Randomized, Double-blind, Placebo-controlled Clinical Trial for Evaluating the Efficacy of Fractional CO2 Laser Compared With Topical Estriol in the Treatment of Vaginal Atrophy in Postmenopausal Women

Vera L. Cruz, MD; Marcelo L. Steiner, MD, PhD; Luciano M. Pompei, MD, PhD; Rodolfo Strufaldi, MD, PhD; Fernando L. Afonso Fonseca, PhD; Lucila H. Simardi Santiago, MD, PhD; Tali Wajsfeld, MD; Cesar E. Fernandes, MD, PhD

Disclosures

Menopause. 2018;25(1):21-28. 

In This Article

Discussion

Improvement of vulvovaginal symptoms after fractional CO2 laser has been demonstrated in multiple case series.[3,6,15,16] This study was the first to evaluate the effects of fractional CO2 laser in comparison to estriol topical therapy, considered the gold standard treatment for local VVA symptoms.[12]

All treatment options used in this study, either fractional CO2 laser alone, estriol alone, or the combination of both treatments, resulted in improvement of vaginal health and VVA symptoms, and were also seen in vaginal specimen analyses.

The LE, E, and L groups showed statistically significant improvement in the VHI at week 8, suggesting that both fractional CO2 laser and estrogen therapies promote a fast and significant improvement in the vaginal mucosa. Similar results were reported in studies evaluating the efficacy of fractional CO2 laser.[16,25]

An incremental improvement of VHI was also noted in the LE arm between week 8 and week 20, suggesting that the combined use of local estrogen and fractional CO2 laser seems to be advantageous. Although maintaining a significantly higher score compared with baseline, the L group VHI score was found to be lower in comparison to other treatment groups at week 20. Sokol and Karram evaluated the efficiency and safety of fractional CO2 laser for VVA in a 1-year follow-up, and demonstrated that the positive effects on VVA symptoms (burning, dryness, and dyspareunia), VHI, and FSFI full-scale score persisted for at least 1 year after three sessions of fractional CO2 laser.[20]

It is important to highlight that fractional CO2 laser effects on the vaginal mucosa persisted for at least 16 more weeks after the last session and that if topical estrogen applications had been interrupted, the efficiency of this treatment would not have been maintained.[11,26]

Fractional CO2 laser alone and the combined therapy improved reported VVA symptoms of burning, dryness, and dyspareunia throughout the study. The E group presented milder symptoms of burning, dyspareunia, and dryness at baseline; thus dryness was the only symptom that presented a statistically significant improvement at week 20. It is important to observe that symptomatic improvement could have been significant if participants assigned to estriol therapy were more symptomatic.

A significant increase in dyspareunia using FSFI was noted on the L group, although the same symptom improved when assessed by the VAS scale. It is difficult to explain the reason for different results in sexually related pain reported through VAS and FSFI. FSFI is a self-report instrument, whereas the assessment of dyspareunia with the VAS was verbally asked by the physician. There are no studies comparing the accuracy of these assessments in the literature. Salvatore et al used the same laser system and parameters used in this study, but three laser sessions (weeks 0, 4, and 8) were performed instead. Contrasting our findings, FSFI full-scale score and pain individually showed significant improvement at week 12.[3]

Estriol absorption might have had a beneficial effect in the vaginal introitus, decreasing penetration-related pain. Otherwise, it is difficult to explain increasing penetration-related pain in the CO2 laser arm. Many previous vaginal CO2 laser studies have reported this side effect.[3,6,8,16,18,20]

Yoruk et al reported a correlation of MV values and vaginal pH to serum estrogen levels in women. The overall improvement of MV indicates higher estrogen effects in the mucosa in all treatment arms.[23] Average percentage of P cells was similar among groups at baseline, but only the L group showed incremental estrogen effect at week 20. Salvatore et al reported similar effects in vaginal mucosa histology after fractional CO2 laser therapy, suggesting that fractional CO2 laser promotes morphological changes and mucosal restoration.[17]

The main contribution of this study is the first time comparison of fractional CO2 laser performance to the use of local estrogen for vulvovaginal symptoms. The study demonstrates vaginal health benefits resulting from fractional CO2 laser treatment persisting for at least 16 weeks. Fractional CO2 laser is a convenient alternative to local estriol, in which contraindications, low compliance due to vaginal discharge, and daily self-applications can be of concern.

The inclusion of sham laser treatment in the estriol arm is a strength of this study design. It allowed for a more reliable treatment control group and decreased result bias. Also, a combined estriol plus fractional CO2 laser treatment arm, the fact that all visits were conducted by the same physician and the small dropout percentage are strong points of this trial. On the contrary, this is a small study, powered to detect difference in VHI and not for all the multiple comparisons made. All findings should be interpreted with extreme caution, mainly VVA symptoms using VAS. Milder VVA symptoms in the estriol group at baseline and the reduced number of viable vaginal smears for vaginal mucosa cytological analysis (MV of Meisels) were also limitations of this study.

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