Title: INTRAVAGINAL NONABLATIVE RADIOFREQUENCY IN THE TREATMENT
OF GENITOURINARY SYNDROME OF MENOPAUSE SYMPTOMS: A SINGLE-ARM
PILOT STUDY
Version: 4 Date: 26 Mar 2021
Reviewer's report:
Dear Authors,
Congratulations on the chosen theme. Radiofrequency has a good potential to be an alternative
as a complementary treatment for genitourinary syndrome of menopause. I wish you much
success in your future randomized controlled trial as it will add important value to evidence-
based physiotherapy. Please find my suggestions and questions below:
Title: I would suggest a slight change in your study title. Instead of “…: a phase I clinical trial”,
I would suggest “… : a single-arm pilot study. I believe this better describes your study design.
Introduction:
Page 4: I would suggest removing the introduction hypothesis. The hypothesis test is
not recommended in pilot studies due to the limited size of the proposed sample, being
underpowered for this purpose.
Materials and Methods:
Page 4: Please also inform the date of the IRB approval.
Page 4: In the last line of page 4 you wrote: “… and a negative preventive measure for
malignancy…”. Please clarify this sentence. What is this preventive measure for malignancy?
Page 4: You did not perform randomization in your single-arm study. It would be informative if
you could add a sentence justifying the absence of the randomization process, even though you
are not focused on estimates the effectiveness of radiofrequency in your pilot study.
Page 4: I would suggest adding that the procedures and assessments were conducted by
physiotherapists instead of evaluators.
Page 5: Please consider providing more details of the VMI.
Page 6: Please provide citations for the following instruments: FSFI, QS-F, ICIQ-SF, and 5-
point Likert Scale.
Page 7: In the second paragraph on page 7 you described the adverse events. How often and how
were they evaluated? Were these patients referred for treatment? Were they excluded from the
study? The sentence ‘We considered it high risk if it had 4 or more effects” needs clarification.
It is not clear when you considered suspending treatment after these adverse events appeared.
They are quite serious if you think of ulcers, fistulas, bleeding, etc. Consider clarifying damage
management in your study.
Results:
Page 9: The sentence “In the third month, there was also a predominance of maintain the initial
state” is not clear. Please clarify it.
Page 10: “six patients had pre-treatment urinary complaints.” Which treatment did they receive?
Those treatments could influence the UI results of your future study (source of bias?). Please
discuss this.
Table 1: In table 1 you reported that 6 patients were sexually inactive. It is not clear how 8
patients presented sexual dysfunction. How did you measure this in FSFI for example?
Table 2: It is also not clear how did you record these symptoms (VD, VL, VI, B, etc.)? Did you
use a questionnaire? Was it an interview? Please clarify this. Please clarify this. Please correct
the table 2 legend (“burni”).
Discussion:
Page 22: Include a section of limitations in your discussion, addressing issues related to the
worsening of patient 5 in the IMV and two other patients (18.2%) who had a reduction in the VH
index. Two other patients (Were they the same for VHI?) got worse on VMI. Sexual function
worsened in two moments in patient 11. And, finally, two patients (33.3%) increased the ICIQ-
SF score. How can you overcome these limitations in your future main RCT?
Page 22: How would this pilot study help your research team to plan their future definitive RCT?
I would suggest including only sexually active women in your future study, if you plan to assess
sexual function.