Efficacy of Vaginal 17β-Estradiol on the Urinary Storage Symptoms in Postmenopausal Women
NCT Number: NCT06508944
Status: ACTIVE_NOT_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE4
Conditions: Lower Urinary Tract Symptoms|Female Genitourinary Disease|Urinary Stress Incontinence|Urinary Urge Incontinence|Nocturia|Quality of Life|Voiding Disorders|Vagina Atrophy|Urethral Atrophy|Overactive Bladder|Overactive Bladder Syndrome|Bladder, Overactive
Interventions: DRUG: vaginal 17 beta-estradiol|DRUG: Placebo|BEHAVIORAL: Behavioral modifications
Sponsor: Mahidol University
Sex: FEMALE
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 86
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2024-04-08
Completion Date: 2024-10-31
Locations: Faculty of Medicine Ramathibodi Hospital, Mahidol University, Ratchathewi, Bangkok, 10400, Thailand

Summary:
The goal of this clinical trial is to evaluate whether vaginal 17β-estradiol effectively treats storage symptoms of lower urinary tract symptoms (LUTS) and enhances quality of life. The main questions it aims to answer are:

* What is the efficacy of vaginal 17β-estradiol treatment compared to placebo in alleviating storage symptoms of LUTS?
* How does vaginal 17β-estradiol treatment affect the urethral maturation index and vaginal pH compared to placebo?
* What impact does vaginal 17β-estradiol treatment have on overall quality of life and patients' perception of global improvement (PGI)?

Participants in the trial will undergo the following procedures:

* Screening procedures at the first visit to exclude correctable causes of LUTS and to complete a bladder diary.
* Visit the clinic at 1-2 weeks for a review of the bladder diary and a check-up. Participants will receive the assigned dosage of vaginal 17β-estradiol or placebo: one vaginal tablet daily for two weeks, followed by one vaginal tablet twice a week for 10 weeks.
* The third and fourth visits (at 4 and 12 weeks after treatment) will involve: completion of bladder diaries, questionnaires, vaginal pH testing, collection of urethral maturation index (UMI), observation of intervention's side effects and monitoring of LUTS symptoms.

Primary Outcome Measures: Storage symptom improvement, Storage Symptom Improvement: This will be evaluated using the International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), validated in Thai. The questionnaire includes 5 items addressing storage symptoms:

* 2a) Nocturia
* 3a) Urgency
* 5a) Daytime frequency
* 9a) Urgency urinary incontinence (UUI)
* 11a) Stress urinary incontinence (SUI)

Each severity item is rated from 0 to 4, and each bothersome item from 0 to 10. The total severity score ranges from 0 to 20, and the total bothersome score ranges from 0 to 50. Higher scores indicate worse outcomes.

Outcome Interpretation:

* Improved: Mean ICIQ-FLUTS post-treatment score \< pre-treatment score.
* Not Improved: Mean ICIQ-FLUTS post-treatment score ≥ pre-treatment score., The patients were monitored closely for 1 and 3 months after treatment.
Secondary Outcome Measures: The impact of urinary storage symptoms on quality of life, • Assess the impact of urinary storage symptoms on quality of life with reference to social effects by Thai version of International Consultation on Incontinence Questionnaire Urinary Incontinence Quality of Life (ICIQ-LUTSqol), which comprises 20 items. The ranges from 19 to 76, with greater values indicating increased impact on quality of life. ICIQ-LUTSqol is a validated Thai adaptation of King's Health Questionnaire (KHQ)., The patients were monitored closely for 1 and 3 months after treatment.|Global Improvement score, The Global Improvement score is evaluated using the Thai version of the Patient Global Impression of Improvement (PGI-I) scale. This scale is a widely used, patient-reported measure that assesses the patient's overall perception of improvement following a treatment. The PGI-I is typically rated on a 7-point scale, where the minimum value is 1 and the maximum value is 7. On this scale, a score of 1 indicates that the patient feels "very much improved," while a score of 7 indicates that the patient feels "very much worse." Therefore, lower scores on the PGI-I represent better outcomes, reflecting greater improvement in the patient's condition, while higher scores denote worse outcomes, indicating little to no improvement or a decline in the patient's condition., The patients were monitored closely for 1 and 3 months after treatment.|Urethral maturation index (UMI) and maturation value (MV), We will use wet cotton buds coated with normal saline solution (NSS) to gently swab the distal urethra for cytologic preparation. Smear slides will be prepared for cytologic evaluation by immediately immersing them in 95% alcohol for 24 hours and staining them with a Papanicolaou stain. The urethral epithelial cell will be examined under a microscope and classified into three types: parabasal cells, intermediate cells, and superficial cells by an independent cytologist. Two hundred cells were counted at each high-power field which was randomly chosen. Six high-power fields were evaluated and the mean of the cell numbers was calculated. MV is a derived value from the proportion of different cell types and is, therefore, unitless.

Maturation value (MV) = (% parabasal cells × 0) + (% intermediate cells × 0.5) + (% superficial cells × 1.0)

Interpretation:

* MV = 0-49 will indicate low estrogen effect
* MV = 50-64 = moderate estrogen effect
* MV = 65-100 = high estrogen effect, The patients were monitored closely for 1 and 3 months after treatment.|Vaginal pH, To assess pH, a piece of litmus paper (MQuant® pH-indicator stripe) will be placed on the lateral vaginal wall until moistened. A pH of 4.6 or greater indicates vulvovaginal atrophy (VVA)(31). According to a preliminary double-blinded study in 67 symptomatic postmenopausal women confirmed that atrophic vaginitis is associated with an increase in the lateral wall vaginal pH and this finding is paralleled by similar changes in pH in the urethra. Also, locally applied vaginal conjugated estrogen cream can normalizes the pH in the vagina and urethra Thus, the testing of the vaginal pH serves both as a surrogate for evaluating urethral pH and as a monitor of compliance with treatment., The patients were monitored closely for 1 and 3 months after treatment.