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

Abstract and Introduction


Objective: To compare the efficacy of fractional CO2 laser therapy with topical estrogen therapy for the treatment of postmenopausal genitourinary syndrome of menopause.

Methods: We conducted a randomized controlled clinical trial involving 25 postmenopausal women. Participants were aged between 50 and 65 years with at least 1 year of amenorrhea and follicle-stimulating hormone levels of >40 IU/L. The women were randomized into two groups: the laser therapy group (n = 13) and the vaginal topical estrogen therapy group (n = 12). Changes in the vaginal epithelium thickness, Frost index, and cell maturation were analyzed in both the groups. The female sexual quotient of each woman was also evaluated. Subjective evaluation was performed through a physical examination.

Results: Histological analysis showed a significant increase in the vaginal epithelium thickness at the end of treatment in females in both the laser therapy (P < 0.001) and topical estrogen therapy (P = 0.001) groups. The topical estrogen therapy group tended to present a higher maturation index at the end of treatment when compared with that of the other group. Sexual function increased significantly over time in both the topical estrogen therapy (P < 0.001) and laser therapy (P < 0.001) groups. Subjective evaluation through physical examination showed a significant improvement in atrophy in both the groups.

Conclusion: Despite the nonequivalence with topical estrogen therapy, our data suggest that laser therapy is an effective method for the treatment of vulvovaginal atrophy.


Hormonal changes have a great physiological impact on postmenopausal quality of life and sexual function in women.[1–3] Genitourinary syndrome of menopause (GSM) is associated with a decline in hormone levels, especially estrogens,[4–7] and affects at least 50% of postmenopausal women. GSM does not spontaneously decrease and commonly worsens in the fifth year after menopause.[5,8–10]

Estrogen, which has a large number of receptors, plays an important role in the genitourinary system physiology. Hormone deficiency or absence triggers morphological changes that lead to vulvovaginal atrophy (VVA),[5,11,12] which is the most common complaint among women.[3,13] Symptoms often include dyspareunia, vaginal dryness, pruritus, irritation, and dysuria,[4,7,9,13–16] with the prevalence of dyspareunia and vaginal dryness in approximately 55% and 44% of cases, respectively.[4,7,9,14,16] Among the many classification systems for hormonal influence on the vaginal epithelium, the maturation value or Frost index seems to be the most informative.[17]

The North American Menopause Society recommends the use of low-dose vaginal estrogen as the gold standard, rather than systemic hormonal therapy, to relieve GSM symptoms.[6,7,15,18,19] Although recent studies have reported on the safe use of estrogens with minimal doses, the effectiveness of the response to these levels does not meet the needs of participants with severe VVA, whose symptoms persist at these dosages.[20] Topical lubricants or moisturizers are recommended for cases where estrogen treatment is contraindicated or undesired; however, these treatments have less efficacy compared with topical estrogen (TE).[5,7,11,21] Microablative fractional CO2 laser therapy (LT) is a potential alternative for VVA treatment in such cases.[22,23]

LT seems to restore the vaginal epithelium (VE),[13] by improving vascularization and angiogenesis, stimulating the production of collagen and elastic fiber production, and leading to thickening of VE.[4,14,18,24,25] Usually, LT is applied in three laser sessions at monthly intervals. Improvement symptoms of GSM are noted after the protocol or 4 weeks after the final therapy.[13,14,23,26] Some of these observations included superficial epithelium restoration, rugae, and lubrification, which are indistinguishable from estrogenized tissue at 3 weeks after the final treatment.[25]

An improvement in dyspareunia in participants with VVA was observed by Salvatore et al[22] at 12 weeks after the start of laser treatment, with a satisfaction rate of 84%. Previous studies have reported epithelial remodeling and an increase in the number of glycogen-rich cells in participants after treatment with LT.[7,27,28] However, most studies are open prospective, comparing vaginal effects before and after laser application, lacking a comparison group, or with small samples or short-term follow-ups.[24,29]

Recently, the efficacy of isolated LT as compared with that of local TE was evaluated.[9,18,29] Furthermore, LT alone or associated with TE was found to be an effective option for improvement of VVA,[9] but data on histological evaluation is still lacking.

Although LT is a new treatment option for genitourinary syndrome, more research is needed before its widespread use can be recommended.[29] Thus, for a better understanding of LT effects in postmenopausal women, we compared the efficacies of LT with TE therapy and assessed the changes of histological biopsies of the vaginal epithelium. We aimed to subjectively evaluate the symptoms of VVA before and after LT and to compare the same with those of TE by evaluating the hormonal influence in the VE (using the maturation indices of Frost and Meisel), sexual function, and histomorphometric assessment of the vaginal mucosa.