Comparative Study: Vaginal Promestriene Use, Fractional CO2 LASER and Radiofrequency in the Vaginal Atrophy Treatment

Comparative Study : The Effect of Vaginal Estrogen Use, Fractional CO2 LASER and Microablative Fractional Radiofrequency in the Treatment of Vaginal Atrophy: Clinical, Histological, Immunohistochemical and Molecular Biology Study

Postmenopausal hypoestrogenism may determine genital atrophy, which may be accompanied by a non-specific inflammatory process and may hinder or even prevent sexual intercourse. In more severe cases, the patient may have local pain that interferes with their daily activities. The best treatment for increasing genital trophism is still estrogen. However, there are women who can not use this therapy or do not want it. Therefore, there is a need for alternatives, such as ablation techniques: use of CO2 LASER and fractional radiofrequency.

The study was carried out at the outpatient clinic of Lower Genital Tract ambulatory of the Discipline of Gynecology, Department of Obstetrics and Gynecology, Clinical Hospital, Faculty of Medicine, University of São Paulo, involving 75 women who were divided after randomization in three groups:

Group 1 - treatment with topical vaginal promestriene (n = 25 patients); Group 2 - treatment with fractional CO2 LASER (n = 25 patients); Group 3 - fractional microablative radiofrequency treatment (n = 25 patients).

An evaluation of the complaints were be performed through questionnaires on sexuality, quality of life and urinary incontinence, as well as biopsies of the vaginal wall for histomorphometric, immunohistochemical and molecular biology study before and after six months of treatment. The duration of the study were fifteen months.

Study Overview

• Status: Completed
• Conditions: Vaginal Atrophy
• Intervention / Treatment: Other: Fractional CO2 LASER; Other: Microablative Fractional radiofrequency; Drug: Promestriene Vaginal

Detailed Description

After completing the eligibility criteria, patients signed the consent inform.

Division of groups:

Were included in the study 75 patients, divided into three groups:

Group 1 - Treatment with topical vaginal promestriene - 25 patients in this group were included patients free of systemic or topical hormonal treatment for at 3 months

Group 2 - Treatment with CO2 LASER - 25 patients, in this group were included patients free of systemic or topical hormonal treatment for at 3 months.

Group 3 - Treatment with microablative fractionated radiofrequency - 25 patients in this group were included patients free of systemic or topical hormonal treatment for at least 3 months.

The present study was open and randomized. The randomization was be performed through the software "Test Generator Software Standard Edition"

At the first visit, all patients responded to the clinical questionnaire of female sex quotient (QS-F), the quality of life questionnaire (SF-36) and the urinary incontinence questionnaire.

All patients were submitted to specular gynecological examination to collect cervical-vaginal cytology, biopsy of 1/3 proximal vaginal wall for histological analysis and immunohistochemistry.

After the results of the examinations and possible treatments required, the patients were referred for the proposed treatments according to their randomized group.

Sampling Cytology :Cervical and vaginal oncology cytology were collected through a smear on a slide with fixative.

The histological expression of the following immunohistochemical parameters will be evaluated:

• Presence and density of estrogen receptors
• Vascular density
• Thickness of the epithelium
• Density of collagen fibers
• Vaginal microbiota
• Vaginal pH

In this study, it will be done a Morphological Analysis, a Histomorphometric analysis and e Immunohistochemical analysis.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • São Paulo, Brazil, 01246-100
    • Disciplina de ginecologia - departamento de ginecologia e obstetrícia - faculdade de medicina da USP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

Age equal or superior to 40 years and under 65 years

• Clinical menopause - last menstrual period from 1 to 5 years from the date of recruitment
• FSH measurement> 25 IU / ml, estrogen <20 æg / ml
• Patients with vaginal atrophy and clinical and / or sexual symptoms
• Patients without hormonal treatment for at least five years

Exclusion Criteria:

• Whole Hymen

  • Altered oncology cytology of the cervix and / or vagina
  • Vaginal infections
  • Connective tissue diseases
  • Immunosuppression
  • Coagulation change
  • Diabetes Mellitus
  • Thyroid diseases
  • Use of systemic or local feminine hormones
  • Use of other substances with estrogenic properties

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Fractional CO2 LASER; Vaginal fractional CO2 LASER 3 sessions applications	Other: Fractional CO2 LASER; LASER treatment with fractional CO2 Laser was performed in 3 sessions with intervals of 4 weeks between them. Before each session, the patients underwent specular examination. Fractional CO2 LASER was applied following these parameters, fixed in all sessions: vagina wall - power40 W, dwel time 1000 mcs, spacing 1000 mcm and stack 2, vestibule - power 10W, dwel time 500mcs, spacing 300mcg and satck 1
Active Comparator: Microablative fractional radiofrequency; Vaginal Microablative fractional radiofrequency 3 sessions application	Other: Microablative Fractional radiofrequency; Microablative fractional radiofrequency was performed with the equipment calibrated in FRAXX mode, 45W, Low Energy program 40 milliseconds in the vaginal and introitus wall. Lidocaine spray was applied to vaginal introitus before the procedure. The patient was in the gynecological position. The vaginal speculum was placed and, afterwards, the vaginal antisepsis was performed with aqueous chlorhexidine and cleaning with 0.9% saline solution. All liquid contents were wiped off before beginning the procedure. The fractured tip will be pressed lightly and as perpendicular as possible into the vulvar or vaginal surface, ensuring full contact of all points in the tissue, starting at the lateral vaginal walls and from the proximal to the distal third.
Active Comparator: Promestriene Vaginal; Promestriene vaginal use during 3 months	Drug: Promestriene Vaginal; Patients used promestriene vaginal cream for 3 months. The use was recommended to be diary fot the first 2 weeks, and then, repeat every 3 days.; Other Names: Promestrieno

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Life's quality questionnaire	It was acessed at the beginnig and in the end of the treatment. We used the Short Form Health Survey 36 questionnaire for this parameter. It contains 36 items measuring eight dimensions, that vary the pontuation between 1-5 to 1-6. All but one of the 36 items are used to score the SF-36 eight domains that are aggregated in two summary measures, Physical and Mental components. Among the eight domains, three scales (Physical Functioning, Role-Physical, and Bodily Pain) contributes mostly to the Physical Component Summary (PCS) and three (Mental Health, Role-Emotional, and Social Functioning) contributes to the Mental Component Summary. The domains Vitality, General Health, and Social Functioning present noteworthy correlations with both summary componentNormalized scores below 50 are interpreted as below the generals population. The better is to have a higher pontuation.	3-4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sexuality questionnaire - Female Sexual Function Index	This questionnaire analyses 6 parameters: desire, excitation, lubrication, orgasm, satisfaction and pain. Tha maximum pontuation for each parameter is 6, and for the entire questionnaire is 36 (the best pontuation).	3-4 months
pH values	We used a pH tape to determine the vaginal pH. The normal measure é between 3,8 and 4,5.	3-4 months
score symptoms	Patients describe these symptoms dryness, itching, burnig and pain as absent (0 points); mild :1 point; moderate : 2 points and severe : 3 points, at the begging and in the end of the treatment. The best pontuation is zero and the worst is 12.	3-4 months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Investigators: Study Director: Jose Maria Soares Junior, PHD, Universidade de São Paulo departamento de ginecologia

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Actual): March 7, 2019
• Study Completion (Actual): February 18, 2020

Study Registration Dates

• First Submitted: August 28, 2018
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 25, 2021
• Last Update Submitted That Met QC Criteria: January 20, 2021
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: quality of life; sexuality; fractional CO2 laser; genital atrophy; microablative fractional radiofrequency; promestriene; Menopause genitourinary syndrome
• Additional Relevant MeSH Terms: Pathological Conditions, Anatomical; Atrophy
• Other Study ID Numbers: CAI

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No