Phytotherapy in the treatment of benign prostatic hyperplasia: an update (1999)

It has been almost 3 years since the previous review of phytotherapeutic agents for benign prostatic hyperplasia (BPH) by Lowe appeared in Urology.1Lowe F.C Ku J.C Phytotherapy in treatment of benign prostatic hyperplasia a critical review.Urology. 1996; 48: 12-20Abstract Full Text PDF PubMed Scopus (119) Google Scholar During this period, there has been a rapid increase in the use of these products in the United States as well as substantial widespread use in Europe. It has been estimated that total sales of medicinal botanicals in the United States has risen from more than $500,000 to approximately $1 billion during this time.1Lowe F.C Ku J.C Phytotherapy in treatment of benign prostatic hyperplasia a critical review.Urology. 1996; 48: 12-20Abstract Full Text PDF PubMed Scopus (119) Google Scholar, 2Marwick C Growing use of medicinal botanicals forces assessment by drug regulators.JAMA. 1995; 273: 607-609Crossref PubMed Google Scholar, 3Dreikorn K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar In the urology practice of one of us (F.C.L.), more than 90% of the newly referred patients with lower urinary tract symptoms (LUTS) secondary to BPH have already tried or are using some form of alternative/complementary medications.4Lowe F What I tell patients about phytotherapeutic agents for benign prostatic hyperplasia.AUA News. 1998; 3: 12Google Scholar The most commonly used agents are saw palmetto berry (SPB) extract, “men’s health pills” (which contain multiple botanicals), zinc, selenium, and vitamin E. A recent national survey conducted by National Family Opinion Inc. and reported in JAMA determined that the widespread use of these agents was due to philosophical congruence with peoples’ own values, beliefs, and orientation toward health and life.5Astin J.A Why patients use alternative medicine result of a national study.JAMA. 1998; 279: 1548-1553Crossref PubMed Scopus (2344) Google Scholar In fact, the younger, better educated, healthier people tended to be the greatest users of complementary medications.5Astin J.A Why patients use alternative medicine result of a national study.JAMA. 1998; 279: 1548-1553Crossref PubMed Scopus (2344) Google Scholar Therefore, it is not surprising that many of these medicinal botanicals/phytotherapeutic agents are being sold over the Internet. Last year, more than 100 websites marketing SPB or some other formulation of “men’s health” or “prostate health” pills containing SPB were identified.4Lowe F What I tell patients about phytotherapeutic agents for benign prostatic hyperplasia.AUA News. 1998; 3: 12Google Scholar Despite the increased use of these agents in the United States, most American urologists have little knowledge or understanding of them. In fact, most American physicians are very skeptical about the use of phytotherapeutic agents because of the limited evidence of their efficacy.6Lowe F.C Fagelman E Phytotherapy in the treatment of benign prostatic hyperplasia.Curr Opin Urol. 1998; 8: 27-29Crossref PubMed Scopus (5) Google Scholar However, over the past 3 years numerous studies assessing the efficacy and determining the mechanism of action of these agents have been published.3Dreikorn K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar These reports are critically evaluated herein. Numerous plant extracts have been used in the treatment of LUTS secondary to BPH (Table I). Some of these extracts are derived from the roots, seeds, bark, or fruits of the plants shown in Table I. These phytotherapeutic agents are available as either a single agent (monopreparation) or more likely as a combination product. This variation obviously makes comparisons between products difficult.TABLE IOrigin of plant extracts used in treatment of benign prostatic hyperplasia legendAdapted with permission of Elsevier Science from Urology, 48, F. C. Lowe and J. C. Ku, Phytotherapy in treatment of benign prostatic hyperplasia: a critical review, 12–20, 1996.Vernacular NameScientific NameAfrican plumPygeum africanumPurple cone flowerEchinacea purpureaPumpkin seedsCucurbita pepoRyeSecale cerealeSaw palmetto berry/ dwarf palmSerenoa repensSouth African star grassHipoxis rooperiStinging nettleUrtica dioicalegend Adapted with permission of Elsevier Science from Urology, 48, F. C. Lowe and J. C. Ku, Phytotherapy in treatment of benign prostatic hyperplasia: a critical review, 12–20, 1996. Open table in a new tab Additionally, plant extracts are composed of numerous components (Table II). The extracts are synthesized by different extraction procedures. Therefore, the botanical product of one company may be different from that of another with regard to specific composition and effective components (because we do not know what the active components of these products are), even if they originate from the same plant.3Dreikorn K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar There is also natural variability among the plants themselves.TABLE IISome of the components of plant extracts∗Data from Dreikorn et al.3PhytosterolsPhytoestrogensTerpenoidsFatty acidsLectinsPlant oilsPolysaccharidesFlavonoids∗ Data from Dreikorn et al.3Dreikorn K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar Open table in a new tab Because the results of basic research and clinical trials cannot be automatically accepted and/or transferred from one new manufacturer’s product to another, the different preparations from each individual manufacturer need to be evaluated individually. This necessity was emphasized by the Committee on Other Medical Therapies of the Fourth International Consultation on Benign Prostatic Hyperplasia.3Dreikorn K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar SPB extract remains the most popular and widely used phytotherapeutic agent for LUTS secondary to BPH. Two extensive reviews of this agent have been published since our last review in this journal.7Lowe F.C Saw palmetto berry in the treatment of benign prostatic hyperplasia.Clin Res Reg Affairs. 1997; 14: 53-66Crossref Scopus (4) Google Scholar, 8Plosker G Grogden R.M Serenoa repens (Permixon®)—a review of its pharmacology and therapeutic efficacy in benign prostatic hyperplasia.Drugs Aging. 1996; 9: 379-395Crossref PubMed Scopus (120) Google Scholar Most in vitro studies that have sought to elucidate the mechanisms of action of SPB extract have been performed using Permixon, the liposterolic extract of SPB. In recent publications, it has been postulated that the liposterolic extract of Serenoa repens has antiandrogenic effects,9Ravenna L Di Silverio F Russo M et al.Effects of the lipidosterolic extract of Serenoa repens (Permixon®) on human prostatic cell lines.Prostate. 1996; 29: 219-230Crossref PubMed Scopus (42) Google Scholar inhibits the type 1 and type 2 isoenzymes of 5-alpha-reductase,10Di Silverio F D’Eramo G Lubrano C et al.Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients.Eur Urol. 1992; 21: 309-314PubMed Google Scholar, 11Iehle C Delos S Guirou O et al.Human prostatic steroid 5-reductase isoforms a comparative study of selective inhibitors.J Steroid Biochem Mol Biol. 1995; 54: 273-279Crossref PubMed Scopus (119) Google Scholar, 12Bayne CW, Grant ES, Chapman K, et al: Characterisation of a new coculture model for BPH which expresses 5-alpha-reductase types I and II: the effects of Permixon on DHT formation (abstract 70). Fourth International Consultation on BPH, Paris, 1997, p 70.Google Scholar inhibits prolactin and growth factor-induced cell proliferation,13Vacher P Prevarskaya N Skryma R et al.The lipidosterolic extract from Serenoa repens interferes with prolactin receptor signal transduction.J Biomed Sci. 1995; 2: 357-365Crossref PubMed Scopus (26) Google Scholar, 14Paubert-Braquet M, Raynaud JP, Braquet P, et al: Permixon {lipid sterolic extract of serenoa repens (LSESr)} and some of its components inhibits b-FGF- and EGF-induced proliferation of human prostate organotypic cell lines (abstract 74). Fourth International Consultation on BPH, Paris, 1997, p 74.Google Scholar and has antiestrogenic15Paubert-Braquet M Servent N Serikoff A et al.Permixon (lipido-sterol extract of Serenoa repens-LSESr) inhibits estrogen-androgen-induced prostate enlargement in the rat.Pharmacol Res. 1995; 31: 31-35Crossref Google Scholar and anti-inflammatory16Paubert-Braquet M, Cousse H, Raynaud JP, et al: Effect of lipidosterolic extract of Serenoa repens (Permixon®) on the inophore A 23187-stimulated-production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils (abstract 72). Fourth International Consultation on BPH, Paris, 1997.Google Scholar effects. However, most of these in vitro studies were performed in cell cultures or used supraphysiologic dosages of SPB extract. Therefore, the significance of these mechanism studies is uncertain. Di Silverio et al.,17Di Silverio F Sciarra A D’Eramo G et al.Response to tissue androgen and epidermal growth factor concentrations to the administration of finasteride, flutamide and Serenoa repens in patients with BPH (abstract).Eur Urol. 1996; 30: 80PubMed Google Scholar in a recent ex vivo study, supported the concept that the liposterolic extract of SPB (Permixon) has antiandrogenic effects that inhibit the type 1 and type 2 isoenzymes of 5-alpha-reductase. In a randomized study, 33 patients with BPH underwent being with either for 3 flutamide for 2 or Permixon for 3 or of these a in tissue concentrations of However, Permixon and a in prostate with flutamide or with this was in the In et S et al.Effects of the extract and its on 5-alpha-reductase activity in human benign prostatic 1996; PubMed Scopus Google Scholar performed a using an extract of to the on and in BPH were with either or for 3 which they underwent The were evaluated for and and There was in 5-alpha-reductase and and activity between with However, activity was increased in patients with Because the of is it is that the of in to The clinical significance of this is not comparisons of the tissue were also and reported et of benign prostatic hyperplasia treatment with extract or 1995; 3: Scholar with a in and and The clinical significance of these is In previous studies by et L C et of a 5-alpha-reductase and plant extracts in in vitro and in vivo 5-alpha-reductase PubMed Scopus (120) Google Scholar not of DHT to prostatic androgen receptor or of DHT Additionally, clinical studies and in patients SPB extracts for of to L C et of a 5-alpha-reductase and plant extracts in in vitro and in vivo 5-alpha-reductase PubMed Scopus (120) Google Scholar, C M M of effects of a liposterolic extract of Serenoa repens on of and Scholar, G P G et of and Serenoa repens (Permixon®) in the of in Urol. Google Scholar, J The extract of Serenoa repens in the treatment of benign prostatic hyperplasia a Res. Full Text PDF Scopus Google Scholar, et palmetto in with lower urinary tract symptoms effects on and 1998; Full Text Full Text PDF PubMed Scopus Google Scholar of these studies in and Therefore, the on and 5-alpha-reductase activity by repens has to be determined our previous review, another study has been published in which of to were randomized to Permixon or for P et of the efficacy and of in benign prostatic hyperplasia of 1995; 9: Scopus Google Scholar that and urinary were in patients with and patients (Table However, the of the study, the patients and physicians were to efficacy of the different there was in between Permixon and and treatment and this study of Permixon not clinical by the patients or their of Permixon and for benign prostatic from et urinary not in in in urinary not Data from et P et of the efficacy and of in benign prostatic hyperplasia of 1995; 9: Scopus Google Scholar Open table in a new tab Because clinical do not with regard to the efficacy of SPB extract in BPH, a of the clinical trials of Permixon was F.C C et of clinical trials of Urol. 1998; Scholar of the Permixon trials were evaluated for the available urinary and Because these studies were performed the of the American and the International the results for were available in the the was as an increase in of The estimated of Permixon to was a increase of P The of was by an of for Permixon by P The of this be by the that most of the studies were than 100 and of than and However, was by the The of studies and the total were and of the was The most and SPB extract (Permixon) was the comparative with J.C Raynaud G et of (Permixon®) with in the treatment of benign prostatic hyperplasia a randomized study of 1996; 29: PubMed Scopus Google Scholar This randomized of patients was conducted to that the efficacy of Permixon was to (Table of with Permixon or from et International urinary of International urinary Data from et C M M of effects of a liposterolic extract of Serenoa repens on of and Scholar Open table in a new tab Permixon and the total by a and increased by in the with in the Permixon These were with There was also a in in the were in the Permixon and in the by more in the than in the Permixon This and the of Permixon to in with to symptoms of BPH, with in However, the of a the efficacy F.C Fagelman E Phytotherapy in the treatment of benign prostatic hyperplasia.Curr Opin Urol. 1998; 8: 27-29Crossref PubMed Scopus (5) Google Scholar, F.C Saw palmetto berry in the treatment of benign prostatic hyperplasia.Clin Res Reg Affairs. 1997; 14: 53-66Crossref Scopus (4) Google Scholar the study being in it is that the is due to the which with of (Permixon®) with in the treatment of benign prostatic hyperplasia a randomized study of patients 1996; 29: Scopus Google Scholar Additionally, the study by et et al.The efficacy of or in benign prostatic J 1996; PubMed Scopus Google Scholar that was not better than Therefore, Permixon with be to F.C Fagelman E Phytotherapy in the treatment of benign prostatic hyperplasia.Curr Opin Urol. 1998; 8: 27-29Crossref PubMed Scopus (5) Google Scholar, F.C Saw palmetto berry in the treatment of benign prostatic hyperplasia.Clin Res Reg Affairs. 1997; 14: 53-66Crossref Scopus (4) Google Scholar In a study SPB extract were evaluated and of the et palmetto in with lower urinary tract symptoms effects on and 1998; Full Text Full Text PDF PubMed Scopus Google Scholar The from to a than in was in and of patients and in urinary or were This study between of of and a in an the drug of SPB extract cannot be F.C Saw palmetto in with lower urinary tract symptoms effects on and symptoms 1998; Scholar the may be to the et palmetto in with lower urinary tract symptoms effects on and 1998; Full Text Full Text PDF PubMed Scopus Google Scholar the and comparative trials SPB extract are not in the efficacy of this product in the treatment of BPH. The studies are by and of F.C Ku J.C Phytotherapy in treatment of benign prostatic hyperplasia a critical review.Urology. 1996; 48: 12-20Abstract Full Text PDF PubMed Scopus (119) Google Scholar The of Permixon clinical efficacy for this F.C C et of clinical trials of Urol. 1998; the was performed using et P et of the efficacy and of in benign prostatic hyperplasia of 1995; 9: Scopus Google Scholar that patients have in and urinary with Permixon and of efficacy were different between Permixon and P et of the efficacy and of in benign prostatic hyperplasia of 1995; 9: Scopus Google Scholar Despite its being the most widely evaluated phytotherapeutic the efficacy of SPB extract in the treatment of LUTS secondary to BPH has to be trials are for each individual manufacturer’s product to its extract from the of the African and is widely used in and Europe. Other and numerous are available in health and the United the research and clinical trials of this product have been using the product In vitro that the extract has of growth and epidermal growth factor-induced M J.C J.C et extract inhibits and proliferation of 48: Scopus Google Scholar, G I P et for the use of extract during BPH is by in vitro proliferation of human prostate and (abstract).Eur Urol. 1996; 30: Scholar, F et of extract on prostatic Urol. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar of of and other M A R et of extract on of from human polymorphonuclear 9: Google Scholar and antiestrogenic G M et extract with action the of and prostatic 1995; PubMed Scopus Google Scholar studies by et R.M F et al.Effects of on and Urol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, R.M F et of on secondary to Urol. 1996; Full Text Full Text PDF PubMed Scopus (42) Google Scholar that the effects of on LUTS be in a model with model for secondary to et R.M F et al.Effects of on and Urol. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar that in in and in to of be and by In a study, 2 of in a treatment with and that were R.M F et of on secondary to Urol. 1996; Full Text Full Text PDF PubMed Scopus (42) Google Scholar However, of to 100 are the in is 100 Therefore, the of this to is uncertain. A review of the published with patients with this patients in studies and in comparative extract for the treatment of patients with benign prostatic hyperplasia a review of years of published Res. 1995; Scopus Google Scholar studies were between and one study more than 100 and were than of trials the by the International Consultation on the the efficacy of are not In the a and with was in were to be The be by with available in It is that this some on the efficacy of this et J O A et and of in the treatment of benign prostatic hyperplasia (BPH) a in Res 1998; 14: PubMed Scopus Google Scholar a a of The was and the of this in was urinary were and the of effects were in the study this study a of this be from this et A C et an a plant extract a randomized in patients with benign prostatic hypertrophy (BPH) (abstract).Eur Urol. 1996; 30: Scholar an selective with an extract of this was to be more effective than with regard to in and in This study little to our knowledge of the efficacy of is for In a recent review of the and from patients with 100 of for 2 and of the of on human study (abstract Fourth International Consultation on BPH, Paris, 1997, p Scholar patients were and were were not these which were by little the of on and the study is the available the efficacy of in LUTS secondary to BPH are There is a of there are available with regard to of the other from the of a are widely used in K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. 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This study was evaluated by F.C Ku J.C Phytotherapy in treatment of benign prostatic hyperplasia a critical review.Urology. 1996; 48: 12-20Abstract Full Text PDF PubMed Scopus (119) Google Scholar the Fourth International Consultation on BPH in in 1997, reported on the for these K Borkowski A Braeckman J et al.Other medical therapies.in: Denis L Griffiths K Murphy G Proceedings of the Fourth International Consultation on Benign Prostatic Hyperplasia (BPH), July 1997. Health Publications, Plymouth, UK1998: 635-659Google Scholar In patients to were were with also of in and Most patients were with over the of This the that be a of this study to it agent containing was evaluated in a clinical of for the treatment of benign prostatic J Urol. 1997; PubMed Google Scholar patients during the of in urinary and were The by for patients and by for by for and by for Therefore, the drug was The of of with in patients in this study is and has not been reported for medical for BPH. these results are they of The trials by et J et clinical of in patients with benign prostatic 1995; Scopus Google Scholar and et clinical of for the treatment of benign prostatic J Urol. 1997; PubMed Google Scholar are were performed to the of the International on BPH. The results of the studies are studies to this of be In the review, the recent and clinical trials using phytotherapeutic agents were Two other recent have of this Phytotherapy for the J Urol. 1996; PubMed Google Scholar, F.C Dreikorn K Borkowski A et review of the recent trials phytotherapeutic agents for the treatment of 1998; PubMed Scopus Google Scholar critical and review of the that clinical trials using these phytotherapeutic agents are studies the clinical efficacy of studies with these specific products are the widespread use of phytotherapeutic products our the and of efficacy of these is also to the active or and their mechanism of the efficacy of phytotherapeutic agents for BPH has to be trials a for this type of