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

Официальное название

Effects of Erbium:YAG Laser Combined With Vaginal Estriol Therapy in Postmenopausal Women With Genitourinary Syndrome of Menopause: A Protocol for a Randomised, Double-blind Controlled Trial

Обзор

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.

Подробное описание

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.

The Vulvovaginal Health Index (VHI) is defined as the primary outcome of this study. 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.

Comparisons between the two groups will be conducted at Baseline, 30 days after each laser session and 4 months after the third laser application. Although data will be collected at multiple time points using validated instruments and laboratory assessments, the primary analysis will focus on predefined time points. Specifically, comparisons will be conducted between baseline and two post-intervention time points: (1) at the third laser session and (2) at follow-up, defined as four months after the third laser session.

Data will be collected using coded identifiers and stored on a secure, password-protected institutional server with restricted access. Regular data back-ups will be performed. Access to identifiable data will be limited to authorised members of the research team. De-identified data will be made available upon reasonable request, subject to appropriate ethical approval and the completion of a data sharing agreement. Further details are available via the study repository on the Open Science Framework (OSF): https://osf.io/dwgvx/.

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.

Вмешательства

• Препарат 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
• Лучевая терапия 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.
• Лучевая терапия 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

Первичные конечные точки

• Analysis of the Vaginal Health Index (VHI) [Срок оценки: Baseline, 30 days after each laser session and 4 months after the third laser application.]

Вторичные конечные точки (4)

• Vaginal Microbiome [Срок оценки: Before first laser session and four weeks after the third laser application.]
• Visual Analog Scale (VAS) [Срок оценки: baseline, 30 days after each laser session and four months after the third laser application]
• Quality of Life Evaluation Questionnaires: Menopause Rating Scale (MRS) [Срок оценки: Baseline, 30 days after each laser session and 4 months after the third laser application.]
• Female Sexual Function Index (FSFI) [Срок оценки: Baseline, 30 days after each laser session and 4 months after the third laser application.]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Бразилия · 1 центр

• Universidade Nove de Julho — São Paulo

Публикации

• Souza MCDCD, de Jarmy-Di Bella ZIK, Bianchi-Ferraro AMHM, Souza SDL, Amanda Rafaelly Honorio M, Sobral APT, Ribeiro CDPV, Bussadori SK, Fernandes KPS, Chavantes MC, Zamuner SR. Effects of Erbium:YAG laser combined with vaginal estriol therapy in postmenopausal women with Genitourinary Syndrome of Menopause: protocol for a randomised, double-blind, controlled trial. BMJ Open. 2026 Jun 11;16(6):e117 PMID 42276807

Идентификаторы

NCT: NCT06873971 · ERBIUM-YAG-LASER

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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