In Brief: Serenoa repens (Permixon ® ), an extract
of the dwarf American palm, has been available for several years for the
treatment of benign prostatic hypertrophy (BPH).
In men with BPH, oral administration of Serenoa repens 160mg twice daily for 1 to 3 months was generally superior to placebo in improving subjective and objective symptoms of BPH. The drug appears to have similar efficacy to finasteride as evidenced by data from over 1000 men. Few significant differences were demonstrated between Serenoa repens and a 1-adrenoceptor blockers in small comparative studies.
Gastrointestinal effects, such as nausea and abdominal pain, have been the most commonly reported adverse effects associated with Serenoa repens in clinical trials.
BPH is a heterogeneous disease, consequently no single agent or group
of drugs is likely to be effective in all patients. Available data suggest
that Serenoa repens may be useful as an alternative to the better established
agents a 1-adrenoceptor blockers
and finasteride. [Drugs & Therapy Perspectives 10(3):1-4, 1997. ©
1997 Adis International Limited]
Introduction
Benign prostatic hypertrophy (BPH) is a common condition in older men; approximately 50% of men aged 60 years and 90% of those aged 85 years present with BPH. [1] The condition is characterised by a nonmalignant enlargement of the prostate resulting from excessive cellular growth of both the glandular and the stromal elements of the gland. [1] Although many men do not seek medical attention, individuals with an enlarged prostate may exhibit urinary tract symptoms, such as acute or chronic urinary retention, frequency, urgency, nocturia or urge incontinence. These symptoms vary in severity and do not appear to be directly related to prostatic volume. [1,2]
The Underlying Cause of BPH
The aetiology of BPH is unknown. One hypothesis infers that BPH occurs following age-related changes in prostatic androgen metabolism which favours accumulation of dihydrotestosterone. [3] This androgen is primarily responsible for prostatic growth and enlargement and is produced in prostatic cells when testosterone is reduced by the enzyme 5a -reductase. Symptoms may also result from increased smooth muscle tone of the bladder neck and prostate, which is regulated by a 1-adrenergic receptors. [1]
What Is Serenoa Repens?
Serenoa repens* (Permixon ® ) is currently available in some European and other countries (e.g. France, Germany and Spain) for the treatment of BPH. The drug is the n-hexane lipidosterolic extract of the pulp and seed of the dwarf American palm (also known as Serenoa repens). It is a complex mixture of various compounds. [1]
Like finasteride, Serenoa repens has inhibitory effects on 5a -reductase. Some of the features of these 2 agents are compared in the Differential Features Table. Various additional mechanisms for the efficacy of Serenoa repens in BPH have also been suggested, including inhibition of binding of dihydrotestosterone to cytosolic androgen receptors in prostate cells. [1]
Management Options
A number of treatment options are available for the management of patients with BPH ranging from invasive procedures to medical therapy with orally administered drugs. Current treatment guidelines suggest that many patients, particularly those who are asymptomatic or have only mild symptoms, require no active treatment (i.e. watchful waiting). [8-10]
TURP Is the Most Effective Option
For those requiring therapy, transurethral resection of the prostate (TURP) has been the mainstay of treatment. Despite being very effective, TURP is associated with a high risk of complications and morbidity, including potential impotence. [2] Additionally, about 20 to 25% of patients do not have a long-term satisfactory outcome after TURP, and many men prefer to avoid the procedure and its potential complications. [1] Other methods may, therefore, be preferable for some individuals.
Rapid Relief with a -Blockers...
Treatment with a 1-adrenoceptor blockers (such as alfuzosin+, doxazosin+, prazosin and terazosin+) can produce rapid relief of symptoms. However, results are not as good as with surgery and adverse effects such as orthostatic hypotension may be problematic. Long-term therapy is required to maintain the benefits. [2]
...But Not with Finasteride
Alternative agents such as finasteride produce moderate reductions in prostate volume when given for a year or more, although this is not always associated with much symptomatic relief. [2] The drug has a slow onset of effect and beneficial effects may not become apparent until after at least 6 or possibly 12 months of therapy. [3]
Phytotherapy an Alternative?
Better than Placebo
Improvements in urinary frequency and peak urinary flow rates generally appear to be greater with Serenoa repens than placebo in patients with BPH. However, a large placebo effect is often seen in these individuals. In 3 studies (each evaluating >50 patients), Serenoa repens 160mg twice daily for 1 to 3 months was associated with: [11-13]
- reductions in urinary frequency at night (33 to 74% vs 13 to 39% with placebo)
- reductions in urinary frequency during the day (11 to 43% vs 1 to 29% with placebo)
- increases in peak urinary flow rate (26 to 50% vs 2 to 35% with placebo).
Dysuria, postmicturition residual urinary volume and subjective symptoms were also improved with Serenoa repens in some studies. [1]
Similar to Finasteride...
Serenoa repens and finasteride have been shown to reduce urinary symptoms to a similar extent (37 vs 39%). Serenoa repens 160mg twice daily was compared with finasteride 5mg once daily for 6 months in over 1000 men with BPH. Urinary symptoms were assessed by the International Prostate Symptom Score. Similar improvements in self-rated quality-of-life scores (69 vs 73%) were also noted between patient groups. [7]
Although both drugs improved peak urinary flow rates and reduced prostate volume, these changes were significantly greater with finasteride. However, a similar percentage of patients in each group had a 30% increase in peak urinary flow rate. Improvements in symptoms occurred rapidly, after 6 weeks of therapy in both groups. [7] Given the high placebo responses seen in these individuals, the inclusion of a placebo group would seem to be an important consideration in studies evaluating men with BPH.
...and Other Comparators
Although there are few comparisons available, clinical efficacy tended to favour the a 1-adrenoceptor blockers, alfuzosin (2.5mg 3 times daily) [14] and prazosin (2mg every 12 hours) [15] over Serenoa repens (160mg twice daily) in 2 studies. However, few significant differences were observed between treatment groups for improvements in urinary frequency, urinary flow rate and postmicturition residual urine volume. These studies evaluated small patient numbers and were of short duration.
Tolerability
Adverse events were reported spontaneously by about 2 to 4% of patients receiving Serenoa repens in clinical trials; therapy was rarely discontinued because of poor tolerability. [1] Gastrointestinal effects, such as nausea and abdominal pain, appear to be the most common adverse effects associated with Serenoa repens. [1] The drug tended to be associated with a higher incidence of hypertension, headache, urinary retention and back pain than finasteride in 1 large study, but a lower incidence of gastrointestinal complaints, impotence, dysuria and decreased libido. [7]
Serenoa repens should be taken with meals to minimise possible gastrointestinal disturbances. [1]
Formulary and Prescribing Considerations
Clearly, Serenoa repens may have some benefit in men with BPH. Overall, however, few comparative studies are available with other agents currently used for the management of BPH, particularly the a 1-adrenoceptor blockers. [1] BPH is a heterogeneous disease and, as such, no single agent or group of drugs is likely to be effective in all patients. In view of this, Serenoa repens will probably be used as an alternative to the better established agents, a 1-adrenoceptor blockers and finasteride.
Adis Evaluation
Key Points in the Overall Evaluation of Serenoa Repens in Benign Prostatic Hypertrophy
Clinical Benefits
- Appears to have greater efficacy than placebo
- Appears to have similar efficacy to finasteride and a 1-adrenoceptor blockers
- Low incidence of sexual dysfunction
Potential Limitations
Benign Prostatic Hypertrophy: Decision-Making Programme Useful
A shared decision-making programme (SDP) can improve treatment decisions for benign prostatic hy-pertrophy (BPH). [16] In a 1-year randomised survey conducted in 227 men with BPH in the US, 104 men underwent the SDP. [16] This programme involved an in-troductory brochure and an individually tailored multi-media presentation; 123 men received a control brochure. Both the SDP presentation and the control brochure contained information regarding the various treatment options (`watchful waiting', drug therapy or surgery), but only the SDP presentation included esti-mates of treatment outcome probabilities.
Although there was no significant difference between the 2 groups in the treatment options selected, patients in the SDP group were significantly better informed about BPH than control patients at 2 weeks after enrolment. The SDP group was also significantly more satisfied with the decision-making process at 3 and 12 months. General health and physical functioning remained stable among patients in the SDP group but deteriorated among control patients.
| * | Serenoa repens is not available in Australia, Canada, Denmark, The Netherlands, the UK and the US. |
| + | Alfuzosin is not available in Australia and the US; doxazosin is not available in France; terazosin is not available in France. |
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