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

NCT06873971 | Recruiting

• 1 other identifier: ERBIUM-YAG-LASER
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Genitourinary Syndrome of Menopause

Keywords

Genitourinary syndrome of menopause; postmenopausal women; Erbium: YAG laser; vaginal microbiome; vaginal estriol

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, 30 days after each laser session and 4 months after the third laser application.

Secondary Outcomes (4)

• Vaginal Microbiome

  Before first laser session and four weeks after the third laser application.

• Visual Analog Scale (VAS)

  baseline, 30 days after each laser session and four months after the third laser application

• Quality of Life Evaluation Questionnaires: Menopause Rating Scale (MRS)

  Baseline, 30 days after each laser session and 4 months after the third laser application.

• Female Sexual Function Index (FSFI)

  Baseline, 30 days after each laser session and 4 months after the third laser application.

Study Arms (2)

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

SHAM COMPARATOR

All participants will receive vaginal estriol therapy combined with Er:YAG laser intervention with minimal fluence (0.5 J/cm²), below the therapeutic range reported for GSM, and not expected to induce clinically meaningful tissue effects, 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.

Drug: Topical estrogen therapy based on estriol (E3); Radiation: Sham Er:YAG laser (minimal fluence)

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

ACTIVE COMPARATOR

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.

Drug: Topical estrogen therapy based on estriol (E3); Radiation: Active Er:YAG Laser

Interventions

Sham Er:YAG laser (minimal fluence) 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.

Also known as: Laser in Minimal Fluence

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

Topical estrogen therapy based on estriol (E3) 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.

Also known as: Estriol ( E3), Vaginal estriol ( E3)

GROUP 1 (Vaginal estriol plus Sham Er:YAG laser (minimal fluence)); GROUP 2 ( Vaginal estriol plus active Er:YAG laser)

Active Er:YAG Laser 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.

Also known as: Laser On, Laser in Active Intervention Mode

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

Eligibility Criteria

• Age: 45 Years - 70 Years
• Gender Eligibility Details: Postmenopausal women
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Nove de Julho: lead

Study Sites (1)

Universidade Nove de Julho

São Paulo, São Paulo, 01525-000, Brazil

RECRUITING

MeSH Terms

Interventions

Estriol; Lasers

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Optical Devices; Equipment and Supplies; Radiation Equipment and Supplies

Central Study Contacts

Stella Zamuner

CONTACT

+55 11 3385-9241; stella.rz@uni9.pro.br

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 21, 2025
• First Posted: March 13, 2025
• Study Start: December 10, 2025
• Primary Completion (Estimated): November 10, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Data will be available immediately following publication and will remain accessible for five years thereafter.
• Access Criteria: Data will be shared with researchers who provide a methodologically sound proposal for its use, subject to approval by the study investigators. Access may require the signing of a data access agreement.

Locations

BR (1)