Эффективность лазерной ремоделирующей терапии при генитоуринарном менопаузальном синдроме

Оразов М.Р., Силантьева Е.С., Радзинский В.Е., Михалева Л.М., Хрипач Е.А., Долгов Е.Д. Эффективность лазерной ремоделирующей терапии при генитоуринарном менопаузальном синдроме. Гинекология. 2022;24(6):465–470. DOI: 10.26442/20795696.2022.6.201897

© ООО «КОНСИЛИУМ МЕДИКУМ», 2022 г.

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Orazov MR, Silantyeva ES, Radzinsky VE, Mikhaleva LM, Khripach EA, Dolgov ED. Efficacy of laser remodeling in the genitourinary syndrome of menopause: A review. Gynecology. 2022;24(6):465–470.
DOI: 10.26442/20795696.2022.6.201897

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Аннотация

Лечение генитоуринарного менопаузального синдрома в реальной клинической практике имеет ряд ограничений: наличие противопоказаний к местной гормональной терапии препаратами эстрогена, которая в настоящее время признана «золотым стандартом» лечения вульвовагинальной атрофии (ВВА), страх перед системным действием эстрогенов при их топическом применении или/и канцерофобия, а также недостаточная приверженность пациенток использованию интравагинальных средств. В этой связи актуален поиск альтернативных неинвазивных или минимально инвазивных методов терапии, преимущественно негормональных. Выполнен поиск научной литературы в базах данных PubMed, CochraneLibrary, Science Direct, ELibrary по ключевым словам CO2-laser/СО2-лазер, Er:YAG-laser/эрбиевый лазер, vulvovaginal atrophy/вульвовагинальная атрофия, genitourinary syndrome of menopause/генитоуринарный менопаузальный синдром, treatment/лечение, postmenopausal age/постменопаузальный возраст за 2012–2022 гг. Ремоделирующая микроаблятивная лазерная терапия с использованием углекислого газа (СО2) – перспективный метод для лечения ВВА, действующий патогенетически и симптоматически. Использование СО2-лазера при ВВА позволяет не просто купировать симптомы, но и улучшить состояние слизистой оболочки влагалища путем усиления регенерации, восстановления вагинального рН. Однако перед введением метода в широкую клиническую практику необходимы доказательства эффективности и долгосрочной безопасности метода, полученные в исследованиях высокого качества.
Цель. Выполнить анализ и обобщить полученные к настоящему времени доказательные и экспериментальные данные об эффективности и безопасности лазерной терапии ВВА и генитоуринарного менопаузального синдрома.

Ключевые слова: вульвовагинальная атрофия, генитоуринарный менопаузальный синдром, перименопауза, постменопауза, терапия, ремоделирующая лазерная терапия, СО2-лазер, эрбиевый лазер, обзор

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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 CO2-laser, Er:YAG-laser, vulvovaginal atrophy, genitourinary syndrome of menopause, treatment, postmenopausal age for 2012–2022. Remodeling microablative laser therapy using carbon dioxide (CO2) is a promising method for treating VVA, acting pathogenetically and symptomatically. CO2 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.
Aim. 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.

Keywords: vulvovaginal atrophy, genitourinary syndrome of menopause, perimenopause, postmenopause, therapy, remodeling laser therapy, CO2 laser, erbium laser, review

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Список литературы

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14. 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
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16. Vizintin Z, Lukac M, Kazic M, Tettamanti M. Erbium laser in gynecology. Climacteric. 2015;18(Suppl. 1):4-8.
17. 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.
18. 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.
19. 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.
20. Mension E, Alonso I, Tortajada M, et al. Genitourinary Syndrome of Menopause Assessment Tools. J Midlife Health. 2021;12(2):99-102.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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
36. 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.
37. 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.
38. Eder SE. Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy. Laser Ther. 2018;27(1):41-7.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.
46. Arroyo C. Fractional CO2 laser treatment for vulvovaginal atrophy symptoms and vaginal rejuvenation in perimenopausal women. Int J Womens Health. 2017;9:591-5.
47. 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.

________________________________________________

1. Menopauza i klimaktericheskoe sostoianie u zhenshchiny. Klinicheskie rekomendatsii. Moscow, 2021 (in Russian).
2. 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.
3. 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.
4. Spadt SK, Larkin LC. Genitourinary syndrome of menopause: the unmet need. Menopause. 2021;28(4):444-6.
5. 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
6. 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.
7. 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.
8. 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.
9. 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.
10. 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
11. Capon A, Mordon S. Can thermal lasers promote skin wound healing? Am J Clin Dermatol. 2003;4(1):1-12.
12. Maksimovich NE, Bon' EI. Belki teplovogo shoka. Svoistva. Rol' v adaptatsii. Metodicheskie podkhody k opredeleniiu. Biomeditsina. 2020;16(2):60-7 (in Russian).
13. 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.
14. 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
15. 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.
16. Vizintin Z, Lukac M, Kazic M, Tettamanti M. Erbium laser in gynecology. Climacteric. 2015;18(Suppl. 1):4-8.
17. 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.
18. 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.
19. 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.
20. Mension E, Alonso I, Tortajada M, et al. Genitourinary Syndrome of Menopause Assessment Tools. J Midlife Health. 2021;12(2):99-102.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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
29. 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.
30. 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.
31. 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.
32. 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.
33. 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.
34. 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.
35. 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
36. 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.
37. 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.
38. Eder SE. Early effect of fractional CO2 laser treatment in Post-menopausal women with vaginal atrophy. Laser Ther. 2018;27(1):41-7.
39. 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.
46. Arroyo C. Fractional CO2 laser treatment for vulvovaginal atrophy symptoms and vaginal rejuvenation in perimenopausal women. Int J Womens Health. 2017;9:591-5.
47. 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.

Авторы

М.Р. Оразов*1, Е.С. Силантьева2, В.Е. Радзинский1, Л.М. Михалева3, Е.А. Хрипач4, Е.Д. Долгов1

1 ФГАОУ ВО «Российский университет дружбы народов», Москва, Россия;
2 ГК «Мать и дитя», Москва, Россия;
3 ФГБНУ «Российский научный центр хирургии им. акад. Б.В. Петровского», Москва, Россия;
4 Многопрофильный медицинский центр «DEKA Medical», Москва, Россия
*omekan@mail.ru

________________________________________________

Mekan R. Orazov*1, Elena S. Silantyeva2, Viktor E. Radzinsky1, Liudmila M. Mikhaleva3, Elizaveta A. Khripach4, Evgeny D. Dolgov1

1 People’s Friendship University of Russia (RUDN University), Moscow, Russia;
2 GC "Mother and Child", Moscow, Russia;
3 Petrovsky National Research Centre of Surgery, Moscow, Russia;
4 Multidisciplinary Medical Center "DEKA Medical", Moscow, Russia
*omekan@mail.ru

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