The Effect of Menstrual Cycle and Contraceptives on ACL Injuries and Laxity: A Systematic Review and Meta-analysis

Abstract

Background:Women are at substantially greater risk for anterior cruciate ligament (ACL) injuries than are men.Purpose:To conduct a systematic review and meta-analysis of the literature to clarify the effect of the menstrual cycle and contraceptives on the laxity of and noncontact injuries to the ACL.Study Design:Systematic review; Level of evidence, 4.Methods:Searches were conducted using MEDLINE (1946–August 2016), the Cochrane Library Database, clinical trial registries, and related reference lists. Search terms included athletic injuries, knee injuries, ligaments, joint instability, menstrual cycle, ovulation, hormones, and contraceptives. Investigators independently dually abstracted and reviewed study details and quality using predefined criteria and evaluated overall strength of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.Results:Twenty-one studies totaling 68,758 participants were included: 5 on the menstrual cycle and ACL injury, 7 on hormonal contraceptives and ACL injury, as well as 13 on menstrual cycle and ligament laxity. Four of 5 studies of women not using hormonal contraception indicated that the luteal phase was the least associated with ACL injuries. The 2 largest and highest quality studies on hormonal contraceptives suggested that hormonal contraceptives may be protective against ACL injury. Six of 12 studies on ACL laxity provided quantitative data for meta-analysis, finding significantly increased laxity during the ovulatory phase compared with the follicular phase.Conclusion:The literature suggests an association between hormonal fluctuations and ACL injury. Recent studies have suggested that oral contraceptives may offer up to a 20% reduction in risk of injury. The literature on ACL injuries and the menstrual cycle has more than doubled over the past decade, permitting quantitative analysis for the first time. However, the overall strength of this evidence is low. 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.

Sex hormones in association with general joint laxity and hypermobility in the temporomandibular joint in adolescents—results of the epidemiologic LIFE child study

“…Accordingly, we had expected an effect of oestrogenic hormones on the joints in girls, which, however, did not occur. Because of the known effect of oral contraceptives on the general mobility, it was at least plausible to exclude subjects taking that medication from the analyses.…”

“…However, this assumption is debatable, because even if the knee mobility changes during the menstrual cycle, hormone differences could not be measured . However, it has been frequently verified that the oral contraceptives (female sex hormone) heighten the joint mobility . At the same time, the male sex hormone testosterone reduces the overall joint mobility, as shown in animal tests—a fact that might explain the lower prevalence of hypermobility in males.…”

Retrospective analyses must be interpreted cautiously. A reply to ‘oral contraceptives provide protection against anterior crucial ligaments tears’

“…It is described that a decrease in fibroblast proliferation and collagen synthesis was seen with increasing estradiol concentration and this effect was attenuated with increasing progesterone concentration [3]. Previous studies have demonstrated the luteal phase to have the highest rate of ACL injuries [4] yet the progesterone level peaks in this phase. Would this not result in increased fibroblast proliferation and collagen synthesis hence contradicting the proposed mechanism?…”

Constant performance in balance and proprioception tests across the menstrual cycle – a pilot study in well trained female ice hockey players on hormonal contraception

“…This is why numerous studies have tried to link a specific phase of the menstrual cycle associated with specific levels of estrogen and progesterone to the ACL injury risk . However, results from studies differ widely, and even reviews vary in their conclusions . While one review stated that definite conclusions are not warranted regarding the association between menstrual cycle and ACL injury risk, another review identified a predisposition to injury in the pre‐ovulatory phase and yet another one suggested that the injury risk was increased during the ovulatory phase …”