By: Angelo Changas, DO
Director’s Note: September 27, 2023 is National Women’s Health and Fitness Day in the United States. Thus, we are featuring a summary of research published in 2019 in The Journal of Bone and Joint Surgery that investigated rates of knee injury among women across phases of the menstrual cycle.[1] In this summary, Dr. Angelo Changas, a former FACTS elective participant, highlights the value of utilizing fertility awareness-based methods (FABMs) to better demarcate distinct phases of the cycle and improve the quality of future studies in this area of women’s health. To learn more about the use of FABMs throughout a woman’s life, please join us for our virtual conference, The Continuum of Women’s Health Care, on Saturday, November 11, 2023.
Introduction
The anterior cruciate ligament (ACL) is one of the main ligaments that provide stability to the knee. As a connection between the femur and the tibia, it is responsible for 85% of the anterior restraint of the tibia.[2] Epidemiology data has shown ACL rupture is more common among female athletes, who have 2-4 times higher risk than male athletes.[1] Other knee injuries, such as meniscus or medial collateral ligament lesions, lack this distinct sex disparity. Due to the potential for long-standing sequelae and impact on quality of life, researchers seek to uncover possible mechanisms for this difference. Multifactorial mechanisms have been proposed including differences in bone structure, biomechanics, and hormones.
“Epidemiology data has shown ACL rupture is more common among female athletes, who have 2-4 times higher risk than male athletes.”
Evidence of estrogen, progesterone, and relaxin receptors on ACL tissue indicates that tissue characteristics can change during a woman’s cycle. In fact, previous studies have shown anterior laxity during the menstrual cycle and, specifically, increased laxity during the ovulatory or post-ovulatory phases.[3] The purpose of this 2019 study by Somerson et al was to examine all current literature on ACL injury rates and anterior knee laxity during the female cycle.
Methodology
Somerson et al utilized the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for their systematic review and meta-analysis.[1] The literature search identified articles investigating an association between ACL injury and/or knee laxity and the menstrual cycle. The authors identified and reviewed 1,308 items which were narrowed to a final total of 28 articles. Of these 28 articles, 9 examined ACL tears and 19 explored anterior knee laxity. Articles that included the use of oral or hormonal contraceptives, irregular menses, and prior ACL or contralateral ACL injury were excluded.
Anterior knee laxity was measured using standard arthrometer instruments. Determination of the female cycle phase was done with hormonal measures or the start of menstruation. The hormonal methods commonly used measured estradiol or progesterone levels to determine the cycle phase. Few studies use patient recall, calendar methods, or basal body temperature. A meta-analysis was performed to calculate the effect of the cycle phase on knee laxity or ACL injury rate.
Results
Anterior Knee Laxity
After a literature search and review, 19 studies were included with a combined 573 subjects. Eleven of these studies included athletes. Studies used a KT2000 or KT1000 arthrometer. The female cycle was broken down into follicular, ovulatory, and luteal phases. The largest mean effect was found between the ovulatory and follicular phases. Laxity of the anterior knee was greater in the ovulatory phase compared to follicular by 0.40 ± 0.29 mm. Anterior knee laxity was also greater in the luteal phase compared to the follicular phase by 0.21 ± 0.21 mm. Differences between the luteal and ovulatory phases were nonsignificant. Effects were largely homogenous across the articles, and publication bias was not significant.
“Anterior knee laxity was greater in the ovulatory and luteal phases compared to the follicular phase.”
ACL injuries
For ACL tear analysis, 9 studies were included after a literature search and abstract review. This resulted in 2,519 subjects with a total of 316 ACL tears. Seven of the studies included athletes. Three studies determined cycle phase by hormones group, 1 by menstrual event group, and 5 by other methods. The luteal phase accounted for a mean of 36% of ACL tears, which is 14% lower than would be expected if there was no difference in risk between phases. Subjects had a 0.72 times risk of an ACL tear compared to the follicular and ovulatory phases. These effects were heterogeneous across all studies and publication bias was not significant.
Discussion
The results of this systematic review and meta-analysis contradict the proposed mechanism that increased anterior knee laxity would increase ACL rupture. Based on this mechanism, the occurrence of ACL tear should be the lowest in the follicular phase. A proposed explanation is the increase in estradiol in the follicular and ovulatory phases leads to a decrease in fibroblasts and collagen synthesis. These effects have been demonstrated previously and could result in stiffer but weaker ligaments. The rise in progesterone during the luteal phase could have a protective effect on the ACL ligament through progesterone increasing fibroblast activity and collagen synthesis. Increased ligament laxity and higher resistance to tears would be opposite effects compared to estradiol. In the follicular phase, both hormones are at their lowest but estradiol is higher than progesterone, suggesting the higher ratio of estrogen to progesterone has a higher risk of ACL tear.
The overall evidence grade was very low; more high-quality studies are needed. Future studies should utilize a standardized method of monitoring the cycle such as fertility awareness-based methods (FABMs) or quantitative hormone levels. FABMs would be useful in this setting because they are inexpensive and established methods to reliably determine cycle phases and ovulation instead of using a recall calendar method. This study highlights the lack of high-quality evidence surrounding the female cycle and its effect on physiology. This is significant because by knowing why and where in the cycle an injury occurs, strategies can be used to lower the risk.
“This study highlights the lack of high-quality evidence surrounding the female cycle and its effect on physiology. This is significant because by knowing why and where in the cycle an injury occurs, strategies can be used to lower the risk.”
There are several limitations of this study. The lower risk of ACL tears in the luteal phase is small at 0.72 relative risks and may have little to no clinical significance. Variability in the how the cycle was tracked along with the magnitude of hormone levels made it hard to standardize the studies. Additionally, there is no standard definition of an ACL tear, and a majority of the studies reviewed followed an athlete population.
In conclusion, anterior knee laxity was found to be high in the ovulatory and luteal phases of menstrual cycles. Surprisingly, the risk of ACL rupture was found to be higher when there was less knee laxity during the follicular phase, when estradiol is higher than progesterone.
References
[1] Somerson JS, Isby IJ, Hagen MS, Kweon CY, Gee AO. The Menstrual Cycle May Affect Anterior Knee Laxity and the Rate of Anterior Cruciate Ligament Rupture: A Systematic Review and Meta-Analysis. JBJS Rev. 2019;7(9):e2. doi:10.2106/JBJS.RVW.18.00198.
[2] Noyes FR. The function of the human anterior cruciate ligament and analysis of single- and double-bundle graft reconstructions. Sports Health. 2009 Jan;1(1):66-75. doi: 10.1177/1941738108326980. PMID: 23015856; PMCID: PMC3445115.
[3] Zazulak BT, Paterno M, Myer GD, Romani WA, Hewett TE. The effects of the menstrual cycle on anterior knee laxity: a systematic review. Sports Med. 2006;36(10):847-62.
[4] Hewett TE, Zazulak BT, Myer GD. Effects of the menstrual cycle on anterior cruciate ligament injury risk: a systematic review. Am J Sports Med. 2007 Apr;35(4):659-68. Epub 2007 Feb 9.
ABOUT THE AUTHOR
Angelo Changas, DO
Angelo Changas, DO is a transitional year resident at Northeast Georgia Medical Center and a recent graduate of the Philadelphia College of Osteopathic Medicine Georgia Campus. He completed his undergraduate degree in chemistry at Kennesaw State University in Georgia. He enrolled in the FACTS elective to gain a better understanding of natural family planning methods and ways to share them with future patients so they feel more empowered over their health and reproductive decisions.
Inspired by what you read?
You can support the ongoing work of FACTS here. To connect with a member of our team, please email development@FACTSaboutFertility.org. Interested in becoming an individual or organizational member? You can learn more and register here. To discuss with a member of our team, please email membership@FACTSaboutFertility.org.
