Study design, materials and methods
We prospectively enrolled 40 clinically diagnosed BPH patients, of which 23 and 17 received medical and surgical treatment, respectively. All patients were followed up for 3 months, and the successful outcome was defined as a global response assessment (GRA) of ≧2. Clinical symptom scores, uroflowmetry, the quantification of urine biomarkers, and the examinations of HRV were compared at baseline and at 3 months. The targeted analytes in urine include oxidative stress biomarkers (8-hydroxy-2 deoxyguanosine [8-OHdG], F2-isoprostane, total antioxidant capacity [TAC]), hypoxia-related inflammatory cytokines (TNFα, IL-1β, IL-6, and, IL-8), and prostaglandin E2 (PGE2). Linear regression analysis with Pearson correlation was carried out to determine the relationship between the changes of urine biomarker levels/ HRV parameters and the changes of clinical characteristics in BPH patients receiving treatments.
Results
After treatment, 75% (30 of 40) of BPH patients reported a successful outcome, including 73.9% (17 of 23) and 76.5% (13 of 17) in medical and surgical treatment, respectively. After treatment, BPH patients had significant improvements in International Prostate Symptom Score (IPSS), quality of life score (QoL), and maximal urinary flow rate (Qmax) (Table 1). The levels of F2-isoprostane, IL-1β, and TNF-α in urine significantly decreased after treatment, especially in the successful outcome group. In comparison with the non-successful outcome group, the successful outcome group had a significantly lower level of TNF-α in urine before treatment, and a significant increase in low frequency/ high frequency (LF/ HF) ratio after treatment.
After treatment for BPH, there were significant correlations between the changes of urine biomarkers (including 8-OHdG, F2-isoprostane, TAC, PGE2, IL-8, and TNF-α) and the changes of clinical characteristics (Table 2). The changes of the LF/ HF ratio also negatively correlated with the changes of IPSS-V (IPSS voiding subscore), IPSS, and bladder capacity (BC).
Interpretation of results
This clinical study demonstrated the significant roles of urine oxidative stress biomarkers and HRV in BPH patients. The successful treatment outcome group had a significantly lower level of TNF-α in urine before treatment. The lower level of TNF-α in urine before treatment, indicating less severity in oxidative stress, was associated with better treatment outcomes. It suggested that there might be better treatment outcomes in the earlier stage of BPH progression influenced by oxidative stress. After treatment, the levels of oxidative stress biomarkers in urine significantly decreased, and the changes in urine biomarkers were correlated with the changes in clinical characteristics, including clinical symptoms and uroflowmetry parameters. This suggests that the treatment effectively reduced oxidative stress in BPH progression to achieve clinical therapeutics, which were shown in the changes of urine oxidative stress biomarkers. Urine oxidative stress biomarkers might have diagnostic and prognostic roles in BPH patients. Additionally, after treatment, the successful treatment group had a significant increase in LF/ HF ratio, and the changes of the LF/ HF ratio negatively correlated with the changes of IPSS-V, IPSS, and BC. These indicated that ANS function might be involved in the pathogenesis of treated BPH, and be a potential clinical biomarker reflecting the clinical symptoms and bladder function in BPH patients.