The Association of Salivary Estradiol Levels with Anterior Cruciate Ligament Stiffness and Laxity
DOI:
https://doi.org/10.53646/atq23m66Keywords:
Oral contraceptives, ACL injury females, hormone fluctuations, ligament, stiffness, laxity, menstrual cycleAbstract
BACKGROUND: Females are three to six times more likely to sustain an anterior cruciate ligament (ACL) injury than males. Researchers have previously identified hormonal fluctuations as a possible intrinsic factor related to the higher incidence of ACL injuries among female athletes. Whether hormonal levels, with or without use of oral contraceptives (OC), influence ligamentous mechanical properties resulting in increased ACL injury risk remains unclear. Furthermore, previous studies have mainly focused on anterior tibial translatory (ATT) laxity, with limited research on changes in ATT tissue compliance/stiffness. The purpose of this study is to investigate the influence of estradiol levels, menstrual cycle phases, with and without use of OC on ATT tissue compliance/stiffness and laxity.
METHODS: Fifty-two female participants (age 24-30 years), divided into two groups of 26 each (Group OC using oral contraception, and Group NOC not using oral contraceptive). Data collection was performed on two different dates corresponding to two menstrual cycle phases: follicular or inactive phase (days 1-3) and the ovulation or active pill phase (days 12-14). Estradiol levels via saliva sampling, ATT tissue compliance/stiffness and laxity measures via the GNRB knee arthrometer were collected each testing session. Spearman’s rank-order correlation product-moment correlations were run to determine the relationship between follicular and ovulation phase estradiol and GNRB outputs related to translation and compliance.
RESULTS: Estradiol levels showed a significant change between follicular and ovulation phases across both groups combined (p = 0.01). There were weak non-significant correlations between measured estradiol levels and GNRB measures of anterior translation and compliance, (p> 0.05). No significant relationships were found across subjects whether they were on oral contraceptive or not using hormone regulated birth control.
CONCLUSION: Estradiol level changes in the follicular and ovulation phases and oral contraceptive use did not significantly influence ACL laxity (anterior tibial translation) or compliance/stiffness. Additional studies on hormonal fluctuations as a potential risk factor for higher female ACL injury are indicated.
References
1. Grassi A, Pizza N, Al-Zu’bi BBH, Fabbro GD, Lucidi GA, Zaffagnini S. Clinical outcomes and osteoarthritis at very long-term follow-up after ACL reconstruction: A systematic review and meta-analysis. Orthop J Sports Med. 2022;10(1):23259671211062238. doi:10.1177/23259671211062238
2. Siebold R, Seil R, Engebretsen L. ACL tear in kids: serious injury with high risk of osteoarthritis. Knee Surg Sports Traumatol Arthrosc. 2016;24(3):641-643. doi:10.1007/s00167-015-3912-1
3. Pruneski JA, Heyworth BE, Kocher MS, et al. Prevalence and predictors of concomitant meniscal and ligamentous injuries associated with ACL surgery: An analysis of 20 years of ACL reconstruction at a tertiary care children’s hospital. Am J Sports Med. 2024;52(1):77-86. doi:10.1177/03635465231205556
4. Lord L, Cristiani R, Edman G, Forssblad M, Stålman A. One sixth of primary anterior cruciate ligament reconstructions may undergo reoperation due to complications or new injuries within 2 years. Knee Surg Sports Traumatol Arthrosc. 2020;28(8):2478-2485. doi:10.1007/s00167-020-06127-w
5. Kaeding CC, Léger-St-Jean B, Magnussen RA. Epidemiology and diagnosis of anterior cruciate ligament injuries. Clin Sports Med. 2017;36(1):1-8. doi:10.1016/j.csm.2016.08.001
6. Mancino F, Kayani B, Gabr A, Fontalis A, Plastow R, Haddad FS. Anterior cruciate ligament injuries in female athletes: risk factors and strategies for prevention. Bone Jt Open. 2024;5(2):94-100. doi:10.1302/2633-1462.52.BJO-2023-0166
7. Montalvo AM, Schneider DK, Webster KE, et al. Anterior cruciate ligament injury risk in sport: a systematic review and meta-analysis of injury incidence by sex and sport classification. J Athl Train. 2019;54(5):472-482. doi:10.4085/1062-6050-407-16
8. Sutton KM, Bullock JM. Anterior cruciate ligament rupture: differences between males and females. J Am Acad Orthop Surg. 2013;21(1):41-50. doi:10.5435/JAAOS-21-01-41
9. Hewett TE, Myer GD, Ford KR, Paterno MV, Quatman CE. Mechanisms, prediction, and prevention of ACL injuries: Cut risk with three sharpened and validated tools. J Orthop Res. 2016;34(11):1843-1855. doi:10.1002/jor.23414
10. Paterno MV, Schmitt LC, Ford KR, et al. Biomechanical measures during landing and postural stability predict second anterior cruciate ligament injury after anterior cruciate ligament reconstruction and return to sport. Am J Sports Med. 2010;38(10):1968-1978. doi:10.1177/0363546510376053
11. Zebis MK, Aagaard P, Andersen LL, et al. First-time anterior cruciate ligament injury in adolescent female elite athletes: a prospective cohort study to identify modifiable risk factors. Knee Surg Sports Traumatol Arthrosc. 2022;30(4):1341-1351. doi:10.1007/s00167-021-06595-8
12. 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. Orthop J Sports Med. 2017;5(7):2325967117718781. doi:10.1177/2325967117718781
13. Maruyama S, Yamazaki T, Sato Y, et al. Relationship between anterior knee laxity and general joint laxity during the menstrual cycle. Orthop J Sports Med. 2021;9(3):2325967121993045. doi:10.1177/2325967121993045
14. McNulty KL, Elliott-Sale KJ, Dolan E, et al. The effects of menstrual cycle phase on exercise performance in eumenorrheic women: A systematic review and meta-analysis. Sports Med. 2020;50(10):1813-1827. doi:10.1007/s40279-020-01319-3
15. 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
16. Bercovy M, Weber E. [Evaluation of laxity, rigidity and compliance of the normal and pathological knee. Application to survival curves of ligamentoplasties]. Rev Chir Orthop Reparatrice Appar Mot. 1995;81(2):114-127.
17. Uhorchak JM, Scoville CR, Williams GN, Arciero RA, St Pierre P, Taylor DC. Risk factors associated with noncontact injury of the anterior cruciate ligament: a prospective four-year evaluation of 859 West Point cadets. Am J Sports Med. 2003;31(6):831-842. doi:10.1177/03635465030310061801
18. Myer GD, Ford KR, Paterno MV, Nick TG, Hewett TE. The effects of generalized joint laxity on risk of anterior cruciate ligament injury in young female athletes. Am J Sports Med. 2008;36(6):1073-1080. doi:10.1177/0363546507313572
19. Nouveau S. Acl grafts compliance during time: influence of early sollicitations on the final stiffness of the graft after surgery. ORP. 2017;3(2):1-9. doi:10.24966/ORP-2052/100035
20. Gray AM, Gugala Z, Baillargeon JG. Effects of oral contraceptive use on anterior cruciate ligament injury epidemiology. Med Sci Sports Exerc. 2016;48(4):648-654. doi:10.1249/MSS.0000000000000806
21. Rahr-Wagner L, Thillemann TM, Mehnert F, Pedersen AB, Lind M. Is the use of oral contraceptives associated with operatively treated anterior cruciate ligament injury? A case-control study from the Danish Knee Ligament Reconstruction Registry. Am J Sports Med. 2014;42(12):2897-2905. doi:10.1177/0363546514557240
22. Samuelson K, Balk EM, Sevetson EL, Fleming BC. Limited evidence suggests a protective association between oral contraceptive pill use and anterior cruciate ligament injuries in females: A systematic review. Sports Health. 2017;9(6):498-510. doi:10.1177/1941738117734164
23. Collette M, Courville J, Forton M, Gagnière B. Objective evaluation of anterior knee laxity; comparison of the KT-1000 and GNRB® arthrometers. Knee Surg Sports Traumatol Arthrosc. 2012;20(11):2233-2238. doi:10.1007/s00167-011-1869-2
24. Jenny JY, Arndt J, Computer Assisted Orthopaedic Surgery-France. Anterior knee laxity measurement using stress radiographs and the GNRB(®) system versus intraoperative navigation. Orthop Traumatol Surg Res. 2013;99(6 Suppl):S297-300. doi:10.1016/j.otsr.2013.07.008
25. Smith K, Miller N, Laslovich S. The reliability of the gnrb® knee arthrometer in measuring ACL stiffness and laxity: Implications for clinical use and clinical trial design. Int J Sports Phys Ther. 2022;17(6):1016-1025. doi:10.26603/001c.38252
26. Klouche S, Lefevre N, Cascua S, Herman S, Gerometta A, Bohu Y. Diagnostic value of the GNRB ® in relation to pressure load for complete ACL tears: A prospective case-control study of 118 subjects. Orthop Traumatol Surg Res. 2015;101(3):297-300. doi:10.1016/j.otsr.2015.01.008
27. Semay B, Rambaud A, Philippot R, Edouard P. Evolution of the anteroposterior laxity by GnRB at 6, 9 and 12 months post-surgical anterior cruciate ligament reconstruction. Annals of Physical and Rehabilitation Medicine. 2016;59:e19. doi:10.1016/j.rehab.2016.07.045
28. Craig CL, Marshall AL, Sjöström M, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35(8):1381-1395. doi:10.1249/01.MSS.0000078924.61453.FB
29. Mounib N, Sultan C, Bringer J, et al. Correlations between free plasma estradiol and estrogens determined by bioluminescence in saliva, plasma, and urine during spontaneous and FSH stimulated cycles in women. J Steroid Biochem. 1988;31(5):861-865. doi:10.1016/0022-4731(88)90297-x
30. Hellhammer D. Assessment of Hormones and Drugs in Saliva in Biobehavioral Research. (Kirschbaum C, Read GF, eds.). Hogrefe & Huber Pub; 1992.
31. Vauhnik R, Perme MP, Barcellona MG, Rugelj D, Morrissey MC, Sevsek F. Robotic knee laxity testing: reliability and normative data. Knee. 2013;20(4):250-255. doi:10.1016/j.knee.2012.10.010
32. Vauhnik R, Morrissey MC, Perme MP, Sevsek F, Rugelj D. Inter-rater reliability of the GNRB® knee arthrometer. Knee. 2014;21(2):541-543. doi:10.1016/j.knee.2013.10.004
33. Beldame J, Bertiaux S, Roussignol X, et al. Laxity measurements using stress radiography to assess anterior cruciate ligament tears. Orthop Traumatol Surg Res. 2011;97(1):34-43. doi:10.1016/j.otsr.2010.08.004
34. Nasseri A, Lloyd DG, Bryant AL, Headrick J, Sayer TA, Saxby DJ. Mechanism of anterior cruciate ligament loading during dynamic motor tasks. Med Sci Sports Exerc. 2021;53(6):1235-1244. doi:10.1249/MSS.0000000000002589
35. Cojean T, Batailler C, Robert H, Cheze L. Sensitivity, repeatability and reproducibility study with a leg prototype of a recently developed knee arthrometer: The DYNEELAX®. Medicine in Novel Technology and Devices. 2023;19:100254. doi:10.1016/j.medntd.2023.100254
36. Stern J, Arslan RC, Penke L. Stability and validity of steroid hormones in hair and saliva across two ovulatory cycles. Compr Psychoneuroendocrinol. 2022;9:100114. doi:10.1016/j.cpnec.2022.100114
37. Anckaert E, Jank A, Petzold J, et al. Extensive monitoring of the natural menstrual cycle using the serum biomarkers estradiol, luteinizing hormone and progesterone. Pract Lab Med. 2021;25:e00211. doi:10.1016/j.plabm.2021.e00211
38. Stricker R, Eberhart R, Chevailler MC, Quinn FA, Bischof P, Stricker R. Establishment of detailed reference values for luteinizing hormone, follicle stimulating hormone, estradiol, and progesterone during different phases of the menstrual cycle on the Abbott ARCHITECT® analyzer. Clinical Chemistry and Laboratory Medicine (CCLM). 2006;44(7):883-887. doi:10.1515/CCLM.2006.160
39. Ren J, Rodriguez L, Johnson T, Henning A, Dhaher YY. 17β-estradiol effects in skeletal muscle: A 31P MR spectroscopic imaging (MRSI) study of young females during early follicular (EF) and peri-ovulation (PO) phases. Diagnostics (Basel). 2024;14(3):235. doi:10.3390/diagnostics14030235
40. Klump KL, Keel PK, Racine SE, et al. The interactive effects of estrogen and progesterone on changes in emotional eating across the menstrual cycle. Journal of abnormal psychology. 2013;122(1):131. doi:10.1037/a0029524
41. Eiling E, Bryant AL, Petersen W, Murphy A, Hohmann E. Effects of menstrual-cycle hormone fluctuations on musculotendinous stiffness and knee joint laxity. Knee Surg Sports Traumatol Arthrosc. 2007;15(2):126-132. doi:10.1007/s00167-006-0143-5
42. Behrens M, Mau-Moeller A, Wassermann F, Plewka A, Bader R, Bruhn S. Repetitive jumping and sprinting until exhaustion alters hamstring reflex responses and tibial translation in males and females. J Orthop Res. 2015;33(11):1687-1692. doi:10.1002/jor.22935
43. Shultz SJ, Morrissey MC, Vauhnik R. Anterior knee laxity is greater in athletic females who attain menarche at a younger age. Knee Surg Sports Traumatol Arthrosc. 2024;32(4):889-895. doi:10.1002/ksa.12138
44. Sundemo D, Hamrin Senorski E, Karlsson L, et al. Generalised joint hypermobility increases ACL injury risk and is associated with inferior outcome after ACL reconstruction: a systematic review. BMJ Open Sport Exerc Med. 2019;5(1):e000620. doi:10.1136/bmjsem-2019-000620
45. Zsidai B, Piussi R, Thomeé R, et al. Generalised joint hypermobility leads to increased odds of sustaining a second ACL injury within 12 months of return to sport after ACL reconstruction. Br J Sports Med. 2023;57(15):972-978. doi:10.1136/bjsports-2022-106183
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Journal of Women's Sports Medicine

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.