To compare the efficacy of mirabegron or tolterodine, alone or in combination, and their effects on symptoms and the autonomic nervous system and bladder blood flow.

Consecutive women with overactive bladder syndrome (OAB) were randomly assigned to receive mirabegron 25 mg, tolterodine, or the combined treatment (mirabegron plus tolterodine) for 12 weeks. All enrolled women completed questionnaires, kept a 3-day bladder diary, underwent heart rate variability testing, and underwent transvaginal Doppler ultrasound before and after treatment. Intergroup comparisons were performed using analysis of variance (ANOVA) with a Bonferroni correction.

A total of 130 women were enrolled in this study. Forty-seven women received mirabegron 25 mg daily, 40 women received tolterodine daily, and 43 women received mirabegron combined with tolterodine daily. However, after 4 weeks, only 32 women who received mirabegron, 32 who received tolterodine, and 38 who received mirabegron plus tolterodine remained in the study. There was a trend toward a difference in the loss to follow-up rate between the groups (p=0.062). Post hoc analysis showed a lower loss to follow-up rate in the combined treatment group than in the mirabegron group. With the exception of voided volume, there were no differences in baseline characteristics among the three groups.  
      After 4 weeks of treatment, no differences in efficacy were observed among the three groups, as assessed by Global Response Assessment (GRA), Urgency Severity Score (USS), Overactive Bladder Symptoms Score (OABSS), and bladder diary (Analysis of heart rate variability (including low-frequency, high-frequency, and low-frequency/high-frequency ratio) also revealed no differences between the groups (Table 1). However, the incidence of dry mouth was significantly higher in the combined treatment group than in the mirabegron monotherapy group (Table 1).
      After 12 weeks of treatment, efficacy was assessed using GRA, USS, OABSS, and bladder diary, showing no statistically significant differences among the three groups (Table 2). Analysis of heart rate variability, including low-frequency and high-frequency, and the low-frequency/high-frequency ratio, also showed no statistically significant differences among the three groups (Table 2). However, the change in the vascularization index was significantly greater in the mirabegron monotherapy group than in the tolterodine monotherapy group (p = 0.045).

After 12 weeks of treatment, the efficacy of mirabegron, tolterodine alone or in combination appeared to be similar. Furthermore, their effects on the autonomic nervous system were also similar. However, the incidence of dry mouth appeared to be higher in the combination therapy group.

Women with OAB may benefit from initial treatment with monotherapy compared with combination therapy because both have similar therapeutic efficacy and impact on the autonomic nervous system but with fewer adverse effects of dry mouth in the monotherapy group, particularly when treated with low-dose mirabegron.