Abstract

Objectives: To understand the role of chronic inflammation, inflammasome activation, and cellular senescence in Genitourinary Syndrome of Menopause (GSM). To present the biological rationale and clinical evidence supporting Rosa damascene–derived exosome therapy as a regenerative treatment for GSM. To compare the efficacy, durability, and safety of exosome therapy versus vaginal estriol in a randomized clinical trial. To discuss exosomes as a promising non-hormonal, long-lasting therapeutic alternative for menopausal vaginal atrophy. Introduction: Damascene Rose-Derived Exosome Therapy for Genitourinary Syndrome of Menopause. A Randomized Trial Demonstrating Mucosal Regeneration and Sustained Symptom Relief Materials / method: This randomized, open-label clinical trial evaluated the efficacy and safety of intravaginal Rosa damascena–derived exosomes (ExoCobio, Korea) compared to vaginal estriol in 26 postmenopausal women with symptomatic GSM. Participants were randomly assigned (1:1) to receive either three applications of exosome therapy or daily estriol for 30 days. Randomization was performed using the Microsoft Excel RAND() function, with allocation concealment ensured via sequentially numbered, opaque, sealed envelopes opened by an independent coordinator. Patients were followed for 18 months and assessed using Results: Both treatment arms demonstrated statistically significant clinical improvement after one month of therapy (p < 0.01 for intragroup comparison in VHI, VAS, and FSFI scores). At the 3-month evaluation, these improvements persisted in both groups; however, long-term follow-up revealed a divergent trend. At 6 and 12 months, the estriol group showed a progressive decline in symptomatic and functional outcomes, returning close to baseline values. In contrast, the Rosa damascena-derived exosome group maintained clinical benefits in up to 50% of participants through 12 months and partial persistence Conclusion: Rosa damascena–derived exosome therapy represents a safe and effective non hormonal option for treating GSM, providing long-term mucosal regeneration and symptom relief. These findings support its use in patients contraindicated for hormonal therapy and highlight the need for larger, double-blinded multicenter trials.