The effect of CO2 laser therapy on vaginal microcirculatory parameters in an animal model for genitourinary syndrome of menopause

Background Vaginal laser therapy for the treatment of genitourinary syndrome of menopause (GSM) has been introduced to the market with limited (pre)clinical and experimental evidence supporting its efficacy. It is suggested that vaginal laser therapy increases epithelial thickness and improves vascularization, but the underlying biological working mechanism has not been substantiated yet. Objective To evaluate the effects of CO2 laser therapy on vaginal atrophy using noninvasive incident dark field (IDF) imaging in a large animal model for GSM. Design, Setting, and Participants An animal study was conducted between 2018 and 2019 and included 25 Dohne Merino ewes, of which 20 underwent bilateral ovariectomy (OVX) to induce iatrogenic menopause, and 5 did not. The total study duration was 10 months. Interventions Five months after OVX, ovariectomized ewes received monthly applications of CO2 laser (n = 7), vaginal estrogen (n = 7), or no treatment (n = 6) for 3 months. IDF imaging was performed monthly in all animals. Outcome Measurements and Statistical Analysis The primary outcome was the proportion of image sequences containing capillary loops (angioarchitecture). Secondary outcomes included focal depth (epithelial thickness), and quantitative measures of vessel density and perfusion. Treatment effects were evaluated using ANCOVA and binary logistic regression. Results and Limitations Compared to OVX‐only, ewes treated with estrogen demonstrated a higher capillary loops proportion (4% vs. 75%, p