Efficacy of Vaginal 17β-Estradiol on the Urinary Storage Symptoms in Postmenopausal Women

NCT06508944 | Completed Phase 4 DMC

• 2 other identifiers: MURA2024/10RF_67069
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief 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.

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

Keywords

17 beta-estradiol; lower urinary tract symptoms; postmenopause; female genitourinary diseases; urethral maturation index; vaginal pH; ICIQ-FLUTS; ICIQ-LUTSqol; PGI-I; randomized controlled trial; vaginal estrogen; urinary stress incontinence; urinary urge incontinence; nocturia; quality of Life; voiding Disorders; vagina Atrophy; urethral Atrophy; daytime frequency; urgency; behavioral modification; Kegel's exercise; bladder training; bladder diary

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• The impact of urinary storage symptoms on quality of life

  The patients were monitored closely for 1 and 3 months after treatment.

• Global Improvement score

  The patients were monitored closely for 1 and 3 months after treatment.

• Urethral maturation index (UMI) and maturation value (MV)

  The patients were monitored closely for 1 and 3 months after treatment.

• Vaginal pH

  The patients were monitored closely for 1 and 3 months after treatment.

Study Arms (2)

Group A: Behavioral modifications and vaginal 17beta-estradiol

EXPERIMENTAL

• 17beta-Estradiol 10 mcg + Behavioral modifications

Drug: vaginal 17 beta-estradiol; Behavioral: Behavioral modifications

Group B: Behavioral modifications + Placebo

PLACEBO COMPARATOR

• Placebo + Behavioral modifications

Drug: Placebo; Behavioral: Behavioral modifications

Interventions

vaginal 17 beta-estradiol DRUG

* Femiest® Haupt Pharma Munster GMBH, Muenster, Germany * The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks.

Also known as: Femiest, ESTRADIOL HEMIHYDRATE, vagifem

Group A: Behavioral modifications and vaginal 17beta-estradiol

Placebo DRUG

* Placebo is produced by Chulalongkorn University Drug and Health Products Innovation \& Promotion Center. * The assigned dosage will be one vaginal tablet daily for two weeks then one vaginal tablet twice a week for 10 weeks.

Also known as: Agglomerated Lactose, Microcrystalline cellulose PH 102, Magnesium stearate

Group B: Behavioral modifications + Placebo

Behavioral modifications BEHAVIORAL

Behavioral modifications for women with storage symptoms of lower urinary tract symptoms (LUTS) involve strategies such as regulating fluid intake, avoiding bladder irritants, practicing bladder training techniques (scheduled and delayed voiding), performing pelvic floor muscle exercises, managing weight, increasing dietary fiber, maintaining a bladder diary, setting a regular voiding schedule, utilizing stress management techniques, and educating patients about LUTS.

Group A: Behavioral modifications and vaginal 17beta-estradiol; Group B: Behavioral modifications + Placebo

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Presenting with storage phase symptom score more than/equal to 1 evaluated by the ICIQ-FLUTS questionnaire in these items
• Item 2a) nocturia and/or
• Item 3a) urgency and/or
• Item 5a) daytime frequency and/or
• Item 9a) UUI and/or
• Item 11a) SUI
• Being natural or surgical menopause for more than 1 year
• Absence of urinary tract infection or other identifiable cause
• Not using hormone replacement therapy or any route of estrogen within 4 weeks
• Never undergone onabotulinumtoxinA therapy, percutaneous tibial nerve stimulation (PTNS), or neuromodulation for overactive bladder (OAB) treatment
• Willing to adhere to the research protocol and actively participate in the scheduled follow-up appointments as delineated within the framework of this study

You may not qualify if:

• Contraindication for estrogen therapy: undiagnosed abnormal vaginal bleeding, previous thromboembolic event, breast cancer, gynecologic/genitourinary malignancy, active liver disease
• Pelvic organ prolapse of anterior compartment stage III and IV
• Immunocompromised patient or taking immunosuppressant drug
• History of antibiotics drug use within the past 7 days
• History of bladder outlet obstruction
• History of using anti-muscarinics, beta3-adrenoceptor agonists, vaginal energy-based devices (laser and radiofrequency) or electromagnetic energy-based therapies within the past 2 weeks
• History of documented positive urine culture in the past 6 weeks
• Have an allergic reaction to study's drug
• Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study

Sponsors & Collaborators

• Mahidol University: lead

Study Sites (1)

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Ratchathewi, Bangkok, 10400, Thailand

Location

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MeSH Terms

Conditions

Lower Urinary Tract Symptoms; Female Urogenital Diseases; Urinary Incontinence, Stress; Urinary Incontinence, Urge; Nocturia; Urinary Bladder, Overactive

Interventions

Estradiol; stearic acid

Condition Hierarchy (Ancestors)

Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Incontinence; Urination Disorders; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Pornthip Harncharoenkul, MD

  Ramathibodi Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2024
• First Posted: July 18, 2024
• Study Start: April 8, 2024
• Primary Completion: October 22, 2024
• Study Completion: October 31, 2024
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

TH (1)