Genitourinary syndrome (GS) is a complex of symptoms that manifest as dysfuction in the genitourinary system in women after 45 years and are primarily associated with a decrease of estrogens and other sex hormones. 
Significant information is cumulating in regard to using minimally invasive laser technologies in urogynecology, but evidence on its clinical effectiveness and safety of use in the treatment of stress urinary incontinence in women is limited.
The structural mechanisms of implementation of the therapeutic effect of laser radiation on the morpho-functional state of the vaginal walls after treatment with laser technologies remain insufficiently studied, information about which is given only in some publications.
The aim of the study was to study the effects of use of CO2 laser in the complex treatment of genitourinary syndrome in premenopausal patients.

We performed a prospective examination of 132 women aged 45-55 years who were treated in the gynecological department with manifestations of genitourinary syndrome. All women, depending on the prescribed therapy, were divided into two groups. The main group included 56 premenopausal women with genitourinary syndrome, who in order to correct the manifestations of GS were offered therapy using a CO2 laser, which provided for 4 sessions with an interval of 30-45 days with a laser power of 40 W, an exposure time of 1000 ms and a distance between points - 1000 microns in combination with local hormone therapy-local application of estradiol-based cream once a day for the first month, followed by a reduction in the dosage to one application twice a week for 7 months. The comparison group was formed by 76 women with manifestations of GS, who were prescribed only therapy with topical use of estradiol at the rate of one application of cream per day for a month, followed by switching to a single one twice a week for 7 months. The total duration of treatment for women in both groups was 8 months.
All patients underwent a complex of examinations before starting treatment, including gynecological examination, cytological examination of PAP-smears, ultrasound examination of the pelvic organs and urinary bladder.
All patients were evaluated for the level of connective tissue synthesis markers (Total P1NP, total P3NP) and resorption (Deoxypyridinoline Pyriliks – D) before treatment, immediately after treatment, and 6 months after treatment.
To assess the severity of GS symptoms, patients were surveyed using a specialized PFDI-20 questionnaire (Pelvic Floor Disorders Distress Inventory) [19] and a questionnaire for calculating the index of sexual dysfunction in women (FSFI — Female Sexual Function Index)]. Assessment of VVA symptoms was performed using the VSQ questionnaire (the Vulvovaginal Symptom Questionnaire).
Statistical processing of the obtained results was carried out using descriptive and Variational statistics. Discrepancies were defined as significant at p<0.05.

The inclusion of a CO2-laser in the complex therapy of Genitourinary Syndrome can significantly reduce the manifestations of genital disorders, which is confirmed by a significant decrease in the median score from 55 to 18 in women of the main group according to the results of the PFDI-20 questionnaire (p<0.05). The index of sexual function in women who received laser therapy according to the results of the FSFI questionnaire showed a significant increase from 25 to 46 points (p<0.05). The average value of VSQ scores in women of the main group after applying the proposed treatment significantly decreased from 16.2±0.4 to 5.3±0.2 (p<0.05). The results of a survey using the UDI-6 questionnaire indicate a significant reduction in the symptoms of Genitourinary Syndrome in women of the main group compared to women who received only drug therapy.
Episodes of gas incontinence were observed in 10 (17.9%) women of the main group after treatment (the main group before treatment – 29 (51.8%); comparison group after treatment – 24 (31.6%); p<0.05), and urinary incontinence when coughing and sneezing – 14 (25.0%) (the main group before treatment – 54 (96.4%); comparison group after treatment – 30 (39.5%); p<0.05).
After using a CO2 laser, 18 (32.1%) women of the main group complained of urinary incontinence due to a strong urge to urinate (the main group before treatment – 38 (67.9%); comparison group after treatment – 36 (47.4%); p<0.05). Drop – by – drop urine loss was observed in 4 (7.1%) women (main group before treatment-28 (50.0%); comparison group after treatment-13 (17.1%); p < 0.05).
Results of determination of the average concentration of the marker of collagen synthesis and the Total P1NP type in the dynamics of treatment after 4 months show a significant increase in it by 72.8% in women who received CO2-laser therapy in combination with drug therapy (the main group before treatment-23.2±3.24 ng/mL, the main group 4 months after treatment – 40.1±4.28 ng/mL; p<0.05). 
For women of the comparison group against the background of drug therapy, we observed a significant increase in this indicator by 46.2% (comparison group before treatment – 29.2±2.66 ng/mL; comparison group 4 months after treatment – 42.7±3.16 ng/mL; p<0.05).
When re-determining the concentration of the marker of collagen synthesis and Type Total P1NP after 8 months, against the background of the use of the proposed complex, women of the main group showed a stable value of the indicator (the main group 4 months after treatment – 40.1±4.28 ng/mL; the main group 8 months after treatment – 42.7±3.61 ng/mL; p>0.05),

The positive therapeutic effect of the CO2-laser, from our point of view, is realized by influencing the etiopathogenetic mechanisms of the occurrence of the syndrome complex - an age – related imbalance of markers of connective tissue synthesis and resorption. Women who received laser treatment showed a significant increase and stable plasma concentrations of the total P1NP Type I collagen synthesis marker (baseline – 23.2±3.24 ng/mL; after 4 months – 40.1±4.28 ng/mL (p<0.05); after 8 months – 42.7±3.61 (p>0.05). An increase in the concentration of the Type I collagen synthesis marker contributed to a synergistic decrease in the concentration of the Total P3NP Type III collagen marker in women of the main group and stabilization of its value in treatment dynamics (baseline value – 29.2±2.66 ng/mL; after 4 months – 18.2±0.41 ng/mL (p<0.05); after 8 months – 21.6±0.21 (p>0.05). There was no significant difference in the concentration of the connective tissue resorption marker Pyriliks–D in women of the study group, depending on the chosen treatment.
The current data on changes of levels of connective tissue markers synthesis and resorption demonstrate the effects of laser radiation on the vaginal mucosa and activation of endogenous collagen production.

From our perspective it is promising to study the hormonal status of women with genitourinary syndrome in order to improve the tactics of etiotropic treatment and prevention of relapses.

Behnia-Willison F, Sarraf S, Miller J, et al. Safety and long-term efficacy of fractional CO (2) laser treatment in women suffering from genitourinary syndrome of menopause. Eur J Obstet Gynecol Reprod Biol. 2017; 213: 39 – 44. DOI: 10.1016/j.ejogrb.2017.03.036.
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