Sex-related difference in self-reported pain intensity at early stages of orthodontic treatment with multibracket fixed appliances, clear aligners, and interproximal elastic separators: A systematic review and meta-analysis

Introduction: Sex dimorphism in pain has been suggested in medicine and demonstrated in oral disease prevalence. However, contradictory findings are present regarding orthodontic pain perception. This study summarized sex-related differences in pain perception in healthy patients during the initial stages of orthodontic treatment and systematically explored sex-based analysis in orthodontic pain literature. Methods: Seven databases (PubMed, EMBASE, CINAHL, DOSS, Web of Science, Cochrane's Database of Systematic Reviews, and CENTRAL) and gray literature were systematically searched in November 2023 for original prospective studies in healthy humans and published in the English language that analyzed sex-related differences in pain intensity within 1 week of application of multibracket fixed appliance, clear aligners, or interproximal elastic separators. Quality assessment was performed with the Joanna Briggs Institute Critical Appraisal Checklist. Sex-related differences were extracted at 24 hours and day 7. The meta-analysis summarized the standardized mean difference, with the quality of evidence evaluated by using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: The search retrieved 12,750 articles; 5961 were screened, and 284 were selected for full-text review. Forty studies (2999 participants; 57.0% females) were included. Study quality was good (82.5%) and fair (17.5%). At 24 hours, 77.3% did not reveal sex-related differences in pain perception, whereas 15.9% and 6.8% suggested significantly higher female and male predilection, respectively. At day 7, 79.3% did not observe significant differences, whereas 20.7% supported higher pain intensity among females. The meta-analysis (n = 7) indicated no significant sex-related difference (pooled effect size between -0.34 [95% confidence interval {CI}, -0.82 to 0.14] and 0.33 [95% CI, -0.77 to 1.43]), except for interproximal elastics at day 7 among females (effect size -0.49 [95% CI -0.80 to -0.18]). The certainty of the evidence was low to moderate. Despite a rise in publications on orthodontic pain assessment, few studies provided sex-based analysis. Conclusions: Most studies did not find significant sex-related differences in pain perception during the initial stages of orthodontic treatment. Sex-based analysis was rarely conducted.