Elsevier

European Urology

Volume 41, Issue 5, May 2002, Pages 497-507
European Urology

Comparison of a Phytotherapeutic Agent (Permixon) with an α-Blocker (Tamsulosin) in the Treatment of Benign Prostatic Hyperplasia: A 1-Year Randomized International Study

https://doi.org/10.1016/S0302-2838(02)00066-0Get rights and content

Abstract

Objective: While the lipido-sterolic extract of Serenoa repens (LSESr)—Permixon®—has been shown to have an equivalent efficacy to finasteride in patients with benign prostatic hyperplasia (BPH), to date, there has been no valid comparison of phytotherapy with α-blockers. The aim of this study was to assess the equivalent efficacy of Permixon and tamsulosin.

Methods: Eight hundred and eleven men with symptomatic BPH (I-PSS≥10) were recruited in 11 European countries for a 12-month, double-blind randomized trial. After a 4-week run-in period, 704 patients were randomly assigned to either tamsulosin 0.4 mg/day (N=354) or Permixon 320 mg/day (N=350). I-PSS, QoL and Qmax were evaluated at baseline and periodically for 1 year. Prostate volume and serum prostate-specific antigen (PSA) were measured at selection and at endpoint. The endpoint analysis was performed on the per-protocol population of 542 patients (tamsulosin: N=273; Permixon: N=269).

Results: At 12 months, I-PSS decreased by 4.4 in each group and no differences were observed in either irritative or obstructive symptom improvements. The increase in Qmax was similar in both treatment groups (1.8 ml/s Permixon, 1.9 ml/s tamsulosin). PSA remained stable while prostate volume decreased slightly in the Permixon-treated patients. The two compounds were well tolerated, however, ejaculation disorders occurred more frequently in the tamsulosin group.

Conclusion: This study demonstrates that Permixon and tamsulosin are equivalent in the medical treatment of lower urinary tract symptoms in men with BPH, during and up to 12 months of therapy.

Introduction

Low urinary tract symptoms (LUTS) are frequently associated with benign prostatic hyperplasia (BPH), a non-malignant enlargement of the prostate which occurs predominantly in men aged over 60 years. Since medical therapy offers an attractive alternative to surgery, the number of transurethral resections of the prostate has declined in recent years and 5α-reductase inhibitors, α-blockers and phytotherapeutic agents are assuming increasing importance in the treatment of LUTS [1], [2], [3], [4], [5], [6]. However, the tolerability of these agents varies. Indeed, some α1-blockers are associated with postural hypotension and 5α-reductase inhibitors with sexual dysfunction [7]; thus, the use of phytotherapy (plant extracts) to alleviate the symptoms of BPH is of growing interest.

The most extensively prescribed and studied phytotherapeutic agent approved as a medical treatment of symptomatic BPH, is a lipido-sterolic extract of Serenoa repens (LSESr), Permixon®. The clinical efficacy of Permixon in the medical management of BPH has been demonstrated in four different short-term trials [8], [9], [10], [11]. A recent meta-analysis of all published Permixon trials has added evidence on its efficacy over placebo [12]. In a comparative 6-month study, Permixon showed equivalent efficacy to finasteride in the treatment of men with mild or moderate symptoms of BPH [13].

Randomized controlled trials and meta-analyses have demonstrated that all α-blockers (alfuzosin, doxazosin, prazosin, terazosin, tamsulosin) are similarly effective in relieving LUTS and increasing urinary flow and that they are superior to both placebo and finasteride [14], [15], [16], [17].

Although a small comparative study with alfuzosin was performed [18], it was limited in time and number of patients, which prompted our study group to undertake a long-term comparative study with an α-blocker. The present study was designed to compare the efficacy and safety of Permixon with tamsulosin over 12 months in men with LUTS secondary to BPH.

Section snippets

Patients

The trial was conducted in 98 centers throughout Europe from March 1998 to April 2000 in accordance with the declaration of Helsinki and European Good Clinical Practice guidelines. Approval was obtained from local ethics committees. All patients gave written informed consent prior to the study.

Men, aged between 50 and 85 years, were recruited for the study according to their International Prostate Symptom Score (I-PSS≥10 points). Other inclusion criteria included a maximum urinary flow rate (Q

Results

Eight hundred and eleven men were screened, and 704 were randomized to treatment: 350 to Permixon and 354 to tamsulosin (Fig. 1). During the run-in period, the mean total I-PSS decreased from a mean (S.D.) of 16.8 (4.6) to 15.3 (5.0) in the ITT efficacy dataset. The mean Qmax increased from 10.1 (2.8) ml/s to 11.0 (4.1) ml/s. The randomized groups had comparable distributions in terms of age, body mass index (BMI), I-PSS, Qmax, prostate volume and PSA as shown in Table 1. The mean patient age was

Discussion

This study was designed to assess the equivalent efficacy of Permixon, a phytotherapeutic agent, and tamsulosin, a selective α-blocker, commonly used for the treatment of LUTS related to BPH. To account for the well-documented and substantial placebo effect, always present in the management of symptomatic patients with BPH, a 4-week placebo run-in phase was included in the study.

In the absence of a placebo arm, the possible sources of biases were minimized. Indeed, the number of patients

Acknowledgements

Supported by a grant from Pierre Fabre Médicament, Castres, France, manufacturer of Permixon. The authors have received research grants from or have served as consultants or members or speakers for Pierre Fabre Médicament and/or for other companies that make products used in the treatment of BPH.

References (37)

  • C. Iehlé et al.

    Human prostatic steroid 5alpha-reductase isoforms. A comparative study of selective inhibitors

    J. Steroid Biochem. Mol. Biol.

    (1995)
  • J.E. Oesterling

    Benign prostatic hyperplasia. Medical and minimally invasive treatment options

    N. Engl. J. Med.

    (1995)
  • A.C. Buck

    Phytotherapy for the prostate

    Br. J. Urol.

    (1996)
  • T.J. Wilt et al.

    Saw palmetto extracts for treatment of benign prostatic hyperplasia: A systematic review

    JAMA

    (1998)
  • A. Chacon et al.

    Medical management of benign prostatic hyperplasia

    Geriatr. Nephrol. Urol.

    (1999)
  • G.M. Clifford et al.

    Medical therapy for benign prostatic hyperplasia: A review of the literature

    Eur. Urol.

    (2000)
  • G. Champault et al.

    A double-blind trial of an extract of the plant Serenoa repens in benign prostatic hypertrophy

    Br. J. Clin. Pharmacol.

    (1984)
  • A. Tasca et al.

    Treatment of obstructive symptomatology caused by prostatic adenoma with an extract of Serenoa repens. Double-blind clinical study vs. placebo

    Minerva Urol. Nefrol.

    (1985)
  • Cited by (153)

    • Phytotherapy in Benign Prostatic Hyperplasia

      2018, Lower Urinary Tract Symptoms and Benign Prostatic Hyperplasia: From Research to Bedside
    • The use of medication in urology

      2017, FMC Formacion Medica Continuada en Atencion Primaria
    • Prostate diseases

      2017, FMC Formacion Medica Continuada en Atencion Primaria
    • Saw Palmetto for Symptom Management during Radiation Therapy for Prostate Cancer

      2016, Journal of Pain and Symptom Management
      Citation Excerpt :

      It demonstrated no adverse interactions with commonly used medications32,33 nor any effects on the two most common enzymes involved in the metabolic pathway of more than 50% of all marketed prescriptions and over-the-counter medications.34–36 In addition, SP was found to significantly lower the risk of ejaculatory disorders compared to an alpha-adrenergic blocker (0.6%, 4.2%, respectively) among BPH patients.16 In other BPH studies, SP did not affect prostate-specific antigen (PSA) levels in vivo or in vitro when taken as a purified extract,23,37,38 compared to no treatment,38 or to placebo.23

    View all citing articles on Scopus

    Published simultaneously in Progrès en Urologie.

    e1

    [email protected]

    View full text