Objective The aim of the study was to evaluate the clinical response and collagen remodeling in the vaginal wall after three sessions of carbon dioxide (CO2) laser application. Methods Fourteen postmenopausal women with vulvovaginal atrophy, aged 45–65 years and sexually active, were evaluated with clinical questionnaires, gynecological examinations and histological techniques before and after 20 weeks of treatment (ClinicalTrials.gov NCT03939078). Treatment consisted of 3-monthly sessions of the CO2 laser. Clinical questionnaires included the Vaginal Health Index, the Female Sexual Function Index and the International Consultation on Incontinence Questionnaires Short Form. Biopsies were taken from the lateral vaginal wall at week 0 (left wall) and week 20 (right wall). Tissue samples were stained with hematoxylin and eosin, Periodic Acid-Schiff, Picrosirius Red Stain and Orcein dyes. Immunohistochemical study was used to quantify collagens I and III in the samples. Results The mean age was 54.4 ± 4.5 years, and the average time of amenorrhea was 7.6 ± 5.1 years. The Female Sexual Function Index and the Vaginal Health Index Score values increased while the International Consultation on Incontinence Questionnaire Short Form score decreased after the programmed treatment. There was no significant change in vaginal pH. Histological studies showed increases in the total and superficial epithelial cell layers, and type III collagen fibers (from 10.86 ± 7.66 to 16.87 ± 3.96, p < 0.05), and immunohistochemical studies confirmed the significant increase in collagen III. Conclusion Histological findings revealed epithelial atrophy reversal and collagen remodeling of the vaginal wall. Immunohistochemical analysis showed an increase in collagen type III fibers.
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