Treatment for Vaginal Atrophy Using Microablative Fractional CO2 Laser

A Randomized Double-Blinded Sham-Controlled Trial

Purim Ruanphoo, MD; Suvit Bunyavejchevin, MD, MHS

Disclosures

Menopause. 2020;27(8):858-863. 

In This Article

Methods

From June 2016 to May 2017, a prospective randomized controlled trial was conducted at the Gynecology Clinic, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. This study was approved by the Research Ethics Committee of the Faculty of Medicine, Chulalongkorn University on March 31, 2016 (COA No. 276/2016). The study was registered in the Thai Clinical Trial Registry (No. TCTR20160627002).

Participants

Postmenopausal women (aged at least 50 years and had their last menstruation at least 1 year ago) with any VAS (moderate to severe intensity) were invited to participate in the study. Details of the study protocol, nature of the randomized trial, benefit, and risk of participating in the study were provided to the participants before enrollment. Written informed consent was obtained from all participants before enrollment. Women who had any history of hormonal therapy within the past 6 months, vaginal moisturizer or lubricant applications within the past 30 days, acute/recurrent urinary tract infection, or active genital infection were excluded from the study. In addition, if the participant was found to have a genital hiatus diameter of less than 2 cm (smaller than the vaginal probe size) or have pelvic organ prolapse stage 2 or higher according to pelvic organ prolapse quantification system classification,[16] they were also excluded.

Study Protocol

Participants were randomized to either the laser group or the sham group (1:1 ratio). Simple randomization was generated by the computer. Allocation concealment of the generated codes was kept in opaque, sealed envelopes. The envelopes were opened by a research assistant at the first visit before initiating treatment. Demographic data and detailed medical history of all participants were collected including age, age at menopause, parity, type of delivery, history of vaginal reconstructive surgery, history of hormonal treatment, and sexual activity status. All participants were scheduled for four visits (V1, V2, V3, and V4) with a 4-week interval.

At each visit (V1, V2, V3, and V4), the participants were interviewed to assess the intensity of VAS using the VAS score.[17] Signs of vaginal atrophy were evaluated during pelvic examination using a validated tool—VHI score[18] by an investigator (S.B.) who was blinded to the participant's treatment. All participants were asked to answer item number 7 of the Thai-version International Consultation on Incontinence Modular Questionnaire-Vaginal Symptoms (ICIQ-VS) questionnaire[19] to assess vaginal atrophy. After pelvic examination and completion of the questionnaire, the interventions were performed. The participants received the interventions in the first three visits (V1, V2, and V3). Laser or sham treatment was performed by an investigator (P.R.) who did not know the clinical outcomes of the treatment. In the last visit (V4), the study assessed the participants' satisfaction with the treatment and any adverse events they experienced during the study period.

Vaginal Microablative Fractional CO2 Laser Treatment

The participants in the laser treatment group received the intervention by using the CO2 laser machine (SmartXide2 V2LR, DEKA, Florence, Italy). The laser settings were DEKA pulse mode, dot power 40 W, dwell time 1,000 ms, dot spacing 1,000 μm, and the smart stack parameter from 1 to 3. In the lithotomy position, the vaginal laser probe was inserted into the total length of the vagina and subsequently withdrawn 0.5 cm following each laser beam application until the distal end of the vaginal probe reached the introitus. The laser application was performed on an outpatient basis without local anesthesia. Participants were advised to avoid sexual intercourse or intravaginal devices for at least 3 days after the procedure owing to transient local inflammation at the vaginal mucosa generated by the laser application.

Sham Procedure

Sham procedure was defined as a procedure mimicking the laser procedure without using the laser. Vaginal probe was inserted and withdrawn in the same manner as the laser treatment while the participants were in lithotomy position. Postprocedural recommendation was similar to the women who received the laser treatment.

Outcome Measurements

The primary outcome was VHI score. The secondary outcomes were VAS score, score for the item for vaginal dryness (from ICIQ-VS questionnaire), participant's satisfaction with the procedures, and adverse events after the interventions. The outcome measurements were defined as follows.

Vaginal Atrophy Symptoms Score. VAS score in this study was modified from Davila et al's study.[17] We assessed four domains of VAS: dryness, irritation, soreness, and dyspareunia. The intensity of each domain was graded as none (0), mild (1), moderate (2), or severe (3). The total VAS score was calculated by the sum of these individual symptom scores divided by 4 for sexually active participants. For those participants who were not sexually active, the sum of individual symptom scores were divided by 3. Higher scores represent more severity of VAS.

Vaginal Health Index Score. VHI score determines the severity of five signs of vaginal atrophy: elasticity, fluid volume, pH, epithelial integrity, and moisture. Each sign is rated from one to five. Summation of these scores represents the total VHI score which ranges from 5 to 25. High scores indicated less severity of vaginal atrophy.[18]

Vaginal Dryness Score of International Consultation on Incontinence Modular Questionnaire-vaginal Symptoms Questionnaire. ICIQ-VS questionnaire is a self-completed tool to assess the severity and impact of vaginal symptoms including vaginal atrophy. It has been translated and validated in the Thai language. The questionnaire consists of 14 items divided into 3 domains: vaginal symptoms, sexual matter, and quality of life. We chose item number 7 which provides information regarding vaginal dryness to assess for the symptom of vaginal atrophy.[19]

Adverse Events. At the last visit (V4), all participants were asked about any adverse events after the interventions (eg, vaginal bleeding, discharge, vaginitis, pain after the procedure was done, and de novo dyspareunia).

Participant's Satisfaction. At the last visit (V4), the participants were asked to answer a self-completed satisfaction questionnaire. The questionnaire used a five-point Likert scale (ie, very dissatisfied, dissatisfied, neutral, satisfied, and very satisfied) to assess the participant's satisfaction with the intervention.

Sample Size Calculation

The sample size calculation was based on the primary efficacy variable (VHI score), a 5% level of significance (two-sided), and a power of 80% were assumed. Previously, we conducted a pilot study so that the results obtained from that study were used to calculate the sample size for this trial. Data from our pilot study showed mean ± SD of VHI after 12 weeks of laser treatment was 20.5 ± 4.5 and mean ± SD of VHI after 12 weeks of no laser treatment was 18 ± 2.8. With 1:1 ratio, a sample size of 44 women per group was required taking into account a 20% dropout rate.

Statistical Analysis

For baseline characteristics, categorical data were presented as number and percentage. Continuous data were presented as mean and standard deviation or median and interquartile range as appropriate. Intention-to-treat (ITT) analysis was used for primary outcome. When comparing the outcomes between pretreatment and posttreatment, paired t test or Wilcoxson sign rank test was used for continuous data. To compare outcomes between groups, continuous data were analyzed using unpaired t test or Mann-Whitney U test and categorical data were analyzed using chi-square test.

When there were missing data for any baseline characteristic variables, those participants would be excluded from the analysis. When outcome variables were missing, multiple imputation was used by regressing the outcomes on the other observed data using a linear regression model because we assessed the outcomes at multiple time points. All data were analyzed using SPSS software version 22.0 (SPSS science, Chicago, IL) for Windows. P value less than 0.05 was considered statistically significant.

Our statistical analysis plan did not include a plan for managing confounding variables on the primary outcome. Data from baseline characteristics demonstrated that sexually active lifestyle was different between the two groups. There is evidence that sexual function may relate to vaginal atrophy,[20–22] so we performed analysis of covariance to control the confounding effect of the sexually active variable.

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