GynecologyGynecology2079-56962079-5831Consilium Medicum12845510.26442/20795696.2022.6.201897Review ArticleEfficacy of laser remodeling in the genitourinary syndrome of menopause: A reviewOrazovMekan R.<p>D. Sci. (Med.), Prof., People’s Friendship University of Russia (RUDN University)</p>omekan@mail.ruhttps://orcid.org/0000-0002-1767-5536SilantyevaElena S.<p>D. Sci. (Med.), GC "Mother and Child"</p>omekan@mail.ruhttps://orcid.org/0000-0002-7667-3231RadzinskyViktor E.<p>D. Sci. (Med.), Prof., Corr. Memb. RAS, People’s Friendship University of Russia (RUDN University)</p>radzinsky@mail.ruhttps://orcid.org/0000-0003-4956-0466MikhalevaLiudmila M.<p>D. Sci. (Med.), Prof., Petrovsky National Research Centre of Surgery</p>omekan@mail.ruhttps://orcid.org/0000-0003-2052-914XKhripachElizaveta A.<p>Obstetrician-Gynecologist, “DEKA Medical”</p>elizaveta.ark@mail.ruhttps://orcid.org/0000-0003-2895-1193DolgovEvgeny D.<p>Clinical Resident, People’s Friendship University of Russia (RUDN University)</p>1586dolgde@gmail.comhttps://orcid.org/0000-0001-6709-5209People’s Friendship University of Russia (RUDN University)GC "Mother and Child"Petrovsky National Research Centre of SurgeryMultidisciplinary Medical Center "DEKA Medical"211220222464654701901202319012023Copyright © 2022, Consilium Medicum2022<p>The real-world treatment of genitourinary syndrome of menopause has several limitations: contraindications to topical estrogen therapy, which is currently recognized as the "gold standard" treatment for vulvovaginal atrophy (VVA), fear of the systemic effects of topical estrogens or/and carcinophobia, and poor compliance of patients to intravaginal agents. Therefore, there is an unmet need for alternative noninvasive or minimally invasive therapies, mostly non-hormonal. A PubMed, Cochrane Library, Science Direct, and ELibrary databases were searched for the keywords CO<sub>2</sub>-laser, Er:YAG-laser, vulvovaginal atrophy, genitourinary syndrome of menopause, treatment, postmenopausal age for 20122022. Remodeling microablative laser therapy using carbon dioxide (CO<sub>2</sub>) is a promising method for treating VVA, acting pathogenetically and symptomatically. CO<sub>2</sub> laser relieves VVA symptoms and improves the condition of the vaginal mucosa by enhancing regeneration and restoring vaginal pH. However, evidence of the efficacy and long-term safety of the method, obtained in high-quality studies, is needed before the method can be introduced into widespread clinical practice.</p>
<p><strong>Aim. </strong>To analyze and summarize the evidence-based and experimental data on the efficacy and safety of laser therapy for VVA and genitourinary syndrome of menopause.</p>vulvovaginal atrophygenitourinary syndrome of menopauseperimenopausepostmenopausetherapyremodeling laser therapyCO2 lasererbium laserreviewвульвовагинальная атрофиягенитоуринарный менопаузальный синдромперименопаузапостменопаузатерапияремоделирующая лазерная терапияСО2-лазерэрбиевый лазеробзор[Менопауза и климактерическое состояние у женщины. Клинические рекомендации. М., 2021 [Menopauza i klimaktericheskoe sostoianie u zhenshchiny. Klinicheskie rekomendatsii. Moscow, 2021 (in Russian)].][Nappi RE, Palacios S, Bruyniks N, et al. EVES Study investigators. The burden of vulvovaginal atrophy on women’s daily living: implications on quality of life from a face-to-face real-life survey. Menopause. 2019;26(5):485-91.][Palma F, Volpe A, Villa P, Cagnacci A; Writing group of AGATA study. Vaginal atrophy of women in postmenopause. Results from a multicentric observational study: The AGATA study. Maturitas. 2016;83:40-4.][Spadt SK, Larkin LC. Genitourinary syndrome of menopause: the unmet need. Menopause. 2021;28(4):444-6.][Peters KJ. What Is Genitourinary Syndrome of Menopause and Why Should We Care? Perm J. 2021;25:20.248. DOI:10.7812/TPP/20.248][Kingsberg SA, Wysocki S, Magnus L, Krychman ML. Vulvar and vaginal atrophy in postmenopausal women: findings from the REVIVE (REal Women’s VIews of Treatment Options for Menopausal Vaginal ChangEs) survey. J Sex Med. 2013;10(7):1790-9.][Nappi RE, Palacios S, Panay N, et al. Vulvar and vaginal atrophy in four European countries: evidence from the European REVIVE Survey. Climacteric. 2016;19(2):188-97. DOI:10.3109/13697137.2015.1107039. Erratum in: Climacteric. 2016;19(2):i.][Kingsberg SA, Krychman M, Graham S, et al. The Women’s EMPOWER Survey: Identifying Women’s Perceptions on Vulvar and Vaginal Atrophy and Its Treatment. J Sex Med. 2017;14(3):413-24.][Biglia N, Bounous VE, Sgro LG, et al. Genitourinary Syndrome of Menopause in Breast Cancer Survivors: Are We Facing New and Safe Hopes? Clin Breast Cancer. 2015;15(6):413-20.][Lubián López DM. Management of genitourinary syndrome of menopause in breast cancer survivors: An update. World J Clin Oncol. 2022;13(2):71-100. DOI:10.5306/wjco.v13.i2.71][Capon A, Mordon S. Can thermal lasers promote skin wound healing? Am J Clin Dermatol. 2003;4(1):1-12.][Максимович Н.Е., Бонь Е.И. Белки теплового шока. Свойства. Роль в адаптации. Методические подходы к определению. Биомедицина. 2020;16(2):60-7 [Maksimovich NE, Bon' EI. Belki teplovogo shoka. Svoistva. Rol' v adaptatsii. Metodicheskie podkhody k opredeleniiu. Biomeditsina. 2020;16(2):60-7 (in Russian)].][Dafforn TR, Della M, Miller AD. The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis. J Biol Chem. 2001;276(52):49310-9.][Salvatore S, Leone Roberti Maggiore U, Athanasiou S, et al. Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause. 2015;22(8):845-9. DOI:10.1097/GME.0000000000000401][Zerbinati N, Serati M, Origoni M, et al. Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci. 2015;30(1):429-36.][Vizintin Z, Lukac M, Kazic M, Tettamanti M. Erbium laser in gynecology. Climacteric. 2015;18(Suppl. 1):4-8.][Benini V, Ruffolo AF, Casiraghi A, et al. New Innovations for the Treatment of Vulvovaginal Atrophy: An Up-to-Date Review. Medicina (Kaunas). 2022;58(6):770.][Sokol ER, Karram MM. Use of a novel fractional CO2 laser for the treatment of genitourinary syndrome of menopause: 1-year outcomes. Menopause. 2017;24(7):810-4.][Perino A, Calligaro A, Forlani F, et al. Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional CO2 laser. Maturitas. 2015;80(3):296-301.][Mension E, Alonso I, Tortajada M, et al. Genitourinary Syndrome of Menopause Assessment Tools. J Midlife Health. 2021;12(2):99-102.][Mooney KM, Poirier É, Pukall CF. Persistent Genital Arousal in Relationships: A Comparison of Relationship, Sexual, and Psychological Well-Being. J Sex Med. 2022;19(2):234-48.][Gabrieli D, Suissa-Cohen Y, Jaber S, Lev-Sagie A. “Modified Schirmer Test” as an Objective Measurement for Vaginal Dryness: A Prospective Cohort Study. Diagnostics (Basel). 2022;12(3):574.][Politano CA, Costa-Paiva L, Aguiar LB, et al. Fractional CO2 laser versus promestriene and lubricant in genitourinary syndrome of menopause: a randomized clinical trial. Menopause. 2019;26(8):833-40.][Paraiso MFR, Ferrando CA, Sokol ER, et al. A randomized clinical trial comparing vaginal laser therapy to vaginal estrogen therapy in women with genitourinary syndrome of menopause: The VeLVET Trial. Menopause. 2020;27(1):50-6.][Li J, Li H, Zhou Y, et al. The Fractional CO2 Laser for the Treatment of Genitourinary Syndrome of Menopause: A Prospective Multicenter Cohort Study. Lasers Surg Med. 2021;53(5):647-53.][Aguiar LB, Politano CA, Costa-Paiva L, Juliato CRT. Efficacy of Fractional CO2 Laser, Promestriene, and Vaginal Lubricant in the Treatment of Urinary Symptoms in Postmenopausal Women: A Randomized Clinical Trial. Lasers Surg Med. 2020;52(8):713-20.][Veron L, Wehrer D, Annerose-Zéphir G, et al. Effects of local laser treatment on vulvovaginal atrophy among women with breast cancer: a prospective study with long-term follow-up. Breast Cancer Res Treat. 2021;188(2):501-9.][Pitsouni E, Grigoriadis T, Tsiveleka A, et al. Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: An observational study. Maturitas. 2016;94:131-6. DOI:10.1016/j.maturitas.2016.09.012][Athanasiou S, Pitsouni E, Falagas ME, et al. CO2-laser for the genitourinary syndrome of menopause. How many laser sessions? Maturitas. 2017;104:24-8.][Pitsouni E, Grigoriadis T, Falagas M, et al. Microablative fractional CO2 laser for the genitourinary syndrome of menopause: power of 30 or 40 W? Lasers Med Sci. 2017;32(8):1865-72.][Tovar-Huamani J, Mercado-Olivares F, Grandez-Urbina JA, et al. Efficacy of fractional CO2 laser in the treatment of genitourinary syndrome of menopause in Latin-American Population: First Peruvian experience. Lasers Surg Med. 2019;51(6):509-15.][Quick AM, Hundley A, Evans C, et al. Long-Term Follow-Up of Fractional CO2 Laser Therapy for Genitourinary Syndrome of Menopause in Breast Cancer Survivors. J Clin Med. 2022;11(3):774.][González Isaza P, Jaguszewska K, Cardona JL, Lukaszuk M. Long-term effect of thermoablative fractional CO2 laser treatment as a novel approach to urinary incontinence management in women with genitourinary syndrome of menopause. Int Urogynecol J. 2018;29(2):211-5.][Eder SE. Long-Term Safety and Efficacy of Fractional CO2 Laser Treatment in Post-Menopausal Women with Vaginal Atrophy. Laser Ther. 2019;28(2):103-9.][Rosner-Tenerowicz A, Zimmer-Stelmach A, Zimmer M. The CO2 ablative laser treatment in perimenopausal patients with vulvovaginal atrophy. Ginekol Pol. 2022;93(5):374-80. DOI:10.5603/GP.a2021.0140][Alexiades MR. Fractional CO2 Laser Treatment of the Vulva and Vagina and the Effect of Postmenopausal Duration on Efficacy. Lasers Surg Med. 2021;53(2):185-98.][Adabi K, Golshahi F, Niroomansh S, et al. Effect of the Fractional CO2 Laser on the Quality of Life, General Health, and Genitourinary Symptoms in Postmenopausal Women With Vaginal Atrophy: A Prospective Cohort. J Lasers Med Sci. 2020;11(1):65-9.][Eder SE. Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy. Laser Ther. 2018;27(1):41-7.][Marin J, Lipa G, Dunet E. The results of new low dose fractional CO2 Laser – A prospective clinical study in France. J Gynecol Obstet Hum Reprod. 2020;49(3):101614.][Quick AM, Dockter T, Le-Rademacher J, et al. Pilot study of fractional CO2 laser therapy for genitourinary syndrome of menopause in gynecologic cancer survivors. Maturitas. 2021;144:37-44.][Li FG, Maheux-Lacroix S, Deans R, et al. Effect of Fractional Carbon Dioxide Laser vs Sham Treatment on Symptom Severity in Women With Postmenopausal Vaginal Symptoms: A Randomized Clinical Trial. JAMA. 2021;326(14):1381-9.][Cruff J, Khandwala S. A Double-Blind Randomized Sham-Controlled Trial to Evaluate the Efficacy of Fractional Carbon Dioxide Laser Therapy on Genitourinary Syndrome of Menopause. J Sex Med. 2021;18(4):761-9.][Becorpi A, Campisciano G, Zanotta N, et al. Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects. Lasers Med Sci. 2018;33(5):1047-54.][Pagano T, De Rosa P, Vallone R, et al. Fractional microablative CO2 laser in breast cancer survivors affected by iatrogenic vulvovaginal atrophy after failure of nonestrogenic local treatments: a retrospective study. Menopause. 2018;25(6):657-62. DOI:10.1097/GME.0000000000001053. Erratum in: Menopause. 2018;25(10):1169.][Gambacciani M, Levancini M. Vaginal erbium laser as second-generation thermotherapy for the genitourinary syndrome of menopause: a pilot study in breast cancer survivors. Menopause. 2017;24(3):316-9.][Arroyo C. Fractional CO2 laser treatment for vulvovaginal atrophy symptoms and vaginal rejuvenation in perimenopausal women. Int J Womens Health. 2017;9:591-5.][Pagano T, De Rosa P, Vallone R, et al. Fractional microablative CO2 laser for vulvovaginal atrophy in women treated with chemotherapy and/or hormonal therapy for breast cancer: a retrospective study. Menopause. 2016;23(10):1108-13.]