Extracorporeal shock wave therapy (ESWT) has been purposed for the management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) with encouraging results. Phytotherapeutic compounds have been used in everyday clinical practice for patients with CP/CPSS due to their anti-inflammatory properties. The present study aimed to investigate the effects of ESWT in association with the use of bromelain and escin extracts in patients with CP/CPSS. For this purpose, 95 patients with a clinical diagnosis of CP/CPSS were enrolled in the study. The patients were randomly allocated to either the ESWT plus bromelain and escin group (group A; n=48) or the ESWT only group (group B; n=47). A total of five weekly ESWT treatment sessions were administered alone or in combination with bromelain and escin. Each session consisted of 3,000 focused shock waves. Doses of 160 and 500 mg/day bromelain and escin were administered respectively for 5 weeks. The changes in urinary symptoms, pain and quality of life were considered the main outcome measures and were assessed at baseline, and at 4, 12 and 24 weeks of follow-up. Urinary symptoms, pain and quality of life were evaluated using the international prostatic symptoms score (IPSS), visual analog scale (VAS) and the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). After 4 weeks, the mean VAS score, mean IPSS and mean satisfaction rate score had significantly improved in patients receiving ESWT plus bromelain and escin. After 12 weeks, the mean IPSS and mean satisfaction rate score were stable in the ESWT plus bromelain and escin group, while the mean VAS score was significantly lower when compared with the baseline values in both groups. On the whole, the present study demonstrates that in patients affected by CP/CPPS, treatment with ESWT plus bromelain and escin leads to pain resolution, and both treatments improve the IPSS, VAS and NIH-CPSI results.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a clinical syndrome characterized by pain in the perineum, pelvis, suprapubic area, or external genitalia, and variable degrees of voiding and ejaculatory disturbance, without evidence of a bacterial infection. Symptoms are usually prolonged and the treatment results are unsatisfactory. CP/CPPS is classified as type 3 prostatitis following the National Institutes of Health (NIH) classification of prostatitis (
A prospective, randomized study was conducted from February, 2019 to November, 2020 on 100 male patients affected by CPPS, attending the ‘Mater Domini’ Hospital. The study was approved by the local ethics committee (Ethical Committee of Calabria Region, Central Section). The enrolled subjects were randomly assigned to receive either low-intensity ESWT (Li-ESWT) or Li-ESWT plus bromelain and escin. Urinary symptoms, pain and satisfaction were assessed at baseline evaluation.
Urinary symptoms were evaluated using the international prostatic symptoms score (IPSS) (
A total of 95 patients with a clinical diagnosis of CP/CPSS were enrolled in the study. The patients were randomly allocated to either the ESWT plus bromelain and escin group (group A; n=48) or the ESWT only group (group B; n=47). Participants in group A received identical Li-ESWT therapy plus bromelain (a dose of 160 mg/day) and escin (a dose of 500 mg/day) for 5 weeks. Treatments were performed without anesthesia. Treatment complications were recorded. Follow-up evaluations were performed at 4 and 12 weeks after the final intervention session (
The inclusion criteria were the presence of pelvic pain symptoms for at least 3 months over the past 6 months prior to study entry in accordance with the European Association of Urology (EAU) guidelines: A score in the pain domain of the NIH-CPSI of >4; and a microbiologically negative result in the Meares-Stamey four-glass test (
The present study was approved by the University of Catanzaro Institutional Review Board (no. 48 of 22th February 2019). The study was conducted in line with Good Clinical Practice guidelines, in compliance with the ethical principles published in the latest version of the Declaration of Helsinki (
The homogeneity of the groups at baseline was assessed using Mann-Whitney U test for continuous variables. Multiple comparisons between the two groups at the baseline and each follow-up evaluation time point was performed using the Kruskal-Wallis test. Post hoc analysis was performed using the Dunn's multiple comparison test. General characteristics of the study participants were expressed with descriptive statistics (means, standard deviations or ranges). The calculation of the sample size needed for enrollment was based on the expected questionnaire results (improvement of quality of life) in line with published results from other studies (
At the end of the follow-up period, 95 patients were available for follow-up examinations and analyzed: 48 patients in group A (Li-ESWT in association with bromelain and escin) and 47 in group B (Li-ESWT only). Differences in pre-treatment characteristics between the Li-ESWT and control groups were not statistically significant. No major complications were observed in patients receiving both treatments, and all patients tolerated the treatments well. None of the patients required the administration of analgesics during treatment. The patient clinical characteristics at baseline are presented in
At 4 weeks follow-up, out of the patients assigned to the group treated with Li-ESWT alone, 3 (6%) patients reported pain disappearance, 25 (53%) reported pain reduction, 17 (36%) reported pain stability and 5 (10%) reported pain worsening. In the Li-ESWT plus bromelain and escin group, 4 (8%) reported pain disappearance and 29 (60%) reported pain reduction; pain remained stable in 14 patients (29%) and worsened in 3 patients (6%). The median IPSS scores were significantly lower in both groups when compared with the baseline values [15; (IQR 4) and 15 (IQR 4) vs. 10 (IQR 5) and 10 (IQR 6) for group A and B, respectively; P<0.001; P<0.001] (
At 12 weeks of follow-up in both groups, the median IPSS scores were lower, although not significantly, when compared with the follow-up values at 4 weeks [10 (IQR 5) and 10 (IQR 6) vs. 10 (IQR 5) and 9 (IQR 5) for groups A and B, respectively; P=0.99; P=0.08]. No significant differences emerged in the scores between the two different groups. The median VAS score was not significantly lower compared to the 4 weeks of follow-up for group B [4 (IQR 2) vs. 4 (IQR 3); P=0.98]. Conversely the median score was significantly lower in group A when compared to the first follow-up [4 (IQR 2) vs. 1 (IQR 2) P<0.001] and to group B [4 (IQR 3) vs. 1 (IQR 2); P<0.001] (
At 24 weeks follow-up in both groups, the median IPSS scores were similar compared with the 4- and 12-week follow-up values, without any significant difference between the two groups [11 (IQR 5) vs. 11 (IQR 5) for A and B group respectively; P=0.99]. The median VAS score was significantly lower for group A than group B [1 (IQR 2) vs. 4 (IQR 2) P<0.001]. As regards the median scores of the three domains of NIH-CPSI, the pain and quality of life domains exhibited significant differences between groups A and B [8 (IQR 2) vs. 5 (IQR 2); P<0.001; 7 (IQR 2) vs. 4 (IQR 2) P<0.001]. At 24 weeks of follow-up, out of the patients assigned to the Li-ESWT plus bromelain and escin group, 2 (4.16%) reported pain disappearance and 19 (39.58%) reported stable pain reduction; pain remained stable in 18 patients (37.5%) and worsened in 8 patients (16.6%). In the Li-ESWT -alone group, 2 (4.25%) patients reported pain disappearance, 15 (31.91%) reported stable pain reduction, 23 (48.93%) reported pain stability, and 8 (17.02%) reported pain worsening. The mean IPSS score was lower when compared with baseline values in the Li-ESWT plus bromelain and escin group, but not significantly, while no statistically significant differences were found in the Li-ESWT group (
No clinically significant adverse effects were reported. Two patients reported mild pain (VAS 1) during the procedure in the ESWT application area. All results of safety profile are presented in
The present study demonstrated that the use of bromelain plus escin improved the clinical efficacy of Li-ESWT in patients affected by CP/CPPS, by ameliorating urinary symptoms, pain and the quality of life.
At the present time, to the best of our knowledge, there are no studies available that used both Li-ESWT and phytotherapy and that have compared the two treatments. It was hypothesized that the higher clinically significant improvement observed in the quality of life of patients treated with Li-ESWT and phytotherapy was due to the anti-inflammatory effects of bromelain and escin which were enhanced by Li-ESWT. Several researchers, in this sense, have reported a significant anti-inflammatory effects of bromelain and escin in several aspects of clinical practice (
The present study has certain limitations. Firstly, the lack of a placebo should be considered. This aspect was considered in the analysis and interpretation of the results. The placebo effect in phytotherapy research ranges from 20 to 30%, as highlighted by Capasso
In conclusion, the present study demonstrates that in patients with CP/CPPS, Li-ESWT plus bromelain and escin leads to pain resolution and both treatments ameliorate IPSS, VAS and NIH-CP/CPSI. However, further studies are warranted to confirm these results.
Not applicable.
The datasets generated and/or analyzed during the current study are not publicly available due to Italian law on privacy but are available from the corresponding author on reasonable request.
LDL, ADG, LC and GLC collected and analyzed the data. AP, CDA, TC, LG and MC were involved in the study conception, design, analysis of data and in the writing of the manuscript. LDL and AP confirm the authenticity of all the raw data. All authors have read and approved the final manuscript.
The present study was approved by the University of Catanzaro Institutional Review Board (no. 48 of 22th February 2019). The study was conducted in line with Good Clinical Practice guidelines, in compliance with the ethical principles published in the latest version of the Declaration of Helsinki. Written informed consents were obtained from all patients prior to treatment.
Not applicable.
The authors declare that they have no competing interests.
Schematic diagram of the study design and schedule.
Baseline assessment.
Parameter | Group A (n=48 | Group B (n=47) | P-value |
---|---|---|---|
Age (years) | 32(5) | 31(6) | 0.89 |
IPSS | 15(4) | 15(4) | 0.99 |
VAS | 5(2) | 6(3) | 0.78 |
NIH-CP/CPSI | |||
Pain domain | 13(2) | 13(2) | 0.99 |
Urinary symptoms | 6(2) | 6(2) | 0.99 |
Quality of life | 9(3) | 10(4) | 0.84 |
The table shows the baseline characteristics of all enrolled patients. IPSS, international prostatic symptoms score; VAS, visual analogue scale; NIH-CPSI, National Institutes of Health-Chronic Prostatitis Symptom Index. All data are presented as the median and Interquartile range (IQR). The Mann-Whitney U test was used for the analysis.
Comparison between baseline and follow-up data.
Group A (n=48) | |||||
---|---|---|---|---|---|
Parameter | Baseline | 4 weeks | 12 weeks | 24 weeks | P-value (vs. baseline) |
IPSS | 15(4) | 10(5) | 10(5) | 11(5) | <0.001 (all) |
P-value | <0.001 | 0.99 | 0.33 | ||
VAS | 5(2) | 4(2) | 1(2) | 1(1) | <0.001 (all) |
P-value | <0.001 | <0.001 | 0.99 | ||
NIH-CP/CPSI | |||||
Pain domain | 13(2) | 8(4) | 8(4) | 8(2) | <0.001 (all) |
P-value | <0.001 | 0.99 | 0.87 | ||
Urinary symptoms | 6(2) | 4(4) | 4(3) | 4(2) | <0.001 (all) |
P-value | <0.001 | 0.88 | 0.76 | ||
Quality of life | 9(3) | 7(4) | 4(2) | 5(2) | <0.001 (all) |
P-value | <0.001 | <0.001 | 0.67 | ||
Group B (n=47) | |||||
Parameter | Baseline | 4 weeks | 12 weeks | 24 weeks | P-value (vs. baseline) |
IPSS | 15(4) | 10(6) | 9(5) | 11(4) | <0.001 (all) |
P-value | <0.001 | 0.08 | 0.33 | ||
VAS | 6(3) | 4(2) | 4(3) | 4(2) | <0.001 (all) |
P-value | <0.001 | 0.98 | 0.98 | ||
NIH-CP/CPSI | |||||
Pain domain | 13(2) | 7(4) | 4(2) | 5(2) | <0.001 (all) |
P-value | <0.001 | 0.98 | 0.65 | ||
Urinary symptoms | 6(2) | 4(3) | 4(2) | 4(2) | <0.001 (all) |
P-value | <0.001 | 0.98 | 0.99 | ||
Quality of life | 10(4) | 7(5) | 7(3) | 7(2) | <0.001 (all) |
P-value | <0.001 | 0.98 | 0.98 |
The table shows the follow-up findings in comparison with the baseline and the other follow-up evaluations. Comparisons were made between 4 weeks and baseline, 12 weeks and 4 weeks, and between 24 weeks to 12 weeks. IPSS, international prostatic symptoms score; VAS, visual analogue scale; NIH-CPSI, National Institutes of Health-Chronic Prostatitis Symptom Index. All data are presented as the median and Interquartile range (IQR). The Kruskal-Wallis test and Dunn's multiple comparison test were used for statistical analysis.
Assessment at 4 weeks of follow-up.
Parameter | Group A (n=48) | Group B (n=47) | P-value |
---|---|---|---|
IPSS | 10(5) | 10(6) | 0.99 |
VAS | 4(2) | 4(2) | 0.99 |
NIH-CP/CPSI | |||
Pain domain | 8(4) | 7(4) | 0.86 |
Urinary symptoms | 4(4) | 4(3) | 0.99 |
Quality of life | 7(4) | 7(5) | 0.99 |
The table shows the follow-up findings at 4 weeks. IPSS, international prostatic symptoms score; VAS, visual analogue scale; NIH-CPSI, National Institutes of Health-Chronic Prostatitis Symptom Index. All data are presented as the median and Interquartile range (IQR). The Mann-Whitney U test was used for the analysis.
Assessment at 12 weeks of follow-up.
Parameter | Group A (n=48) | Group B (n=47) | P-value |
---|---|---|---|
IPSS | 10(5) | 9(5) | 0.78 |
VAS | 4(3) | 1(2) | 0.001 |
NIH-CP/CPSI | |||
Pain domain | 8(4) | 4(2) | 0.001 |
Urinary symptoms | 4(3) | 4(2) | 0.99 |
Quality of life | 7(3) | 4(2) | 0.001 |
The table shows the follow-up findings at 12 weeks. IPSS, international prostatic symptoms score; VAS, visual analogue scale; NIH-CPSI, National Institutes of Health-Chronic Prostatitis Symptom Index. All data are presented as the median and Interquartile range (IQR). The Mann-Whitney U test was used for the analysis.
Assessment at 24 weeks of follow-up.
Parameter | Group A (n=48) | Group B (n=47) | P-value |
---|---|---|---|
IPSS | 11(5) | 11(4) | 0.99 |
VAS | 4(2) | 1(1) | 0.001 |
NIH-CP/CPSI | |||
Pain domain | 8(2) | 5(2) | 0.001 |
Urinary symptoms | 4(2) | 4(2) | 0.99 |
Quality of life | 7(2) | 4(2) | 0.001 |
The table shows the follow-up findings at 24 weeks. IPSS, international prostatic symptoms score; VAS, visual analogue scale; NIH-CPSI, National Institutes of Health-Chronic Prostatitis Symptom Index. All data are presented as the median and Interquartile range (IQR). The Mann-Whitney U test was used for the analysis.
Safety profile.
Parameter | Group A (n=48) | Group B (n=47) | P-value |
---|---|---|---|
Discomfort | |||
VAS (0-2) | 1(2) | 1(2) | 0.99 |
Gastrointestinal symptoms | |||
Mild | 1 | 0 | 0.87 |
The table shows the safety profile.