Genitourinary syndrome of menopause (GSM) causes significant symptomatic aggravation that affects the quality of life (QoL). Vulvovaginal atrophy (VVA), the hallmark of GSM, is managed with topical non-hormonal therapy, including moisturizers and lubricants, and topical estrogen application. Patients not responding/being unsatisfied with previous local estrogen therapies are candidates for a noninvasive modality. Carbon dioxide (CO2) laser therapy, especially the fractionated type (FrCO2), has drawn considerable attention over the past two decades as a non-invasive treatment for GSM. This systematic review describes the accumulated evidence from 40 FrCO2 laser studies (3466 participants) in GSM/VVA. MEDLINE, Scopus and Cochrane databases were searched through April 2021. We analyze the effects of FrCO2 laser therapy on symptoms, sexual function, and QoL of patients with GSM/VVA. As shown in this review, FrCO2 laser therapy for GSM shows good efficacy and safety. This modality has the potential to advance female sexual wellness. Patient satisfaction was high in the studies included in this systematic review. However, there is a lack of level I evidence, and more randomized sham-controlled trials are required. Furthermore, several clinical questions, such as the number of sessions required that determine cost-effectiveness, should be addressed. Also, whether FrCO2 laser therapy may exert a synergistic effect with systemic and/or local hormonal/non-hormonal treatments, energy-based devices, and other modalities to treat GMS requires further investigation. Lastly, studies are required to compare FrCO2 laser therapy with other energy-based devices such as erbium:YAG laser and radiofrequency.

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