Comparison of a Phytotherapeutic Agent (Permixon) with an α-Blocker (Tamsulosin) in the Treatment of Benign Prostatic Hyperplasia: A 1-Year Randomized International Study☆
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.
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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.
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2016, Journal of Pain and Symptom ManagementCitation 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
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Published simultaneously in Progrès en Urologie.