Stesura Seveso 25Archivio Italiano di Urologia e Andrologia 2015; 87, 1 ORIGINAL PAPER Effectiveness on urinary symptoms and erectile function of Prostamev Plus® vs only extract Serenoa repens Raffaele Marzano, Nicola Dinelli, Valeria Ales, Maria Antonella Bertozzi Andrology Unit, Santa Chiara Hospital, Pisa, Italy. Prostatic inflammation is widespread in the male population. Two groups of 50 patients each with symptoms of prostatic inflammation and ecocolorDoppler indicative of prostatitis were identi- fied. Both groups were further subdivided into two sub- groups (respectively A1, A2, B1, and B2). Group A1 underwent therapy with oral levofloxacin 500 mg daily for 10 days plus co-treatment with oral Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®) daily for two months; Group A2 with oral levofloxacin 500 mg daily for 10 days plus oral Serenoa repens extract 320 mg/day for two months; Group B1 specific antibiotic treatment for 10 days (included levofloxacin if sensitive) plus co-treatment with oral Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®) daily for two months; Group B2 with specific antibiotic treatment for 10 days plus Serenoa repens 320 mg/day for two months. The groups treated with Prostamev Plus® in comparison to the groups treated with Serenoa repens extract (saw palmetto) achieved better improvements of both IPSS score, urinary flow and sexual life. KEY WORDS: Prostatitis; Urinary flow; Erectile function. Submitted 18 December 2014; Accepted 31 January 2015 Summary No conflict of interest declared. repens alone in reducing the symptoms of prostatitis in patients with inflammatory prostatitis (bacterial and nonbacterial) detected at ecocolor Doppler. It was also evaluated the impact of this combination therapy on quality of life of individuals and their erectile function. MATERIALS AND METHODS We identified two groups of 50 patients each, matched for age and symptoms of inflammation of the prostate and with ecocolor Doppler of the prostate indicative of prostatitis. Inclusion criteria were: age between 40 and 65 years, digital rectal examination (DRE) negative for prostate cancer, ecocolor Doppler indicative for prostatitis at enrollment, IPSS > or = 15, prostatic volume < 60 mL, RPM < 50 mL, reported normal libido and testosterone levels between 1.75 and 7.80 ng/mL. Exclusion criteria: ongoing therapy with alpha-lytic, finasteride, dutasteride or tadalafil; presence of kidney or bladder stones, neurogenic bladder, bladder diverticu- lum, urethral stricture, bladder or prostate cancer, recent abdominal surgery, psychiatric therapy. Group A consisted of patients (mean age 58.2) with ure- thral swab or seminal culture negative for common germs, Mycoplasma and Chlamydia; group B (mean age 57.9) included patients with microbiology positive for E. coli and Enteorcoccus faecalis. Both groups were further divided into two subgroups (respectively A1-A2 and B1-B2) which were subjected to different treatments. Thus we obtained four sub-groups of 25 subjects each. The treatments administered are shown in Table 1. During the study, 6 patients were excluded from follow up due to the need to take other drugs or for other per- sonal reasons. All patients were assessed at enrollment and after two months with uroflowmetry, evaluation of post-voiding volume (PVV), IPSS (International Prostatic Symptoms Score), NIH-CPSI (National Institute of Health- Chronic Symptom Index) and IIEF-5 (International Index of Erectile Function-5). The efficacy of treatment within each subgroup was assessed by T test for paired data (within each group, comparing data before and after treatment). The comparison between the different groups was per- formed using chi-square test. DOI: 10.4081/aiua.2015.1.25 INTRODUCTION Prostatic inflammation is very common and it is a fre- quent presentation to our outpatient urological and andrology clinic. However, patients, despite the evidence of inflammation at color Doppler examination of the prostate, often show negative results of seminal culture or urethral swabs. For this reason the presence of posi- tive laboratory findings cannot be considered essential for the diagnosis of prostatitis. Serenoa repens (SR) is a remedy for prostatitis which is recognized in the litera- ture showing effectiveness in both patients with prostat- ic hyperplasia (BPH) and in those with prostatic volume in the normal range. Several products on the market associate Serenoa repens to other substances with anti- inflammatory action. The aim of the study is to evaluate the effectiveness of co- treatment with Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®) in comparison to Serenoa Marzano_Stesura Seveso 02/04/15 10:17 Pagina 25 Archivio Italiano di Urologia e Andrologia 2015; 87, 1 R. Marzano, N. Dinelli, V. Ales, M.A. Bertozzi 26 RESULTS Uroflowmetry (Qmax): Patients in group A1 showed an improvement of the average value of Qmax from 23 ml/sec to 29 ml/sec (+ 26%), while in the group A2 average value of Qmax rose from 22 ml/sec to 26 ml/sec (+ 18%). Patients in group B1 showed an improvement of the average value of Qmax from 19 ml/sec to 24 ml/sec (+ 28%), while in the group B2 Qmax increased from 21 ml/sec to 25 ml/sec (+ 20%). Therefore the groups A1 and B1 showed an higher over- all improvement than the groups A2 and B2 (both groups showed significant increases in flow after 2 months of therapy). Post Voiding Volume (PVV) Not statistically significant Improvements were observed (p > 0.1). IPSS All groups showed a reduction of mean IPSS score after treatment, although of limited clinical significance. NIH-CPSI Results of NIH-CPSI scores are listed in Table 2. IIEF-5 Finally, patients of groups A1, B1 and B2 showed an improvement of sexual life according to the IIEF-5 ques- tionnaire by an average of about 10% in comparison to 4% of the group A2. DISCUSSION The groups treated with Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®), with or without antibiotic therapy, showed an improvement in all param- eters compared to the groups treated with saw palmetto, with or without associated antibiotic therapy. This effect could be explained by the effectiveness of the combina- tion of Serenoa repens, Bromeline and Nettle. Bromeline has mainly an anti-inflammatory effect and is particularly effective in localized inflammation especially in the presence of edema. The use of Bromeline is safer than other anti-inflammatory drugs due to the difference in the mechanism of action. In fact, conventional non steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase, so blocking the synthesis of prosta - glandins. On the contrary, Bromeline “hijacks” this syn- thesis, increasing the production of prostaglandins with anti-inflammatory activity to the detriment of those with pro-inflammatory activity thereby preventing the gas- trointestinal damage typical of NSAIDs. This difference in the mechanism of action explains the synergy that it may have with NSAIDs, thus obtaining an enhancement of their anti-inflammatory effects. Furthermore it is known its synergism with antibiotic and anticancer ther- apies. Nettle (Urtica dioica) confirmed a synergistic action with antibiotics in prostatitis (10-12). CONCLUSIONS Both groups of patients treated with the combination of Serenoa repens, Bromeline and Nettle in association with antibiotic therapy showed an improvement in all the Table 1. Treatment administered. Group A1 = levofloxacin 500 mg daily for 10 days + Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®) daily for two months. Group A2 = levofloxacin 500 mg daily for 10 days + Serenoa repens (320 mg)/day for two months. Group B1 = specific antibiotic treatment for 10 days (including levofloxacin if sensitive) + co-treatment with Serenoa repens (320 mg) plus Bromeline plus Nettle (Prostamev Plus®) daily for two months. Group B2 = specific antibiotic treatment for 10 days + Serenoa repens (320 mg)/day for two months. Figure 1. Results of uroflowmetry. Figure 2. Data about sexual life. PAIN MICTURITION QUALITY OF LIFE (T0/2 months) (T0/2 months) (T0/2 months) A1 8.1/5.2 7.5/5.4 10.2/6.3 A2 8.2/5.5 7.1/5.3 9.7/7 B1 8.7/4.5 8.2/4.7 8.9/5.5 B2 8.5/5.7 7.1/5.8 8.5/6.1 Table 2. Results of NIH-CPSI (N° of cases = 96). Marzano_Stesura Seveso 02/04/15 10:17 Pagina 26 27Archivio Italiano di Urologia e Andrologia 2015; 87, 1 Effectiveness on urinary symptoms and erectile function of Prostamev Plus® vs only extract Serenoa repens parameters considered in this study after 2 months of therapy. The advantage of using a co-treatment that associates Nettle and Bromeline to saw palmetto is evident both in the improvement of flowmetry values and in the scores of IIEF-5 and NIH-CPSI questionnaires (groups A1 and B1 vs A2 and B2). There were no reported side effects in addition to those provided for the simple antibiotic therapy. The groups treated with the combination of Serenoa repens, Bromeline and Nettle obtained substantial improvements from the point of view of sexual life. REFERENCES 1. Giulianelli R, et al. Multicentre study on the efficacy and tolera- bility of an extract of Serenoa repens in patients with chronic benign prostate conditions associated with inflammation. Arch Ital Urol Androl. 2012; 84:94-98. 2. Lowe FC, et al. Phytotherapy in treatment of benign prostatic hyperplasia: a critical review. Urology. 1996; 48:12-20. 3. Bent S, et al. Saw palmetto for benign prostatic hyperplasia.N Engl J Med. 2006; 354:557-66. 4. Barnes, et al. Saw palmetto, Serenoa repens. Also known as Serenoa serrulata, Sabal serrulata and the dwarf palm. J Prim Healt Care. 2009; 1:323. 5. Debruyne F1, Boyle P, Calais Da Silva F, et al. Evaluation of the clinical benefit of Permixon and tamsulosin in severe BPH patients- PERMAL study subset analysis. Eur Urol. 2004; 45:773-9. 6. Carraro JC, et al. Comparison of phitotherapy (Permixon) with finasteride in the treatment of benign prostatic hyperplasia: a ran- domized international study of 1098 patients. Prostate. 1996; 29:231-40. 7. Debruyne, et al. Comparison of phitotherapy (Permixon) with an alpha-blocker (Tamsulosin) in the treatment of benign prostatic hyperplasia: a 1-year randomized international study. Eur Urol. 2002; 41:497-506. 8. Gerber GS. The role of a lipido-sterolic extract of Serenoa repens in the mamagement of lower urinary tract symtoms associated with benign prostatic hyperplasia. BJU Int. 2004; 94:338-44. 9. Schaeffer AJ. Chronic Prostatitis Collaborative Research Network. Overview summary statement. Diagnosis and management of Chronic Prostatitis/Chronic Pelvic pain syndrome (CP/CPPS). Urology 2002; 60:1-4. 10. Pavone C, Abbadessa D, Tarantino ML, et al. Associating Serenoa repens, Urtica dioica and Pinus pinaster. Safety and effica- cy in the treatment of lower urinary tract symptoms. Prospective study on 320 patients. ]. Urologia. 2010; 77:43-51. 11. Giannarini G, Autorino R. Re: Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents. 2009; 34:283-4. 12. Cai T, Mazzoli S, Bechi A, et al. Serenoa repens associated with Urtica dioica (ProstaMEV) and curcumin and quercitin (FlogMEV) extracts are able to improve the efficacy of prulifloxacin in bacterial prostatitis patients: results from a prospective randomised study. Int J Antimicrob Agents. 2009; 33:549-53. Correspondence Raffaele Marzano, MD Nicola Dinelli, MD (Corresponding Author) n.dinelli@ao-pisa.toscana.it Valeia Ales, MD Maria Antonella Bertozzi, MD, Director Andrology Unit, Santa Chiara Hospital, Pisa, Italy Marzano_Stesura Seveso 02/04/15 10:17 Pagina 27