Cosmetic Botulinum Toxin A Injections to the Upper Face: A Systematic Review and Meta-Analysis of Clinical Studies.

[BACKGROUND] Botulinum toxin type A (BoNT-A) is widely recognized as the leading nonsurgical cosmetic treatment worldwide for diminishing dynamic wrinkles in the glabellar, forehead, and periorbital areas. While BoNT-A is widely acknowledged for its effectiveness and popularity, there are notable inconsistencies in results, methodologies, and safety reporting across clinical studies, highlighting the necessity for the careful development of strong, evidence-driven guidelines.

[OBJECTIVES] This study aimed to compile and evaluate data from clinical research focusing on upper-face BoNT-A injections, specifically regarding safety outcomes, effectiveness, patient satisfaction, and response rates. This investigation concentrated on the outcomes of the clinical trials conducted.

[METHODS] This analysis includes prospective cohorts, randomized controlled trials, and observational studies that report on BoNT-A cosmetic treatments specifically in the upper face area. A thorough examination of MEDLINE, EMBASE, Cochrane Library, and Web of Science studies was conducted, covering literature up to May 2025. The assessment included response rates, levels of patient satisfaction, and the extent of wrinkle reduction. The analysis employed a random-effects model to produce combined estimates, followed by an assessment of heterogeneity utilizing τ, I, and Cochran's Q. Forest diagrams and Egger's test were utilized to evaluate publication bias and the effects of small studies when applicable.

[RESULTS] After the administration of BoNT-A therapy, a notable decrease in the severity ratings of wrinkles was observed, as indicated by the synthesis of ten clinical trials examining this aspect (Cohen's d = 1.93; 95% CI: 1.60-2.25; p = 0.001). However, the data also revealed a considerable degree of variability (I = 90%). The findings indicated substantial variability in effect sizes related to patient satisfaction across four distinct trials (Cohen's d = 22.54; 95% CI: -2.07-47.15; p = 0.07), accompanied by significant heterogeneity (I = 99.9%) and potential indications of publication bias. The findings revealed significant variability (I = 100%) and wide prediction intervals, indicating substantial inconsistency and limited applicability of the response outcomes in future research. Analysis of five studies regarding response rates revealed a significant overall effect (Cohen's d = 34.30; 95% CI: 3.65-64.94; p = 0.28). The overall impact was determined to be noteworthy.

[CONCLUSIONS] BoNT-A injections contribute to a decrease in wrinkle severity and improve clinical results for rejuvenating the upper face. Research indicates notable variability and susceptibility to bias regarding patient satisfaction and response rates. The findings emphasize the necessity for subgroup analyses, enhanced reporting methodologies, and uniform outcome evaluations to identify factors contributing to variability in responses to BoNT-A therapy.

[TRIAL REGISTRATION] This study was conducted in accordance with PROSPERO guidelines.