Er:YAG Laser Combined With Vaginal Estriol for Genitourinary Syndrome of Menopause

NCT ID: NCT06873971

Last Updated: 2026-01-21

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-10
• Study Completion Date: 2026-12-31

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 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.

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 assess the effects of combining Er: YAG laser therapy with vaginal estriol compared with estriol therapy alone in postmenopausal women with GSM. This is a randomised, double-blind clinical study. Sixty patients will be recruited and randomly divided into two groups. All participants will receive low-dose topical estrogen therapy (vaginal estriol cream (1 mg/g) administered intravaginally using disposable applicators pre-set to deliver 0.5 g per application (equivalent to 0.5 mg of estriol per dose) for 14 consecutive days and then twice weekly until completing three sessions of laser treatment, with a 4-week interval between sessions. In Group 1 (Sham), the laser will be applied with minimal fluence (0.5 J/cm²) to maintain blinding (auditory cues) below the threshold for biological tissue, while in Group 2, will be applied an active Er:YAG laser intervention. The intimate laser session consists of two stages: the internal stage ( vaginal canal) with energy settings of 9J/cm² at 2Hz and the external stage (vulvar and vestibule region) with energy settings of 6J/cm² at 2Hz.

Inclusion criteria include age between 45 and 70 years, vaginal 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 Baseline, 30 days after each laser session and 4 months after the third laser application. The primary outcome will be the Vaginal Health Index (VHI). Secondary outcomes 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), quality of life, and sexual health questionnaires.

Data will be collected using coded identifiers and stored on a secure, password-protected institutional server with restricted access. Regular data backups will be performed. Only authorised members of the research team will have access to identifiable data. De-identified data may be shared upon reasonable request, subject to ethical approval and data-sharing agreements.

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.

Conditions

Genitourinary Syndrome of Menopause

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

GROUP 1 (Vaginal estriol plus Sham Er:YAG laser (minimal fluence))

All participants will receive vaginal estriol therapy combined with Er:YAG laser intervention with minimal fluence (0.5 J/cm²), below the threshold for biological tissue effect, applied to maintain participant blinding through auditory and procedural cue. Participants will undergo three laser applications at four-week intervals. 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 (vulvar and vestibule region) with energy settings of 0.5J/cm² at 2 Hz.

Group Type: SHAM_COMPARATOR

Topical estrogen therapy based on estriol (E3)

Intervention Type: DRUG

All 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.

Sham Er:YAG laser (minimal fluence)

Intervention Type: RADIATION

All 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.

GROUP 2 ( Vaginal estriol plus active Er:YAG laser)

All participants will receive vaginal estriol therapy combined with an active Er:YAG (λ = 2940 nm) . Participants will undergo three laser applications at four-week intervals. 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.

Group Type: ACTIVE_COMPARATOR

Topical estrogen therapy based on estriol (E3)

Intervention Type: DRUG

All 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

Intervention Type: RADIATION

All 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.

Interventions

Topical estrogen therapy based on estriol (E3)

All 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.

Intervention Type: DRUG

Active Er:YAG Laser

All 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.

Intervention Type: RADIATION

Sham Er:YAG laser (minimal fluence)

All 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.

Intervention Type: RADIATION

Other Intervention Names

Estriol ( E3); Vaginal estriol ( E3); Laser On; Laser in Active Intervention Mode; Laser in Minimal Fluence

Eligibility Criteria

Inclusion Criteria

• 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.
• No use of vaginal moisturizers in the previous 30 days.
• Demonstrated capacity and willingness to provide written informed consent and adhere to study protocols.

Exclusion Criteria

• 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.
• Presence of abnormal uterine bleeding in the previous 30 days.
• History of vaginal surgery in the previous 180 days or grade II or higher uterine prolapse (POP-q).
• History of malignant neoplasms or exposure to vaginal radiotherapy.
• Diagnosis of severe liver or kidney disease, autoimmune disease, or severe psychiatric disorder.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

University of Nove de Julho

OTHER

Sponsor Role: lead

Responsible Party

Stella Regina Zamuner

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Universidade Nove de Julho

São Paulo, São Paulo, Brazil

Site Status: RECRUITING

Countries

Brazil

Central Contacts

Stella Zamuner

Role: CONTACT

stella.rz@uni9.pro.br

+55 11 3385-9241

Facility Contacts

Stella Regina Zamuner, pHD, MD

Role: primary

stella.rz@uni9.pro.br

+551133859241

Other Identifiers

ERBIUM-YAG-LASER

Identifier Type: -

Identifier Source: org_study_id