Comparison of Topical Fractional CO2 Laser and Vaginal Estrogen for the Treatment of Genitourinary Syndrome in Postmenopausal Women

A Randomized Controlled Trial

Paula Fernanda Santos Pallone Dutra, MD; Thais Heinke, MD, PhD; Stella Catunda Pinho, MD; Gustavo Rubino Azevedo Focchi, PhD; Fernanda Kesselring Tso, MD, PhD; Bruna Cristine de Almeida, PhD; Ivaldo Silva, PhD; Neila Maria Góis Speck, MD, PhD


Menopause. 2021;28(7):756-763. 

In This Article


In our subjective analysis, it was possible to verify the changes in the vaginal mucosa features, where improvement of pallor and absence of petechiae was noted in both the LT and TE groups. None of the women subjected to LT experienced any harmful thermal effects on the vaginal epithelium.

In contrast to the findings of Cruz et al[9] and Politano et al,[29] who observed a significant increase in the maturation index in the participants undergoing LT, we did not notice any such significant effect in our study. Regarding the Frost index, we observed a significant reduction in deep cells only in the group subjected to TE. The women in this group were associated with an increase in the number of cells in the intermediate layer and a tendency toward an increase in the number of superficial cells. Thus, there was a tendency for the TE group to present a higher maturation index than the LT group at the final time point. In a previous study, it was observed that participants treated with fractional CO2 laser showed some evidence of recovery in hormonal activity at the level of VE by the maturation of parabasal cells. At the end of the first month, there was a marked decrease in these cells, while the number of intermediate and superficial cells had increased accordingly.[33]

Despite the complexity of sexual function, which depends not only on local but also on hormonal vaginal factors,[31,44] we observed that the use of LT is an effective method for vaginal atrophy treatment, corroborating with the improvement in sexual function, as seen in previous studies.[3,9,14,23,27,31]

Using objective measurements, we observed that both treatments resulted in a significant increase in the thickness of the VE, similar to the findings obtained in previous studies.[9,12,21,45,46] Based on similar protocols[12] for the application of LT and totaling approximately 240 women, some authors demonstrated the effectiveness of fractional CO2 laser in the treatment of VVA, presenting it not only as another option to be offered to the patient, but also as an alternative option as viable as TE.[9,12,21,45,46] Until now, TE was considered more effective for these symptoms. However, it is worth mentioning that LT is an onerous procedure, since it is necessary to purchase the machine by the professional as well as it requires adequate training, and thus far, it has not been paid for by health insurers.

In a recent publication using collagen analysis and subjective assessment of VE layers, Politano et al[29] compared treatments with CO2 laser, promestriene, and vaginal lubricant and found a similar response between promestriene and CO2 laser.

Zerbinati et al[28] observed in their histological findings the recovery of the whole structures supporting full functionality in the epithelial and connective tissue of vaginal mucosa after fractional CO2 laser therapy, similar to a premenopausal structure. LT was found to promote profound regenerative effects on the vaginal wall.[23] Our histomorphometric evaluation and comparison add to the histological basis of the laser application as a therapeutic option for postmenopausal women. In a study carried out by Salvatore et al in 2014,[22] the use of the LT on vaginal tissue of postmenopausal women was demonstrated to provide important remodeling with an increase in the thickness of the VE and no associated tissue damage. Furthermore, a recent study published by Samuels et al[27] showed that the epithelial thickness increased in participants subjected to LT, and there was an increase in the number of cell layers and a better degree of superficial maturation. These studies are in synergy with our findings that demonstrated an improvement in the Meisels indices in both groups. In the present study, the thickness of the epithelium increased over time in both the groups. Our study adds new data showing that LT can be used in a different way and is as safe and effective as TE. Few studies have been conducted in the literature in which histological evaluation of VE was performed.

We also observed regression of the signs of vaginal atrophy on colposcopy, as mentioned by Simões et al.[46] Fractional CO2 laser has been shown to be a useful and minimally invasive alternative for the treatment of GSM,[45,47] and it provides advantages over currently available treatments.[46] In particular, it has the convenience of not using creams and produces a longer-lasting effect. The great advantage of this treatment is the absence of immediate or late complications. It is important to consider that LT is a painless, fast technique with an almost immediate effect and has a prolonged duration when compared with other therapies.[46]

Our histomorphometric evaluation demonstrated that the significant increase in the thickness of the VE in both groups equates the efficiency of the LT to the current topical estrogen therapy standard that is recognized as the "gold standard" for treating VVA. The increase in SQ-F at the end of treatment in all women demonstrates the impact of VVA on quality of life as well as the importance of its treatment and recovery of physiological conditions of the vagina. None of the participants showed any signs of side effects or adverse events during the study with both treatments, which was in line with a multicenter study performed with a large sample size (645 women) by Filippini et al.[11] LT was well tolerated by most studied women, and only a few studies reported discontinuation or withdrawal from LT.[48] The treatment recommendations and follow-up time discussed or proposed in earlier studies of the three laser sessions showed improvement in the quality of life of the participants. Eder[14] and Tovar-Huamani et al[33] emphasized that the effectiveness of fractional CO2 LT was noted even after a single session.

Nevertheless, it is important to note that our study had some limitations, including the fact that it was conducted in a single center, had a short-term follow-up, had a small number of the participants, and involved the cost of LT. LT is not covered by insurance and it is not available in the public health system yet. The age range of the women included in the study was based on the hypothesis that vaginal atrophy is progressive and that there could be a discrepancy between the studied populations. It is essential to highlight that new prospective and controlled studies evaluating a wider range of women are needed to obtain a greater understanding of the duration and long-term effects of vaginal LT as well as the functioning of this remodeling process, so that LT can be disseminated and used routinely and safely in the treatment of menopausal genitourinary syndrome.