Effect of Fractional Carbon Dioxide vs Sham Laser on Sexual Function in Survivors of Breast Cancer Receiving Aromatase Inhibitors for Genitourinary Syndrome of Menopause

Importance: Survivors of breast cancer present more severe symptoms of genitourinary syndrome of menopause (GSM) than patients without history of breast cancer. Recently, new treatments, such as vaginal laser therapy, have appeared, but evidence of their efficacy remains scarce. Objective: To assess the safety and efficacy of carbon dioxide (CO2) vs sham vaginal laser therapy after 6 months of follow-up in survivors of breast cancer with GSM receiving aromatase inhibitors. Design, Setting, and Participants: This prospective double-blind sham-controlled randomized clinical trial with two parallel study groups was performed during October 2020 to March 2022 in a tertiary referral hospital. Survivors of breast cancer using aromatase inhibitors were assessed for eligibility, and eligible patients were randomized into the 2 treatment groups. Follow-up was conducted at 6 months. Data were analyzed in July 2022. Interventions: All patients from both groups were instructed to use the first-line treatment (FLT) based on nonhormonal moisturizers and vaginal vibrator stimulation. Patients for each group were allocated to 5 monthly sessions of fractional CO2 laser therapy (CLT) or sham laser therapy (SLT). Main Outcomes and Measures: The primary outcome was sexual function, evaluated through Female Sexual Function Index (FSFI) score. Other subjective measures of efficacy included a visual analog scale of dyspareunia, vaginal pH, a Vaginal Health Index, quality of life (assessed via Short-Form 12), and body image (assessed with the Spanish Body Image Scale). Objective measures of efficacy included vaginal maturation index, vaginal epithelial elasticity (measured in Pascals) and vaginal epithelial thickness (measured in millimeters). Measures were assessed before and after the intervention. Tolerance (measured on a Likert scale), adverse effects, and estradiol levels were recorded. Results: Among 211 survivors of breast cancer assessed, 84 women were deemed eligible and 72 women (mean SD age, 52.6 8.3 years) were randomized to CLT (35 participants) or SLT (37 participants) and analyzed. There were no statistically significant differences between groups at baseline. At 6 months, both groups showed improvement in FSFI (mean SD score at baseline vs 6 months: CLT, 14.8 8.8 points vs 20.0 9.5 points; SLT, 15.6 7.0 points vs 23.5 6.5 points), but there was no significant difference between CLT and SLT groups in the improvement of sexual function evaluated through the FSFI test overall (mean SD difference, 5.2 1.5 points vs 7.9 1.2 points; P = .15) or after excluding women who were not sexually active (mean SD difference, 2.9 1.4 points vs 5.5 1.1 points; P = .15). There were also no differences between improvement of the 2 groups at 6 months of follow-up in the other assessed subjective outcomes, including dyspareunia (mean SD difference, -4.3 3.4 vs -4.5 2.3; P = .73), Vaginal Health Index (mean SD difference, 3.3 4.1 vs 5.0 4.5; P = .17), body image (mean SD difference, -3.7 4.5 vs -2.7 4.8; P = .35), and quality of life (mean SD difference, -0.3 3.6 vs -0.7 3.2; P = .39). Similarly, there were no differences in improvements in objective outcomes, including vaginal pH (mean SD difference, -0.6 0.9 vs -0.8 1.2; P = .29), vaginal maturation index (mean SD difference, 10.2 17.4 vs 14.4 17.1; P = .15), vaginal epithelial thickness (mean SD difference, 0.021 0.014 mm vs 0.013 0.012 mm; P = .30), vaginal epithelial elasticity (mean SD difference, -1373 3197 Pascals vs -2103 3771 Pascals; P = .64). There were significant improvements in the overall analysis regardless of group in many outcomes. The 2 interventions were well tolerated, but tolerance was significantly lower in the CLT group than the SLT group (mean SD Likert scale score, 3.3 1.3 vs 4.1 1.0; P = .007). No differences were observed in complications or serum estradiol levels. Conclusions and Relevance: In this randomized clinical trial, vaginal laser treatment was found to be safe after 6 months of follow-up, but no statistically significant differences in efficacy were observed between CLT and SLT. Trial Registration: ClinicalTrials.gov identifier: NCT04619485.