Tadalafil (phosphodiesterase type 5 [PDE5]) has many different effects such as smooth muscle relaxation in the prostate and bladder neck, increased vascular flow in the tissues of the lower urinary tract, and inhibition of bladder afferent nerve activity. Thus, it is being widely used in male patients with lower urinary tract symptoms (LUTS) globally.
Recent studies have suggested an association between excessive increase in oxidative stress and LUTS, especially overactive bladder (OAB). Although the mechanisms of action of tadalafil described above may reduce oxidative stress, few studies have reported on tadalafil-derived changes in LUTS, including OAB, and changes in oxidative stress, as well as their associations. Hence, the aim of this present study was to examine the changes in OAB symptoms and oxidative stress with tadalafil monotherapy and assess their associations in male patients with LUTS.

This 12-week prospective study was performed at a single institution. The study included male patients with LUTS, who met the criteria for OAB (≥2 points for question 3 [urinary urgency] in the OAB symptom score [OABSS] assessment and ≥3 points for the total score).
We orally administered tadalafil (Zalutia®, Nippon Shinyaku, Kyoto, Japan) at 5 mg once a day to the patients and assessed their symptoms and signs before the administration and at 12 weeks after the administration.
Patients who had already received medication to improve urinary function (e.g., α1-adrenergic receptor blockers, anticholinergic drugs, and 5α-reductase inhibitors) were excluded from this study. In addition, patients who developed apparent neurogenic bladder, those with a prostate volume 30 mL or more, those who had received nitric acid agents, and those who developed severe liver failure and renal dysfunction were excluded from this study.
The OABSS was used for the end-point of subjective symptoms. Objective findings were assessed using uroflowmetry and post-residual urine volume. The changes in oxidative stress were assessed using urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). For assessing urinary 8-OHdG, the first morning urine sample was used, and the 8-OHdG value was determined using ELISA (New 8-OHdG Check®, Japan Institute for the Control of Aging, Nikken Seil Co., Ltd., Shizuoka, Japan). The value was adjusted for urinary creatinine (Cr) concentration (Cayman Chemical, Ann Arbor, MI, USA).

The study included 29 patients, and their mean age was 71.6 ± 8.1 years old. After tadalafil administration, all items of the OABSS assessment showed significant improvement, and the total OABSS showed significant improvement from 6.8 ± 2.0 points to 3.0 ± 1.9 points (P < 0.001). Additionally, the voided volume improved from 111.7 ± 78.8 ml to 163.4 ± 100.2 ml (P = 0.031), and the maximum flow rate improved from 8.1 ± 3.6 ml/s to 10.5 ± 5.3 ml/s (P = 0.008) after tadalafil treatment. Urinary 8-OHdG/Cr decreased from 12.2 ± 9.7 ng/mg Cr to 7.2 ± 11.3 ng/mg Cr (P = 0.002). In patients who showed OAB improvement with tadalafil treatment and did not meet the criteria for OAB after treatment (22 patients, 75.9%), urinary 8-OHdG/Cr significantly decreased from 11.6 ± 8.7 ng/mg Cr to 6.1 ± 10.0 ng/mg Cr (P = 0.004). On the other hand, in patients who did not show OAB improvement (7 patients, 24.1%), there was no significant decrease in urinary 8-OHdG/Cr (P = 0.438).

Tadalafil monotherapy for 12 weeks resulted in improvement in OAB symptoms and significant improvement in objective findings of male non-neurogenic OAB patients. In patients who showed disappearance of OAB symptoms, urinary 8-OHdG, as a marker of oxidative stress, showed a significant decrease, suggesting that there were associations between changes in subjective OAB symptoms and changes in oxidative stress.

Tadalafil administration treatment may improve LUTS, including OAB, by reducing oxidative stress in male patients.