Lower urinary tracts symptoms (LUTS) are prevalent in adult men and are often associated with the presence of benign prostatic hypeplasia (BPH) and bladder outlet obstruction (BOO) due to benign prostatic enlargement. Serenoa repens (S. repens) is the phytotherapeutic agent most commonly used to treat LUTS/BPH.  Systematic reviews and meta-analyses of S. repens data from RCTs have reported different results. In a Cochrane meta-analysis Tacklind et al.  concluded that different extracts of S. repens does not improve LUTS or maximum urinary flow rate (Qmax) compared with placebo in men with LUTS/BPH [1]. The assessment report of the S. repens by European Medicine Agency  (EMA) 2015 find out that the activity can differ from one extract to another, probably dependent upon type of extraction and the content of fatty acids [2]. Only hexane extract of S.repens (HESr) was recognized EMA as a well-established medicinal product was with proved efficacy and acceptable safety. Systematic review and meta-analysis Vela-Navarrete et al. (2018) concluded that HESr improve LUTS or maximum urinary flow rate (Qmax) compared with placebo in men with LUTS/BPH and has comparable symptomatic and objective effects with alfa-blockers [3].   It was shown that treatment by alfa-blockers lead to decrease bladder outlet obstruction on 20-35%. But there is lack data of urodynamic effect HESr.  The aim of study was to evaluate the urodynamic and symptomatic impact of the HESr (Permixon®) in the treatment of patients with LUTS/BPH.

This study was pilot, single center, prospective, randomized, single blinded, placebo controlled. A total of 75 patients, aged 51,2 ± 7,9 years  with mild/moderate LUTS according  International Prostate Symptom Score (I-PSS)  were included in the study, of which 60 patients received Permixon 320 mg daily for 12 weeks. The control group (n=15) receive placebo and did not received any medical treatment for LUTs. Patients were randomized into the study groups by investigator. 
Patients were included in the study if they had mild/moderate BPH according to their mean International Prostate Symptom Score (I-PSS) (<19 points), a residual urine volume less than of 100 ml, maximum urinary flow (Qmax) more than 5 ml/s but less than 15 ml/s, no indications for emergency BPH treatment. Exclusion criteria were the presence of urinary tract infections, suggestion of prostate cancer (PSA>4 ng/ml), urological disease affecting micturition, previous urological surgery, detrusor overactivity, neurogenic bladder, concomitant neurogenic disease and renal or liver insufficiency. Patients were also excluded if they were taking concomitant medication that might interfere with study medication, including other 5alfa-reductase inhibitors, alfa blockers, cholinolytics  and antidepressants.
At the initial visit, each patient completed the I-PSS questionnaire and their medical history and concomitant medications were recorded. Prostatic volume evaluation, free flow uroflowmetry  were assessed at baseline and  at the end of the 12-week treatment.
Cystometry and pressure/flow study with a 7F urethral catheter was performed in Medtronic Duet urodynamic equipment. The methods used conformed to the standards of the International Continence Society.

Baseline parameters were comparable between the active treatment and placebo control groups. Treatment with HESr resulted in a significant improvement in symptoms from baseline: I-PSS total score decreased by 26.5% from a baseline of 8.3 points (P<0.001) and the quality of life (QoL) score decreased by 18.5% from a baseline of 3.3 points (P<0.001). None of these parameters improved significantly in control patients. Qmax increased by 6.2% (0.7 ml/s) from a baseline value of 11.7 (P<0.001) in the HESr group. The volume of residual urine in this group also decreased by 12.4% from a baseline value of 49.4 (P<0.05). Prostate volume after HESr treatment (71.6 ml) did not change. There were also improvement in maximum DP (5.2%) in the HESr  group which did not reach significance (p=0.07). After 12 weeks there was no significant difference in mean I-PSS score, QoL score, Qmax, residual volume,  urodynamic parameters  in the control group. Two patients receiving HESr experienced gastrointestinal disturbances but these did not lead to withdrawal or require additional therapy.

In patients with mild/moderate LUTs/BPH, HESr  treatment reduced infravesical obstruction and produced a improvement in urodynamic parameters and symptoms. There were no significant improvements for any of these parameters in the control group despite the fact that both groups were comparable at baseline. The improvement in BOO seen with HESr confirms the positive effects of the drug on urinary function and this may be mainly due to its anti-inflammatory action. The drug was well tolerated.

Treatment of LUTS/BPH  with HESr produced a improvement in urodynamic parameters and symptoms, illustrating a reduction in bladder outlet obstruction. These data demonstrate that HESr  is well tolerated and support its efficacy as first-line phytotherapeutic agent in patients with uncomplicated symptomatic BPH.

Tacklind J, Macdonald R, Rutks I, Stanke JU, Wilt TJ. Serenoa repens for benign prostatic hyperplasia. Cochrane Database Syst Rev 2012; (12): CD001423.
European Medicines Agency. Assessment Report on Serenoa repens (W. Bartram) Small, fructus. Final. Availabl at: http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_HMPC_assessment_report/2016/03/WC500203896.pdf. Published 24 November 2015. Accessed May 2017
Vela-Navarrete R, Alcaraz A, Rodriguez-Antolin A et al. Efficacy and safety of a hexanic extract of Serenoa repens (Permixon) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH):systematic review and meta-analysis of randomised controlled trials and observational studies. BJU Int 2018; 122: 1049–1065