Treatment of Genitourinary Syndrome of Menopause with Microablative CO₂ Laser versus Fractional Microablative Radiofrequency: A Double-Blind, Randomized, Non-Inferiority Clinical Trial Protocol

Background: Genitourinary Syndrome of Menopause (GSM) affects a significant number of postmenopausal women, leading to symptoms such as vaginal atrophy, dryness, and discomfort. Hormonal therapies are not suitable for all patients, particularly those with contraindications to hormone replacement therapy. This study aimed to compare the efficacy and safety of two non-hormonal treatments—microablative CO₂ laser and fractional microablative radiofrequency—in the management of GSM. Methods: This is a double-blind, randomized, non-inferiority clinical trial involving 40 postmenopausal women diagnosed with GSM. Participants will be randomized to receive either microablative CO₂ laser or fractional microablative radiofrequency in three monthly sessions. The primary outcome is the Vaginal Health Index Score (VHIS), which assesses elasticity, pH, lubrication, epithelial integrity, and mucosal condition. Secondary outcomes include sexual function (Female Sexual Function Index - FSFI), GSM symptom severity, and urinary symptoms. Follow-up assessments will occur at 3, 6, and 12 months after the intervention. Histological analysis will be performed on vaginal biopsies from a subset of participants. The study was approved by the Research Ethics Committee of Universidade Brasil (approval no. 5.357.602), and all participants will provide informed consent prior to enrollment. Discussion: The findings from this study contribute to the comparative understanding of the effectiveness of CO₂ laser and fractional microablative radiofrequency as non-hormonal treatment options for GSM. The results have the potential to influence clinical practice by providing safe and effective therapeutic alternatives for women who are not candidates for hormonal therapy. Trial registration: This trial is registered in the Brazilian Clinical Trials Registry (ReBEC): RBR-2hgwvgy. Registered on July 2023. UTN: U1111-1282-9195. https://ensaiosclinicos.gov.br/rg/RBR-2hgwvgy. This is a retrospectively registered trial.