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LE Magazine April 2006
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Pygeum

Pygeum africanum for the treatment of patients with benign prostatic hyperplasia: a systematic review and quantitative meta-analysis.

PURPOSE: To conduct a systematic review and quantitative meta-analysis of the therapeutic efficacy and tolerability of Pygeum africanum in men with symptomatic benign prostatic hyperplasia. METHODS: Studies were identi- fied through the search of Medline (1966 to 2000), Embase, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies. Randomized trials were included if participants had symptomatic benign prostatic hyperplasia, the intervention was a preparation of P. africanum alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacologic therapies for benign prostatic hyperplasia, and treatment duration was at least 30 days. Two investigators independently extracted key data on design features, subject characteristics, and therapy allocation.RESULTS: A total of 18 randomized controlled trials involving 1,562 men met the inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Only 1 of the studies reported a method of treatment allocation concealment, although 17 were double-blinded. The mean study duration was 64 days (range 30 to 122). Compared with placebo in 6 studies, P. africanum provided a moderately large improvement in the combined outcome of urologic symptoms and flow measures as assessed by an effect size defined by the difference of the mean change for each outcome divided by the pooled standard deviation for each outcome (-0.8 SD [95% confidence interval (CI): -1.4 to -0.3]). Summary estimates of individual outcomes were also improved by P. africanum. Men were more than twice as likely to report an improvement in overall symptoms (risk ratio = 2.1, 95% CI: 1.40 to 3.1). Nocturia was reduced by 19% and residual urine volume by 24%; peak urine flow was increased by 23%. Adverse effects due to P. africanum were mild and similar to placebo. The overall dropout rate was 12% and was similar for P. africanum (13%), placebo (11%), and other controls (8%; P = 0.4 versus placebo and P = 0.5 versus other controls). CONCLUSIONS: The literature on P. africanum for the treatment of benign prostatic hyperplasia is limited by the short duration of studies and the variability in study design, the use of phytotherapeutic preparations, and the types of reported outcomes. However, the evidence suggests that P. africanum modestly, but significantly, improves urologic symptoms and flow measures. Further research is needed using standardized preparations of P. africanum to determine its longterm effectiveness and ability to prevent complications associated with benign prostatic hyperplasia.

Am J Med. 2000 Dec 1;109(8):654-64

Low-dose tadenan protects the rabbit bladder from bilateral ischemia/ reperfusion-induced contractile dysfunction.

Recent studies indicate that focal ischemia/reperfusion (I/R) can cause the contractile dysfunctions induced in animal models of partial bladder outlet obstruction. Tadenan (Pygeum africanum) pretreatment can prevent the rabbit bladder from developing the contractile and biochemical dysfunctions induced by partial outlet obstruction, possibly by protecting the bladder from ischemic injury. The current study was designed to determine whether pre-treating rabbits with a clinically relevant dose of Tadenan could prevent the bladder from developing the contractile dysfunctions that are induced by bilateral ischemia followed by reperfusion. New Zealand White rabbits were separated into two groups. One group was pretreated by oral gavage for 3 weeks with Tadenan (3.0 mg/kg body wt./ day). The second group was treated with vehicle (peanut oil). Five rabbits from each group were subjected to either bilateral ischemia for 1 or 3 h and than reperfused for either 1 h or 1 week. Five rabbits from each group were subjected to sham surgery and run with each of the experimental groups. The results of the current study show that Tadenan pretreatment at the clinically relevant dose of 3.0 mg/kg body wt./day protected the bladder from the contractile dysfunctions induced by bilateral ischemia followed by reperfusion. These data are consistent with the assertion that Tadenan therapy in both rabbits and humans acts by protecting the bladder smooth muscle against cellular damage caused by ischemia and reperfusion.

Phytomedicine. 2005 Jan;12(1-2):17-24

Dihydrotestosterone and the role of 5 alpha-reductase inhibitors in benign prostatic hyperplasia.

The genesis of benign prostate hyperplasia (BPH) depends on two factors: testicular androgen and the aging process. The most important androgen in the prostate is dihydrotestosterone (DHT). In the aging male the level of DHT in the prostate remains largely constant although the plasma level of testosterone decreases. DHT is formed by the reduction of testosterone by the enzyme 5-alpha-reductase, which has two isoenzymes. The 5-alphareductase type 2 is the predominant isoenzyme in genital tissue and thus also in the prostate. Finasteride is a 5-alpha-reductase inhibitor, which is applied in the treatment of BHP and male baldness. In the doses used finasteride acts mainly by inhibiting the 5-alpha-reductase type 2, thereby reducing the serum level of DHT by approximately 70% and by about 85-90% in the prostate. Indeed the effect of finasteride in BPH was proven in clinical studies. However, the circulating and intraprostatic DHT could be further reduced by a more effective dual 5-alpha-reductase inhibitor, which would be efficacious in the treatment of benign prostate hyperplasia and other DHT-related disorders.

Urologe A. 2002 Sep;41(5):412-24

Importance of the natural history of benign prostatic hyperplasia in the evaluation of pharmacologic intervention.

The variable natural history of untreated symptomatic benign prostatic hyperplasia (BPH) and the fact that therapeutic intervention is based more on subjective than objective criteria of progressive disease have important consequences for appropriately evaluating the effects of pharmacologic intervention on clinical BPH. To evaluate accurately the success of drug therapy for symptomatic BPH, any trial must include a placebo treatment arm for comparison. However, for such a placebo control to be legitimate, it must not affect the natural history of BPH. To evaluate the effect of placebo treatment on BPH, a large body of data following the natural history of untreated clinical BPH from a variety of independent studies was combined and compared to those from a large variety of independent studies in which a April 2006 LIFE EXTENSION 107 Journal ABSTRACTS placebo-treated group of patients with clinical BPH also followed. These comparisons demonstrate that 1) placebo treatment does not affect the natural history of the disease; 2) spontaneous improvement usually occurs within the first 6 months of initial presentation of symptoms, if it is to occur at all; and 3) 3-6 months of followup are needed to determine if a patient is going to get worse. Thus, to evaluate accurately the potential benefit of any medical intervention for symptomatic BPH, placebocontrolled clinical trials will be required and should be of at least 6 month’s duration.

Prostate Suppl. 1990;3:1-7

Antiproliferative effect of Pygeum africanum extract on rat prostatic fibroblasts.

The effect of a Pygeum africanum extract (Tadenan) (Pa), used in the treatment of micturition disorders associated with BPH, has been examined on the proliferation of rat prostatic stromal cells stimulated by different growth factors. EGF, bFGF, and IGF-I but not KGF are mitogenic for prostatic fibroblasts in culture. Pygeum africanum inhibits both basal and stimulated growth with IC50 values of 4.5, 7.7, and 12.6 micrograms./ml. for EGF, IGF-I and bFGF, respectively, compared to 14.4 micrograms./ml. for untreated cells, the inhibition being stronger towards EGF. Pygeum africanum inhibited the proliferation induced by TPA or PDBu in a concentration-dependent manner with IC50 values of 12.4 and 8.1 micrograms./ ml. respectively. The antiproliferative effects of Pa were not ascribed to cytotoxicity. These results show that Pygeum africanum is a potent inhibitor of rat prostatic fibroblast proliferation in response to direct activators of protein kinase C, the defined growth factors bFGF, EGF and IGF-I, and the complex mixture of mitogens in serum depending on the concentration used. PKC activation appears to be an important growth factor-mediated signal transduction for this agent. These data suggest that therapeutic effect of Pygeum africanum may be due at least in part to the inhibition of growth factors responsible for the prostatic overgrowth in man.

J Urol. 1997 Jun;157(6):2381-7

Comparison of once and twice daily dosage forms of Pygeum africanum extract in patients with benign prostatic hyperplasia: a randomized, double-blind study, with long-term open label extension.

OBJECTIVES: To compare the efficacy and safety of Pygeum africanum extract, 50 mg twice daily and 100 mg once daily. METHODS: Patients with symptomatic benign prostatic hyperplasia (BPH) entered a 2-month randomized, parallelgroup, double-blind, comparative phase (group A, 50 mg twice daily; group B, 100 mg once daily), followed by a 10-month, open phase (100 mg once daily). Main efficacy assessment parameters included International Prostate Symptom Score (IPSS), quality of life (QOL), and maximum urinary flow rate (Qmax). RESULTS: Two hundred nine patients completed the comparative phase in compliance with the protocol; 174 were included in the open phase. Both treatments had similar efficacy. IPSS (baseline 17 in both groups) improved by 38% in group A and 35% in group B. QOL improved by 28% in both groups. Qmax increased by 1.63 mL/s (16%) in group A and 2.02 mL/s (19%) in group B. After 12 months, the IPSS fell from 16 (baseline) to 9 (-46%). Half of the patients had an IPSS below 8. Mean Qmax increased by 1.65 Journal ABSTRACTS 108 LIFE EXTENSION April 2006 mUs (15%). The safety profile was similar between groups and study phases. CONCLUSIONS: P. africanum extract at 50 mg twice daily and 100 mg once daily proved equally effective and safe at 2 months. Further improvements in efficacy with a satisfactory safety profile were documented after 12 months.

Urology. 1999 Sep;54(3):473-8

Urological and sexual evaluation of treatment of benign prostatic disease using Pygeum africanum at high doses.

This clinical study has been designed to evaluate the efficacy of an extract of Pygeum Africanum ( Tadenan) (Roussel-Pharma) in patients suffering from prostatic hypertrophy or chronic prostatitis. The drug has been administrated to 18 patients, for 60 days, as double of standard dosage (200 mg/die per os, instead of 100 mg/die). Because of the high frequency of association of sexual disorders with those two pathologies, we have extended the study also to sexual disorders selecting patients suffering from prostatic hypertrophy or chronic prostatitis and, simultaneously, from sexual disturbances. No side effects have been observed during the treatment. The urinary disturbances have been evaluated by anamnesis and prostatic transrectal echography; sexual disorders have been evaluated by anamnesis and nocturnal penile tumescence and rigidity (NPTR) monitoring. Furthermore, dosage of serum levels of the hormones LH, FSH, Prolactin, 17 beta-Estradiol and Testosterone has been performed before and after therapy. Pygeum Africanum extract administration improved all the urinary parameters we investigated; prostatic echography relieved reduction of peri-urethral edema. Also an improvement of sexual behaviour has been obtained; but we have not found significant differences between serum hormonal levels before and after therapy, as well as for NPTR.

Arch Ital Urol Nefrol Androl. 1991 Sep;63(3):341-5

Efficacy and acceptability of tadenan (Pygeum africanum extract) in the treatment of benign prostatic hyperplasia (BPH): a multicentre trial in central Europe.

Pygeum africanum extract is available as Tadenan in many countries, including those in central and eastern Europe, for the treatment of mild to moderate BPH. Its efficacy and acceptability have been demonstrated in numerous open and placebo-controlled studies in large populations. The present open three-centre efficacy and safety study was conducted according to common protocol at urology clinics in the Czech and Slovak Republics and in Poland, in order to confirm the therapeutic profile of Pygeum africanum in conditions of daily practice, using International Prostate Symptom Score (IPSS) and flowmetry assessments. Men aged 50-75 years and in compliance with the selection criteria (including IPSS > or = 12, quality of life (QoL) score > or = 3, and maximum urinary flow < or = 15 ml/s) were first examined then recalled after two weeks during which no treatment was provided (washout and check of stability). If still compliant, they were entered at this point into a two-month period of treatment with Pygeum africanum extract 50 mg twice daily. There followed a further one-month period without treatment, the objective being to evaluate the persistence of any effects observed during the previous two months of Pygeum africanum administration. The primary efficacy parameter investigated was IPSS; the other efficacy parameters were QoL, nocturnal frequency, maximum urinary flow, average urinary flow, post-voiding residual volume and prostatic volume, after one and two months of Pygeum africanum treatment and one month after stopping treatment. A total of 85 patients were evenly distributed between the three centres and completed the entire study. At inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia was 2.6 times per night. The changes in subjective scores, IPSS and QoL after the twomonth treatment period were highly statistically significant with mean improvements of 40% and 31%, respectively. Nocturnal frequency was reduced by 32% and the mean reduction was again highly statistically significant. Mean maximum urinary flow, average urinary flow and urine volume were also statistically signifi- cantly improved, but the modest improvement in post-voiding volume did not reach statistical significance. The improvements, which exceeded those observed with placebo in earlier studies, were maintained after one month without treatment indicating an interesting persistence of clinically useful activity. Prostatic volume and quality of sexual life remained unchanged throughout. No treatment-related adverse effects were observed. In conclusion, under conditions of daily practice, Pygeum africanum extract induces significant improvement in IPSS and uroflowmetry parameters. These positive effects are accompanied by a very satisfactory safety profile with the overall result of a substantial improvement in QoL.

Curr Med Res Opin. 1998;14(3):127-39

Efficacy of Pygeum africanum extract in the medical therapy of urination disorders due to benign prostatic hyperplasia: evaluation of objective and subjective parameters.

A placebo-controlled doubleblind multicenter study. The efficacy of an extract of Pygeum africanum in the treatment of micturitional disorders due to benign prostatic hyperplasia was tested in a multicentre doubleblind trial versus placebo. Capsules containing 50 mg of Pygeum africanum extract or placebo were administered at a dosage of 1 capsule in the morning and 1 capsule in the evening over a period of 60 days. 263 patients were included in this study, which was carried out in 8 centers in Germany, France, and Austria. Evaluation was mainly based on quantitative parameters such as residual urine, uroflowmetry and the precise monitoring of diurnal and nocturnal pollakiuria. Treatment with the Pygeum africanum extract led to a marked clinical improvement: a comparison of the quantitative parameters showed a significant difference between the Pygeum africanum group and the placebo group with respect to therapeutic response. The characteristic subjective symptoms of micturitional disorders, which were evaluated by the patients in a qualitative manner, were also significantly improved by administration of Pygeum africanum extract. Overall assessment at the end of therapy, showed that micturition improved in 66% of the patients treated with Pygeum africanum extract, as compared with an improvement of 31% in the placebo group. The difference was significant at the statistical level of p less than 0.001. During therapy with Pygeum africanum extract, gastrointestinal side effects occurred in 5 patients. Treatment was discontinued in three of those cases.

Wien Klin Wochenschr. 1990 Nov 23;102(22):667-73