Fractional CO2 Laser for Genitourinary Syndrome of Menopause: Comparator-Aware Systematic Review and Meta-Analysis.

INTRODUCTION AND HYPOTHESIS: Genitourinary syndrome of menopause (GSM) is common and may persist despite first-line measures. Fractional CO2 vaginal laser is increasingly offered as a nonhormonal option, but interpretation is complicated by heterogeneous comparators and subjective outcomes vulnerable to procedural and expectancy effects. The objective was to systematically review clinical evidence on fractional CO2 laser for genitourinary syndrome of menopause and evaluate short-term efficacy and safety using a comparator-aware meta-analysis restricted to eligible randomized trials. METHODS: We systematically reviewed clinical studies and restricted quantitative synthesis to CO2-only randomized controlled trials reporting extractable short-term post-treatment outcomes. Random-effects meta-analyses were performed, with prespecified subgroup analyses by comparator type: sham procedures versus nonsham controls. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and certainty of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation. RESULTS: Thirty-six clinical studies involving 1,709 participants, including 11 randomized controlled trials and 407 cancer survivors, met the inclusion criteria. Quantitative synthesis included nine CO2-only randomized controlled trials. Fractional CO2 laser was associated with improved short-term Female Sexual Function Index scores compared with controls; however, effects were smaller in sham-controlled trials. Although the pooled mean difference favored laser, this should be clinically interpreted with caution because validated minimal clinically important difference thresholds for this specific population are not well established. Vaginal health, urinary, and safety outcomes were inconsistently reported. CONCLUSIONS: Fractional CO2 laser may improve short-term sexual function and GSM-related outcomes, but benefits attenuate in sham-controlled trials and evidence certainty remains limited. Durability, urinary effects, oncology-specific safety, and comparative effectiveness versus contemporary low-dose vaginal estrogen regimens remain insufficiently defined.