Clinical trial NCT06873971: Effects of Erbium-Yag Laser in Women With Genitourinary Syndrome of Menopause Undergoing Estrogen Therapy
Official title: Effects of Erbium-Yag Laser in Women With Genitourinary Syndrome of Menopause Undergoing Estrogen Therapy: Randomized, Controlled, Double-Blind Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Genitourinary Syndrome of Menopause
Lead sponsor: University of Nove de Julho
Sponsor class: OTHER
First posted: 2025-03-13
Enrollment: 60
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 randomized, double-blind clinical study aims to evaluate the effects of Er:YAG laser in women with GSM undergoing isolated topical estrogen therapy. Sixty patients will be recruited and randomly assigned to two groups. All participants will receive low-dose topical estrogen for 14 days, followed by twice-weekly applications until completing three laser sessions at four-week intervals. Group 1 (Placebo) will receive the laser in off mode, while Group 2 will undergo active laser treatment.

Inclusion criteria include age 45-70 years, 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 cervical-vaginal cytology in the last six months, corticosteroid therapy within 90 days, and BMI ≥35kg/m².

Assessments will occur at baseline and at 4, 8, and 12 weeks post-treatment. The primary outcome is the Vaginal Health Index (VHI), while secondary outcomes include symptom evaluation via the Visual Analog Scale, vaginal microbiota analysis through 16S gene sequencing, pH measurement, and quality-of-life and sexual health questionnaires. Statistical analyses will be conducted using SPSS 22.0, employing repeated measures ANOVA for continuous data and the Friedman test for categorical data, with a significance threshold of p\<0.05.

The study anticipates positive outcomes from combined therapies, with superior results expected in the laser-treated group, including improved vaginal trophism, microbiota restoration, and symptom relief.

Detailed description: Chronic, progressive hypoestrogenism, without adequate treatment during the postmenopausal period, significantly affects the epithelium of the urogenital system, causing Genitourinary Syndrome of Menopause (GSM). This disorder impacts the quality of life of thousands of women, favoring the emergence of other pathologies, including increasing the risk of gynecological infections from opportunistic microorganisms due to the elevation of vaginal pH, destabilizing the natural immunological barrier. Therapies using the Erbium:YAG (Er:YAG) 2940nm laser and low-dose topical estrogen therapy have demonstrated safety and efficacy in improving vaginal trophism, being crucial for the reestablishment of appropriate flora.

This study aims to evaluate the effects of Er:YAG laser on women with GSM undergoing isolated topical estrogen therapy. This is a randomized, double-blind clinical study. Sixty patients will be recruited and randomly divided into two groups. All participants will receive low-dose topical estrogen therapy for 14 consecutive days and then twice a week until completing three sessions of laser treatment, with a 4-week interval between sessions. In Group 1 (Placebo), the laser will be applied in the off mode (Laser-off), while in Group 2, the laser will be applied in the on mode (Laser-on = Er:YAG (9J/cm² and 2Hz for the internal region and 6J/cm² and 2Hz for the external region)).

Inclusion criteria include age between 45 and 70 years, pH level ≥5, absence of hormone therapy and intimate treatments using energy for 180 days, and presence of moderate symptoms of vaginal atrophy (SCORE \>4). Exclusion criteria include altered cervical-vaginal cytology in the last six months, corticosteroid therapy within the last 90 days, and BMI ≥35kg/m².

Comparisons between the two groups will be conducted at the initial consultation and at 4, 8, and 12 weeks after the first laser session. The primary variable will be the Vaginal Health Index (VHI). Secondary variables will include the Visual Analog Scale for four symptoms of GSM (burning, irritation, dyspareunia, and persistent leukorrhea), vaginal microbiological sampling for DNA sequencing analysis using the 16S gene amplification technique, specifically at the V3/V4 region (before the first laser therapy session and 4 weeks after the third application), pH measurement, 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 the Friedman test for categorical data. A p-value \<0.05 will be considered statistically significant.

Satisfactory results are expected from the combined therapies, with superior outcomes anticipated in Group 2, including restoration of adequate vaginal trophism, reconstitution of vaginal flora, and consequent relief of symptoms.

Eligibility criteria: Inclusion Criteria:

* Women with amenorrhea present for at least 24 months.
* Women with amenorrhea for more than 12 months and FSH levels \> 30 mUI/MI and estradiol \< 30 mUI/MI, collected specifically for this research.
* Age between 45 to 70 years.
* Vaginal pH measurement \>= 5.
* Present at least one of these moderate symptoms of GSM (dyspareunia, dryness, burning, and persistent leukorrhea). Each of these will be assessed separately by the patient, according to the Visual Analog Scale (VAS) criteria, from 0 (absence of symptoms) to 10 (very severe symptoms). Moderate symptoms will be considered as values equal to or greater than 4.
* Not users of hormonal replacement therapy (oral or systemic) in the last 6 months.
* Not users of vaginal moisturizers in the last 30 days.

Exclusion Criteria:

* Vaginal treatments using energy in the last 6 months.
* Patients with altered Pap smear results with cellular changes such as ASCUS, LSIL, or HSIL in the last 6 months.
* Corticotherapy in the last 90 days.
* BMI \>= 35 kg/m².
* Abnormal uterine bleeding in the last 30 days.
* History of vaginal surgeries in the last 180 days or uterine prolapse Grade II or higher.
* Patients with a prior diagnosis of malignant neoplasms of any nature or currently undergoing treatment; prior vaginal radiotherapy, severe liver and kidney diseases already diagnosed by previous tests, autoimmune diseases, and severe psychiatric disorders.

Primary outcomes:
measure: Analysis of the Vaginal Health Index (VHI)
timeFrame: Day 1, 30 days after, 60 days after and 90 days after
Secondary outcomes:
measure: Vaginal Microbiome
timeFrame: Day 1 and 90 days after
measure: Visual Analog Scale (VAS)
timeFrame: Day 1, 30 days after, 60 days after and 90 days after
measure: Vaginal pH Measurement
timeFrame: Day 1, 30 days after, 60 days after and 90 days after
measure: Quality of Life Evaluation Questionnaires: Menopause Rating Scale (MRS)
timeFrame: Day 1, 30 days after, 60 days after and 90 days after
measure: Female Sexual Function Index (FSFI)
timeFrame: Day 1, 30 days after, 60 days after and 90 days after
Other outcomes:
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