Evaluation of Fractional CO2 Laser Treatment Efficacy and Comparison to Vaginal Estrogen Therapy in Postmenopausal Women With Vulvovaginal Atrophy

Study Overview
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Brief Summary
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Forty-five women will be included in a double-blind randomized trial in order to compare fractional CO2 laser treatment, local estrogen therapy and the combination of both treatments for Vulvovaginal Atrophy (VVA) and determine the efficacy and possible adverse effects CO2 laser treatment.

Detailed Description
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Vulvovaginal atrophy (VVA) symptoms are strongly associated with declining ovarian function and estrogen levels in postmenopausal women, having a considerable impact on women's life quality. Topical hormonal therapy and hormonal replacement are widely used to alleviate VVA symptoms. In this context, minimal invasive fractional CO2 laser emerges as an alternative non-hormonal therapy, especially in patients that present contraindications to hormonal therapy. Objective: Compare fractional CO2 laser treatment, local estrogen therapy and the combination of both treatments for VVA and determine the efficacy and possible adverse effects CO2 laser treatment. Materials and Methods: Forty-five postmenopausal women will be randomized in three double-blinded groups of treatment consisting of CO2 laser and placebo of estrogen vaginal cream, placebo of CO2 laser and estrogen vaginal cream and CO2 laser and estrogen vaginal cream. Assessment of baseline characteristics and follow-up will be obtained through self-completion questionnaires (Female Sex Function Index, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), Vulvovaginal Symptom Questionnaire and The Menopause-Specific Quality of Life (MENQOL)). Frost Index and Vaginal Health Index (VHI) are part of objective clinical and histologic analyses. Colposcopy, vaginal cytology and middle third lateral vaginal wall biopsy will also be performed at baseline and at week 17.

Official Title
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Evaluation of Fractional CO2 Laser Treatment Efficacy and Comparison to Vaginal Estrogen Therapy in Postmenopausal Women With Vulvovaginal Atrophy

Conditions
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Vulvovaginal Atrophy

Intervention / Treatment
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* Device: CO2 laser
* Drug: Estrogen
* Drug: Placebo of Estrogen
* Device: Placebo of CO2 laser


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 45-65 women with amenorrhea for over 24 months. Clinical vaginal atrophy diagnosis. Exclusion Criteria: BMI > 35. Previous use of oral estrogen therapy in the last 6 months. History or current diagnosis of cancer. Altered cervical smear in the last 12 months. Renal or hepatic insufficiency. Drug-induced menopause. Previous use of steroids. Previous vaginal radiotherapy therapy. Vulvovaginitis.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CO2 laser & Estrogen<br>Effective fractional CO2 laser therapy and effective estrogen vaginal cream | Device: CO2 laser<br>* SMARTXIDE2 V2LR (DEKA-Pulse) was used in each application using minimal parameters suggested by the laser's software ( Power of 30 W, 1000us emission time, 1000um spacing and a level of SmartStack 2)<br>* Other names: Fractionated CO2 laser;Drug: Estrogen<br>* Topical estrogen cream treatment: Estriol 1mg daily.<br>* Other names: Estriol 1mg;|
| Active Comparator: CO2 laser & Placebo of Estrogen<br>Effective fractional CO2 laser therapy and placebo of estrogen vaginal cream. | Device: CO2 laser<br>* SMARTXIDE2 V2LR (DEKA-Pulse) was used in each application using minimal parameters suggested by the laser's software ( Power of 30 W, 1000us emission time, 1000um spacing and a level of SmartStack 2)<br>* Other names: Fractionated CO2 laser;Drug: Placebo of Estrogen<br>* Placebo of topical estrogen cream.<br>|
| Sham Comparator: Placebo of CO2 laser & Estrogen<br>Placebo fractional CO2 laser therapy and effective estrogen vaginal cream. | Drug: Estrogen<br>* Topical estrogen cream treatment: Estriol 1mg daily.<br>* Other names: Estriol 1mg;Device: Placebo of CO2 laser<br>* SMARTXIDE2 V2LR (DEKA-Pulse) was used in each applications using minimal parameters suggested by the laser's software but power of 0.5 W was stipulated for the placebo intervention and other parameters remained unchanged.<br>* Other names: SMARTXIDE2 V2LR - Monalisa Touch - Deka Laser;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Vulvovaginal Symptom Questionnaire | Vulvovaginal Symptom Questionnaire will be used to evaluate improvement of vulvovaginal atrophy symptoms. | Baseline, week 10 and week 17 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaginal Cytology Improvement | Vaginal cytology will be obtained from the middle third lateral vaginal wall in order to evaluate initial conditions of the vaginal wall and modifications after treatment. Frost Index, Karyopyknotic Index and Eosinophilic Index will be applied to each sample to measure improvement of vaginal atrophy. | Baseline, week 10 and week 17 | 
| Change from Baseline in Female Sex Function Index | Female Sex Function Index will be used to evaluate improvement of vulvovaginal atrophy symptoms. | Baseline, week 10 and week 17 | 
| Change from Baseline in The Menopause-Specific Quality of Life | The Menopause-Specific Quality of Life will be used to evaluate improvement of vulvovaginal atrophy symptoms. | Baseline, week 10 and week 17 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vulvovaginal atrophy, Menopause, Fractional CO2 laser, Estrogen cream