G
Guest
Guest
Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J, Mulrow C
Department of Veterans Affairs Coordinating Center of the Cochrane Collaborative Review Group in Prostatic Diseases and Urologic Malignancies, Minneapolis Veterans Affairs Medical Center, Minn 55417, USA. wilt.timothy@minneapolis.va.gov
OBJECTIVES: To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH).
DATA SOURCES: Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies.
OBJECTIVES: STUDY SELECTION: Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days.
DATA EXTRACTION: Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies.
DATA SYNTHESIS: A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively.
CONCLUSIONS: The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.
[[SWIRL 2]]
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Since 10-01-1999
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Saw Palmetto
Study A: Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.
This study suggests that Fenistride (active ingredient of Propecia) only inhibited the Type 2 form of 5 alpha reductase where Saw Palmetto extract inhibited both type 1 and 2 forms of 5 alpha-reductase and was more potent than Fenistride.
AUTHOR
Iehlé C; Délos S; Guirou O; Tate R; Raynaud JP; Martin PM
JOURNAL
J Steroid Biochem Mol Biol, 54: 5-6, 1995 Sep, 273-9
ABSTRACT
The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.
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Saw Palmetto
Study B: Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts.
This Study shows that Fenistride and 4-MA inhibited the formation of some testostrone Metabolites (including DHT), where as Saw Palmetto inhibited the formation of all the Testostrone metabolites studied.
AUTHOR
Délos S; Carsol JL; Ghazarossian E; Raynaud JP; Martin PM
JOURNAL
J Steroid Biochem Mol Biol, 55: 3-4, 1995 Dec, 375-83
ABSTRACT
We compare testosterone (T) metabolism in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH) and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts, respectively. Northern blot analysis of total RNA from epithelial cells (BPH or adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1 isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts, only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) and finasteride, inhibited DHT formation with a preferential action of 4-MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon, Saw Palmetto) inhibited the formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and fibroblasts, respectively]. These results have important therapeutic implications when selecting appropriate treatment options for BPH.
RETURN TO RESEARCH
Saw Palmetto
Study C: The effect of Permixon on androgen receptors.
This study shows that Saw Palmetto extract was able to effectively reduce Binding of Testostrone and DHT to their receptors on various tissues.
AUTHOR
el-Sheikh MM; Dakkak MR; Saddique A
JOURNAL
Acta Obstet Gynecol Scand, 67: 5, 1988, 397-9
ABSTRACT
Permixon, the liposterolic extract of the plant Serenoa Repens is a recently introduced drug for the treatment of benign prostatic hyperplasia. The effect of Permixon on dihydrotestosterone and testosterone binding by eleven different tissue specimens was tested. The drug reduced the mean uptake of both hormones by 40.9% and 41.9% respectively in all tissue specimens. Since hirsutism and virilism are among other gynecological problems caused either by excessive androgen stimulation or excess endorgan response, we suggest that Permixon could be a useful treatment in such conditions and recommend further investigations of the possible therapeutic values of the drug in gynecological practice.
Department of Veterans Affairs Coordinating Center of the Cochrane Collaborative Review Group in Prostatic Diseases and Urologic Malignancies, Minneapolis Veterans Affairs Medical Center, Minn 55417, USA. wilt.timothy@minneapolis.va.gov
OBJECTIVES: To conduct a systematic review and, where possible, quantitative meta-analysis of the existing evidence regarding the therapeutic efficacy and safety of the saw palmetto plant extract, Serenoa repens, in men with symptomatic benign prostatic hyperplasia (BPH).
DATA SOURCES: Studies were identified through the search of MEDLINE (1966-1997), EMBASE, Phytodok, the Cochrane Library, bibliographies of identified trials and review articles, and contact with relevant authors and drug companies.
OBJECTIVES: STUDY SELECTION: Randomized trials were included if participants had symptomatic BPH, the intervention was a preparation of S repens alone or in combination with other phytotherapeutic agents, a control group received placebo or other pharmacological therapies for BPH, and the treatment duration was at least 30 days.
DATA EXTRACTION: Two investigators for each article (T.J.W., A.I., G.S., and R.M.) independently extracted key data on design features, subject characteristics, therapy allocation, and outcomes of the studies.
DATA SYNTHESIS: A total of 18 randomized controlled trials involving 2939 men met inclusion criteria and were analyzed. Many studies did not report results in a method that permitted meta-analysis. Treatment allocation concealment was adequate in 9 studies; 16 were double-blinded. The mean study duration was 9 weeks (range, 4-48 weeks). As compared with men receiving placebo, men treated with S repens had decreased urinary tract symptom scores (weighted mean difference [WMD], -1.41 points [scale range, 0-19] [95% confidence interval (CI), -2.52 to -0.30] [n = 1 study]), nocturia (WMD, -0.76 times per evening [95% CI, -1.22 to -0.32] [n = 10 studies]), and improvement in self-rating of urinary tract symptoms; risk ratio for improvement (1.72 [95% CI, 1.21-2.44] [n = 6 studies]), and peak urine flow (WMD, 1.93 mL/s [95% CI, 0.72-3.14] [n = 8 studies]). Compared with men receiving finasteride, men treated with S repens had similar improvements in urinary tract symptom scores (WMD, 0.37 International Prostate Symptom Score points [scale range, 0-35] [95% CI, -0.45 to 1.19] [n = 2 studies]) and peak urine flow (WMD, -0.74 mL/s [95% CI, -1.66 to 0.18] [n = 2 studies]). Adverse effects due to S repens were mild and infrequent; erectile dysfunction was more frequent with finasteride (4.9%) than with S repens (1.1%; P<.001). Withdrawal rates in men assigned to placebo, S repens, or finasteride were 7%, 9%, and 11%, respectively.
CONCLUSIONS: The existing literature on S repens for treatment of BPH is limited in terms of the short duration of studies and variability in study design, use of phytotherapeutic preparations, and reports of outcomes. However, the evidence suggests that S repens improves urologic symptoms and flow measures. Compared with finasteride, S repens produces similar improvement in urinary tract symptoms and urinary flow and was associated with fewer adverse treatment events. Further research is needed using standardized preparations of S repens to determine its long-term effectiveness and ability to prevent BPH complications.
[[SWIRL 2]]
Return to the SAW PALMETTO Page
<http://fastcounter.bcentral.com/fastcounter?2954848+5909703>
Since 10-01-1999
<http://store3.yimg.com/I/revivogen_1572_100068>
Saw Palmetto
Study A: Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.
This study suggests that Fenistride (active ingredient of Propecia) only inhibited the Type 2 form of 5 alpha reductase where Saw Palmetto extract inhibited both type 1 and 2 forms of 5 alpha-reductase and was more potent than Fenistride.
AUTHOR
Iehlé C; Délos S; Guirou O; Tate R; Raynaud JP; Martin PM
JOURNAL
J Steroid Biochem Mol Biol, 54: 5-6, 1995 Sep, 273-9
ABSTRACT
The present study describes the independent expression of the type 1 and 2 isoforms of human 5 alpha-reductase in the baculovirus-directed insect cell expression system and the selectivity of their inhibition. The catalytic properties and kinetic parameters of the recombinant isozymes were consistent with published data. The type 1 isoform displayed a neutral (range 6-8) pH optimum and the type 2 isoform an acidic (5-6) pH optimum. The type 2 isoform had higher affinity for testosterone than did the type 1 isoform (Km = 0.5 and 2.9 microM, respectively). Finasteride and turosteride were selective inhibitors of the type 2 isoform (Ki (type 2) = 7.3 and 21.7 nM compared to Ki (type 1) = 108 and 330 nM, respectively). 4-MA and the lipido-sterol extract of Serenoa repens (LSESr) markedly inhibited both isozymes (Ki (type 1) = 8.4 nM and 7.2 micrograms/ml, respectively; Ki (type 2) = 7.4 nM and 4.9 micrograms/ml, respectively). The three azasteroids were competitive inhibitors vs substrate, whereas LSESr displayed non-competitive inhibition of the type 1 isozyme and uncompetitive inhibition of the type 2 isozyme. These observations suggest that the lipid component of LSESr might be responsible for its inhibitory effect by modulating the membrane environment of 5 alpha-reductase. Partially purified recombinant 5 alpha-reductase type 1 activity was preserved by the presence of lipids indicating that lipids can exert either stimulatory or inhibitory effects on human 5 alpha-reductase.
RETURN TO RESEARCH
Saw Palmetto
Study B: Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts.
This Study shows that Fenistride and 4-MA inhibited the formation of some testostrone Metabolites (including DHT), where as Saw Palmetto inhibited the formation of all the Testostrone metabolites studied.
AUTHOR
Délos S; Carsol JL; Ghazarossian E; Raynaud JP; Martin PM
JOURNAL
J Steroid Biochem Mol Biol, 55: 3-4, 1995 Dec, 375-83
ABSTRACT
We compare testosterone (T) metabolism in primary cultures of epithelial cells and fibroblasts separated from benign prostate hypertrophy (BPH) and prostate cancer tissues. In all cultures, androstenedione (delta 4) formed by oxidation of T by 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) represented 80% of the metabolites recovered. The amounts of 5 alpha-dihydrotestosterone (DHT), formed by reduction of T by 5 alpha-reductase (5 alpha-R), were small: 5 and 2% (BPH) and 8 and 15% (adenocarcinoma) for epithelial cells and fibroblasts, respectively. Northern blot analysis of total RNA from epithelial cells (BPH or adenocarcinoma) attributed the reductive activity to the 5 alpha-reductase type 1 isozyme and oxidative activity to the 17 beta-HSD type 2. In cancer fibroblasts, only little 17 beta-HSD type 2 mRNA was detected. The 5 alpha-reductase inhibitors, 4-MA (17 beta-(N,N-diethyl)carbamoyl-4-methyl-4-aza-5 alpha-androstan-3-one) and finasteride, inhibited DHT formation with a preferential action of 4-MA on epithelial cells (BPH or adenocarcinoma) and of finasteride on fibroblasts from adenocarcinoma. Neither inhibitor acted on delta 4 formation. On the other hand, the lipido-sterol extract of Serenoa repens (LSESr, Permixon, Saw Palmetto) inhibited the formation of all the T metabolites studied [IC50 S = 40 and 200 micrograms/ml (BPH) and 90 and 70 micrograms/ml (adenocarcinoma) in epithelial cells and fibroblasts, respectively]. These results have important therapeutic implications when selecting appropriate treatment options for BPH.
RETURN TO RESEARCH
Saw Palmetto
Study C: The effect of Permixon on androgen receptors.
This study shows that Saw Palmetto extract was able to effectively reduce Binding of Testostrone and DHT to their receptors on various tissues.
AUTHOR
el-Sheikh MM; Dakkak MR; Saddique A
JOURNAL
Acta Obstet Gynecol Scand, 67: 5, 1988, 397-9
ABSTRACT
Permixon, the liposterolic extract of the plant Serenoa Repens is a recently introduced drug for the treatment of benign prostatic hyperplasia. The effect of Permixon on dihydrotestosterone and testosterone binding by eleven different tissue specimens was tested. The drug reduced the mean uptake of both hormones by 40.9% and 41.9% respectively in all tissue specimens. Since hirsutism and virilism are among other gynecological problems caused either by excessive androgen stimulation or excess endorgan response, we suggest that Permixon could be a useful treatment in such conditions and recommend further investigations of the possible therapeutic values of the drug in gynecological practice.