Efficacy of Combined Pharmacotherapy Versus Solifenacin With Vaginal Estrogen Cream for Women With Detrusor Overactivity

Women with detrusor overactivity who were refractory to anti-muscarinics were enrolled for prospective study. Patients were divided into two groups: one receive combined pharmacotherapy with solifenacin and mirabegron, and the other received solifenacin and vaginal estrogen cream. Incontinence-related symptoms distress and impact on quality of life were evaluated by short form of Urinary Distress Inventory, (UDI-6), Incontinence Impact Questionnaire (IIQ-7) and Overactive Bladder Symptom Score (OABSS). Objective outcomes include changes from baseline in episodes of daily micturition, urgency, urinary incontinence and nocturia.

• Solifenacin with vaginal estrogen cream (Drug), also known as Premarin: Solifenacin 5mg with vaginal conjugated equine estrogen (CEE) 0.625 mg
• Combination pharmacotherapy (Drug), also known as Vesicare and Betmiga: Solifenacin 5mg and Mirabegron 25mg

Primary outcomes

• Short form of Urinary Distress Inventory (UDI-6) [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: UDI-6 is a valid questionnaire, used particularly to investigate symptoms associated with lower urinary tract dysfunction and inquire on irritative, stress, and obstructive or discomfort complaints. UDI-6 consists of six items: frequent urination; leakage related to feeling of urgency; leakage related to activity, coughing, or sneezing; small amounts of leakage (drops); difficulty emptying the bladder; and pain or discomfort in the lower abdominal or genital area. The total score ranges from 0 to 18 , with a higher score indicating more severe of incontinence.
• Short form of Incontinence Impact Questionnaire (IIQ-7) [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: The IIQ-7 assess the impact of urinary incontinence on QoL. 7 items assess influence of urinary incontinence on physical activity, travel, social/relationships \& emotional health. Each item is scored between 0 (activities not affected at all) to 3 (activities greatly affected). The total score ranges from 0 to 21, with a higher score indicating more severe of incontinence.
• Overactive Bladder Symptom Score (OABSS) [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: The total OABSS is the sum of four symptom scores: daytime frequency (score 0-2), nighttime frequency (score 0-3), urgency (score 0-5), and urgency incontinence (score 0-5). The total score ranges from 0 to 15, with a higher score indicating more severe of OAB symptoms.

Secondary outcomes

• Episodes of daily micturition [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: Patients report daily lower urinary tract symptoms episodes
• Episodes of daily urgency [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: Patients report daily lower urinary tract symptoms episodes
• Episodes of daily incontinence [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: Patients report daily lower urinary tract symptoms episodes
• Episodes of daily nocturia [Assess before treatment and 1 month, 3 months, 6 months and 1 year after treatment]: Patients report daily lower urinary tract symptoms episodes

Sex: Female, ages: 40 Years to 90 Years

Inclusion Criteria:

* Patients with detrusor overactivity which defined as a urodynamic observation characterized by involuntary detrusor contractions during the filling phase. Those who were refractory to monotherapy with anti-muscarinics were enrolled for prospective study.

Exclusion Criteria:

* Postvoid urine retention before treatment
* Women who had medical illness and contraindication for using solifenacin and mirabegron, such as narrow-angle glaucoma and hypertension
* Concerns for using estrogen include: Women with history of cerebrovascular disease; thromboembolic disorders; gallbladder disease; known or suspected breast carcinoma; estrogen-dependent neoplasm or undiagnosed abnormal genital bleeding.
* Women who were on hormone replacement therapy within 3 months were also excluded from the study

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• Hui-Hsuan Lau, MD, Principal investigator, Mackay Memorial Hospital