REMODELING LASER THERAPY OF THE VAGINA IN GENITOURINARY MENOPAUSAL SYNDROME

Vaginal atrophy is one of the most frequent pathological conditions of women in peri and postmenopause and its manifestations negatively affect their quality of life.One of the most urgent problems of modern gynecology is changes in the genitourinary tract of women associated with the end of the reproductive period of life and its inevitable aging. To describe estrogen - dependent age - related changes affecting the external genitourinary system, vagina, urethra and bladder, a new term-genitourinary menopausal syndrome-GUMS (IMS, 2014) - was adopted by written vote. Pathogenetically justified therapy for any disorders associated with menopause, is the use of estrogens (IMS 2016). But in the arsenal of the clinician should be and non-drug means with comparable efficiency, in particular, hybrid two-wave fractional laser therapy.The aim of the investigation was to expand the possibilities of therapy for genitourinary syndrome based on clinical and morphological evaluation of the effectiveness of remodeling fractional laser therapy.Material and methods: The study was not comparative, independent, prospective, clinical-morphological study of 26 patients (n=26) aged 49.5±5 years, applied to the period between October 2017 and February 2018 for conservative treatment on the clinical database Department of obstetrics and gynecology with course perinatology RUDN University (Central clinical hospital №6 of Russian Railways) with a diagnosis of «Postmenopausal atrophic vaginitis» (No. 95.2) and who gave voluntary informed consent for inclusion in the study: obtain biological material to study the clinical, hardware and laboratory parameters, therapy, statistical processing and publication of the results. Diagnoses were confirmed clinically and based on laboratory and instrumental studies.Laser remodeling using the «Hybrid fractional laser vaginal diVaTM with a wavelength of nm 1470 /2940» in the system of the multi-platform JOULE followed all patients. Each patient in three stages - before laser therapy, 1 and 3 months after it - took two samples of vaginal tissue - from the front and rear walls. In total, there were 156 conducted research of the histological structure of the vaginal wall (26 patients * 2 BM * 3 phase) at the Department of pathological anatomy to I. M. Sechenov (Sechenov University) methods of microscopy (hematoxylin-eosin and Masson), immunohistochemistry, computer morphometry and study of expression of some genes by Polymerase-chain reaction-real time.results: GUMS is characterized not only by a decrease in the number of epithelial layers, but also by the thinning of the basal membrane, connective tissue and muscle compartment of the vaginal wall with a pronounced inflammatory reaction against the background of significantly reduced trophism, compaction, collagenization and disorders of architectonics. Even a single procedure is a hybrid fractional laser showed statistically significant changes, particularly manifested after 3 months: reduction reaction imunohistochemical Coll.I from 46.1±2.9 % of field of view to 29.5±1.1 (p<0.05) 3 months after laser procedure and inflammatory reaction by CD8+ marker, respectively, from 5.2±0.2 to 1.1±0.6 (p<0.05). The expression of the genes ECM1 and CD80 decreased significantly. Immunohistochemical reaction for the markers Coll.III, α-SMA, CK5, VEGF-a, as well as expression of genes MMP-1, 2, 3, 9, POSTN and CD163 increased significantly by 1.3-2.2 times (p<0.05). Histological changes were consistent with a significant improvement in the clinical picture in 22 out of 26 women of the studied cohort (84.6%).Conclusion: Remodeling under the influence of laser therapy affected the morphological and functional properties of all the components of the vaginal wall, not just the mucous membrane. Even without the estrogenic effects of increased trophic tissues, degraded compact arrangement of collagen fibers type I to replace them began to actively synthesize new collagen fibers type III increased the total number of microfilaments, recovered their orientation in space, decreased proinflammatory and increased preregenerative the activity of the fibroblasts stabilized before thinning basal layer of the epithelium. Our study, albeit on a small sample, showed reliable and versatile positive effects, which is quite important - long-term effects even from a single application of a hybrid fractional laser with the possibility of simultaneous use of ablative and non-ablative wavelength and rapid recovery after the procedure.

генитоуринарный менопаузальный синдром, вульво-вагинальная атрофия, лазерное ремоделирование, genitourinary menopausal syndrome, vulvovaginal atrophy, laser remodeling

1. Генитоуринарный менопаузальный синдром. Новые возможности патогенетически оправданной местной терапии. Информаци- онное письмо. - М.: Редакция журнала StatusPraesens, 2015. - C.4-6

2. Portman D.J., Gass M.L.S. Vulvovaginal Atrophy Terminology Consensus Conference Panel. 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. 2014. Vol. 79. №3. P. 349-354. [PMID: 25179577.]

3. Calleja-Agius J., Brincat M.P. The urogenital system and the meno- pause // Climacteric J. Int. Menopause Soc. 2015. Vol. 18. №1. P. 18-22. [PMID: 26366796.]

4. Савичева А.М., Рыбина Е.В. Исследование in vitro роста, размножения, антибиотикорезистентности, конкурентных взаимоотно- шений штамма Lactobacillus casei rhamnosus // Акушерство и гинекология. 2014. №7. C. 79-83.

5. Santen R.J., Allred D.C., Ardoin S.P. et al. Postmenopausal hor- mone therapy: an Endocrine Society scientific statement // J. Clin. Endocri- nol. Metab. 2010.Vol. 95. №7 (1). P. s1-s66. [PMID: 20566620.]

6. Cardozo L. et al. A systematic review of the effects of estrogens for symptoms suggestive of overactivebladder // Acta Obstet. Gynecol. Scand. 2004. Vol. 83. №10. P. 892-897. [PMID: 15453881.]

7. Suckling J.A., Kennedy R., Lethaby A. et al. Local oestrogen for vaginal atrophy in postmenopausal women // Cochrane Database of Sys- tematic Reviews /Ed. The Cochrane Collaboration. Chichester, UK: John Wiley & Sons, Ltd, 2006. [PMID: 17054136.]

8. Mosser DM, Edwards JP. Exploring the full spectrum of macro- phage activation. Nature Reviews Immunology. Dec 2008; 8 (12): 958-969.

9. Lugrin J, Rosenblatt-Velin N, Parapanov R, Liaudet L. The role of oxidative stress during inflammatory processes. Biol Chem. 2014;395: 203-230

10. Coulombe PA, Omary MB. ‘Hard’ and ‘soft’ principles defining the structure, function and regulation of keratin intermediate filaments. Cur- rent Opinion in Cell Biology. Feb 2002; 14 (1): 110-22.

11. Conway SJ, Izuhara K, Kudo Y, Litvin J, Markwald R, Ouyang G, Arron JR, Holweg CT, Kudo A. «The role of periostin in tissue remodel- ing across health and disease». Cellular and Molecular Life Sciences. Apr 2014;71 (7): 1279-88.

12. Duffy AM, Bouchier-Hayes DJ, Harmey JH. Vascular Endothelial Growth Factor (VEGF) and Its Role in Non-Endothelial Cells: Autocrine Signalling by VEGF. In: Madame Curie Bioscience Database. Austin (Tx): Landes Bioscience; 2000-2013.

13. Официальная инструкция по применению препарата «Триожиналь». ГРЛС, 2015.

14. Light and Energy Based Therapeutics for Genitourinary syn- drome of Menopause: Consensus and Controversies. Lasers in Surgery and Medicine.Jan 2017; 49:137-159.

15. Токтар Л.Р. Женская пролаптология: от патогенеза к эффективности профилактики и лечения// Акушерство и гинекология: но- вости, мнения, обучение. - 2017. - №3. - С.98-107

16. Тотчиев Г.Ф., Токтар Л.Р., Тигиева А.В., Завадина Е.В. Сос- тояние влагалищного биотопа у пациенток репродуктивного возрас- та, страдающих несостоятельностью тазового дна //Вестник РУДН. Серия «Медицина». Акушерство и гинекология. - 2013. - №5. - С.146-150.

17. Медицина климактерия /под ред. В.П. Сметник. - Ярославль: ООО «Издательство Литера», 2006. - 848 с.

18. Barlow D.H., Samsioe G., van Geelen I.M. A study of European women experience of the problems of urogenital aging and its management // Maturitas. - 1997. - №27 (3). - P. 239-247.

19. Оразов М.Р., Хамошина М.Б., Носенко Е.Н., Силантьева Е.С., Кампос Е.С. Патогенетические механизмы формирования пролапса тазовых органов//Акушерство и гинекология: новости, мнения, об- учение. -2017. -№ 3 (17). -С. 108-116.

20. Оразов М.Р., Демяшкин Г.А., Токтар Л.Р., Силантьева Е.С., Хамошина М.Б., Кампос Е.С., Лологаева М.С. Ультраструктурные характеристики тканей тазового дна как патогенетическое обоснование применения направленной контактной диатермии при пролапсе тазовых органов// Доктор.Ру. -2017. № 13-14 (142-143). -С. 19-26.