Effect of Vaginal Estrogen on Alterations in the Urine Microbiome of Menopausal Women With Overactive Bladder

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:

• Measuring changes in Lactobacillus abundance in urine after vaginal estrogen therapy. (Primary objective)
• Measuring changes in the overall urinary microbiome diversity. (Secondary objective)
• 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.

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