Clinical trial NCT06780163: Effect of Vaginal Estrogen on Alterations in the Urine Microbiome of Menopausal Women With Overactive Bladder
Official title: A Pre-Post Quasi-Experimental Study to Evaluate the Effects of Vaginal Estrogen on the Urine Microbiome and Overactive Bladder Symptoms in Menopausal Women
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Overactive Bladder (OAB)
Menopause
Microbiome
Lead sponsor: Mahidol University
Sponsor class: OTHER
First posted: 2025-01-17
Enrollment: 30
Sex: FEMALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this Pre-Post Quasi-experimental study is to investigates the effect of vaginal estrogen therapy on changes in the urinary microbiome and its association with improvement in overactive bladder (OAB) symptoms in menopausal women

Primary Objective:

To evaluate the effects of vaginal estrogen on the level of Lactobacillus in the urine of postmenopausal women with OAB.

Secondary Objectives

1. To evaluate the effects of vaginal estrogen on urine microbiome in postmenopausal women with OAB.
2. To identify the association of alterations of urine microbiome after vaginal estrogen treatment with overactive bladder symptoms.

After informed and consents process, urine samples for microbiome study will be collected from participants with sterile technique. 17β-estradiol 10 mcg will be given to the participants. The participants will be ask to use 1 tab daily for 2 weeks vaginally before bed, then 1 tab twice a week vaginally before bed until 12 weeks. Then they will come back to hospital to take urine sample for microbiome study.

Detailed description: Overactive bladder (OAB) is a common condition affecting 12-20% of adults, particularly women in the menopausal phase. OAB is characterized by urinary urgency, frequency, nocturia, and sometimes urgency urinary incontinence, significantly impairing quality of life. Menopause is associated with a decline in estrogen levels, which affects the integrity of the lower urinary tract and may contribute to OAB symptoms.

Vaginal estrogen therapy has been used to alleviate urogenital symptoms in postmenopausal women by improving vaginal atrophy, enhancing urethral closure pressure, and potentially improving bladder function. Recent studies have suggested that the urinary microbiome plays a critical role in urinary tract health and dysfunction. Alterations in the urinary microbiome, known as dysbiosis, have been linked to conditions such as OAB, urgency urinary incontinence, and recurrent urinary tract infections.

This pre-post quasi-experimental study aims to evaluate the effects of vaginal estrogen therapy on the urinary microbiome and its association with OAB symptom improvement in menopausal women. Specifically, the study will focus on:

1. Measuring changes in Lactobacillus abundance in urine after vaginal estrogen therapy. (Primary objective)
2. Measuring changes in the overall urinary microbiome diversity. (Secondary objective)
3. Identifying associations between changes in the microbiome and improvements in OAB symptoms. (Secondary objective)

The study will enroll 30 postmenopausal women with a clinical diagnosis of OAB who meet specific inclusion criteria. Participants will receive 17β-estradiol vaginal tablets (10 mcg) daily for the first two weeks, followed by twice-weekly doses for a total of 12 weeks. Urine samples will be collected via sterile catheterization at baseline and after 12 weeks to analyze microbiome diversity and Lactobacillus levels. OAB symptoms will be assessed using validated Thai versions of the Overactive Bladder Symptom Score (OABSS) and Overactive Bladder Questionnaire Short Form (OAB-q SF).

The findings from this study will provide valuable insights into the role of the urinary microbiome in the pathophysiology of OAB and the therapeutic effects of vaginal estrogen. This knowledge could pave the way for personalized treatments targeting hormonal and microbial factors in postmenopausal women with OAB.

Eligibility criteria: Inclusion Criteria:

* Natural or surgical menopause at least 1 year
* Present with overactive bladder symptoms by using validated Thai version of OVERACTIVE BLADDER SYMPTOM SCORE (score in No.3 ≥ 2 and overall score ≥ 3)
* Absence of urinary infection
* Post-void residual urine less than 100ml

Exclusion Criteria:

* Currently or prior use of systemic hormone replacement therapy or vaginal estrogen within the past 3 months
* Contraindication or allergy to estrogen therapy
* Use of antibiotics, prebiotics and probiotics within the past 2 weeks
* Currently on antimuscarinic or β3 agonists medication or within the past 3 months
* Pelvic organ prolapse greater than stage II

Primary outcomes:
measure: Change in Lactobacillus abundance
timeFrame: From enrollment to the end of treatment at 12 weeks
Secondary outcomes:
measure: Change in urine microbiome diversity
timeFrame: From enrollment to the end of treatment at 12 weeks
measure: Association of change in urine microbiome with overactive bladder symptoms
timeFrame: From enrollment to the end of treatment at 12 weeks
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: Faculty of Medicine Ramathibodi Hospital, Mahidol University
Study officials:
affiliation: Faculty of Medicine Ramathibodi Hospital, Mahidol University
name: Jittima Manonai, MD
role: STUDY_CHAIR
References:
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citation: Gasiorek M, Hsieh MH, Forster CS. Utility of DNA Next-Generation Sequencing and Expanded Quantitative Urine Culture in Diagnosis and Management of Chronic or Persistent Lower Urinary Tract Symptoms. J Clin Microbiol. 2019 Dec 23;58(1):e00204-19. doi: 10.1128/JCM.00204-19. Print 2019 Dec 23.
citation: Pearce MM, Hilt EE, Rosenfeld AB, Zilliox MJ, Thomas-White K, Fok C, Kliethermes S, Schreckenberger PC, Brubaker L, Gai X, Wolfe AJ. The female urinary microbiome: a comparison of women with and without urgency urinary incontinence. mBio. 2014 Jul 8;5(4):e01283-14. doi: 10.1128/mBio.01283-14.