Vaginal Biorevitalization With Polydeoxyribonucleotides for the Improvement of the Genitourinary Syndrome of Menopause

Study Overview
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Brief Summary
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The aim of the study was to compare the efficacy of vaginal biorevitalization to improve the genitourinary syndrome of menopause (GSM) between the gold-standard treatment with local estrogen-based hormone therapy versus local salmon polydeoxyribonucleotide (PDRN) therapy.

Detailed Description
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The aim of the study was to compare the efficacy of vaginal biorevitalization to improve the genitourinary syndrome of menopause (GSM) between the gold-standard treatment with local estrogen-based hormone therapy versus local salmon polydeoxyribonucleotide (PDRN) therapy. Thus, a randomized clinical trial was conducted in 136 first-time postmenopausal women with GSM, from the peri-postmenopause and bone metabolism clinic of the Regional Hospital October 1st  of the Institute of Security and Social Services for State Workers (ISSSTE), from June 2021 to December 2021. Participants were referred by the family medicine service or by another service of the hospital. The control group (n=63) received local estrogen-based hormonal therapy, applied topically to the vagina mucosa on Monday, Wednesday, and Friday of each week, for 3 months, while the experimental group (n=70) received local salmon PDRNs on vaginal suppositories, applied solely for six days every night in the first week. Then, experimental group participants were maintained without further treatment up to the control evaluation. The follow-up assessment was done after 3 months. The alterations in the urogenital domain of the MRS score (items 9-11), vaginal maturity index (VMI), vaginal pH, estrogenic effect, floor pelvic contraction capacity, as well as colposcopy findings, were the main outcomes of the study.

Official Title
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VABIP Study (Vaginal Biorevitalization With Polydeoxyribonucleotides) for the Improvement of the Genitourinary Syndrome of Menopause

Conditions
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Menopause, Genitourinary Syndrome of Menopause, Postmenopausal Disorder, Vagina Atrophy

Intervention / Treatment
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* Drug: 3 g Polynucleotide vaginal suppositories
* Drug: Conjugated estrogens cream 1g Tube


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First-time patients with the diagnosis of Genitourinary Syndrome of Menopause with an MRS > 5 in the urogenital domain, with alterations in the vaginal maturity index (VMI). Exclusion Criteria: Incomplete clinical records. History of prolonged use of steroids. Use of alternative local therapies applied in the vagina's mucosa. Use of local therapies with vaginal suppositories for any reason 15 days before the beginning of the study. Clinical evidence of infectious cervical-vaginitis or vulvovaginitis. Evidence of urinary tract infection (UTI). Lack of adherence to medical treatment. Diagnosis of cancer. Diagnosis of depression. Diagnosis of uncontrolled primary or secondary immunodeficiencies. Allergies to any of the medications administered. BIRADS >2 or high risk of developing breast cancer, ovarian cancer or endometrial cancer. Use of oral hormonal or non-hormanl therapy.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 75 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
Interventional Model Description: A randomised clinical trial was conducted in 136 postmenopausal women with GSM from the peri-postmenopause and bone metabolism clinic of the Regional Hospital October 1st  of ISSSTE, Mexico, from June to December 2021. The control group (n=64) received local estrogen-based hormonal therapy, applied to the vagina mucosa on Monday, Wednesday, and Friday of each week, for 3 months, while the experimental group (n=72) received local salmon PDRNs on vaginal suppositories, applied solely for six days every night in the first week. The follow-up assessment was done after 3 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Polynucleotide vaginal suppositories<br>In this arm 72 first-time participants of the peri-postmenopause and bone metabolism clinic of the Regional Hospital October 1st  of ISSSTE Mexico, were randomly enrolled to be treated with local salmon polydeoxyribonucleotide (PDRN) therapy. | Drug: 3 g Polynucleotide vaginal suppositories<br>* 3 g polynucleotide vaginal suppositories were administered nightly for 6 days.<br>* Other names: Tunover®;|
| Active Comparator: Conjugated estrogens cream<br>In this arm 64 first-time participants of the peri-postmenopause and bone metabolism clinic of the Regional Hospital October 1st  of ISSSTE Mexico, were randomly enrolled to be treated with the gold-standard treatment with local estrogen-based hormone therapy. | Drug: Conjugated estrogens cream 1g Tube<br>* Conjugated estrogen cream 1g was applied intravaginally on Monday, Wednesday and Friday for three months.<br>* Other names: Generic;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline urogenital domain score in the Menopause Rating Scale (MRS) at 3 months | Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Items 9, 10 and 11 evaluate the urogenital domain. 0 points were considered asymptomatic, 1point indicated mild symptoms, 2-3 points moderate symptoms and > 4 indicated severe symptoms. | 3 months | 
| Change from baseline Item 9 Menopause Rating Scale (MRS) total score at 3 months | Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 9 assesses the severity of sexual problems, including changes in libido, sexual activity, and dyspareunia. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms. | 3 months | 
| Change from baseline Item 10 Menopause Rating Scale (MRS) total score at 3 months | Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 10 assesses the severity of urinary problems such as polyuria, urinary urgency, bladder instability, and urinary incontinence. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms. | 3 months | 
| Change from baseline Item 11 Menopause Rating Scale (MRS) total score at 3 months | Menopause Rating Scale measures the severity of ageing symptoms and their impact on Health-Related Quality of Life. Item 11 assesses the severity of vaginal dryness. 0 points were assigned if the participants reported no symptoms, 1 point if they reported mild symptoms, 2 points if they reported moderate symptoms, 3 points if they reported severe symptoms, and 4 points if they reported extremely severe symptoms. | 3 months | 
| Change from baseline Vaginal Maturity Index (VMI) at 3 months | The vaginal maturation index (VMI) is used to assess the hormonal status of the vaginal epithelium, which quantifies the proportions of cell types in the vaginal epithelium. The VMI was evaluated through vaginal cytology, where the percentage of basal/parabasal, intermediate and superficial cells were calculated. | 3 months | 
| Change from baseline Estrogenic Effect at 3 months | The estrogenic effect is used to evaluate the local action of estrogens in the vaginal epithelium. The higher value, it means that it is having a greater trophic effect due to local estrogen stimulation. To calculate this outcome, it was used the next formula: Estrogenic effect= [(% of basal/parabasal cells*0)+(% of intermediate cells*0.5)+(% of superficial cells*1)] | 3 months | 
| Change from baseline Oxford grading scale at 3 months | The Oxford grading scale evaluates the contraction capacity of the muscles of the pelvic floor. It was used at the time of vaginal examination. 0 points meant no contraction , 1 point a flicker contraction, 2 points a weak contraction, 3 points a moderate contraction, 4 points a good contraction, and 5 points a strong contraction. | 3 months | 
| Change from baseline vaginal pH at 3 months | Vaginal pH tests measure the acidity of the vagina. A normal vaginal pH value was considered when it was between 4.0 and 5. | 3 months | 
| Change from baseline colposcopic findings at 3 months | The presence or absence of vaginal folds, paleness and vaginal lesions were colposcopic findings that were evaluated as nominal dichotomous variables. Lugol's staining was performed during colposcopy. The degree of Lugol's staining was evaluated as an ordinal variable with 4 degrees, depending on the intensity of staining of the vaginal mucosa. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Polynucleotides, Genitourinary syndrome of menopause, Postmenopause, Vagina atrophy, Vaginal biorevitalization