Chronic hypoestrogenism in postmenopausal women significantly impacts the urogenital epithelium, leading to Genitourinary Syndrome of Menopause (GSM) and increasing susceptibility to gynecological infections due to vaginal pH elevation. Therapies using the Erbium:YAG (Er:YAG) 2940nm laser and low dose topical estrogen have demonstrated efficacy in improving vaginal trophism and restoring microbiota balance.
This randomised, double-blind clinical study aims to assess the effects of combining Er: YAG laser therapy with vaginal estriol compared with estriol therapy alone in postmenopausal women with GSM. Sixty patients will be recruited and randomly assigned to two groups. All participants will receive low-dose topical estrogen therapy (estriol cream ) for 14 days, followed by twice-weekly applications until completing three laser sessions at four-week intervals. Group 1 (Sham) will receive the laser with minimal fluence (0.5J/cm²) applied to maintain blinding (auditory cues) below the threshold for biological tissue, while Group 2 , will undergo active laser treatment.
Inclusion criteria include age 45-70 years, vaginal pH ≥5, absence of hormone therapy or energy-based intimate treatments for 180 days, and moderate vaginal atrophy symptoms (SCORE \>4). Exclusion criteria include abnormal cervicalvaginal cytology in the last six months, corticosteroid therapy within 90 days, and BMI ≥35kg/m².
Assessments will occur at Baseline, 30 days after each laser session and 4 months after the third laser application. The primary outcome is the Vaginal Health Index (VHI), while secondary outcomes include GSM symptom evaluation via the Visual Analog Scale, vaginal microbiota analysis through 16S gene sequencing, and quality-of-life and sexual health questionnaires. Statistical analysis of the groups will be performed using SPSS version 22.0. For analytical statistics, repeated measures ANOVA will be used for continuous data, and non-parametric tests for repeated measures, such as the Friedman test, when appropriate. A p-value \<0.05 will be considered statistically significant.
Postmenopausal women (45-70 years of age).
At least one of moderate symptom of GSM (vaginal dryness, burning sensation, dyspareunia, and persistent leukorrhea), defined by ≥ 4 on Visual Analog Scale (VAS) ranging from 0 to 10.
Vaginal pH ≥5.0 at baseline assessment.
Not having undergone hormone replacement therapy (vaginal or systemic) in the previous six months.
Vaginal or vulvar energy-based interventions (e.g., laser, radiofrequency) in the previous six months.
Abnormal cervical cytology, specifically ASCUS, LSIL, or HSIL, documented in the previous six months.
Systemic corticosteroid therapy administered in the previous 90 days.
Body mass index (BMI) ≥35 kg/m².
Parallel
Topical estrogen therapy based on estriol (E3)
DrugAll participants will use low-dose Vaginal estriol cream (1 mg/g) administered intravaginally using disposable, individualized vaginal applicators pre-set at the recommended dosage of 0.5g/ per application (equivalent to 0.5 mg of estriol per dose). Induction phase: 0.5 g once daily at bedtime for 14 consecutive days. Maintenance phase: 0.5 g twice weekly for 16 weeks, on Mondays and Thursdays. The treatment will be provided in fractions for each 30 day period and will always be delivered after each laser session, along with a leaflet containing usage, storage, and application instructions for the vaginal cream. The patients will be monitored through a messaging app, reinforcing the instructions and the days of application correctly.
Active Er:YAG Laser
RadiationAll participants in the group will undergo 3 applications of active Er:YAG laser with an interval of 4-5 weeks between them. The intimate laser session consists of two stages using a PS03 fractional tip: the internal stage (vaginal canal) with energy settings of 9 J/cm² at 2 Hz, and the external stage (vulvar and vestibule region) with energy settings of 6 J/cm² at 2 Hz.The laser device to be used is the Smooth XS Dynamics Dualis (FOTONA, Ljubljana, Slovenia) with a wavelength of 2940 nm.
Sham Er:YAG laser (minimal fluence)
RadiationAll participants in the group will undergo 3 sham applications of Sham Er:YAG laser intervention delivered at minimal fluence (0.5 J), below the threshold for biological tissue effect, applied to preserve participant blinding through auditory and procedural cues , with an interval of 4-5 weeks between them. The intimate laser session consists of two stages using a PS03 fractional tip: the internal stage (vaginal canal) with energy settings of 0.5 J/cm² at 2 Hz, and the external stage (vestibule and introitus region) with energy settings of 0.5 J/cm² at 2 Hz.The laser device to be used is the Smooth XS Dynamics Dualis (FOTONA, Ljubljana, Slovenia) with a wavelength of 2940 nm.
Analysis of the Vaginal Health Index (VHI)
Clinically assesses the degree of genital atrophy through physical examination, which analyzes "urogenital health." This is useful for the longitudinal follow-up of patients, where changes occurring in the genitourinary tract are noted, including the analysis of the need for therapeutic intervention. The parameters analyzed are: total elasticity, type and consistency of fluid secretion, Vaginal pH, epithelial mucosa, and moisture, which, according to their characteristics, receive scores from 1 to 5. The lower the score, the greater the degree of urogenital atrophy. Vaginal pH will be assessed as an integral component of the Vaginal Health Index and will not be analysed as a separate outcome measure.
Vaginal Microbiome
The analytical methodology involves sequencing the 16S rRNA gene (V3/V4) after DNA extraction using the "ZymoBIOMICS DNA Miniprep" kit, following the manufacturer's guidelines provided by "Biomehub Research and Development S.A." For bacterial identification, library preparation will be performed through amplification of the V3/V4 regions (341F and 806R) using a two-step PCR. The first PCR employs universal oligonucleotides for the V3/V4 region, while the second incorporates sequencing indexes. Sample collection will be conducted individually by the responsible researcher before the first laser session and four weeks after the third application. Statistical evaluations will include descriptive analysis, alpha diversity, beta diversity, and differential abundance between groups. Samples will be stored for three months and subsequently discarded by the contracted laboratory, adhering to the manufacturer's recommendations.
Visual Analog Scale (VAS)
Four types of symptoms of GSM (dryness, burning, dyspareunia, and chronic leukorrhea) will be evaluated separately by the patient according to the VAS criteria, ranging from 0 (absence of symptoms) to 10 (very severe symptoms). Moderate symptoms will be considered with values equal to or greater than 4.
Quality of Life Evaluation Questionnaires: Menopause Rating Scale (MRS)
Used to assess quality of life and symptoms related to climacteric. It consists of 11 questions distributed to analyze three parameters: somato-vegetative symptoms, psychological symptoms, and urogenital symptoms, which are classified into five degrees: none, mild, moderate, severe, and extremely severe. The higher the score, the greater the severity of the symptoms and, consequently, the worse the quality of life for the woman during the climacteric.
Female Sexual Function Index (FSFI)
A tool used to evaluate female sexual response, based on the analysis of six domains: sexual desire, sexual arousal, vaginal lubrication, orgasm, sexual satisfaction, and pain. This assists in understanding how various factors, including health, relationships, and psychosocial factors, influence sexual satisfaction.
Click on the lead sponsor to view all of their trials.
