Hypothesis / aims of study
Chronic prostatic inflammation is well known as an important factor to exacerbate the condition of benign prostatic hyperplasia (BPH). The urine reflux into the prostatic stroma has been thought to be one of the key factors to worsen the magnitude of prostatic inflammation.
Alpha 1 blockers and 5 alpha-reductase inhibitors (5ARIs) have been used for BPH therapy, and several reports demonstrated that alpha 1 blockers and 5ARIs suppressed prostatic inflammation. However, the effect of these medications on prostatic inflammation is still controversial and the mechanisms of these anti-inflammatory effects are still unclear. It is thought that the reduction of urine reflux by reducing bladder outlet obstruction (BOO) would be the main mechanism of this anti-inflammatory effect.
Androgen signaling is also an important factor in the pathogenesis of BPH. 5ARIs inhibit the conversion of testosterone to dihydrotestosterone (DHT), which has anti-inflammatory effects by inhibiting nuclear factor kappa B (NF-κB) [Ref. 1].
Lymphocytes recognize high endothelial venule-like vessels (HEV-like vessels) at the inflamed sites and are recruited there. The HEV-like vessels are thus essential for the development of chronic inflammation, and they are a reliable marker of the magnitude of chronic inflammation [Ref 2]. Here, we investigated the therapeutic effect of alpha 1 blockers and dutasteride on patients with BPH in terms of the magnitude of prostate inflammation as assessed by the number of HEV-like vessels.
Study design, materials and methods
The analysis of human prostate tissues was approved by the Ethics Committee of our institution and informed consent was performed on all patients. Tissue samples were obtained from 148 BPH patients who underwent transurethral resection of the prostate (TURP) or holmium enucleation of the prostate (HoLEP). Thirty-three of the patients had been treated with dutasteride prior to surgery. The magnitude of prostatic inflammation was quantified histologically by the number of HEV-like vessels. HEV-like vessels were detected by the immunohistochemistry of MECA-79 [Ref 2].
We assessed the affection of alpha 1 blockers or dutasteride on the magnitude of chronic prostatic inflammation and the parameters of the international prostate symptom scores (IPSS) and urodynamic study (UDS).
Results
We observed that 126 of the 148 cases harbored HEV-like vessels. 143 patients have treated with alpha 1 blockers and 31 patients were with dutasteride. 113 patients were treated with alpha 1 blocker monotherapy, 30 cases with a combination of alpha 1 blockers and dutasteride, and only one case took monotherapy with dutasteride. 4 cases have never taken any medications for BPH.
The duration of alpha 1 blockers’ administration was significantly negatively correlated with the number of HEV-like vessels (correlation coefficient = -0.194, p = 0.030, Fig. 1). When the study was limited to the alpha 1 blocker monotherapy group only, there was no significant correlation between the duration of administration and the number of HEV-like vessels (correlation coefficient = -0.109, p = 0.180). On the other hand, the number of HEV-like vessels was significantly positively correlated with the duration of dutasteride treatment (correlation coefficient = 0.501, p = 0.001, Fig. 2).
Focusing on the relationships between the UDS parameters and these drugs, the duration of alpha 1 blockers’ administration was significantly negatively correlated with BOOI (correlation coefficient = -0.270 p = 0.029). Meanwhile, the duration of dutasteride administration was not significantly correlated with BOOI.
Next, we evaluated the impact of alpha 1 blockers and dutasteride combination therapy versus alpha 1 blockers alone on LUTS. Regarding the subjective parameters, the total IPSS score, voiding subscore, storage subscore, and QOL score of the group of combination therapy were significantly lower than those of the alpha 1 blocker monotherapy (total score 20.154 vs 14.350, p=0.002; voiding subscore 9.154 vs. 6.095, p=0.003; storage subscore 10.736 vs. 8.429, p=0.033; QOL score 4.476 vs. 3.700, p=0.017).
Interpretation of results
These results indicated that alpha 1 blockers could contribute to the suppression of chronic prostatic inflammation whereas dutasteride would enhance the magnitude of chronic prostatic inflammation. However, the combination therapy of these drugs would contribute to relieving the subjective LUTS.