the European Journal of Orthopaedic Surgery & traumatology (3) notes that observational studies have noted peak ACL tear rates in the luteal phase of the menstrual cycle, a time in which the hormone relaxin peaks in serum concentration. In a review of six studies, the researchers found ACL samples exhibit selective relaxin binding. When pre-treated with estrogen prior to relaxin exposure, female ACL tissue samples exhibit increased expression of collagen-degrading receptors increasing ACL tear rates in female athletes.

 

 

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.”

A September 2023 paper in the journal Frontiers in Bioengineering and Biotechnology (5) investigated the effects of the menstrual cycle and serum sex hormone concentrations on knee kinematic parameters of the 90°cutting in female college soccer athletes. Three female college soccer teams (53 subjects) participated in the study.

  • The subjects’ menstrual cycle was divided into the menstrual phase, late-follicular phase, ovulatory phase, and mid-luteal phase (Groups 1, 2, 3, 4).
  • The researchers found lower maximum knee valgus in group 4 (mid-luteal phase) compared with other groups. This meant that subjects had a lower biomechanical risk of non-contact anterior cruciate ligament (ACL) injury in the mid-luteal phase. There was no significant correlation between serum estrogen, progesterone concentration, and knee kinematic parameters. This meant that sex hormones did not have a protective effect.

The controversy continues.

ACL Injury in Women, oral contraceptives

July 2017 research in the Orthopaedic Journal of Sports Medicine, (5) 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 a 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.”

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

Here are 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. (6)

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 cycles 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.

Complete or a partial ACL tear, is ACL surgery necessary?

After ACL Reconstruction: Complication and post-surgery treatment options: Do you need revision surgery?

References

1 Baghdadabad MB, Mohaghegh S. Balance test results in different hormonal statuses of the menstruation cycle. Are females more susceptible to lower extremities injuries on different days of their menstruation cycles?. Physical therapy in sport. 2024 Jan 1;65:54-8. [Google Scholar]
2 Martinazzi BJ, Bertha N, Nam HH, Lorenz FJ, Bonaddio V, Ptasinski A, Gallo RA. Association of Systemic Hormonal Contraceptives With Reconstruction Procedures for Patellar Instability. Orthopaedic Journal of Sports Medicine. 2023 Oct 4;11(10):23259671231191786. [Google Scholar]
3 Berger GK, Rockov ZA, Byrne C, Trentacosta NE, Stone MA. The role of relaxin in anterior cruciate ligament injuries: a systematic review. European Journal of Orthopaedic Surgery & Traumatology. 2023 Dec;33(8):3319-26. [Google Scholar]
4 Nédélec E, Foli E, Shultz SJ, Swinton PA, Dolan E, Enright K, Piasecki J, Matthews JJ, Sale C, Elliott-Sale KJ. Effect of menstrual cycle phase, menstrual irregularities and hormonal contraceptive use on anterior knee laxity and non-contact anterior cruciate ligament injury occurrence in women: a protocol for a systematic review and meta-analysis. BMJ Open Sport & Exercise Medicine. 2021 Oct 1;7(4):e001170. [Google Scholar]
5 Bingzheng Z, Xinzhuo Z, Zhuo J, Xing Y, Bin L, Lunhao B. The effects of sex hormones during the menstrual cycle on knee kinematics. Frontiers in Bioengineering and Biotechnology. 2023;11. [Google Scholar]
6 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. [Google Scholar]

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