A Double-Blind Randomized Sham-Controlled Trial to Evaluate the Efficacy of Fractional Carbon Dioxide Laser Therapy on Genitourinary Syndrome of Menopause

Background: Despite some prospective case series showing effectiveness of vaginal laser to treat genitourinary syndrome of menopause (GSM), there is a paucity of placebo-controlled level one evidence. Aim: To assess the effect of fractional carbon dioxide (CO2) laser therapy to treat GSM against a sham comparator. Methods: We conducted a parallel, randomized, double-blind, sham-controlled trial to compare menopausal women treated with fractional CO2 laser against sham treatment for improvement in GSM-related dyspareunia. Three treatments were given 6 weeks apart, and participants attended a 6-month visit from study start for primary (proportion improved) and secondary (vaginal health index, VHI; visual analogue scale, VAS; modified global assessment, PGI-I; Female Sexual Function Index, FSFI; Day-to-Day Impact of Vaginal Aging, DIVA; Urinary Distress Inventory short-form, UDI-6) assessments. Outcomes: The primary endpoint was a 2-stage improvement in GSM-related dyspareunia from baseline to 6-months determined by a severity scale, and the proportion of subjects who achieved this were compared between groups. Results: Thirty participants were randomized to laser (n = 14) or sham (n = 16). In the treatment arm, 13 attended all treatments, and 1 attended at least 2 while in the sham arm, 14 attended all treatments, and 2 attended at least 2 treatments. Twelve (86%) in the treatment arm and 16 (100%) in the sham arm attended the 6-month visit. There were no differences in the proportion improved between treatments and controls (64% vs. 67%, respectively, P = 1.000). Both arms showed significant within-group improvements based on VHI and VAS, but not between groups. Similar findings were observed on sexual impact questionnaires with improvements within both groups from baseline to 6 months but not by median differences between the groups at 6 months. There were no adverse events in either of the arms. Clinical Implications: Further well-powered research is needed to determine efficacy of fractional CO2 laser for the treatment of GSM, especially in light of a potential placebo effect. Strengths & Limitations: We present a sham-controlled double-blinded randomized trial using validated tools; the main limitation included an underpowered proportion of sexually active participants for the primary outcome. Conclusion: This study was underpowered to draw conclusions regarding the efficacy of fractional CO2 laser therapy in the treatment of GSM. We did observe improvements in the sham-arm to suggest a possible placebo contribution. Further well-powered level one research is needed to demonstrate the therapeutic effect of this novel modality. Copyright (C) 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Automated summary

This study aimed to assess the effectiveness of fractional CO2 laser therapy for GSM through a randomized, double-blind, sham-controlled trial. The results showed no significant difference in improvement proportion between the treatment and control groups, but both groups showed significant within-group improvements in VHI and VAS. Further research is needed to determine the therapeutic effect of this novel modality.