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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Analysis of the Vaginal Health Index (VHI)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Care Provider)
入排标准
- 年龄范围
- 45 Years 至 70 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
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 (vestibule and introitus region) with energy settings of 0.5J/cm² at 2 Hz.
干预措施: Topical estrogen therapy based on estriol (E3) (Drug)
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 (vestibule and introitus 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.
干预措施: Topical estrogen therapy based on estriol (E3) (Drug)
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 (vestibule and introitus region) with energy settings of 0.5J/cm² at 2 Hz.
干预措施: Sham Er:YAG laser (minimal fluence) (Radiation)
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 (vestibule and introitus 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.
干预措施: Active Er:YAG Laser (Radiation)
结局指标
主要结局
Analysis of the Vaginal Health Index (VHI)
时间窗: Baseline, 30 days after each laser session and 4 months after the third laser application.
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.
次要结局
- 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.)
研究者
Stella Regina Zamuner
Principal Investigator
University of Nove de Julho