293Archivio Italiano di Urologia e Andrologia 2017; 89, 4 ORIGINAL PAPER Effectiveness on mild stress and mixed urinary incontinence and impact on Quality of Life of a phytotherapic product containing astragalus, thyme, lavender, hop, equisetum, red clover, cypress and agrimonia at titrated concentrations. Results from a monocentric study Oreste Risi 1, Michele Manica 1, Rocca Carmela Lisanti 2, Antonio Manfredi 1, Giuseppe Romeo Tecci 1 1 SSD Urodinamica e Andrologia, ASST Bergamo Ovest, Italy; 2 UO Urologia, Humanitas Cliniche Gavazzeni, Bergamo, Italy. Objectives: To assess any beneficial effect on quality of life of a daily treatment with a phytotherapic product containing astragalus, thyme, lavender, hop, equisetum, red clover, cypress and agrimonia at titrated concentrations in a cohort of female patients complaining mild stress urinary incontinence (SUI) or mixed urinary inconti- nence (MUI). Materials and methods: 42 non-consecutive female out-patients with mild SUI or mild MUI were assessed with a clinical evalu- ation, International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) and Patients’ Perception of Intensity of Urgency Scale (PPIUS) at baseline the start of the study and after two months of therapy with the phytothera- pic product. At the end of the therapy the patients also com- piled Patient Global Impression of Improvement (PGI-I). Results: After the completion of the study there was a trend towards better results in each item of ICIQ-SF, but without any statistical significance with an average score in ICIQ-SF-1 of 3.12 ± 0.981 versus 3.21 ± 0.914 (p = 0.556), in ICIQ-SF-2 of 3.69 ± 1.422 versus 3.79 ± 1.372 (p = 0.68) and in ICIQ-SF-3 of 5.95 ± 1.618 versus 6.14 ± 1.670 (p = 0.462). The average reduction of PPIUS was of 0.09 (1.26 ± 1.481 versus 1.357 ± 1.509, p = 0.705). There was a reduction of average consump- tion of pads/die from 1.69 ± 0.636 to 1.54 ± 0.543 (p = 0.101). In relation to the PGI score, 23/42 patients (54.7%) reported no changes after the completion of the therapy, 13/42 (30.9%) reported a slight improvement, 5/42 (11.9%) were much improved and 1/42 (2.3%) was slightly worsened. Only 2/42 (4.7%) patients discontinued the treatment before of the com- pletion of the study. We did not observe any adverse effects during the period of the study. Conclusions: The phytotherapic product seems to cause a slight improvement of the symptoms in a good rate of patients. Moreover it has a low rate of withdrawal, due to the lack of adverse events. KEY WORDS: Mixed urinary incontinence; Stress urinary inconti- nence; Phytoterapy; QoL. Submitted 7 March 2017; Accepted 6 October 2017 Summary No conflict of interest declared. sneezing or coughing. Mixed urinary incontinence (MUI) is defined as the involuntary loss of urine associated with urgency or with effort or physical exertion or on sneezing or coughing (1). In most studies the reported prevalence in females of isolated SUI was of 10-39%, accounting for about a half of all the cases of urinary incontinence. MUI is the second most common type, with reported preva- lence of 7.5-25% in most studies (1). Therefore SUI and MUI represent an important and common problem involving many women with a high social impact (2). Nowadays, according to European Association of Urology Guidelines, the first-line treatment for SUI is a supervised intensive pelvic floor muscle training (PMFT). Biofeedback can be considered as an adjunct in these patients (3). Duloxetine 80 mg was proposed as oral ther- apy for SUI but there is no evidence suggesting that it can be offered to women who are seeking a definitive cure for their incontinence. Furthermore Duloxetine had a high withdrawal rate primarily because of the high rate of adverse events (3-6). Therefore apart from the surgical treatment we have no other choice for SUI treatment after the PMFT and eventually the biofeedback. In MUI, PMFT seems to be less effective than in pure SUI (7). Both Duloxetine and antimuscarinic drugs seem to be effective to treat SUI but it is known that most patients stop drugs because of low level of efficacy, onset of adverse events and high costs of therapy (3, 5, 8). IncontinenzaMEV® 1260 mg is a phytotherapic product with antioxidant properties, proposed as natural remedy to induce physiological effects optimizing the functions of the urinary tract: microcirculation, relaxation, connec- tive tissue tropism. The aim of this study is to assess any beneficial effect on the quality of life (QoL) of a daily treatment with IncontinenzaMEV® in a cohort of female patients complaining mild SUI or MUI. MATERIALS AND METHODS From June 2015 to June 2016, 42 female non-consecu- tive out-patients with a median age of 58 years (range DOI: 10.4081/aiua.2017.4.293 INTRODUCTION Stress Urinary Incontinence (SUI) is defined as the involun- tary loss of urine on effort or physical exertion or on Risi_Stesura Seveso 03/01/18 12:23 Pagina 293 Archivio Italiano di Urologia e Andrologia 2017; 89, 4 O. Risi, M. Manica, R.C. Lisanti, A. Manfredi, G.R. Tecci 294 35-72, mean) referring to the Department of Urodynamics and Andrology of the ASST Bergamo Ovest and suffering from mild SUI or mild MUI were treated with IncontinenzaMEV® and prospectively evaluated. Each patient was assessed before therapy (T0) with an accurate medical history, an urogynaecological examina- tion, a comprehensive examination of urine including urine culture, a 3-day voiding diary, an evaluation of number of pads used per day, a 24-hour pad test, and a compilation of the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF). Moreover each patient compiled the Patients’ Perception of Intensity of Urgency Scale (PPIUS), a patient-reported instrument to measure the intensity of the urgency. Inclusion criteria were: mild SUI or mild MUI defined as a range of urine loss for the 24-hour pad test from 4 to 20 g, incontinence since at least 6 months, a positive stress-test. Exclusion criteria were: positive urine culture, moderate and severe SUI (urine loss > 20 g for the 24-hour pad test), concomitant complicating factors as previous surgery for incontinence, previous pelvic radiotherapy, grade 3 or symptomatic prolapse, hematuria, pain or pelvic mass. The 42 patients included in the study assumed IncontinenzaMEV® one tablet/daily for two months. IncontinenzaMEV® 1260 mg is a phytotherapic product containing astragalus, thyme, lavender, hop, equisetum, red clover, cypress and agrimonia at titrated concentra- tions. During the period of the study no other drugs for incon- tinence were administered. At the end of the therapy (T1) all the patients were inter- viewed again and compiled again ICIQ-SF and PPIUS. Furthermore they filled the Patient Global Impression of Improvement (PGI-I), a 1-item questionnaire to evaluate the subjective feeling of improvement. The statistical analysis was performed using IBM SPSS Statictics 23. The comparison of the data relative to ICIQ-SF an PPIUS before and at the end of the therapy was performed using Wilcoxon Signed Ranks Test. The comparison between the used pads was made with Student's T-Test. We considered statistically significant a p value ≤ 0.05. RESULTS Eight out of 42 (19%) patients had a MUI with relevant urgency incontinence, evaluated by PPIUS; 34/42 (81%) complained an isolated SUI with (17/34) or without (17/34) urgency symptoms. After the completion of the study there was a trend towards better results in each item of ICIQ-SF, without any statistical significance with an average score in ICIQ- SF-1 of 3.12 ± 0.981 versus 3.21 ± 0.914 (p = 0.556), in ICIQ-SF-2 of 3.69 ± 1.422 versus 3.79 ± 1.372 (p = 0.68) and in ICIQ-SF-3 of 5.95 ± 1.618 versus 6.14 ± 1.670 (p = 0.462). Five out of 17 patients (29.4%) who reported urgency symptoms before the beginning of the therapy, improved their PPIUS score, while 1/17 reported a worse value. The average reduction of PPIUS was of 0.09 (1.26 ± 1.481 versus 1.357 ± 1.509, p = 0.705). None of the 8 patients with a component of urge incon- tinence (defined as an initial PPIUS score = 4) changed their initial value. There was a reduction of average consumption of pads/die from 1.69 ± 0.636 to 1.54 ± 0.543 (p = 0.101). These results are showed in Table 1. With regard to the PGI score, 23/42 patients (54.7%) reported no changes after the completion of the therapy, 13/42 (30.9%) reported a slight improvement, 5/42 (11.9%) were much improved and 1/42 (2.3%) was slight- ly worsened. These results are described in Figure 1. Only 2/42 (4.7%) patient discontinued the treatment before of the completion of the study because of the lack of efficacy of treatment. We did not observe any adverse effects during the peri- od of the study. DISCUSSION Pharmacological treatment of stress and mixed urinary incontinence is still a hot topic because of the of low effi- cacy, the adverse events, and the high costs of the of the available drugs (3, 5, 8). Approximately 50% of patients in treatment with antimus- carinic drugs discontinue therapy at 3 months, mainly because of the relevant side effects (9). In the last years Mirabegron was proposed for the use in overactive bladder with a grade B of recommendation (3). This drug seems to cause less dry mouth than anti- cholinergic medications, however the incidence of other side effects such as constipation, hypertension and tachycardia is comparable (10). Duloxetine was proposed besides PMFT as oral therapy for SUI with controversial results and high withdrawal rate (5). Table 1. Results of the ICIQ-SF, PPIUS, pads/die at T0 and at T1. T0 T1 Δ P ICIQ-SF 1 3.21 ± 0.914 3.12 ± 0.981 0.09 0.556 ICIQ-SF 2 3.79 ± 1.372 3.69 ± 1.422 0.10 0.689 ICIQ-SF 3 6.14 ± 1.670 5.95 ± 1.618 0.19 0.462 PPIUS 1.357 ± 1.509 1.26 ± 1.481 0.09 0.705 n pads 1.69 ± 0.636 1.54 ± 0.543 0.15 0.101 Figure 1. Frequency distribution of the answers to PGI-I questionnaire: “check the number that best describes how your post-treatment condition is now, compared with how it was before you had the treatment”. Risi_Stesura Seveso 03/01/18 12:23 Pagina 294 In this study we evaluated the effects on MUI and SUI of a daily therapy with IncontinenzaMEV, a new phytother- apic product. The main limitations of our study are mono- centric design, low number of patients and lack of a place- bo control group. Given these limitations we observed a slight improvement in 30.9% of patients treated with the study product and a more consistent improvement in 5 patients of the series (11.9% of subjects.). These results are inferior respect to a recent study on Mirabegron which prospectively evaluated PGI-I in 317 women after 6 weeks of drug therapy: 11% described themselves as “very much better” and a further 23% as “much better”. Anyway the target of this study was differ- ent because only women with overactive bladder (OAB) were selected. Moreover there was a higher rate of with- drawal (14.6%) (11). The same considerations are possible for another study which evaluated the PGI scores in a series of 50 women patients treated with duloxetine for a pure SUI: 65% showed improvement after a 12 weeks-treatment but the group was more homogeneous than ours. Moreover also in this series there was a higher number of dropouts and adverse events (12). In our study all the questionnaires administrated showed a trend towards better scores after the two months of therapy but we had not a statistical sig- nificance. The more evident improvement was relative to the QoL (ICIQ-SF-3). Conversely an important result is the low rate of withdrawal during all the period of the study, probably due to the lack of adverse effects of this remedy for incontinence. CONCLUSIONS To our knowledge this is the first study on Incon ti - nenzaMEV. With the limits of a small sample of patients and of the lack of a control group this product seems to cause a slight improvement of the symptoms in a good rate of patients. Moreover unlike other drugs it has a very low rate of withdrawal. Further studies with a control group are warranted to offer a recommendation and to better assess the target of this product. REFERENCES 1. Abrams P, Cardozo L, Khoury S, Wein A. Incontinence. 5th edi- tion, ICUD-EAU 2013. 2. Cervigni M, Gambacciani M. Female urinary stress incontinence. Climacteric. 2015; 18 Suppl 1:30-6. 3. Burkhard FC, Lucas MG, Berghmans JL, et al. EAU Guidelines on Urinary Incontinence in Adults. European Association of Urology 2016. 4. Shamliyan TA, Kane RL, Wyman J, Wilt TJ. Systematic review: randomized, controlled trials of nonsurgical treatments for urinary incontinence in women. Ann Intern Med. 2008; 148:459-73. 5. Mariappan P, Alhasso A, Ballantyne Z, et al. Duloxetine, a sero- tonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence: a systematic review. Eur Urol. 2007; 51:67-74. 6. Ghoniem GM, Van Leeuwen JS, Elser DM, et al. A randomized controlled trial of duloxetine alone, pelvic floor muscle training alone, combined treatment and no active treatment in women with stress urinary incontinence. J Urol. 2005; 173:1647-53. 7. Lagro-Janssen T, van Weel C. Long-term effect of treatment of female incontinence in general practice. Br J Gen Pract. 1998; 48:1735-8. 8. Sears CL, Lewis C, Noel K, et al. Overactive bladder medication adherence when medication is free to patients. J Urol. 2010; 183:1077-1081. 9. Wagg A, Compion G, Fahey A, Siddiqui E. Persistence with pre- scribed antimuscarinic therapy for overactive bladder: a UK experi- ence. BJU Int. 2012; 110:1767-74. 10. Warren K, Burden H, Abrams P. Mirabegron in overactive blad- der patients: efficacy review and update on drug safety Ther Adv Drug Saf. 2016; 7:204-6. 11. Balachandran A, Duckett J. The efficacy and tolerability of mirabegron in a non-trial clinical setting. Eur J Obstet Gynecol Reprod Biol. 2016; 200:63-7. 12. Deepak P, Kumar TN, Sen TK. Evaluation of efficacy of duloxe- tine in stress urinary incontinence in women. Indian J Pharmacol. 2011; 43:176-9. 295Archivio Italiano di Urologia e Andrologia 2017; 89, 4 Effectiveness on mild stress and mixed urinary incontinence and impact on Quality of Life of a phytotherapic product containing... Correspondence Oreste Risi, MD (Corresponding Author) oreste_risi@asst-bgovest.it Michele Manica, MD, FEBU manicaxmichele@gmail.com Antonio Manfredi, MD antonio_manfredi@asst-bgovest.it Giuseppe Romeo Tecci, MD rom.doc@libero.it SSD Urodinamica e Andrologia, ASST Bergamo Ovest Piazzale Ospedale 1, 24047 Treviglio (BG), Italy Rocca Carmela Lisanti, MD rocca.lisanti@gavazzeni.it UO Urologia, Humanitas Cliniche Gavazzeni Via Mauro Gavazzeni 21, 24125 Bergamo (BG), Italy Risi_Stesura Seveso 03/01/18 12:23 Pagina 295