Hypothesis / Aims of study
Detrusor underactivity (DU) is induced by bladder outlet obstruction (BOO) and is a common clinical problem in patients presenting with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (LUTS/BPH). DU can lead to significant bother due to both voiding and storage LUTS, in addition to other adverse health effects, such as urinary retention, recurrent urinary tract infections, and renal impairment. Although DU incidence was reported to be 9–48% among men undergoing urodynamic evaluation for non-neurogenic LUTS, there is no effective treatment for DU induced by BPH at present.
Current LUTS/BPH guidelines in several countries recommend the use of α1-adrenoceptor antagonists (α1-blockers) or phosphodiesterase 5 (PDE5) inhibitors for patients with LUTS/BPH. α1-blockers and PDE5 inhibitors were expected to be effective for patients with DU induced by BPH as they increase blood perfusion to the pelvic organs. However, there has been no report on whether they improve DU in clinical practice; it is also not known whether α1-blockers or PDE5 inhibitors are effective for the improvement in bladder functions. In the present study, we compared the long-term effects of tadalafil, a PDE5 inhibitor, and silodosin, an α1-blocker, on storage and voiding function in patients with DU induced by BPH using a urodynamic study (UDS).
Study design, materials and methods
Among treatment-naive men who visited our hospital with the chief complaint of LUTS, 100 patients, who were diagnosed with BPH-induced DU, were included in this prospective study. They were randomized to receive 5 mg tadalafil (T-group) or 8 mg silodosin (S-group) daily for 12 months. At month 12, changes from baseline in the patients’ subjective symptoms and voiding/storage functions, as assessed using the International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and urodynamic studies, were compared between the groups. In this study, BPH-induced DU was defined as bladder contractility index (BCI) < 100, bladder outlet obstruction index (BOOI) <40, total international prostate symptom score (IPSS) ≥ 8, and prostate volume ≥ 25 mL, as determined by transabdominal ultrasonography.
The final analysis included 48 patients in the T group (mean age: 69.5 years, mean prostate volume: 36.4 mL) and 43 patients in the S group (mean age: 69.1 years, mean prostate volume: 38.6 mL). No significant differences in the prostate volume, IPSS, OABSS, BOOI, or BCI were detected between the groups at baseline.
Significant decrease (improvement) in the total IPSS, IPSS-QOL, and OABSS were observed at week 12 compared to the baseline in both groups. Although the beneficial changes after 12 months in the total IPSS (8.0 in the T group vs 7.8 in the S group), and total OABSS (2.2 vs 2.4), were almost equal between the two groups, the T group showed significantly greater improvement in the IPSS-QOL (-2.0 vs. -1.4, p = 0.04).
In the storage phase of the UDS, bladder capacity significantly increased in both groups, and the difference between the two groups was not significant. With respect to voiding function changes, the mean Qmax significantly improved from 6.4 mL/s to 8.4 mL/s in the S group and from 6.5 mL/s to 10.1 mL/s in the T group. The improvement in Qmax was significantly superior in the T group (p = 0.002). The mean BOOI significantly decreased from 34.1 to 28.1 only in the S group. The mean BCI increased significantly in both groups (from 79.2 to 86.7 in the S group and from 77.6 to 101.5 in the T group). However, the improvement in BCI was significantly superior in the T group compared to that in the S group (p < 0.001) . Additionally, detrusor pressure at Qmax (PdetQmax) also increased significantly from 44.5 cmH2O to 50.5 cmH2O only in the T group.
Interpretation of results
The increase of blood perfusion to the pelvic organs by these drugs is thought to contribute to the improvement of bladder functions including bladder contractility. However, the detailed mechanisms underlying the better efficacy of tadalafil than of silodosin in terms of the improvement in bladder contractility and voiding functions remains incompletely understood. A concrete explanation of the difference in efficacy between the two drugs shown in the present study has to wait further clinical and basic investigation.
Tadalafil or silodosin significantly improved the LUTS in patients with DU induced by BPH during 12 months of treatment. Tadalafil is considered more effective than silodosin for the improvement of bladder contractility and urodynamic voiding functions.