Saw Palmetto Effective for BPH

[Guest guest]

Permixon is a commercial extract of saw palmetto. -- Logan

[Evaluation of the clinical benefit of Permixon and tamsulosin in

severe BPH patients--PERMAL study subset analysis]

[Article in French]

Debruyne F, Boyle P, Calais da Silva F, Gillenwater JG, Hamdy FC,

Perrin P, Teillac P, Vela-Navarrete R, Raynaud JP, Schulman C.

Hopital Universitaire Saint Radboud, Nijmegen, Pays-Bas.

f.debruyne@...

Prog Urol. 2004 Jun;14(3):326-31.

OBJECTIVE: To compare the efficacy of the lipido-sterolic extract of

Serenoa repens, Permixon, to that of the a-blocker, tamsulosin, in

the treatment of severe low urinary tract symptoms (LUTS) of benign

prostatic hyperplasia (BPH). METHODS: In a 12-month, double-blind,

randomized study that showed equivalent efficacy of Permixon 320

mg/day and tamsulosin 0.4 mg/day ( " PERMAL study " ), 685 BPH patients

with IPSS > 10 had been analyzed for efficacy. Of these, the 124

patients with severe LUTS (IPSS > 19) at randomization were retained

for this subset analysis. After a 4-week run-in period, 59 and 65

patients had been randomized to tamsulosin and Permixon groups,

respectively. Both treatment groups were compared regarding the

evolution from baseline of total IPSS and its irritative and

obstructive subscores. LUTS-related QpL, prostate volume, Qmax and

MSF-4 (sexual activity questionnaire) at different time points over 1

year An analysis of variance of changes from baseline to end point

was performed for all the parameters. The over-time evolutions of

total, irritative and obstructive IPSS were further compared using a

variance analysis for repeated measurements. RESULTS: At 12 months,

total IPSS decreased by 7.8 with Permixon and 5.8 with tamsulosin (p

= 0.051); the irritative symptoms improved significantly more (p =

0.049) with Permixon (- 2.9 versus - 1.9 with tamsulosin). The

superiority of Permixon in reducing irritative symptoms appeared as

soon as month 3 and was maintained up to month 12 (p = 0.03).

CONCLUSION: Permixon 320 mg/day was shown to be slightly superior to

tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3

months and up to 12 months of treatment.

[Guest guest]

http://www.jr2.ox.ac.uk/bandolier/booth/Mens/permixon.htmlPermixon for BPHClinical bottom lineFrom randomised studies in men with BPH, permixon appears to give a small improvement in maximum flow rate of about 2 mL/second over placebo in studies of three months or less. Nocturia may be reduced by about one episode per night.Permixon is a standardised lipid extract of the American dwarf palm tree, Serenoa repens. Its mechanism of action is uncertain, but it may have antiandrogenic properties.ReferenceP Boyle et al. Meta-analysis of clinical trials of permixon in the treatment of symptomatic benign prostatic hyperplasia. Urology 2000 55: 533-539.ReviewThe review found 13 studies, eleven of which were randomised, and seven placebo controlled. No search strategy is given. Duration was from 21 to 180 days, though most were of less than three months duration. The dosage of permixon was 320 mg/day.The number of patients, and baseline and end of study figures are given for maximum urinary flow rate and episodes of nocturia. Baseline mean urinary flow rates were generally 9-13 mL/second, with 2-4 episodes of nocturia. In three studies maximum flow rate was estimated from average flow rate.ResultsIn randomised studies the mean increase in maximum flow rate with placebo was 0.6 ml/second, and there was an additional 2 mL/second with permixon. The mean number of decreased episodes of nocturia was 0.6 with placebo and an additional 0.5 episodes with permixon.CommentThe results were statistically significant, but the effect was small. Trials used the same preparation, but were of short duration. It was not clear which trials were being combined, and whether they were of sufficient quality to avoid bias.

note:

"The first issue of Bandolier, an independent journal about evidence-based healthcare, written by Oxford scientists, (RAM AND HJM) was printed in February 1994. It has appeared monthly ever since and has become the premier source of evidence based healthcare information in the UK and worldwide for both healthcare professionals and consumers."

My take: better than placebo but it doesn't work. The prostate must be shrunk or TURPed, although an alpha blocker will relax the muscle somewhat - enough for urination for a while maybe 6 months while you accept the inevitable. Nocturia is not a problem - not urinating is the problem.

Deficiency in Urination is not a small problem - it can have a large effect on kidney health, according to my internist.

The problem is choosing between a hormone treatment (proscar) or a TURP.

Regards.

----- Original Message ----- From: loganruns73 Sent: Tuesday, October 05, 2004 1:38 AMSubject: [ ] Saw Palmetto Effective for BPHPermixon is a commercial extract of saw palmetto. -- Logan

[Guest guest]

Serenoa Repens (Permixon): New evidence confirming the drug as a potent inhibitor of 5 alpha–reductase activity whilst maintaining PSA expression in the prostate

FK Habib PhDa, M Ross MSca, BA Lyonsb, K Chapman PhDb

aProstate Research Group, bSchool of Molecular & Clinical Medicine; Endocrine Unit Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, Scotland

AIMS: One of the major issues surrounding the actions of the phytotherapeutic agent, Permixon, widely used for the treatment of BPH, is its capacity to inhibit the 5 alpha–reductase (5 alpha R) isoenzyme activities of the prostate whilst maintaining the PSA response in the epithelium. This seems to conflict with the mechanism of action of other 5 alpha R inhibitors (e.g. Finasteride) which down-regulate PSA expression in the prostate. This study was undertaken to determine differences in the action of Permixon compared to the other 5 alpha–reductase inhibitors, which may account for the differential response by the PSA gene. METHODS: The androgen sensitive LNCaP cell and the simian kidney COS cell were purchased from the American Type Culture Collection and propagated according to the instructions of the supplier. Permixon and Finasteride were gifts from Pierre Fabre Medicament and Merck Sharpe & Dohme respectively. DNA manipulation including transfection, plasmid constructs preparation and probe labelling were performed according to the standard procedures. PSA secretion was determined using a Diagnostic Systems kit. 5 alpha–reductase isoenzyme activities were assessed in the presence and absence of either Permixon or Finasteride by measuring the conversion of testosterone to DHT as described previously. RESULTS: COS cells transfected with 5RII gene demonstrated substantial inhibitory activity (70%) following treatment with either Finasteride (5nM) or Permixon (10ug/ml). To investigate the impact of the 5 alpha–reductase inhibitors on the hormone induced activity of the PSA gene, COS were transiently transfected with the PSA-61-Luc construct and co-transfected with the human androgen receptor expression plasmid. The androgen-induced activity of the constructs was 9-fold more active in the presence of 10nM DHT than in its absence. In the presence of Permixon (10ug/ml), the activity remained essentially the same as in controls. However following treatment with Finasteride (5nM) the activity of the luciferase reporter gene construct was significantly reduced (80%). These results are essentially identical to those obtained with the LNCaP cells following exposure to Permixon and Finasteride. The secretion of PSA was unaffected by the treatment of the cells with Permixon whereas PSA production was significantly reduced (70%) in the presence of Finasteride. CONCLUSIONS: Whilst both Permixon and Finasteride are potent inhibitors of 5 alpha–reductase type II, it is only Finasteride which markedly inhibits PSA secretion and expression. This differential response stems from the decrease in the levels of androgen receptors following treatment of the cells with Finasteride thus triggering the down-regulation of the expression of the PSA. No such change in androgen receptor levels was detected following treatment with Permixon.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 1097 (Anticancer therapy).

In this paper they point out that finasteride reduces PSA production, reducing the effectiveness of the PSA test for Prostate cancer - not a problem - the PSA test is not all that useful - a better test is needed for PCa. It also points out that no "change in androgen receptor levels" with Permixon. If it doesn't effect the hormones it won't shrink the prostate.

The prostate swells because of an inflammation, unknown cause in most cases. There is nothing that treats or prevents the inflammation, per se. That's the problem with BPH. The only nice thing about BPH is it reduces chance of PCa to 17%, if you believe stats.

Regards.

----- Original Message -----

From: loganruns73

Sent: Tuesday, October 05, 2004 1:38 AM

Subject: [ ] Saw Palmetto Effective for BPH

Permixon is a commercial extract of saw palmetto. -- Logan

[Guest guest]

Here's a short list of my BPH stuff.

{side effects}

Author

Carbone, D J Jr 1*; Hodges, S 1

Institution

(1)Department of Urology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina, USA

Title

Medical therapy for benign prostatic hyperplasia: sexual dysfunction and impact on quality of life.[Report]

Source

International Journal of Impotence Research. 15(4):299-306, August 2003.

Abstract

Therapies for benign prostatic hyperplasia (BPH) may either improve or exacerbate sexual function with an ensuing impact on quality of life. Here we review a total of 73 papers on medical therapies for BPH with a focus on the effects of different pharmacological agents on sexual function. For example, certain [alpha]1-adrenergic receptor blockers may improve erectile function; however, ejaculatory dysfunction with one of these agents, tamsulosin, occurs at a rate of 4-18%, rising to 30% with long-term use. In addition, treatment with the 5[alpha]-reductase inhibitor finasteride is associated with problems of ejaculation (2.1-7.7%), erection (4.9-15.8%), and libido (3.1-5.4%). Such significant and undesirable complications in relation to sexual function produce a well-documented negative impact on quality of life. Thus, optimal treatment for men with BPH requires the use of agents that demonstrate efficacy and safety with fewer sexual side effects.

{this one further devalues the PSA test for PCa.}

Author

KEHINDE, E. O.; SHEIKH, M. *; MOJIMONIYI, O. A. +; FRANCIS, I. +; ANIM, J. T. +; NKANSA-DWAMENA, D. +; AL-AWADI, K. A.

Title

High serum prostate-specific antigen levels in the absence of prostate cancer in Middle-Eastern men: the clinician's dilemma.[Miscellaneous Article]

Source

BJU International. 91(7):618-622, May 2003.

Abstract

OBJECTIVE: To investigate the common causes of total serum prostate-specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels.CONCLUSION: Total PSA values of> 10 ng/mL in Arab men may be a result of BPH, BPH with prostatitis or prostate cancer, in that order. A gradual decline in total PSA (decreased PSA velocity) with time to < 4 ng/mL often confirms the diagnosis of BPH with prostatitis. The percentage of free PSA and PSA density may not be helpful in diagnosing prostate cancer with certainty in these patients. Compared with Caucasians in the USA and Europe, BPH and BPH with prostatitis appear to be more frequent causes of serum PSA levels of> 10 ng/mL in Arab men.

{this one reduces the importance of the Free PSA test}

Serial prostate specific antigen, free-to-total prostate specific antigen ratio and complexed prostate specific antigen for the diagnosis of prostate cancer.J Urol. 2001 Jul;166(1):93-8; discussion 98-9.PMID: 11435831

Conclusions: In this population based study total PSA was superior to the free-to-total PSA ratio for predicting the development of prostate cancer. While serial changes in free-to-total PSA ratios with time were statistically significantly different in men diagnosed with prostate cancer and controls, the magnitude of these serial changes were slight enough to render them clinically insignificant.

The results of this study have several implications for clinical practice. Of the tests considered in this study elevated total PSA appeared to be the best predictor of disease. Our series reinforces the concept that increasing PSA is often associated with prostate cancer. A consistent increase in serum PSA in the range of 20% or more yearly should raise prostate cancer suspicion. One must consider that PSA varies with time. The number of PSA determinations necessary to calculate PSA velocity is not known with certainty but the previous recommendation of et al of 3 determinations in a 2-year period is reasonable. 6

{well that doesn't make it too useful for this year, does it?}

6. , H. B., Pearson, J. D. and Metter, E. J. : Longitudinal evaluation of prostate-specific antigen levels in men with and without prostate disease. JAMA, 267: 2215, 1992

{so chimps get it too. Notice it says "As in man, serum androgens did not correlate with BPH in the chimpanzee"}

J Urol. 1999 Oct;162(4):1454-61.

The chimpanzee as a model of human benign prostatic hyperplasia

Abstract

Purpose: The etiology and natural history of benign prostatic hyperplasia (BPH), the most common benign disease in aging men, remain obscure. The canine BPH model has serious limitations but other animal BPH models have not been identified. We evaluated whether the chimpanzee, man's closest primate relative, developed spontaneous BPH.Results: The chimpanzee had evidence of spontaneous histological BPH, and incidence and grade increased with age. Spontaneous BPH was manifested by increased prostate volume, higher serum prostate specific antigen, higher stromal/epithelial ratio and decreased urinary flow rates. As in man, serum androgens did not correlate with BPH in the chimpanzee.Conclusions: Male chimpanzees developed spontaneous histological BPH at the same relative point in their life cycle as humans which resulted clinically in larger prostates and decreased urinary flow rates. Serum hormone levels did not appear to correlate with BPH. A better understanding of the chimpanzee BPH model may lead to new therapeutic strategies for BPH in man.

{What does Finasteride do?}

Does long-term finasteride therapy affect the histologic features of benign prostatic tissue and prostate cancer on needle biopsy? PLESS Study Group. Proscar Long-Term Efficacy and Safety Study.Urology. 1999 Apr;53(4):696-700.PMID: 10197843

INTRODUCTION AND OBJECTIVES: Finasteride, a common agent used to treat benign prostatic hyperplasia (BPH), inhibits 5-alpha-reductase. 5-alpha-reductase converts testosterone to dihydrotestosterone, which is the primary androgen in the prostate. Luprolide (Lupron) is a stronger antiandrogen, which is used to downstage prostate cancer prior to radical prostatectomy.

{but don't stop the alpha blocker}

Induction of prostate apoptosis by doxazosin in benign prostatic hyperplasia.J Urol. 1998 Jun;159(6):1810-5.PMID: 9598465

CONCLUSIONS

To our knowledge our study provides the first evidence to suggest that induction of prostate apoptosis by doxazosin contributes to the relief of urinary obstruction symptoms in men with BPH. Our current results may have significant implications for optimizing combination strategies of alpha 1 blockade and androgen deprivation by targeting apoptosis in the prostatic smooth muscle and glandular epithelial cells in BPH.

{later info}

Pharmacological exploitation of the alpha1-adrenoreceptor antagonist doxazosin to develop a novel class of antitumor agents that block intracellular protein kinase B/Akt activation.J Med Chem. 2004 Aug 26;47(18):4453-62.

Shaw YJ, Yang YT, Garrison JB, Kyprianou N, Chen CS.PMID: 15317457

The alpha1-adrenoreceptor antagonist doxazosin induces apoptosis in malignant cells with moderate potency via an alpha1-adrenoreceptor-independent mechanism.

Decrease in mortality from benign prostatic hyperplasia: a major unheralded health triumph.J Urol. 1996 Jan;155(1):176-80.PMID: 7490826

Conclusions: The decreases noted in western countries, such as the United Kingdom (where 8,700 fewer men die each year presently than would be expected if the BPH mortality rates from the early 1950s still applied), United States (13,681 fewer deaths) and France (2,884 fewer deaths), indicate a considerable but unheralded achievement for modern medicine. Unfortunately, these decreases have not been observed to the same extent in central and eastern Europe and South America, where the residual high mortality rates could be lowered by education, and the widespread availability of modern surgical and anesthetic equipment.

Early treatment of benign prostatic hyperplasia: implications for reducing the risk of permanent bladder damage.Drugs Aging. 2003;20(3):185-95. Review.PMID: 12578399

A significant change has occurred in the management of symptomatic benign prostatic hyperplasia (BPH) since effective pharmacological treatment became available and led to a significant decrease in the number of surgical procedures in many Western countries.

Prostate cancer vs hyperplasia: relationships with prostatic and adipose tissue fatty acid composition.Prostaglandins Leukot Essent Fatty Acids. 2002 May-Jun;66(5-6):467-77.PMID: 12144866

The most pronounced difference between cancer patients and hyperplasia patients was a 3-fold elevated prostatic palmitoleic acid in the former group. Relative to benign hyperplasia patients, cancer patients had reduced prostate tissue arachidonic and docosahexaenoic acid levels. Finally, there was a significantly reduced omega-3/omega-6 polyunsaturated fatty acid ratio in the prostate cancer patient as opposed to the benign hyperplasia group. The pronounced elevations in prostatic tissue palmitoleic acid in cancer patients highlight a possible role of this fatty acid in neoplastic processes. The decreased arachidonic acid levels in cancer patients possibly stem from enhanced metabolism of arachidonic acid via lipoxygenase and cyclooxygenase pathways, and the formation of derivatives such as 5-HETE, 15-HETE, 12(S)-HETE and PGE(2). {interesting anecdote, but it doesn't mean anything about oral supplementation}

{My take is do the alpha blocker and the proscar, and not worry the "alternative" preparations.}

Regards.

----- Original Message -----

From: loganruns73

Sent: Tuesday, October 05, 2004 1:38 AM

Subject: [ ] Saw Palmetto Effective for BPH

Permixon is a commercial extract of saw palmetto. -- Logan[Evaluation of the clinical benefit of Permixon and tamsulosin in severe BPH patients--PERMAL study subset analysis][Article in French]Debruyne F, Boyle P, Calais da Silva F, Gillenwater JG, Hamdy FC, Perrin P, Teillac P, Vela-Navarrete R, Raynaud JP, Schulman C.Hopital Universitaire Saint Radboud, Nijmegen, Pays-Bas. f.debruyne@...Prog Urol. 2004 Jun;14(3):326-31.OBJECTIVE: To compare the efficacy of the lipido-sterolic extract of Serenoa repens, Permixon, to that of the a-blocker, tamsulosin, in the treatment of severe low urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH). METHODS: In a 12-month, double-blind, randomized study that showed equivalent efficacy of Permixon 320 mg/day and tamsulosin 0.4 mg/day ("PERMAL study"), 685 BPH patients with IPSS > 10 had been analyzed for efficacy. Of these, the 124 patients with severe LUTS (IPSS > 19) at randomization were retained for this subset analysis. After a 4-week run-in period, 59 and 65 patients had been randomized to tamsulosin and Permixon groups, respectively. Both treatment groups were compared regarding the evolution from baseline of total IPSS and its irritative and obstructive subscores. LUTS-related QpL, prostate volume, Qmax and MSF-4 (sexual activity questionnaire) at different time points over 1 year An analysis of variance of changes from baseline to end point was performed for all the parameters. The over-time evolutions of total, irritative and obstructive IPSS were further compared using a variance analysis for repeated measurements. RESULTS: At 12 months, total IPSS decreased by 7.8 with Permixon and 5.8 with tamsulosin (p = 0.051); the irritative symptoms improved significantly more (p = 0.049) with Permixon (- 2.9 versus - 1.9 with tamsulosin). The superiority of Permixon in reducing irritative symptoms appeared as soon as month 3 and was maintained up to month 12 (p = 0.03). CONCLUSION: Permixon 320 mg/day was shown to be slightly superior to tamsulosin 0.4 mg/day in reducing LUTS in severe BPH patients after 3 months and up to 12 months of treatment.