International Continence Society defines overactive bladder (OAB) as a condition characterized by urgency, with or without urgency incontinence, often accompanied by frequency and nocturia, in the absence of urinary tract infection or other underlying pathologies [1]. In Korea, OAB prevalence is estimated at approximately 12.2%, slightly higher in women (14.3%) than in men (10.0%) [2].

OAB significantly impacts quality of life (QoL), affecting daily activities and sexual life. It also increases the risk of urinary tract infections and dermatological conditions, leading to higher healthcare costs.

Several pharmacological treatments are available for OAB, with antimuscarinic agents, such as solifenacin, being widely used. Solifenacin, a competitive muscarinic receptor antagonist, has demonstrated efficacy in reducing incontinence episodes and is recommended by clinical guidelines with strong evidence [3]. However, while antimuscarinic drugs can improve symptoms, treatment can be challenging if medication adherence is low due to side effects [4]. Therefore, balancing efficacy or side effects is relatively high, especially in chronic conditions like OAB that require continuous treatment. Common side effects of antimuscarinic drugs include dry mouth and constipation [5].

Studies have reported the prevalence of voiding symptoms in women ranges 6.5%–24% [6]. Given the retrospective nature of many of these studies, the actual number of women with voiding symptoms might be higher. In clinical practice, patients often experience a combination of storage and voiding symptoms. Alpha-blockers like silodosin, traditionally used for benign prostatic hyperplasia (BPH), reduce urethral sphincter resistance and have been shown to improve voiding symptoms, such as those in neurogenic bladder, in previous multicenter placebo-controlled studies [7, 8]. While historically used primarily in men, silodosin is increasingly employed in the clinical management of voiding symptoms in women, where it similarly acts by reducing urethral resistance, facilitating more effective bladder emptying [9].

The effectiveness of combination therapy has been well established in numerous studies on male patients with BPH and storage symptoms [10–13]. Similarly, studies have shown that combination therapy is more effective than monotherapy in women with voiding symptoms [14]. Given the high prevalence of voiding symptoms in female patients with OAB and the potential benefits of combination therapy, this study aimed to evaluate the clinical efficacy and safety of combination therapy with silodosin and solifenacin in females with OAB. Additionally, we aimed to evaluate whether this combination therapy could reduce obstructive symptoms potentially induced by the adverse effects of anticholinergic drugs.

This retrospective study, conducted from January 2022 to June 2023 at Korea University Ansan Hospital, included 420 newly diagnosed women aged 19–80 years with OAB. Patients had an Overactive Bladder Symptom Score (OABSS) question 3 score of 2 or more and a total score of 3 or more. These patients received a combination therapy of solifenacin (5 mg) and silodosin (8 mg) for at least 3 months. An equal number of OAB patients who received solifenacin 5-mg monotherapy during the same period were matched with similar symptoms as the control group.

Patients were excluded if they had signs of acute cystitis, residual urine volume exceeding 200 mL, history of acute urinary retention, recurrent urinary tract infections, and other urological diseases, or drug treatments affecting bladder function or causing lower urinary tract symptoms (LUTS). Patients who had previously received α-blockers or anticholinergics were also excluded. Those with contraindications to α-adrenergic receptor antagonists or anticholinergic agents were ineligible.

At baseline and after 12 weeks of treatment, we assessed age, OABSS, International Prostate Symptom Score (IPSS, including obstruction [IPSS-O] and irritation subscores [IPSS-I]), QoL, maximum flow rate (Qmax), voided volume (VV), and postvoid residual urine volume (PVR).

Data were analyzed to compare the efficacy and safety of combination therapy and monotherapy. Paired t-tests were used for within-group comparisons, and independent t-tests for between-group comparisons. Differences were considered statistically significant at a P-value of <0.05. Continuous data are presented as mean±standard deviation. Statistical analyses were performed using IBM SPSS Statistics ver. 21.0 (IBM Co., Armonk, NY, USA).

A total of 840 patients were enrolled, with 586 included in the final analysis after excluding 254 due to incomplete or unreliable data. The combination therapy group (n=287) received solifenacin 5 mg and silodosin 8 mg, whereas the monotherapy group (n=299) received solifenacin 5 mg alone (Fig. 1). There were no significant baseline differences between groups in terms of age, OABSS, IPSS, QoL, Qmax, VV, or PVR (Table 1).

Both groups demonstrated significant improvements in OABSS and total IPSS after 12 weeks (Table 2). The combination therapy group had a greater mean decrease in OABSS, from 6.3 to 3.2 (−49.2%, P<0.001), compared to 7.1 to 3.7 (−47.9%, P< 0.001) in the monotherapy group. The reduction in total IPSS was also notable, with the combination therapy group decreasing from 19.3 to 14.8 (−23.3%, P<0.001) and the monotherapy group from 18.7 to 13.5 (−27.8%, P<0.001).

Regarding the IPSS subscores, the combination therapy group showed a slight reduction in IPSS-O from 7.2 to 7.0 (−2.8%, P=0.053), whereas the monotherapy group showed a minimal increase from 6.5 to 6.6 (1.5%, P=0.061). The IPSS-I score significantly improved in both groups, with the combination therapy group reducing from 11.1 to 7.2 (−35.1%, P< 0.001), and the monotherapy group decreasing from 11.8 to 6.9 (−41.5%, P<0.001).

QoL scores improved significantly in both groups, with the combination therapy group showing a decrease from 4.1 to 2.5 (−39.0%, P<0.001) and the monotherapy group from 3.88 to 2.9 (−25.3%, P=0.022). The improvement in QoL was significantly greater in the combination therapy group than in the monotherapy group (P=0.031).

In terms of urinary flow metrics, no significant differences were noted in Qmax between groups, with the combination therapy group showing a slight decrease from 16.4 to 16.2 mL/sec (−1.2%, P=0.645) and the monotherapy group from 18.1 to 15.1 mL/sec (−16.6%, P=0.75). VV increased slightly in both groups, with the combination therapy group increasing from 253.1 to 280.8 mL (10.9%, P=0.03) and the monotherapy group from 264.5 to 290.1 mL (9.7%, P=0.01).

However, the combination therapy group had a significant reduction in PVR from 25.1 to 24.8 mL (−1.2%, P=0.072), whereas the monotherapy group experienced an increase from 20.5 to 25.5 mL (24.4%, P=0.024). The difference in PVR reduction between the 2 groups was significant (P<0.001).

Our study findings suggest that combination therapy with silodosin and solifenacin offers significant advantages over solifenacin monotherapy in females with OAB. Both treatment groups experienced marked improvements in OABSS and total IPSS after 12 weeks. However, the combination therapy group demonstrated a significantly greater enhancement in QoL scores, indicating a substantial overall positive impact on patient wellbeing. While no significant differences were observed in Qmax and VV between the 2 groups, the combination therapy group achieved a notable reduction in PVR. This suggests that adding an alpha-blocker to antimuscarinic therapy can effectively reduce residual urine, potentially lowering the risk of urinary retention and associated complications.

Alpha-blockers, traditionally used for BPH in men, have shown positive results in treating LUTS in women, despite differences in mechanisms underlying bladder outlet obstruction (BOO) in the both sexes [15]. However, research on alpha-blockers in women is relatively limited, with smaller sample sizes and shorter study durations, making it challenging to draw definitive conclusions about their long-term safety and efficacy. Boyd and Hilas [16] concluded that alpha-blockers can improve various urinary symptoms, including BOO, in women, with the treatment being generally safe and well tolerated. In Korea, Moon et al. [7] reported that silodosin monotherapy effectively improved symptoms in females with neurogenic bladder, reducing total IPSS and voiding symptom scores. A systematic review and meta-analysis by Kang et al. [9] found that alpha-blockers significantly reduced urinary symptom scores and improved the QoL in women with LUTS.

However, caution is necessary when prescribing alpha-blockers to older women due to the increased risk of hypotension and related events [17]. Alfuzosin has been reported to be ineffective compared to placebo in treating female voiding difficulties [18]. Given the anatomical and physiological differences between men and women, the mechanisms by which alpha-blockers exert their effects on women may differ and are not yet fully understood. While it is believed that alpha-blockers reduce urethral resistance, and improve voiding efficiency, further research is needed to clarify these mechanisms and establish clear treatment guidelines for their use in females.

Combination therapy involving alpha-blockers and anticholinergic medications has shown significant benefits in men with LUTS associated with BPH and storage symptoms [10–12]. Studies have demonstrated that such combinations can effectively improve both storage and voiding symptoms, offering greater relief than monotherapy with either drug class alone. Specifically, combination therapy has been linked to notable improvements in IPSS, reduced urgency episodes, and enhanced QoL scores [10, 11]. Furthermore, it provides these benefits without a significant increase in adverse events or acute urinary retention, common concerns with anticholinergic use in men [11].

While the efficacy of combination therapy has been well-documented in men, research on its effectiveness in women is more limited. Recent randomized controlled trials have shown that combination therapy with alpha-blockers and anticholinergics is effective in women with voiding symptoms [14]. In this study, the voiding symptom scores improved from 9.7 to 6.3 in the monotherapy group and from 9.1 to 7.1 in the combination therapy group. However, the combination therapy group showed a significant decrease in storage symptom scores from 4.2 to 2.9, whereas the monotherapy group showed no significant change, with scores decreasing from 4.8 to 4.3. This combination treatment significantly improved both voiding and storage symptoms without causing significant adverse effects, suggesting that it may be a promising approach for treating females.

Our study demonstrated that combination therapy with silodosin and solifenacin was effective in improving OAB symptoms in females, particularly in significantly reducing the PVR volume compared to solifenacin monotherapy. While the observed results suggest a beneficial interaction between these 2 drugs, further investigation is needed to elucidate the precise mechanisms underlying this effect. The first line medical treatment of the OAB is anticholinergics, but it is not rare that it increases PVR. Interestingly, increased PVR may also trigger frequency or urgency once again. Therefore, the combination treatment may have better synergistic effectivity not only by blocking alpha-1A receptor in bladder, but also by reducing PRV which can be induced by adverse effect of anticholinergic drugs. The discontinuation rate for anticholinergic drugs for OAB is not low. The reasons why patients stop using them remain obscure but could be related both to a limited clinical effect and an unacceptable adverse effect. Adding an alpha-blocker to antimuscarinic therapy may not only improve symptoms but also reduce the discontinuation rate.

Silodosin primarily acts as an alpha-1A adrenergic receptor blocker, reducing urethral resistance and relaxing the detrusor muscle, which may contribute to the reduction in PVR by facilitating complete bladder emptying [8]. Solifenacin is a muscarinic receptor antagonist that decreases the frequency of bladder contractions, thereby improving storage symptoms [3]. The combination of these 2 drugs creates a synergistic effect, where silodosin enhances voiding efficiency by reducing outflow resistance, while solifenacin prevents premature contractions, allowing a more thorough voiding process. This hypothesis suggests that the reduction in PVR observed with combination therapy is not merely the additive effect of the 2 drugs working independently, but rather a result of their complementary actions on different aspects of bladder function. To substantiate this hypothesis, further research is required to elucidate the exact physiological mechanism. Experimental studies involving real-time observation of bladder and urethral muscle responses or the use of animal models could provide deeper insights into how silodosin and solifenacin interact at the molecular and systemic levels to influence bladder function.

Our study had several limitations that must be considered when interpreting the results. As a retrospective study, it is inherently subject to selection bias and confounding variables that may not have been accounted for. This design limits our ability to establish causality between the combination therapy and observed clinical outcomes. Additionally, the study relied on medical records, which may have inconsistencies or missing data, potentially affecting the accuracy of our findings. The relatively short follow-up period (12 weeks) may not capture the long-term efficacy and safety of the combination therapy. Furthermore, patient adherence to the medication regimen was not monitored, which may have influenced the outcomes. Finally, although we observed significant improvements in symptoms and QoL, these findings may not be generalizable to all populations as the study was conducted at a single institution with a specific demographic profile. Exploring the application of combination therapy with silodosin and solifenacin to specific patient groups, such as older patients or those with various underlying conditions, would be helpful. Future prospective randomized controlled trials with longer follow-up periods are necessary to confirm our findings and provide more robust evidence for the use of combination therapy to manage OAB symptoms in women.

Combination therapy with silodosin and solifenacin significantly improved OAB symptoms and enhanced QoL in females, demonstrating superior outcomes in reducing PVR volume compared to solifenacin monotherapy. These results suggest that adding an alpha-blocker to antimuscarinic therapy can contribute not only to symptom improvement but also to the overall enhancement of QoL for patients.