Lasers in Medical Science

, Volume 33, Issue 5, pp 1047–1054 | Cite as

Fractional CO2 laser for genitourinary syndrome of menopause in breast cancer survivors: clinical, immunological, and microbiological aspects

  • Angelamaria Becorpi
  • Giuseppina Campisciano
  • Nunzia Zanotta
  • Zelinda Tredici
  • Secondo Guaschino
  • Felice Petraglia
  • Annalisa Pieralli
  • Giovanni Sisti
  • Francesco De Seta
  • Manola ComarEmail author
Original Article


The composition of vaginal microbiome in menopause and cancer survivor women changes dramatically leading to genitourinary syndrome of menopause (GSM) in up to 70% of patients. Recent reports suggest that laser therapy may be valuable as a not hormonal therapeutic modality. The aim of the present study was to evaluate the effects of fractional CO2 laser treatment on the vaginal secretory pathway of a large panel of immune mediators, usually implicated in tissue remodeling and inflammation, and on microbiome composition in postmenopausal breast cancer survivors. The Ion Torrent PGM platform and the Luminex Bio-Plex platform were used for microbiome and immune factor analysis. The significant reduction of clinical symptoms and the non-significant changes in vaginal microbiome support the efficacy and safety of laser treatment. Moreover, the high remodeling status in vaginal epithelium is demonstrated by the significant changes in inflammatory and modulatory cytokine patterns. Laser therapy can be used for the treatment of GSM symptoms and does not show any adverse effects. However, further studies will be needed to clarify its long-term efficacy and other effects.


Fractional CO2 laser Cytokines/chemokines Microbiome Menopause Breast cancer 



Vulvovaginal atrophy


Genitourinary syndrome of menopause


Verbal Rating Scale


Bacterial vaginosis


Vaginal Health Index


Female Sexual Function Index


Female Sexual Distress Scale revised 2005



Conceptualization, M.C.; methodology, A.M.B., G.C., and N.Z.; software, G.C. and N.Z.; investigation, A.M.B., G.C., and N.Z.; resources, Z.T., S.G., F.P., A.P., and G.S.; data curation, G.C. and N.Z.; writing—original draft, G.C., N.Z., and M.C.; writing—review and editing, M.C.; visualization, G.C. and N.Z.; funding acquisition, M.C.


This study was supported by the Italian Ministry of Health, grant number RC 26/13.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Florence. The study was conducted in accordance with the Declaration of Helsinki.

Consent for publication

All patients who were recruited for the study signed an informed consent form.


  1. 1.
    Gandhi J, Chen A, Dagur G, Suh Y, Smith N, Cali B, Khan SA (2016) Genitourinary syndrome of menopause: an overview of clinical manifestations, pathophysiology, etiology, evaluation, and management. Am J Obstet Gynecol 215(6):704–711. CrossRefPubMedGoogle Scholar
  2. 2.
    Portman DJ, Gass ML (2014) Genitourinary syndrome of menopause: new terminology for vulvovaginal atrophy from the International Society for the Study of Women’s Sexual Health and the North American Menopause Society. Maturitas 79(3):349–354. CrossRefPubMedGoogle Scholar
  3. 3.
    Nappi RE, Kokot-Kierepa M (2010) Women’s voices in the menopause: results from an international survey on vaginal atrophy. Maturitas 67(3):233–238. CrossRefPubMedGoogle Scholar
  4. 4.
    Lester J, Pahouja G, Andersen B, Lustberg M (2015) Atrophic vaginitis in breast cancer survivors: a difficult survivorship issue. Journal of personalized medicine 5(2):50–66. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Crandall C, Petersen L, Ganz PA, Greendale GA (2004) Association of breast cancer and its therapy with menopause-related symptoms. Menopause 11(5):519–530CrossRefPubMedGoogle Scholar
  6. 6.
    Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society (2013). Menopause 20 (9):888–902; quiz 903–884.
  7. 7.
    Sturdee DW, Panay N (2010) Recommendations for the management of postmenopausal vaginal atrophy. Climacteric : the journal of the International Menopause Society 13(6):509–522. CrossRefGoogle Scholar
  8. 8.
    Arunkalaivanan A, Kaur H, Onuma O (2017) Laser therapy as a treatment modality for genitourinary syndrome of menopause: a critical appraisal of evidence. Int Urogynecol J 28(5):681–685. CrossRefPubMedGoogle Scholar
  9. 9.
    Jih MH, Kimyai-Asadi A (2008) Fractional photothermolysis: a review and update. Seminars in cutaneous medicine and surgery 27(1):63–71. CrossRefPubMedGoogle Scholar
  10. 10.
    Perino A, Calligaro A, Forlani F, Tiberio C, Cucinella G, Svelato A, Saitta S, Calagna G (2015) Vulvo-vaginal atrophy: a new treatment modality using thermo-ablative fractional CO2 laser. Maturitas 80(3):296–301. CrossRefPubMedGoogle Scholar
  11. 11.
    Zerbinati N, Serati M, Origoni M, Candiani M, Iannitti T, Salvatore S, Marotta F, Calligaro A (2015) Microscopic and ultrastructural modifications of postmenopausal atrophic vaginal mucosa after fractional carbon dioxide laser treatment. Lasers Med Sci 30(1):429–436. CrossRefPubMedGoogle Scholar
  12. 12.
    Stefano S, Stavros A, Massimo C (2015) The use of pulsed CO lasers for the treatment of vulvovaginal atrophy. Curr Opin Obstet Gynecol 27(6):504–508Google Scholar
  13. 13.
    Gaspar A, Brandi H, Gomez V, Luque D (2017) Efficacy of erbium: YAG laser treatment compared to topical estriol treatment for symptoms of genitourinary syndrome of menopause. Lasers Surg Med 49(2):160–168CrossRefPubMedGoogle Scholar
  14. 14.
    Salvatore S, Leone Roberti Maggiore U, Athanasiou S, Origoni M, Candiani M, Calligaro A, Zerbinati N (2015) Histological study on the effects of microablative fractional CO2 laser on atrophic vaginal tissue: an ex vivo study. Menopause 22(8):845–849. CrossRefPubMedGoogle Scholar
  15. 15.
    Sokol ER, Karram MM (2016) An assessment of the safety and efficacy of a fractional CO2 laser system for the treatment of vulvovaginal atrophy. Menopause 23(10):1102–1107. CrossRefPubMedGoogle Scholar
  16. 16.
    Athanasiou S, Pitsouni E, Antonopoulou S, Zacharakis D, Salvatore S, Falagas ME, Grigoriadis T (2016) The effect of microablative fractional CO2 laser on vaginal flora of postmenopausal women. Climacteric : the journal of the International Menopause Society 19(5):512–518. CrossRefGoogle Scholar
  17. 17.
    Pitsouni E, Grigoriadis T, Tsiveleka A, Zacharakis D, Salvatore S, Athanasiou S (2016) Microablative fractional CO2-laser therapy and the genitourinary syndrome of menopause: an observational study. Maturitas 94:131–136. CrossRefPubMedGoogle Scholar
  18. 18.
    Murina F, Karram M, Salvatore S, Felice R (2016) Fractional CO2 laser treatment of the vestibule for patients with vestibulodynia and genitourinary syndrome of menopause: a pilot study. J Sex Med 13(12):1915–1917. CrossRefPubMedGoogle Scholar
  19. 19.
    Pieralli A, Fallani MG, Becorpi A, Bianchi C, Corioni S, Longinotti M, Tredici Z, Guaschino S (2016) Fractional CO2 laser for vulvovaginal atrophy (VVA) dyspareunia relief in breast cancer survivors. Arch Gynecol Obstet 294(4):841–846. CrossRefPubMedGoogle Scholar
  20. 20.
    Muhleisen AL, Herbst-Kralovetz MM (2016) Menopause and the vaginal microbiome. Maturitas 91:42–50. CrossRefPubMedGoogle Scholar
  21. 21.
    Campisciano G, Florian F, D'Eustacchio A, Stankovic D, Ricci G, De Seta F, Comar M (2017) Subclinical alteration of the cervical-vaginal microbiome in women with idiopathic infertility. J Cell Physiol 232(7):1681–1688. CrossRefPubMedGoogle Scholar
  22. 22.
    Zanotta N, Tornesello ML, Annunziata C, Stellato G, Buonaguro FM, Comar M (2016) Candidate soluble immune mediators in young women with high-risk human papillomavirus infection: high expression of chemokines promoting angiogenesis and cell proliferation. PLoS One 11(3):e0151851. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Donders GG, Bosmans E, Dekeersmaecker A (2000) Pathogenesis of abnormal vaginal bacterial flora. Am J Obstet Gynecol 182:872–878CrossRefPubMedGoogle Scholar
  24. 24.
    Galen BT, Martin AP, Hazrati E (2007) A comprehensive murine model to evaluate topical vaginal microbicides: mucosal inflammation and susceptibility to genital herpes as surrogate markers of safety. J Infect Dis 195:1332–1339CrossRefPubMedGoogle Scholar
  25. 25.
    Petricevic L, Unger FM, Viernstein H (2008) Randomized, double-blind, placebo-controlled study of oral lactobacilli to improve the vaginal flora of postmenopausal women. Eur J Obstet Gynecol Reprod Biol 141:54–57CrossRefPubMedGoogle Scholar
  26. 26.
    Fichorova RN, Lai JJ, Schwartz JL (2011) Baseline variation and associations between subject characteristics and five cytokine biomarkers of vaginal safety among healthy non-pregnant women in microbicide trials. Cytokine 55:134–140CrossRefPubMedGoogle Scholar
  27. 27.
    Salvatore S, Nappi RE, Zerbinati N (2014) A 12-week treatment with fractional CO2 laser for vulvovaginal atrophy: a pilot study. Climacteric 17:363–369. CrossRefPubMedGoogle Scholar
  28. 28.
    Tierney EP, Hanke CW (2009) Ablative fractionated CO2, laser resurfacing for the neck: prospective study and review of the literature. J Drugs Dermatol 8(8):723–731PubMedGoogle Scholar
  29. 29.
    Abrahamse H (2012) Regenerative medicine, stem cells, and low-level laser therapy: future directives. Photomed Laser Surg 30(12):681–682. CrossRefPubMedGoogle Scholar
  30. 30.
    Prignano F, Campolmi P, Bonan P, Ricceri F, Cannarozzo G, Troiano M, Lotti T (2009) Fractional CO2 laser: a novel therapeutic device upon photobiomodulation of tissue remodeling and cytokine pathway of tissue repair. Dermatol Ther 22(Suppl 1):S8–15. CrossRefPubMedGoogle Scholar
  31. 31.
    Sica A, Invernizzi P, Mantovani A (2014) Macrophage plasticity and polarization in liver homeostasis and pathology. Hepatology 59(5):2034–2042. CrossRefPubMedGoogle Scholar
  32. 32.
    Brotman RM, Shardell MD, Gajer P, Fadrosh D, Chang K, Silver MI, Viscidi RP, Burke AE, Ravel J, Gravitt PE (2014) Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy. Menopause 21(5):450–458. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Shen J, Song N, Williams CJ, Brown CJ, Yan Z, Xu C, Forney LJ (2016) Effects of low dose estrogen therapy on the vaginal microbiomes of women with atrophic vaginitis. Sci Rep 6:24380. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  • Angelamaria Becorpi
    • 1
  • Giuseppina Campisciano
    • 2
  • Nunzia Zanotta
    • 2
  • Zelinda Tredici
    • 1
  • Secondo Guaschino
    • 1
  • Felice Petraglia
    • 1
  • Annalisa Pieralli
    • 1
  • Giovanni Sisti
    • 1
  • Francesco De Seta
    • 2
    • 3
  • Manola Comar
    • 2
    • 3
    Email author
  1. 1.Section of Gynecology and Obstetrics, Department of Woman and Child HealthCareggi University HospitalFlorenceItaly
  2. 2.Institute for Maternal and Child Health-IRCCS “Burlo Garofolo”TriesteItaly
  3. 3.Department of Medical SciencesUniversity of TriesteTriesteItaly

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