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Background. Genitourinary syndrome of menopause (GSM) significantly reduces the quality of life (QoL) of women, causing pain during sexual activity, worsening sexual function and relationships with a partner, and reducing self-esteem. Nearly 75% of women with GSM report a negative impact of symptoms on intimacy, and about half of them on overall life satisfaction. Aim. To assess the clinical efficacy and impact on vaginal microbiocenosis of a topical vaginal product containing Lactobacillus acidophilus and estriol in postmenopausal women with GSM. Materials and methods. The study included 34 patients diagnosed with GSM. The follow-up algorithm for these patients included several visits for examination, verification of diagnosis, and prescribing adequate therapy, followed by an assessment of the cure rate. At the first visit, patients' complaints and gynecological history were reviewed, gynecological status was assessed, samples were collected for smear microscopy and polymerase chain reaction (PCR) testing, and cytological examination and colposcopy were performed. At the second visit (after 10 days), according to the clinical and laboratory diagnostic study, all patients were diagnosed with N95.2, "Postmenopausal atrophic vaginitis" and prescribed therapy with a drug containing Lactobacillus acidophilus (lyophilisate) 50.00 mg and estriol 0.03 mg per vaginal tablet (Gynoflor E). The drug was used intravaginally in the evening at bedtime, for 12 days, then the maintenance dose was 1 vaginal tablet 2 times a week. The third and fourth visits were performed 15 and 30 days after the start of treatment, respectively (gynecological examination, microscopy, pH-metry, and cytological examination). The fifth visit of the patient was 3 months after the end of the main course of treatment during the maintenance therapy (gynecological examination, microscopy, pH-metry, PCR, cytological examination, and colposcopy). Treatment effectiveness was assessed using subjective and objective criteria, including the vaginal health index (VHI) and quantitative characteristics of the vaginal biotope, as determined by the FEMOFLOR®II test results. Results. Changes in clinical symptoms during treatment with Gynoflor E showed a statistically significant improvement in 8 subjective symptoms (complaints) and 7 objective parameters. The number of complaints (0.85) per patient decreased by 8.2 times. The VHI at the fifth visit showed no signs of severe atrophy. The severity of atrophy was moderate (47.06%) or mild (52.94%) (p 0.001), compared with the first visit, when 100.0% of patients had severe vulvovaginal atrophy. At the fifth visit, a comparative analysis of QoL using the D. Bаrlоw scale showed that GSM symptoms had become mild, i.e., did not affect daily life (100.0%), whereas at the first visit, their severity negatively affected daily life in all patients (p 0.001). The study of the vaginal biotope at the fifth visit showed that the pool of Lactobacillus spp. (lg, gEq/mL) expanded, the total proportion of which in 52.94% of patients was 61.0–100.0%. Comparative analysis of the results of vaginal biotope assessment at the first and fifth visits showed a statistically significant difference (p 0.001), indicating a reduction in the pool of opportunistic microbiota in the total vaginal biotope during topical therapy with a drug containing Lactobacillus acidophilus and estriol. Conclusion. The use of the main and maintenance courses of local therapy with a combination drug containing Lactobacillus acidophilus and estriol in patients with GSM for 3 months resulted in improvement and increased QoL on the D. Barlow. GSM symptoms became mild and had no negative impact on daily life in 100.0% of the patients.