Mirabegron Improves Nocturia, Nocturia-Associated Quality of Life, and Sleep Quality in Female Patients with Overactive Bladder

Research Article

Austin J Urol. 2017; 4(1): 1054.

Mirabegron Improves Nocturia, Nocturia-Associated Quality of Life, and Sleep Quality in Female Patients with Overactive Bladder

Yoshida M¹*, Gotoh M², Kageyama S³, Kato K4, Matsukawa Y², Narushima M5 and Study Group of N-QOL

¹Department of Urology, National Center for Geriatrics and Gerontology, Japan

²Department of Urology, Nagoya University Graduate School of Medicine, Japan

³Kageyama Urology Clinic, Japan

4Department of Female Urology, Red Cross Nagoya First Hospital, Japan

5Department of Urology, Meitetsu Hospital, Japan

*Corresponding author: Yoshida M, Department of Urology, National Center for Geriatrics and Gerontology, 7-430 Morioka-cho, Obu, Aichi 474-8511, Japan

Received: December 22, 2016; Accepted: February 27, 2017; Published: March 03, 2017


Objective: To evaluate the effects of mirabegron, a ß3-adrenoceptor agonist, on nocturia, nocturia-associated Quality of Life (QOL), and sleep quality in female patients with Overactive Bladder (OAB) patients.

Materials and Methods: This prospective, multicenter study involved 60 female patients with OAB who experienced two or more nocturnal voids per night and visited 1 of 16 medical institutes. Mirabegron (50 mg/day) was administered for 12 weeks. The frequency–volume chart and various questionnaires (International Prostate Symptom Score, QOL index, OAB Symptom Score, Pittsburgh Sleep Quality Index [PSQI], and Nocturia QOL [N-QOL]) were examined before therapy and at 4, 8, and 12 weeks after mirabegron administration. The Wilcoxon signed rank test or paired t-test was used to compare the parameters before and after treatment.

Results: The mean patient age was 75.3 ± 6.8 years. In total, 58 patients were analyzed; 2 withdrew consent and were excluded. After 12 weeks of mirabegron treatment, there was a significant improvement in the nocturnal voiding frequency, nocturnal urine volume per void, urine volume of the first nocturnal void, and N-QOL scores. The mean hours of undisturbed sleep increased after 12 weeks of treatment, although this increase was not statistically significant. The PSQI was significantly improved after 12 weeks of treatment. Side effects were seen in five patients (8.6%); however, all side effects were mild.

Conclusion: Mirabegron improved the nocturnal voiding frequency by increasing the nocturnal bladder capacity, thereby improving QOL by increasing sleep quality in female patients with nocturia.

Keywords: Mirabegron; Nocturia; Overactive bladder; Quality of life; Sleep disorder


OAB: Overactive Bladder; QOL: Quality of Life; N-QOL: Nocturia Quality of Life Questionnaire; OABSS: Overactive Bladder Symptom Score; I-PSS: International Prostatic Symptom Score; PSQI, Pittsburgh Sleep Quality Index; HUS: Hours of Undisturbed Sleep


In 2002, the International Continence Society defined nocturia as “waking one or more times to void during the night” [1]. Nocturia has been associated with urinary bladders to rage disorders, as observed in patients with benign prostatic hyperplasia and Overactive Bladder (OAB); it has also been associated with polyuria, nocturnal polyuria, and sleep disorders [2]. Nocturia significantly compromises patients’ Quality of Life (QOL) [3,4] and is usually the most problematic symptom among a variety of lower urinary tract symptoms [5]. Although treatment for nocturia depends on the underlying pathology, nocturia is reportedly improved by the administration of anticholinergic agents, which are one of the first-line drugs for treatment of OAB [6-8].

Mirabegron, a selective ß3-adrenoceptor agonist, was recently developed as a therapeutic agent for OAB. Relaxation of the human bladder during the period of urine storage occurs due to binding of noradrenaline released from the sympathetic nerves to ß3- adrenoceptors expressed in the smooth muscle of the bladder [9- 12]. Mirabegron binds to ß3-adrenoceptors, resulting in enhanced relaxation of the bladder during urine storage and an increased bladder capacity, thus improving frequency, urgency, and urgency incontinence associated with OAB [13]. Usefulness of mirabegron in relief of OAB symptoms has already been investigated in many studies [14-18], but few reports have evaluated the effectiveness of mirabegron in patients with nocturia.

In this study, we investigated the efficacy and safety of mirabegron for nocturia in female patients with OAB. The Nocturia QOL Questionnaire (N-QOL) [19,20], a QOL questionnaire specific for nocturia, was used to assess the impact of mirabegron on QOL.

Materials and Methods

This study was initiated after approval from the institutional review boards of each of the 16 individual medical centers that participated in this study. All participants provided written informed consent, and the study protocol conformed to the provisions of the Declaration of Helsinki (as revised in Edinburgh 2000).

The patients comprised 60 female outpatients with OAB aged =50 years with an average of two or more nocturnal voids per night according to a voiding diary. All patients were able to complete the questionnaire by themselves, go to the bathroom without assistance, and measure the voided volume by themselves. The exclusion criteria were serious cardiac diseases and arrhythmias; serious hepatic diseases, renal impairment, and glaucoma; having taken anticholinergic agents for treatment of OAB within the previous 3 months; hypokalemia; dysuria; =100 mL of residual urine; polyuria with a mean daily voiding volume of =40 mL/kg; an indwelling catheter or intermittent self-urination; and urinary tract infection, urinary calculi, interstitial cystitis, and/or bladder tumors.

All enrolled patients were administered 50 mg of mirabegron after a meal once daily for 12 weeks.

The patients completed questionnaires on their symptoms (OAB Symptom Score [OABSS], International Prostatic Symptom Score [I-PSS], I-PSS-QOL score, N-QOL, and Pittsburgh Sleep Quality Index [PSQI]) before treatment and at 4, 8, and 12 weeks after the start of treatment. In addition, the patients kept a voiding diary for 3 days before each study visit. At each visit, the residual urine volume, blood pressure, and pulse rate were measured, and medication compliance and adverse events were recorded.

The primary endpoint was a change in the nocturnal voiding frequency as recorded in the voiding diary. The secondary endpoints were changes in the following: the total score and subscale scores on the N-QOL and global health status; total score and individual symptom scores on the OABSS; total score and scores for voiding, storage, and post-micturition symptoms on the I-PSS; the I-PSSQOL; and the PSQI.

Based on the results recorded in the voiding diary, changes over time in the following parameters were investigated: voiding frequency per day, 24-h voiding volume, urine volume per void, daytime voiding frequency, day time urine volume, nocturnal voiding frequency, nocturnal urine volume, nocturnal polyuria index, urgency episodes per day, urgency incontinence episodes per day, Hours of Undisturbed Sleep (HUS), and maximum bladder capacity.

For statistical analyses, the values of each parameter before and after mirabegron administration were compared using the Wilcoxon signed rank test or the paired t-test. The significance level was set at 0.05.


In total, 58 patients were analyzed (mean age, 75.3 ± 6.8 years) after 2 patients were excluded because they withdrew consent.

Changes in nocturia as recorded in the voiding diary for each patient and changes in individual parameters on the voiding record are shown in (Table 1). The nocturnal voiding frequency significantly decreased from 2.5 ± 1.1 times per night before treatment to 1.9 ± 1.0 times per night after 12 weeks of treatment. In addition, significant improvements were observed in the daytime voiding frequency and the 24-h voiding frequency after 12 weeks of treatment. There were no significant changes in the urine volume parameters before and after treatment (24-h urine volume, daytime urine volume, and nocturnal urine volume). There was also no significant change in the nocturnal polyuria index after treatment. However, there was a significant increase in both the day time and night time urine volume per void after 12 weeks of treatment. In addition, the urine volume of the first nocturnal void significantly increased from 184.5 ± 83.6 mL before treatment to 228.1 ± 110.2 mL after 12 weeks of treatment. The mean HUS was extended by =40 min after 12 weeks of treatment, although this difference in HUS before and after treatment was not significant (Table 1).