Female sex is a significant determinant of anterior cruciate ligament (ACL) injury. It is not understood if sex is a key determinant of other sports-related injuries. The aim of this systematic review was to identify where differences in injury profiles are most apparent between the sexes in all sports across the six-tiered participant classification framework. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and the 'implementing PRISMA in Exercise, Rehabilitation, Sport medicine and SporTs science'(PERSiST) guidance. The databases PubMed, CINAHL, Web of Science, SPORTDiscus, Medline, Scopus, Cochrane Library and EBSCO were searched from database inception to 24 April 2023. Longitudinal, prospective and retrospective cohort studies and cross-sectional and descriptive epidemiology studies that used standard injury data collection were included. Studies were excluded if injuries were not medically diagnosed and if injuries were not reported and/or analysed by sex. Two reviewers independently extracted data and assessed study quality using the Downs and Black checklist. Overall, 180 studies were included (8 tier-5, 40 tier-4, 98 tier-3, 30 tier-2, 5 tier-1 studies; one study included data in two tiers). Of those, 174 studies were of moderate quality and six studies were of limited quality. In sex-comparable sports, there was moderate evidence that female athletes had greater risk of knee injury (relative risk (RR) 2.7; 95% CI 1.4-5.5), foot/ankle injuries (RR 1.25; 95% CI 1.17-1.34), bone stress injury (RR 3.4; 95% CI 2.1-5.4) and concussion (RR 8.46; 95%CI 1.04-68.77) than male athletes. Male athletes were at increased risk of hip/groin injuries (RR 2.26; 95% CI 1.31-3.88) and hamstring injuries (RR 2.4; 95% CI 1.8-3.2) compared with females, particularly in dynamic sports. Male athletes were 1.8 (1.37-2.7) to 2.8 (2.45-3.24) times more likely to sustain acute fractures than female athletes, with the highest risk in competition. Most studies in all cohorts were of moderate quality (mean/range of scores tier-5: 17 ± 2.2 [14-20], tier-4: 16.9 ± 1.9 [11-21], tier-3: 16.9 ± 1.5 [11-20], tier-2: 16.3 ± 2.2 [11-20], tier-1 studies: 15.6 ± 1.3 [14-17] out of 28 on the Downs and Black checklist), with only six studies of limited quality. Female athletes' propensity for bone stress injuries highlights opportunities to reinforce development of optimal bone health during adolescence and to outline the effects of energy availability. Earlier strength development and exposure to neuromuscular training programmes and modification of skill development in female athletes may be effective strategies for reducing lower limb injury risk. Key components of neuromuscular training programmes could be beneficial for reducing hip/groin and hamstring injury risk in male athletes. There may be a need for sex-specific prevention and return-to-sport protocols for sports-related concussion in female athletes. Female sex was a key determinant of sports-related injuries beyond ACL injury including foot/ankle injury, bone stress injury and sports-related concussion. Male sex was a key determinant of hip/groin, hamstring injury and upper limb injury. PROSPERO registration number: CRD42017058806 (last updated on 7th June 2023).
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