| Serenoa repens vs
Finasteride in androgenic Alopecia. /
Serenoa Repens vs Finasteride en
alopecia androgenica.
Data-Medicos
Dermagic/Express No. 77
06 Octubre 1.999. 06 October 1.999.
~ Serenoa Repens Vs Finasteride en Alopecia Androgenica, ~
~ Serenoa Repens Vs Finasteride in Androgenic Alopecia ~
EDITORIAL ESPANOL
=================
Hola Amigos de la red, DERMAGIC de nuevo con ustedes, El tema de hoy:
SERENOA VS FINASTERIDE. Cuando el laboratorio Merck, Sharp and D. lanzo su
producto FINASTERIDE al MERCADO, quiza no penso nunca que ya existia una
medicina con iguales caracteristicas al PROSCAR, PROPECIA con la unica
diferencia que esta es una planta, LAS CEREZAS O BAYAS DEL SAW PALMETTO,
mejor conocida como SERENOA REPENS. Si examinamos bien estas referencias
bibliograficas nos encontramos con lo siguiente:
LA SERENOA REPENS:
1.) Tiene iguales propiedades al finasteride en disminucion de la sintomatologia prostatica.
2.) INHIBE LAS izoenzimas 1 y 2 a nivel de la prostata.
3.) Es un potente antiinflamatorio a nivel prostatico.
4.) Disminuye el nivel de la DHT (dihidrotestosterona) la responsable de la alopecia androgenica porque INHIBE la 5 alfa-reductasa.
5.) Tiene menos efectos secundarios que el FINASTERIDE.
Con estas caracteristica principales debemos pensar que LA SERENOA REPENS
tambien tiene EL MISMO EFECTO QUE EL FINASTERIDE en la alopecia
androgenica, mas NO HAY NINGUN ESTUDIO que lo haya confirmado. Lo que si es
cierto es que estas dos medicinas, una NATURAL (EL SAW PALMETTO), otra
QUIMICA (FINASTERIDE) nacieron en la PROSTATA, mejorando los sintomas del
agrandamiento, luego se comprobo que el FINASTERIDE inhibia la 5 alfa reductasa
disminuyendo los niveles de DHT y el resto del cuento lo conocen ustedes.
Pero la historia NO TERMINA ALLI, al SAW PALMETTO o SERENOA REPENS, mejor
conocido como PERMIXON tambien SE LE COMPROBO las mismas PROPIEDADES del
FINASTERIDE en cuanto a la disminucion de los niveles de DHT, siendo considerada actualmente como una PLANTA ANTIANDROGENOS. De modo que AL laboratorio M.S.D se le puede poner la pelota "pesada" CUANDO sepa que una HIERBA, MAS BARATA Y CON MENOS EFECTOS SECUNDARIOS, es igual o SUPERIOR A SU PRODUCTO ESTRELLA el finasteride. Que tal ???
En estas 48 referencias ,,, los hechos
Saludos a todos !!!
Dr. Jose Lapenta R.,,,
EDITORIAL ENGLISH
=================
Hello Friends of the net, DERMAGIC again with you, today's topic: SERENOA VS FINASTERIDE. When the laboratory Merck, Sharp and D. throws its product FINASTERIDE to the MARKET, he didn't maybe think never that a medicine already existed with characteristic equal to the PROSCAR, PROPECIA with the only difference that this it is a plant, THE BERRIES OF THE SAW PALMETTO, better known as SERENOA REPENS. If we examine these
bibliographical references well we meet with the following thing:
THE SERENOA REPENS:
1.) She has same properties to the finasteride in decrease of the prostatic symptoms
2.) it INHIBITS THE isoenzyme 1 and 2 at the prostate.
3.) She has a potent antiinflammatory effects in the prostate
4.) it diminishes the level of the dihydrotestosterone (DHT) the causing one for the androgenic alopecia BECAUSE it INHIBITS the 5 alpha-reductase.
5.) She has less secondary effects than the FINASTERIDE.
With these main characteristic we should think that THE SERENOA REPENS also has THE SAME EFFECT THAT THE FINASTERIDE in the androgenica alopecia , but there is not ANY STUDY that has confirmed it. WHAT it is certain, it is that these two medicines, a NATURAL one (THE SAW PALMETTO), another CHEMISTRY (FINASTERIDE) they were born in the PROSTATE, improving the symptoms of the enlargement, then it was proven that the FINASTERIDE inhibited the 5 alpha-reductase diminishing the levels of DHT and the rest
of the story you know it.
But the history doesn't FINISH THERE, to the SAW PALMETTO or SERENOA
REPENS, better known as PERMIXON was also proven the same PROPERTIES of the
FINASTERIDE as for the decrease of the levels of DHT, being considered at the moment like a ANTIANDROGEN PLANT. So that TO THE laboratory M.S.D it can FEEL THAT THE BALL will be put "HEAVY" WHEN he knows that a HERB, CHEAPER AND WITH LESS SECONDARY EFFECTS, it is same or SUPERIOR TO ITS STAR PRODUCT the finasteride. What ????
In these 48 references, the facts
Greetings to ALL, !!
Dr. Jose Lapenta R.,,,
===================================================================
REFERENCIAS BIBLIOGRAFICAS / BIBLIOGRAPHICAL REFERENCES
===================================================================
===================================================================
SERENOA REPENS
===================================================================
1.) Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts.
2.) Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.
3.) Effect of the lipidic lipidosterolic extract of Serenoa repens (Permixon) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils.
4.) Distribution study of radioactivity in rats after oral administration of the lipido/sterolic extract of Serenoa repens (Permixon) supplemented with [1-14C]-lauric acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol.
5.) Biologically active acylglycerides from the berries of saw-palmetto (Serenoa repens).
6.) Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced experimental prostate enlargement in the rat.
7.) Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in
benign prostatic hyperplasia.
8.) Comparison of finasteride (Proscar) and Serenoa repens (Permixon) in the inhibition of 5-alpha reductase in healthy male volunteers.
9.) Comparative effects of alfuzosin versus Serenoa repens in the treatment of symptomatic benign prostatic hyperplasia.
10.) Inhibition of the activity of 'basic' 5 alpha-reductase (type 1) detected in DU 145 cells and expressed in insect cells
11.) Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new evidence in a coculture model of BPH.
12.) Inhibition of human sperm motility by specific herbs used in alternative medicine.
13.) An alternative medicine study of herbal effects on the penetration of zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid.
14.) Saw palmetto extracts for treatment of benign prostatic hyperplasia: a systematic review.
15.) Inhibitory effects of Serenoa repens on the kinetic of pig prostatic microsomal 5alpha-reductase activity.
16.) Effects of long-term treatment with Serenoa repens (Permixon) on the concentrations and regional distribution of androgens and epidermal growth factor in benign prostatic hyperplasia.
17.) Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms: effects on urodynamic parameters and voiding symptoms.
18.) Derivatization for electrospray ionization mass spectrometry. 3. Electrochemically ionizable derivatives.
19.) Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its major components on basic fibroblast growth factor-induced proliferation of cultures of human prostate biopsies.
20.) Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human prostatic cell lines.
21.) Lack of effects of a lyposterolic extract of Serenoa repens on plasma levels of testosterone, follicle-stimulating hormone, and luteinizing hormone.
22.) [Our experience with a hexane extract of Serenoa repens in the treatment of benign prostatic hypertrophy].
23.) Plant extracts in BPH.
24.) [Pharmacological combinations in the treatment of benign prostatic hypertrophy].
25.) [Anti-inflammatory activity of sabal fruit extracts prepared with
supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and 5-lipoxygenase metabolism].
26.) [Symptomatic treatment of benign hypertrophy of the prostate. Comparative study of prazosin and serenoa repens].
27.) Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients.
28.) The effect of Permixon on androgen receptors.
29.) Inhibition of androgen metabolism and binding by a liposterolic extract of "Serenoa repens B" in human foreskin fibroblasts.
30.) Binding of Permixon, a new treatment for prostatic benign hyperplasia, to the cytosolic androgen receptor in the rat prostate.
====================================================================
FINASTERIDE
====================================================================
31.) [Clinical significance of testosterone and dihydrotestosterone metabolism in women].
32.) Finasteride: the first 5 alpha-reductase inhibitor.
33.) A novel class of inhibitors for human steroid 5 alpha-reductase: phenoxybenzoic acid derivatives. I.
34.) Management of androgenetic alopecia.
35.) Continued improvement in pressure-flow parameters in men receiving finasteride for 2 years. Finasteride Urodynamics Study Group.
36.) Economic analysis of finasteride: a model-based approach using data from the Proscar Long-Term Efficacy and Safety Study.
37.) Comparison of finasteride and flutamide in the treatment of idiopathic hirsutism.
38.) Validation of a population pharmacokinetic/pharmacodynamic model for 5alpha-reductase inhibitors.
39.) Benign prostatic hyperplasia. A review of diagnostic and treatment options. Adv Nurse Pract 1999 Apr;7(4):31-6; quiz 37-8
40.) Finasteride treatment for one year in 35 hirsute patients.
41.) Impact of drug therapy on benign prostatic hyperplasia-specific quality of life.
42.) Finasteride in the treatment of men with frontal male pattern hair loss.
43.) Effect of finasteride and/or terazosin on serum PSA: results of VA Cooperative Study #359.
44.) Androgenetic alopecia in men: the scale of the problem and prospects for treatment.
45.) Inhibition of androgen synthesis in human testicular and prostatic microsomes and in male rats by novel steroidal compounds.
46.) Finasteride: an update of its use in the management of symptomatic benign prostatic hyperplasia.
47.) Efficacy of finasteride is maintained in patients with benign prostatic hyperplasia treated for 5 years. The North American Finasteride Study Group.
48.) Long-term effects of finasteride on prostate tissue composition.
====================================================================
====================================================================
SERENOA REPENS
====================================================================
1.) Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts.
====================================================================
AU: Delos-S; Carsol-JL; Ghazarossian-E; Raynaud-JP; Martin-PM
AD: Laboratoire de Cancerologie Experimentale, Faculte de Medecine Secteur Nord, Marseille, France.
SO: J-Steroid-Biochem-Mol-Biol. 1995 Dec; 55(3-4): 375-83
ISSN: 0960-0760
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: 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) 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.
====================================================================
2.) Human prostatic steroid 5 alpha-reductase isoforms--a comparative study of selective inhibitors.
====================================================================
AU: Iehle-C; Delos-S; Guirou-O; Tate-R; Raynaud-JP; Martin-PM
AD: Laboratoire de Cancerologie Experimentale, Faculte de Medecine, Marseille, France.
SO: J-Steroid-Biochem-Mol-Biol. 1995 Sep; 54(5-6): 273-9
ISSN: 0960-0760
PY: 1995
LA: ENGLISH
CP: ENGLAND
AB: 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.
====================================================================
3.) Effect of the lipidic lipidosterolic extract of Serenoa repens (Permixon) on the ionophore A23187-stimulated production of leukotriene B4 (LTB4) from human polymorphonuclear neutrophils.
====================================================================
AU: Paubert-Braquet-M; Mencia-Huerta-JM; Cousse-H; Braquet-P
AD: Bio-Inova, Life Sciences International, Plaisir, France.
SO: Prostaglandins-Leukot-Essent-Fatty-Acids. 1997 Sep; 57(3): 299-304
ISSN: 0952-3278
PY: 1997
LA: ENGLISH
CP: SCOTLAND
AB: Although the lipidic extract of Serenoa repens (LESSr, Permixon, Sereprostat) is widely used in patients suffering from benign prostatic hypertrophy (BPH), its mechanism of action is not fully elucidated. It has been demonstrated that infiltration of the prostate by inflammatory cells is one of the aetiologic factors involved in the development of BPH. These inflammatory cell types, such as polymorphonuclear neutrophils (PMNs), produce chemotactic mediators and contribute to the development of the disease. Among the chemotactic factors generated by inflammatory cell types, the derivatives of arachidonic acid have been extensively studied. For instance, leukotriene (LT) B4 is one of the most potent chemotactic factors for PMNs and also exhibits a wide range of biological activities. In order to investigate the potential action of LESSr on arachidonate metabolism, and particularly on the synthesis of LTB4, the effect of this extract on the in vitro synthesis of LT by human PMNs stimulated with the calcium ionophore A23187 was investigated. LESSr significantly inhibits the production of 5-lipoxygenase metabolites (5-HETE, 20-COOH LTB4, LTB4 and 20-OH LTB4) at concentrations as low as 5 microg/ml. Such an effect of LESSr was also observed in the presence of exogenous arachidonic acid (20 microg/ml) and when f-MLP was used as the agonist, suggesting that inhibition of LTB4 production by the extract was unrelated to phospholipase A2 blockade and independent of the stimulating agent. The capability of LESSr to antagonize 5-lipoxygenase metabolites production may contribute, at least partly, to the understanding of its therapeutic activity on the inflammatory component of BPH.
====================================================================
4.) Distribution study of radioactivity in rats after oral administration of the
lipido/sterolic extract of Serenoa repens (Permixon) supplemented with [1-14C]-lauric
acid, [1-14C]-oleic acid or [4-14C]-beta-sitosterol.
====================================================================
Chevalier G; Benard P; Cousse H; Bengone T
Ecole Nationale Veterinaire, Departement des Sciences Biologiques et
Fonctionnelles, Toulouse, France.
Eur J Drug Metab Pharmacokinet (SWITZERLAND) Jan-Mar 1997 22 (1) p73-83 ISSN:
0398-7639
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9710
Subfile: INDEX MEDICUS
The study carried out on rats given orally the n-hexane lipido/sterolic extract of
Serenoa repens (LSESR), supplemented with [14C]-labelled oleic or lauric acids or
beta-sitosterol, demonstrated that radioactivity uptake in prostatic tissues shows
the highest level in the case of administration of LSESR supplemented with [14C]-
labelled oleic acid. This was clearly demonstrated on a rat with an induced fibro-
muscular hyperplasia of the prostate and by quantitative measurements of
radioactivity. Ratios of radioactivity in tissues compared to plasma show an uptake
of radioactivity greater in prostate as compared to other genital organs, i.e. the
seminal vesicles or to other organs such as liver.
====================================================================
5.) Biologically active acylglycerides from the berries of saw-palmetto (Serenoa
repens).
====================================================================
Shimada H; Tyler VE; McLaughlin JL
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy
and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
J Nat Prod (UNITED STATES) Apr 1997 60 (4) p417-8 ISSN: 0163-3864
Contract/Grant No.: RO1 CA30909--CA--NCI
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9708
Subfile: INDEX MEDICUS
Brine shrimp lethality-directed fractionation of the 95% EtOH extract of the
powdered, dried berries of Serenoa repens (Bart.) Small (saw-palmetto) (Palmae) led
to the isolation of two monoacylglycerides, 1-monolaurin (1) and 1-monomyristin (2).
Compounds 1 and 2 showed moderate biological activities in the brine shrimp lethality
test and against renal (A-498) and pancreatic (PACA-2) human tumor cells; borderline
cytotoxicity was exhibited against human prostatic (PC-3) cells. The fruits and
extracts of saw-palmetto are taken orally as an herbal medicine to prevent prostatic
hyperplasias.
====================================================================
6.) Effect of Serenoa repens extract (Permixon) on estradiol/testosterone-induced
experimental prostate enlargement in the rat.
====================================================================
Paubert-Braquet M; Richardson FO; Servent-Saez N; Gordon WC; Monge MC; Bazan NG;
Authie D; Braquet P
BIO-Inova EuroLab Research Labs, Plaisir, France.
Pharmacol Res (ENGLAND) Sep-Oct 1996 34 (3-4) p171-9 ISSN: 1043-6618
Language: ENGLISH
Document Type: JOURNAL ARTICLE
Journal Announcement: 9707
Subfile: INDEX MEDICUS
The effect of the lipidosterolic extract of Serenoa repens (LSESR) on experimental
prostate enlargement was investigated in three groups of rats: shams treated with
LSESR (sham rats), castrated animals treated with estradiol and testosterone
(castrated rats), castrated animals treated with estradiol/testosterone and treated
with LSESR (castrated and treated rats). Following three months of continuous
hormonal treatment, the weight of prostates in estradiol/testosterone-treated
castrated rats was significantly increased in comparison with sham-operated rats.
Such an increase started rapidly, reached a maximum by 30 days and remained at a
plateau or slightly declined thereafter. The increase of prostate total weight
induced by the hormone treatment was inhibited by administration of LSESR. Indeed,
the weight was significantly lower at day 60 and day 90 for the dorsal and lateral
regions of the prostate. The weight of the ventral region of the prostate was
significantly lower after 30 and 60 days treatment with LSESR. These results
demonstrate that administering LSESR to hormone-treated castrated rats inhibits the
increase in prostate wet weight. This effect of LSESR may explain the beneficial
effect of this extract in human benign prostatic hypertrophy.
====================================================================
7.) Serenoa repens (Permixon). A review of its pharmacology and therapeutic efficacy in
benign prostatic hyperplasia.
====================================================================
Plosker GL; Brogden RN
Adis International Limited, Auckland, New Zealand.
Drugs Aging (NEW ZEALAND) Nov 1996 9 (5) p379-95 ISSN: 1170-229X
Language: ENGLISH
Document Type: JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
Journal Announcement: 9704
Subfile: INDEX MEDICUS
Serenoa repens (Permixon) has been available for several years for the treatment of
men with benign prostatic hyperplasia (BPH). The drug is the n-hexane lipidosterolic
extract of the dwarf American palm (also known as Serenoa repens) and is a complex
mixture of various compounds. A number of pharmacodynamic effects have been
demonstrated with the lipidosterolic extract of Serenoa repens (LSESR), suggesting
multiple mechanisms of action including in vitro inhibition of both type 1 and type 2
isoenzymes of 5 alpha-reductase and interference with binding of dihydrotestosterone
to cytosolic androgen receptors in prostate cells. In controlled clinical trials in
men with BPH, oral administration of Serenoa repens 160 mg twice daily for 1 to 3
months was generally superior to placebo in improving subjective symptoms, such as
dysuria, as well as objective parameters. The frequency of nocturia was reduced by
33 to 74%, while urinary frequency during the day decreased by 11 to 43% and peak
urinary flow rate increased by 26 to 50% with Serenoa repens. Corresponding values
for placebo were 13 to 39%, 1 to 29% and 2 to 35%. The only large comparative trial
conducted to date, in which > 1000 men with moderate BPH were randomised to receive
Serenoa repens 160 mg twice daily or finasteride 5 mg once daily for 6 months,
demonstrated similar efficacy between the two drugs. No statistically significant
difference was demonstrated between treatment groups for improvement in patient self-
rated quality-of-life scores and the primary end-point of objective symptom score;
International Prostate Symptom Score improved by 37% with Serenoa repens compared
with 39% with finasteride. In much smaller comparative trials, few significant
differences were demonstrated between Serenoa repens and alpha 1-receptor
antagonists, and larger randomised trials of adequate duration are required to better
compare the clinical efficacy of these drugs. The most frequently reported adverse
events in clinical trials with Serenoa repens have been minor gastrointestinal
problems (e.g. nausea and abdominal pain). In conclusion, Serenoa repens is well
tolerated and has greater efficacy than placebo and similar efficacy to finasteride
in improving symptoms in men with BPH. Although there is a need for further
comparative studies, particularly with alpha 2-receptor antagonists, available data
indicate that Serenoa repens is a useful alternative to alpha 1-receptor antagonists
and finasteride in the treatment of men with BPH. (86 References)
====================================================================
8.) Comparison of finasteride (Proscar) and Serenoa repens (Permixon)
in the inhibition of 5-alpha reductase in healthy male
volunteers.
====================================================================
Au: Strauch G; Perles P; Vergult G; Gabriel M; Gibelin B; Cummings S;
Malbecq W; Malice MP.
Ad: Eclimed Pharmacologie Clinique, H"pital Universitaire Cochin,
Paris, France.
So: Eur Urol; 26(3):247-52, 1994.
Ab: A total of 32 healthy male volunteers (age range 20-30 years)
were enrolled in a 1-week open, randomized, placebo-controlled
study comparing finasteride (Proscar), a 5 alpha-reductase
inhibitor, with Permixon, the plant extract of Serenoa repens.
The objective of the study was to evaluate the effect of single
and multiple doses of the drugs on the inhibition of 5
alpha-reductase as assessed by serum dihydrotestosterone level
determination. Following baseline measurements on day 1, the
subjects were randomized to finasteride 5 mg once a day (n = 10),
Permixon 80 mg x 2 twice a day (n = 11), or to placebo once a day
(n = 11) for 7 days. Serum testosterone and dihydrotestosterone
levels, were determined on day 1 (baseline and 12 h) and on days
2 (24 h), 3 (48 h), 4 (72 h), 6 (120 h), and 8 (168 h). After 12
h, a single dose of finasteride 5 mg reduced the serum
dihydrotestosterone level by 65% (p < or = 0.01). The decreases
ranged from -52 to -60% with multiple doses of finasteride 5 mg
once a day (p < or = 0.01). As in the placebo group, there was no
effect of Permixon on the serum dihydrotestosterone level. No
significant difference was detected between finasteride and
Permixon or between finasteride and placebo with respect to serum
testosterone, except on days 3 and 6, respectively (p < or =
0.05). However, the corresponding serum testosterone levels
remained within the normal ranges. These data confirm the
efficacy of finasteride as inhibitor of 5
alpha-reductase.(ABSTRACT TRUNCATED AT 250 WORDS) (Au).
====================================================================
9.) Comparative effects of alfuzosin versus Serenoa repens in the
treatment of symptomatic benign prostatic hyperplasia.
====================================================================
Au: Grasso M; Montesano A; Buonaguidi A; Castelli M; Lania C; Rigatti
P; Rocco F; Cesana BM; Borghi C.
Ad: Department of Urology, Scientific Institute San Raffaele
Hospital, Milan, Italy.
So: Arch Esp Urol; 48(1):97-103, 1995 Jan-Feb.
Ab: OBJECTIVES: Sixty-three patients suffering from benign prostatic
hyperplasia (BPH) entered a double-blind, comparative,
parallel-groups study lasting 3 weeks, carried out to compare the
efficacy and safety of alfuzosin 2.5 mg tid (n = 32) vs serenoa
repens 160 mg bid (n = 31) in BPH. METHODS: Efficacy was assessed
both on clinical symptoms (Boyarsky's scale, visual analogue
scale, clinical global impression), urinary flow rates
(uroflowmetry) and residual urinary volume (transabdominal
ultrasound). Events and reported signs were recorded throughout
the entire study. RESULTS: Statistically significant and
clinically relevant differences were found between the two
treatments in favour of alfuzosin for Boyarsky's total score
(decrease from 9.6 +/- 3.0 to 5.9 +/- 3.0, 38.8% for alfuzosin
and from 9.3 +/- 2.5 to 6.8 +/- 2.8, 26.9% for serenoa repens)
and obstructive score (decrease from 4.9 +/- 2.1 to 3.0 +/- 1.9,
37.8% for alfuzosin; from 4.4 +/- 1.7 to 3.4 +/- 1.8, 23.1% for
Serenoa repens; p = 0.01 for both). Clinically relevant
differences were found between the two treatments for visual
analogue scale and overall clinical impression at the end of the
study. Furthermore, the increase in quality of micturition was
better with alfuzosin. The proportion of responders (increase on
day 21 in peak flow rate of at least 25% relative to the baseline
values) was in favour of alfuzosin (71.8% and 48.4% for alfuzosin
and Serenoa repens, respectively; p = 0.057). Both treatments
were well tolerated. No patient treated with alfuzosin complained
of any adverse event at any time during the study. One patient in
the Serenoa group complained of mild pruritus which cleared
spontaneously. Systolic, diastolic blood pressure and heart rate
did not show any clinically relevant change during treatment with
alfuzosin. CONCLUSIONS: The findings confirm the efficacy and
safety of alfuzosin in symptomatic BPH and indicate the
superiority of alfuzosin over Serenoa repens in the treatment of
urinary signs and symptoms of BPH (Au).
====================================================================
10.) Inhibition of the activity of 'basic' 5 alpha-reductase (type 1)
detected in DU 145 cells and expressed in insect cells
====================================================================
Au: Délos S; Iehlé C; Martin PM; Raynaud JP
Ad: Laboratoire de Cancérologie Expérimentale, Faculté de Medecine, Secteur Nord, Marseille, France
So: J Steroid Biochem Mol Biol; 48(4):347-52, 1994 Mar.
Is: 0960-0760
Cp: ENGLAND
La: Eng
Ab: The purpose of this study was 2-fold: (1) to identify the 5 alpha-reductase (5 alpha-R) isozyme(s) present in DU 145 cells, a human cell-line of low androgen sensitivity derived from a cerebral metastasis of an epithelial prostate cancer; and (2) to compare the inhibitory potencies of three compounds on the 'basic' 5 alpha-R isozyme expressed in a baculovirus-directed insect cell system. Conversion of testosterone (T) into 5 alpha-dihydrotestosterone (DHT) in DU 145 cells was measured by HPLC coupled to a Flo-one HP radioactivity detector. DU 145 cells exhibited 5 alpha-R activity (21 pmol DHT/min/mg protein) at pH 7.4 which disappeared at pH 5.5 suggesting that, of the two genomically distinct human isozymes identified so far, type 1 5 alpha-R is expressed in DU 145 cells. This was confirmed by at least two observations: first, 5 alpha-R activity in DU 145 cells was inhibited with much higher potency by 4-MA than by finasteride which is known to be a very poor competitor of the 'basic' enzyme (IC50s = 2.8 +/- 0.2 and 264 +/- 55 nM, respectively). Second, only the type 1 5 alpha-R cDNA and not type 2 5 alpha-R cDNA hybridized with DU 145 RNA. A high potency differential was also recorded for the inhibition of 'basic' type 1 5 alpha-R expressed in a baculovirus-directed-insect cell system by these two compounds, 4-MA being considerably more active than finasteride (Ki = 8.4 +/- 2.3 and 330 +/- 9 nM, respectively). This inhibition was competitive. On the other hand, inhibition by an n-hexane lipid/sterol extract of Serenoa repens (LSESr) was non-competitive and, when expressed in terms of recommended therapeutic doses, was 3-fold greater for LSESr than for finasteride. These studies suggest that LSESr might exert a regulatory inhibitory activity due to its specific lipid/sterol composition (Au)
====================================================================
11.) Serenoa repens (Permixon): a 5alpha-reductase types I and II inhibitor-new
evidence in a coculture model of BPH.
====================================================================
Prostate 1999 Sep 1;40(4):232-41
Bayne CW, Donnelly F, Ross M, Habib FK
Prostate Research Group, University Department of Oncology, Western General
Hospital, Edinburgh, Scotland.
BACKGROUND: The aim of this study was to determine the effect of the
phytotherapeutic agent, Permixon, on a novel coculture model of benign
prostatic hyperplasia (BPH) in an effort to better understand the mode of
action of the drug in vivo. METHODS: The effect of Permixon, at the
calculated therapeutic concentration, on the activity of 5alpha-reductase
isoenzymes was evaluated utilizing a pH-specific assay. Prostate-specific
antigen (PSA) secretions into the medium were measured in the presence and
absence of Permixon and quantified by an ELISA assay. The morphological
patterns before and following Permixon treatment were also examined by
electron microscopy. All results were compared to controls. RESULTS:
Permixon at a concentration of 10 micrograms/ml (calculated plasma
concentration in patient receiving recommended therapeutic dosage) was
shown to be an effective inhibitor of both 5alpha-reductase types I and II
isoenzymes without influencing the secretion of PSA by the epithelial
cells, even after stimulation with testosterone. The morphology of
Permixon-treated cells was found to be markedly different from that of
untreated controls. Cells which had been treated with the drug demonstrated
extensive accumulation of lipids in the cytoplasm and widespread damage of
intracellular membranes, including mitochondrial and nuclear membranes.
CONCLUSIONS: Permixon is an effective dual inhibitor of 5alpha-reductase
isoenzyme activities in the prostate. Unlike other 5alpha-reductase
inhibitors, Permixon induces this effect without interfering with the
cells' capacity to secrete PSA, thus permitting the continued use of PSA
measurements for prostate cancer screening. Copyright 1999 Wiley-Liss, Inc.
====================================================================
12.) Inhibition of human sperm motility by specific herbs used in alternative
medicine.
====================================================================
J Assist Reprod Genet 1999 Feb;16(2):87-91
Ondrizek RR, Chan PJ, Patton WC, King A
Department of Gynecology and Obstetrics, Loma Linda University School of
Medicine, California 92350, USA.
PURPOSE: Our purpose was to analyze sperm motility parameters in the
presence of herbs. METHODS: Washed sperm were incubated in either
saw-palmetto (Serenoa repens, Permixon Sabal serrulatum), echinacea
purpura, ginkgo biloba, St. John's wort (Hypericum perforatum), or control
medium. Parameters were measured on a Hamilton-Thorn analyzer after 1, 4,
24, and 48 hr at 37 degrees C. RESULTS: Sperm motility was inhibited at the
high concentration (0.6 mg/mL) of St. John's wort. Curvilinear velocities
and beat cross frequencies also decreased, but not hyperactivation.
High-concentration saw-palmetto, echinacea, or gikgo inhibited motility at
24 and 48 hr. CONCLUSIONS: A potent inhibition of sperm motility was seen
in St. John's wort unrelated to changes in pH. Furthermore, sperm viability
was compromised in St. John's wort, suggesting a spermicidal effect.
Metabolic changes were observed in saw-palmetto-treated sperm.
High-concentration echinacea purpura interfered with sperm enzymes. Ginkgo
did not have an antioxidant effect on sperm motility.
====================================================================
13.) An alternative medicine study of herbal effects on the penetration of
zona-free hamster oocytes and the integrity of sperm deoxyribonucleic acid.
====================================================================
Fertil Steril 1999 Mar;71(3):517-22
Ondrizek RR, Chan PJ, Patton WC, King A
Department of Gynecology and Obstetrics, Loma Linda University School of
Medicine, California 92350, USA.
OBJECTIVE: To analyze the effects of certain herbs on sperm DNA and on the
fertilization process. DESIGN: Prospective comparative study. SETTING:
Clinical and academic research environment. PATIENT(S): Donor sperm
specimens. INTERVENTION(S): Zona-free hamster oocytes were incubated for 1
hour in saw palmetto (Serenoa repens), echinacea purpura, ginkgo biloba,
St. John's wort (Hypericum perforatum), or control medium before
sperm-oocyte interaction. The DNA of herb-treated sperm was analyzed with
denaturing gradient gel electrophoresis. MAIN OUTCOME MEASURE(S): Oocyte
penetration and integrity of the sperm BRCAI exon 11 gene. RESULT(S):
Pretreatment of oocytes with 0.6 mg/mL of St. John's wort resulted in zero
penetration. A lower concentration (0.06 mg/mL) had no effect. High
concentrations of echinacea and ginkgo also resulted in reduced oocyte
penetration. Exposure of sperm to echinacea purpura and St. John's wort
resulted in DNA denaturation. In contrast, saw palmetto and ginkgo had no
effect. Sperm exposed to 0.6 mg/mL of St. John's wort showed mutation of
the BRCA1 exon 11 gene. CONCLUSION(S): High concentrations of St. John's
wort, echinacea, and ginkgo had adverse effects on oocytes. Saw palmetto
had no effect. The data suggested that St. John's wort, ginkgo, and
echinacea at high concentrations damage reproductive cells. St. John's wort
was mutagenic to sperm cells.
====================================================================
14.) Saw palmetto extracts for treatment of benign prostatic hyperplasia: a
systematic review.
====================================================================
JAMA 1998 Nov 11;280(18):1604-9
Published erratum appears in JAMA 1999 Feb 10;281(6):515
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.
[email protected]
OBJECTIVE: 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. 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.
====================================================================
15.) Inhibitory effects of Serenoa repens on the kinetic of pig prostatic
microsomal 5alpha-reductase activity.
====================================================================
Endocrine 1998 Aug;9(1):65-9
Palin MF, Faguy M, LeHoux JG, Pelletier G
Agriculture and Agri-Food Canada, Dairy and Swine Research and Development
Centre, Lennoxville, Quebec. [email protected]
The pathogenesis of benign prostatic hyperplasia is linked to the
accumulation of dihydrotestosterone (DHT), the active form of testosterone
(T), in prostatic tissue. We have defined characteristics of
5alpha-reductase enzyme which catalyzes the conversion of T into DHT in
prostatic microsomes of growing pigs. Peaks for the 5alpha-reductase
activity were found at pH 5.5 and 8.0, which indicates the presence of both
type 1 and type 2 isozymes. Kinetic parameters of porcine 5alpha-reductase
in the presence of Serenoa repens extracts revealed uncompetitive,
noncompetitive, and mixed types of inhibitions. Our results show the
inhibitory action of S. repens on prostate porcine microsomal
5alpha-reductase activity.
====================================================================
16.) Effects of long-term treatment with Serenoa repens (Permixon) on the
concentrations and regional distribution of androgens and epidermal growth
factor in benign prostatic hyperplasia.
====================================================================
Prostate 1998 Oct 1;37(2):77-83
Di Silverio F, Monti S, Sciarra A, Varasano PA, Martini C, Lanzara S,
D'Eramo G, Di Nicola S, Toscano V
Department of Urology, University of Rome La Sapienza, Italy.
BACKGROUND: The n-hexane lipido-sterol extract of Serenoa repens (LSESr,
Permixon, Pierre Fabre Medicament, Castres, France), a phytotherapeutic
agent used in the treatment of benign prostatic hyperplasia (BPH), has a
multisite mechanism of action including inhibition of types 1 and 2
5alpha-reductase and competitive binding to androgen receptors in prostatic
cells. Here, the response of testosterone (T), dihydrotestosterone (DHT),
and epidermal growth factor (EGF) in BPH tissue of patients treated with
LSESr (320 mg/day for 3 months) is analyzed. METHODS: BPH samples were
sectioned in periurethral, subcapsular, and intermediate regions: in each
region T, DHT, and EGF were determined by radioimmunoassay after
purification on celite columns or Sep-pak C18 cartridges. RESULTS: In the
untreated group, T, DHT, and EGF presented the highest concentrations in
the periurethral region (615 +/- 62 (SE) pg/g tissue, 7,317 +/- 551 pg/g
tissue, and 20.9 +/- 3.3 ng/g tissue, respectively) with respect to the
peripheral subcapsular region (425 +/- 45 pg/g tissue, 4,215 +/- 561 pg/g
tissue, and 10.8 +/- 1.4 ng/g tissue, respectively). In the LSESr-treated
group, a statistically significant reduction was observed, mainly in the
periurethral region of DHT (2,363 +/- 553 pg/g tissue, P < 0.001) and EGF
(6.98 +/- 2.48 ng/g tissue, P < 0.01), with increased T values (1,023 +/-
101 pg/g tissue, P < 0.001). CONCLUSIONS: The decrease of DHT and the rise
of T in BPH tissue of patients treated with Permixon confirms the capacity
of this drug to inhibit in vivo 5alpha-reductase in human pathological
prostate. A marked decrease of EGF, associated with DHT reduction, was also
observed. These biochemical effects, similar to those obtained with
finasteride, are particularly evident in the periurethral region, whose
enlargement is responsible for urinary obstruction, with respect to the
subcapsular region. A possible speculation is that the preferential
reduction of DHT and EGF content in the periurethral region is involved in
the clinical improvement of the obstructive symptoms in BPH during LSESr
therapy.
====================================================================
17.) Saw palmetto (Serenoa repens) in men with lower urinary tract symptoms:
effects on urodynamic parameters and voiding symptoms.
====================================================================
Urology 1998 Jun;51(6):1003-7
Gerber GS, Zagaja GP, Bales GT, Chodak GW, Contreras BA
Department of Surgery, University of Chicago Pritzker School of Medicine,
Illinois, USA.
OBJECTIVES: To assess the effects of saw palmetto on voiding symptoms and
urodynamic parameters in men with lower urinary tract symptoms (LUTS)
presumed secondary to benign prostatic hyperplasia (BPH). METHODS: Fifty
men with previously untreated LUTS and a minimum International Prostate
Symptom Score (IPSS) of 10 or greater were treated with a commercially
available form of saw palmetto (160 mg twice per day) for 6 months. The
initial evaluation included measurement of peak urinary flow rate, postvoid
residual urine volume, pressure-flow study, and serum prostate-specific
antigen (PSA) level. Patients completed an IPSS, serum PSA was determined,
and flow rate was measured every 2 months during the course of the study. A
urodynamic evaluation was repeated at the completion of the 6-month trial.
RESULTS: The mean IPSS (+/-SD) improved from 19.5+/-5.5 to 12.5+/-7.0 (P
<0.001) among the 46 men who completed the study. Significant improvement
in the symptom score was noted after treatment with saw palmetto for 2
months. An improvement in symptom score of 50% or greater after treatment
with saw palmetto for 2, 4, and 6 months was noted in 21% (10 of 48), 30%
(14 of 47), and 46% (21 of 46) of patients, respectively. There was no
significant change in peak urinary flow rate, postvoid residual urine
volume, or detrusor pressure at peak flow among patients completing the
study. No significant change in mean serum PSA level was noted.
CONCLUSIONS: Saw palmetto is a well-tolerated agent that may significantly
improve lower urinary tract symptoms in men with BPH. However, we were
unable to demonstrate any significant improvement in objective measures of
bladder outlet obstruction. Placebo-controlled trials of saw palmetto are
needed to evaluate the true effectiveness of this compound.
====================================================================
18.) Derivatization for electrospray ionization mass spectrometry. 3.
Electrochemically ionizable derivatives.
====================================================================
Anal Chem 1998 Apr 15;70(8):1544-54
Van Berkel GJ, Quirke JM, Tigani RA, Dilley AS, Covey TR
Chemical and Analytical Sciences Division, Oak Ridge National Laboratory,
Tennessee 37831-6365, USA. [email protected]
In this paper, the use of ferrocene-based "electrochemically ionizable"
derivatives to enhance ES-MS analysis of simple alcohols, sterols, and
phenols is discussed. These derivatives are designed to take advantage of
the electrolysis process inherent to operation of the ES ion source for
selective ionization. Derivatization procedures, electrochemical character
of the derivatives, and the ES-MS operational parameters necessary to
maximize electrochemical ionization and to enhance gas-phase detection are
presented with reference to ferrocenecarbamate ester derivatives of a
variety of alcohol standards, as well as the ferroceneboronate derivative
of the diol, pinacol. Tandem mass spectrometric analysis of the derivatives
(precursor and product ion spectra) is shown to provide derivative
confirmation, enhanced detection, and additional analyte structure
information. The utility of this derivatization approach for the selective
detection of alcohols in complicated mixtures is demonstrated using a saw
palmetto (Serenoa repens) fruit extract known to contain a variety of
alcohols at low levels.
====================================================================
19.) Effect of the lipidosterolic extract of Serenoa repens (Permixon) and its
major components on basic fibroblast growth factor-induced proliferation of
cultures of human prostate biopsies.
====================================================================
Eur Urol 1998;33(3):340-7
Paubert-Braquet M, Cousse H, Raynaud JP, Mencia-Huerta JM, Braquet P
Bio-Inova Euro Lab Research Laboratories, Plaisir, France.
OBJECTIVE: To assess the effect of the lipidosterolic extract of Serenoa
repens (LSESr) on in vitro cell proliferation in biopsies of human prostate
MATERIAL AND METHODS: Cell proliferation was assessed by incorporation of
[3H]thymidine followed by historadiography. RESULTS: Basic fibroblast
growth factor (b-FGF) induced a considerable increase in human prostate
cell proliferation (from +100 to +250%); the glandular epithelium was
mainly affected, minimal labeling being recorded in the other regions of
the prostate. Similar results were observed with epidermal growth factor
(EGF), although the increase in cell proliferation was not recorded in some
cases. Lovastatin, an inhibitor of hydroxymethylglutaryl coenzyme A,
antagonized both the basal proliferation and the growth factor-stimulated
proliferation of human prostate epithelium (EGF, mean inhibition
approximately 80-95%; b-FGF, mean inhibition approximately 40-90%).
Geraniol, a precursor of both farnesyl pyrophosphate and geranylgeranyl
pyrophosphate, and farnesol, the precursor of farnesyl pyrophosphate,
increased cell proliferation only in some prostate specimens, this effect
being antagonized by lovastatin. LSESr did not affect basal prostate cell
proliferation, with the exception of two prostate specimens in which a
significant inhibition of basal proliferation was observed with the highest
concentration of LSESr (30 micrograms/ ml). In contrast, LSESr inhibited
b-FGF-induced proliferation of human prostate cell cultures; this effect
was significant for the highest concentration of LSESr (30 micrograms/ml).
In some prostate samples, a similar inhibition was also noted with lower
concentrations. Unsaturated fatty acids (UFA), in the range 1-30 ng/ml),
did not affect the basal prostate cell proliferation, only a slight
increase in cell proliferation was noted in 1 prostate specimen. UFA (1, 10
or 30 micrograms/ml) markedly inhibited the b-FGF-induced cell
proliferation down to the basal value. Lupenone, hexacosanol and the
unsaponified fraction of LSESr markedly inhibited the b-FGF-induced cell
proliferation, whereas a minimal effect on basal cell proliferation was
noted. CONCLUSIONS: Despite the large variability in the response of the
prostate samples to b-FGF, these results indicate that LSESr and its
components affect the proliferative response of prostate cells to b-FGF
more than their basal proliferation.
====================================================================
20.) Effects of the lipidosterolic extract of Serenoa repens (Permixon) on human
prostatic cell lines.
====================================================================
Prostate 1996 Oct;29(4):219-30
Ravenna L, Di Silverio F, Russo MA, Salvatori L, Morgante E, Morrone S,
Cardillo MR, Russo A, Frati L, Gulino A, Petrangeli E
Department of Experimental Medicine and Pathology, University La Sapienza,
Rome, Italy.
BACKGROUND: Permixon is a drug used in the treatment of benign prostatic
hyperplasia. We studied its androgenic and antiandrogenic effects in the
prostatic cell lines LNCaP and PC3, respectively responsive and
unresponsive to androgen stimulation. METHODS: We performed FACScan
analysis to investigate toxicity, 3H thymidine and 35S methionine
incorporation to determine antiproliferative and metabolic effects,
electron microscopy to study ultrastructural changes and cotransfection
experiments to elucidate the role of wild type androgen receptor. RESULTS:
In LNCaP cell line, Permixon induced a double proliferative/differentiative
effect, not observed in PC3 cells. In PC3 cells cotransfected with
wild-type androgen receptors and CAT reporter genes under the control of a
androgen responsive element, the drug inhibited androgen-induced CAT
transcription. CONCLUSIONS: Our data indicate a role of the androgen
receptor in mediating the effects of Permixon in LNCaP cells.
Cotransfection experiments in PC3 cells support a clear antiandrogenic
action of the drug.
====================================================================
21.) Lack of effects of a lyposterolic extract of Serenoa repens on plasma
levels of testosterone, follicle-stimulating hormone, and luteinizing hormone.
====================================================================
Clin Ther 1988;10(5):585-8
Casarosa C, Cosci di Coscio M, Fratta M
Division of Urology, Hospital Riuniti S. Chiara, Pisa, Italy.
Twenty men, aged 50 to 75 years (mean, 67 years), suffering from benign
prostatic hypertrophy received 160 mg of a lyposterolic extract of Serenoa
repens, twice daily for 30 days. Before and at the end of treatment, plasma
levels of testosterone, follicle-stimulating hormone, and luteinizing
hormone were determined. No changes in plasma hormone levels occurred as a
result of treatment. It is concluded that Serenoa extract, which is useful
in the treatment of benign prostatic hypertrophy, does not act via systemic
changes of hormone levels.
====================================================================
22.) [Our experience with a hexane extract of Serenoa repens in the treatment of benign prostatic hypertrophy]. Olle Carreras J
Arch Esp Urol 1987 Jun;40(5):310-3
====================================================================
====================================================================
23.) Plant extracts in BPH.
====================================================================
Minerva Urol Nefrol 1993 Dec;45(4):143-9
Di Silverio F, Flammia GP, Sciarra A, Caponera M, Mauro M, Buscarini M,
Tavani M, D'Eramo G
Department of Urology U. Bracci, University of Rome La Sapienza, Rome.
In Italy plant extracts represent 8.6% of all pharmacological prescriptions
for Benign Prostatic Hyperplasia (data from 1991). This review evaluates
all the suggested mechanisms of action for plant extracts. Recently we
demonstrated an antiestrogenic effect of Serenoa Repens in BPH patients.
Clinical trials with plant extracts have yielded conflicting results. In a
recent review by Dreikorn and Richter, only five placebo controlled studies
were found. Moreover, as opposed to chemically defined drugs, it is
possible that for these extracts the active ingredients are not known;
consequently pharmacodynamic and pharmacokinetic data are often missing.
The International Consultation of Benign Prostatic Hyperplasia (Paris, June
1991) concluded that, to date, phytotherapeutic agents must be considered
as a symptomatic treatment. Now more adequate pharmacological and clinical
studies, placebo controlled, should determine the exact role of these drugs
in the treatment of BPH.
====================================================================
24.) [Pharmacological combinations in the treatment of benign prostatic
hypertrophy].
====================================================================
J Urol (Paris) 1993;99(6):316-20
Di Silverio F, D'Eramo G, Flammia GP, Buscarini M, Frascaro E, Mariani M,
Sciarra A
Department of Urology, U. Bracci, University La Sapienza of Rome, V. Le
Policlinico, Italy.
In the development of the obstructive symptomatology of benign prostatic
hypertrophy (BPH), two components may be identified, mechanical and
dynamic. In the mechanical component, the interaction of a stromal and a
epithelial compartment determines prostatic mass growth. The dynamic
component involves smooth muscle tone in the prostate and urethra. The
consideration that prostatic disease is not only epithelial in origin, but
also stromal, leads to the association of an antiandrogen (which acts on
the epithelial component) and an antiestrogen (active on the stromal
component) in the medical therapy of BPH. In 1985 we carried out a
randomized study on 256 BPH patients treated with Cyproterone acetate (CPA)
plus Tamoxifen (TAM). Recently, we performed a multicenter double blind
study on BPH patients treated with the association CPA plus Serenoa Repens.
A statistically significant difference in prostate volume reduction between
the groups treated with the combinations and those with the monotherapies
was observed. The development of new compounds, such as 5 alpha reductase
and aromatase inhibitors, consents to introduce a combination therapy with
less side effects. A second pharmacological association may be obtained
with drugs acting on the mechanical and others acting on the dynamic (alpha
blockers) component of BPH. This combination may associate the early
symptomatic effect of alpha blockers with the long term results of a 5
alpha reductase inhibitor, antiestrogen or aromatase inhibitor.
====================================================================
25.) [Anti-inflammatory activity of sabal fruit extracts prepared with
supercritical carbon dioxide. In vitro antagonists of cyclooxygenase and
5-lipoxygenase metabolism].
====================================================================
Arzneimittelforschung 1992 Apr;42(4):547-51
[Article in German]
Breu W, Hagenlocher M, Redl K, Tittel G, Stadler F, Wagner H
Institut fur Pharmazeutische Biologie, Ludwig-Maximilians-Universitat
Munchen.
The extract SG 291 (Talso, Talso uno) from the fruits of Sabal serrulata
(syn.: Serenoa repens) prepared by supercritical fluid extraction with
carbon dioxide is used for the treatment of benign prostatic hyperplasia
(BPH) and non bacterial prostatitis. In the present work, the Sabal extract
SG 291 was analyzed by gas chromatography and investigated for its
inhibitory influence on the biosynthesis of inflammatory arachidonic acid
metabolites. The extract SG 291 was found in vitro to be a dual inhibitor
of the cyclooxygenase (IC50-value: 28.1 micrograms/ml) and 5-lipoxygenase
pathway (IC50-value: 18.0 micrograms/ml). By alkaline hydrolysis, ether
extraction and preparative thin layer chromatography the extract SG 291 was
separated in three fractions containing acid lipophilic compounds (A),
fatty alcohols (B) and sterols (C) as main components. Fraction A inhibited
the biosynthesis of cyclooxygenase (CO) and 5-lipoxygenase (5-LO)
metabolites in the same intensity as the native extract SG 291, while the
fractions B, C and beta-sitosterol showed no inhibitory effect on both
enzymes of the arachidonic acid pathways. Therefore, the CO and 5-LO
inhibiting principle of Sabal serrulata extract SG 291 must be localized in
the acidic lipophilic fraction (SLF). The CO and 5-LO inhibitory effects
may give an explanation for the in vivo observed antiphlogistic and
antiedematous activity of the lipophilic Sabal serrulata extract SG 291.
====================================================================
26.) [Symptomatic treatment of benign hypertrophy of the prostate. Comparative
study of prazosin and serenoa repens].
====================================================================
[Article in Spanish]
Arch Esp Urol 1992 Apr;45(3):211-3
Adriazola Semino M, Lozano Ortega JL, Garcia Cobo E, Tejeda Banez E, Romero
Rodriguez F
Servicio de Urologia, Hospital Rio Carrion, Palencia, Espana.
Forty-five patients diagnosed as having BPH and clinically diagnosed
micturition disorders were entered in a therapeutic protocol. Twenty-five
patients received Prazosin and the remaining 20 patients were treated with
Serenoa Repens for a period of 12 weeks. The symptomatology was assessed by
flowmetry and the patients were questioned as to the irritative symptoms.
It can be concluded from the study that Prazosin is slightly more effective
in controlling the irritative symptoms produced by BPH.
====================================================================
27.) Evidence that Serenoa repens extract displays an antiestrogenic activity in
prostatic tissue of benign prostatic hypertrophy patients.
====================================================================
Eur Urol 1992;21(4):309-14
Di Silverio F, D'Eramo G, Lubrano C, Flammia GP, Sciarra A, Palma E,
Caponera M, Sciarra F
Department of Urology U. Bracci, University of Rome La Sapienza, Italy.
A double-blind placebo-controlled study was performed in 35 benign
prostatic hypertrophy (BPH) patients never treated before. The patients
were randomized into two groups, the 1st (18 cases) receiving Serenoa
repens extract (160 mg t.d.) for 3 months up to the day before the
operation of transvesical adenomectomy and the 2nd (17 cases) receiving
placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic
(c) fraction using the saturation analysis technique (Scatchard analysis or
single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors
and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR).
Scatchard analysis of ERc and ERn revealed the presence of two classes of
binding sites, one with high-affinity low-capacity binding and the other
with low-affinity high-capacity binding. In the untreated BPH group, ER
were higher in the n than in the c fraction: ERn were positive in 14 cases
and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract
on the contrary, ERn were negative for both binding classes in 17 cases and
ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15
samples examined, but in the treated group, ERn were significantly (p less
than 0.01) lower than in the untreated group, whilst ERc remained almost
unchanged. Similar results were obtained measuring PgR: the n fraction of
the treated group prostatic samples was significantly (p less than 0.01)
lower than that of the untreated group.
====================================================================
28.) The effect of Permixon on androgen receptors.
====================================================================
Acta Obstet Gynecol Scand 1988;67(5):397-9
el-Sheikh MM, Dakkak MR, Saddique A
Department of Obstetrics and Gynaecology, King Khalid University Hospital,
Riyadh, Saudi Arabia.
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.
====================================================================
29.) Inhibition of androgen metabolism and binding by a liposterolic extract of
"Serenoa repens B" in human foreskin fibroblasts.
====================================================================
J Steroid Biochem 1984 Jan;20(1):515-9
Sultan C, Terraza A, Devillier C, Carilla E, Briley M, Loire C, Descomps B
We previously suggested [Steroids 33, (1979) 3; Steroids 37, (1981) 6] that
cultured genital skin fibroblasts should prove useful for screening of
potential antiandrogens in human and living target cells. "Serenoa repens"
lipidic extract (S.R.E.) was recently reported (Br. J. Pharmacol., in
press) to inhibit androgen action in animals. The present investigation was
designed to study the antiandrogenicity of this compound in human cells: we
therefore analyzed the effects of S.R.E. on the intracellular conversion of
testosterone (T) to 5 alpha-reduced derivatives, and we investigated
interaction of S.R.E. with the intracellular androgen-receptor complex.
Since the chemical structure of the active component of S.R.E. is still
unknown, results are expressed in U/ml (one unit is defined as the amount
of S.R.E. required to inhibit 50% of the specific binding (IC50) of
[3H]1881 to rat prostate cytosol). S.R.E. at different dilutions (5.7 to
28.6 U/ml) is added to culture media containing [3H]T or
[3H]dihydrotestosterone (DHT) and incubated at 37 degrees C with cultured
fibroblasts. 28.6 U/ml S.R.E. significantly alters the formation of DHT and
strongly inhibits 3 ketosteroid reductase mediated conversion of DHT to 5
alpha-androstane-3 alpha, 17 beta-diol, characterized radiochemically by
thin-layer chromatography. S.R.E. is a good competitor for the whole cell
androgen receptor: 7.1 U/ml S.R.E. gives 50% inhibition of the binding of 2
X 10(-9) M [3H]DHT to its receptor. Competitive binding assays after cell
fractionation indicate that S.R.E. is less potent in nuclear than in
cytosol receptors. Sucrose gradient centrifugation of the radioactive cell
lysate of fibroblasts demonstrates that 28.6 U/ml S.R.E. abolishes 70% of
the 3.6 S receptor-complex radioactive peak. The present studies show that
S.R.E. inhibits 5 alpha-reductase, 3-ketosteroid reductase and receptor
binding of androgens in cultured human foreskin fibroblasts. As the search
for the ideal antiandrogen continues, S.R.E. appears to be a new type of
antiandrogenic compound as therapeutics for the treatment of benign
prostatic hypertrophy, hirsutism and so forth.
====================================================================
30.) Binding of Permixon, a new treatment for prostatic benign hyperplasia, to
the cytosolic androgen receptor in the rat prostate.
====================================================================
J Steroid Biochem 1984 Jan;20(1):521-3
Carilla E, Briley M, Fauran F, Sultan C, Duvilliers C
The benign hyperplasia of the prostate is a manifestation of aging,
involving the accumulation, within the gland, of dihydrotestosterone, the
probable mediator of the hyperplasia. Binding studies were performed on the
cytosolic androgenic receptor of the rat prostate using
[3H]methyltrienolone as a ligand. The binding of [3H]methyltrienolone at 5
nM, was inhibited by various drugs, such as methyltrienolone and
cyproterone acetate. Permixon, a liposterolic extract of the plant, Serenoa
Repens B, inhibits competitively the binding to the cytosolic receptor of
the rat prostate. Various vegetable and mineral oils, the plant steroid:
beta sitosterol and the antiprostatic drug: Tadenan, were all found to be
inactive. The antiprostatic activity of Permixon shown in animal studies
and controlled clinical trials, may thus result from a direct action at the
cytosolic receptor.
====================================================================
FINASTERIDE
====================================================================
31.) [Clinical significance of testosterone and dihydrotestosterone metabolism
in women].
====================================================================
Lijec Vjesn 1996 Mar;118 Suppl 1:21-3
[Article in Serbo-Croatian (Roman)]
Korsic M
Zavod za endokrinologiju, dijabetes i bolesti metabolizma Klinike za
unutarnje bolesti, KBC Rebro, Zagreb.
Hyperandrogenism in women refers to both excess androgen production and
clinical manifestations of androgen excess. Clinical evaluation of women
with hyperandrogenism is complex. The synthesis and release of androgenic
steroid in women are normal part of adrenal and ovarian steroidogenesis.
One of the classic questions concerning androgenic disorders concerns the
source of circulating androgens. Relative roles of adrenal and ovary vary
greatly, both can be involved. The use of gonadal or adrenal steroid
administration can sometimes be used to distinguish the source of androgen
excess. In many cases of hyperandrogenism no laboratory diagnosis of
adrenal and ovarian androgen overproduction can be made. These patients may
have increased androgen sensitivity due to increased enzyme 5
alpha-reductase activity in the skin. To be active in the skin,
testosterone (T) must be converted to dihydrotestosterone (DHT) by the 5
alpha-reductase. The increase in DHT production is a localized phenomenon
and there is no generalized increase in enzyme activity in women with
hyperandrogenism. DHT is rapidly converted to other steroid metabolites
including androsteron, androstanediol and their glucuronide and sulfate
conjugates. Although once thought to be specific for skin conversion of T
to DTH these androgen conjugates reflect adrenal steroid production and
metabolism. Antiandrogens (androgen receptor blockers) are the most
effective therapeutic modalities of cutaneous hyperandrogenism. Clinical
trials are in progress to determine efficacy of finasteride for the
treatment of hirsutism and androgenetic alopecia. Finasteride is the first
available medication of a new class of drugs that is an competitive
inhibitor of 5 alpha-reductase and therefore should be beneficial for
medical treatment of cutaneous hyperandrogenism.
====================================================================
32.) Finasteride: the first 5 alpha-reductase inhibitor.
====================================================================
Pharmacotherapy 1993 Jul-Aug;13(4):309-25; discussion 325-9
Sudduth SL, Koronkowski MJ
Program on Aging, School of Pharmacy, University of North Carolina, Chapel
Hill 27599-7360.
Finasteride is a synthetic 4-azasteroid that is a specific competitive
inhibitor of 5 alpha-reductase, an intracellular enzyme that converts
testosterone to dihydrotestosterone (DHT). It has no binding affinity for
androgen receptor sites and itself possesses no androgenic, antiandrogenic,
or other steroid hormone-related properties. It is well absorbed after oral
administration, with absolute bioavailability in humans of 63% (range
34-108%). The mean time to maximum concentration is 1-2 hours, and it is
approximately 90% plasma protein bound. The elimination half-life averages
6-8 hours. The agent is metabolized to a series of five metabolites, of
which two are active and possess less than 20% of the 5 alpha-reductase
activity of finasteride. Little is known about potential drug interactions,
although they appear to be minimal and not clinically relevant. The drug is
indicated for the treatment of symptomatic benign prostatic hyperplasia.
Its efficacy in regression of prostate gland enlargement is rapid and
predictable, although correlation with subsequent improvement in urinary
flow and symptoms is highly variable. Dosages of 0.5-100 mg/day regress
prostate enlargement; the recommended dosage is 5 mg once/day. Finasteride
may hold promise for other DHT-mediated disorders such as acne, facial
hirsutism, frontal lobe alopecia, and prostate cancer, but its use in these
conditions remains investigational. The frequency of adverse drug events is
low, with the most common side effects being impotence, decreased libido,
and decreased volume of ejaculate. No reports of intentional overdose have
been reported, and dosages of up to 80 mg/day for 3 months have been taken
without adverse effect.
====================================================================
33.) A novel class of inhibitors for human steroid 5 alpha-reductase:
phenoxybenzoic acid derivatives. I.
====================================================================
Chem Pharm Bull (Tokyo) 1999 Aug;47(8):1073-80
Igarashi S, Kimura T, Naito R, Hara H, Fujii M, Koutoku H, Oritani H, Mase T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd.,
Ibaraki, Japan.
In a search for novel nonsteroidal inhibitors of human prostatic 5
alpha-reductase, we found a new series of phenoxybenzoic acid derivatives
to be potent human prostatic 5 alpha-reductase inhibitors. Among them,
4-(biphenyl-4-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s
showed more potent inhibitory activities than finasteride with IC50 values
of 0.87, 0.67 and 0.56 nM, respectively. The optimized structures for the
phenoxybenzoic acid derivatives 2d-2i were calculated by molecular modeling
analysis, and the favorable distance between the carbon of the carboxyl
group and the centroid of the phenyl group (benzene ring C) was found to be
in the 9-11 A range.
====================================================================
34.) Management of androgenetic alopecia.
====================================================================
J Eur Acad Dermatol Venereol 1999 May;12(3):205-14
Tosti A, Camacho-Martinez F, Dawber R
Department of Dermatology, University of Bologna, Italy.
[email protected]
BACKGROUND: Androgenetic alopecia (AGA) is the most frequent cause of hair
loss affecting up to 50% of men and 40% of women by the age of 50. METHODS:
This paper outlines the current status of diagnosis and offers guidelines
for optimal management of AGA in both men and women. RESULTS: The diagnosis
of AGA can usually be confirmed by medical history and physical examination
alone. A trichogram can be useful to assess the progression of the hair
loss. A scalp biospy is diagnostic but usually not required. In women with
signs of hyperandrogenism, investigation for ovarian (polycystic ovarian
disease) or adrenal (late-onset congenital adrenal hyperplasia) disorders
is required. Mild to moderate AGA in men can be treated with oral
finasteride or topical minoxidil. Oral finasteride at the dosage of 1
mg/day produced clinical improvement in up to 66% of patients treated for 2
years. The drug is effective for both frontal and vertex hair thinning.
Medical treatment with finasteride or minoxidil should be continued
indefinitely since interruption of therapy leads to hair loss with return
to pretreatment status. Mild to moderate AGA in women can be treated with
oral antiandrogens (cyproterone acetate, spironolactone) and/or topical
minoxidil with good results in many cases. Hair systems and surgery may be
considered for selected cases of severe AGA both in men and in women.
CONCLUSIONS: Patients with AGA should be informed about the pathogenesis of
the condition. If used correctly, available medical treatments arrest
progression of the disease and reverse miniaturization in most patients
with mild to moderate AGA.
====================================================================
35.) Continued improvement in pressure-flow parameters in men receiving
finasteride for 2 years. Finasteride Urodynamics Study Group.
====================================================================
Urology 1999 Aug;54(2):278-83
Schafer W, Tammela TL, Barrett DM, Abrams P, Hedlund H, Rollema HJ,
Nordling J, Andersen JT, Hald T, Matos-Ferriera A, Bruskewitz R, Miller P,
Mustonen S, Cannon A, Malice MP, Jacobsen CA, Bach MA
Department of Urology, University Clinic der RWTH Aachen, Germany.
OBJECTIVES: To assess the long-term effects of finasteride on pressure-flow
parameters in men with urodynamically documented bladder outflow
obstruction (BOO). METHODS: One hundred twenty-one men with benign
prostatic enlargement (BPE) and lower urinary tract symptoms (LUTS)
underwent a pressure-flow study (PFS) at 1 of 11 clinical centers. The PFS
technique was standardized, and all tracings were read by a single reader
unaware of the treatment group. Patients who were obstructed according to a
modified Abrams-Griffiths nomogram were randomized to 5 mg finasteride (n =
81) or placebo (n = 40) for 12 months; all patients continuing into an open
extension received finasteride during the second 12 months of therapy.
Results of the initial 12-month study demonstrated the benefit of
finasteride treatment on PFS parameters. To examine the continuing effects
over time, an analysis of the data from 54 patients who completed 24 months
of treatment with finasteride is provided. RESULTS: Detrusor pressure at
maximum flow (PdetQmax) continued to decrease during the second 12 months
of therapy (decreases of 5.3 and 11.7 cm H2O at months 12 and 24,
respectively). The percentage of patients obstructed by Abrams-Griffiths
classification decreased from 76.2% at baseline to 66.7% at month 12 and
59.6% at month 24. An intention-to-treat analysis yielded similar results.
CONCLUSIONS: Finasteride improves urodynamic measures of obstruction in men
with BPE and LUTS, with continued improvement during the second 12 months
of therapy.
====================================================================
36.) Economic analysis of finasteride: a model-based approach using data from
the Proscar Long-Term Efficacy and Safety Study.
====================================================================
Clin Ther 1999 Jun;21(6):1006-24
Albertsen PC, Pellissier JM, Lowe FC, Girman CJ, Roehrborn CG
University of Connecticut Health Center, Farmington, USA.
Benign prostatic hyperplasia (BPH) is one of the most common medical
conditions in older men in the United States. BPH is often associated with
a reduction in quality of life and may progress to acute urinary retention
(AUR), the inability to pass any urine. Recently, a 4-year
placebo-controlled clinical trial known as the Proscar Long-Term Efficacy
and Safety Study (PLESS) demonstrated that finasteride use reduces the risk
of developing AUR by 57% and the need for BPH-related surgery by 55%. The
economic implications of these findings were investigated using a
model-based decision-analytic approach to compare finasteride with both
watchful waiting and alpha-blocker therapy. The modeling used the
longest-term published controlled data concerning alpha-blockers, which
were for the alpha-blocker terazosin. The base case considered a
64-year-old man (the mean age of a PLESS patient) with prostatic
enlargement on digital rectal examination and moderate-to-severe symptoms
of BPH. The model suggested savings in surgical and AUR costs with
finasteride versus watchful waiting, with an estimated 25% of total
finasteride costs recouped in savings on surgical events avoided in the
first year. Over 2 years, the expected cost per patient starting
finasteride therapy was $2304, whereas the expected cost per patient
starting terazosin was $2334. Analyses also explored the variation in
economic results by baseline levels of prostate-specific antigen (PSA), a
proxy for prostate volume. For patients with PSA levels > or =1.4 ng/mL,
expected 2-year costs with finasteride and terazosin were $2342 and $2479,
respectively. For patients with PSA levels > or =3.3 ng/mL, expected 2-year
costs with finasteride were $373 less than with terazosin ($2347 vs $2720).
Results were robust over a range of model assumptions and cost estimates.
The analyses illustrate that all medical interventions, including watchful
waiting, have associated costs. Finasteride shows cost offsets compared
with watchful waiting and cost savings compared with terazosin over 2
years. Finasteride appears to be more economical in men with higher PSA
levels.
====================================================================
37.) Comparison of finasteride and flutamide in the treatment of idiopathic
hirsutism.
====================================================================
Fertil Steril 1999 Jul;72(1):41-6
Falsetti L, Gambera A
Department of Gynecological Endocrinology, University of Brescia, Italy.
OBJECTIVE: To compare the effectiveness of finasteride and flutamide in the
treatment of idiopathic hirsutism. DESIGN: Randomized study. SETTING:
Department of Gynecological Endocrinology, University of Brescia, Italy.
PATIENT(S): Forty-six women with idiopathic hirsutism were selected.
INTERVENTION(S): Patients were assigned randomly to receive 5 mg of
finasteride once daily or 250 mg of flutamide twice daily for 12
consecutive months. MAIN OUTCOME MEASURE(S): Hirsutism was evaluated at 6
and 12 months of therapy by measuring the Ferriman-Gallwey score and the
terminal-hair diameters (microm) taken from different body areas. Blood
samples were taken and side effects were monitored during the treatment.
RESULT(S): Both finasteride and flutamide induced a statistically
significant decrease in hirsutism scores and hair diameters at the end of
12 months. Finasteride reduced the Ferriman-Gallwey score by 20.5% at 6
months and by 34.2% at 12 months, and hair diameter by 18.9%-23.6% at 6
months and by 29.6%-37.9% at 12 months. Flutamide reduced the
Ferriman-Gallwey score by 26.6% at 6 months and by 50.9% at 12 months, and
hair diameter by 22.3%-28.2% at 6 months and by 47.7%-56.5% at 12 months.
Flutamide did not induce hormonal variations, whereas finasteride increased
T levels by 60% and decreased 3alpha-androstanediol glucuronide by 69.5% at
12 months. CONCLUSION(S): Both drugs were effective in the treatment of
idiopathic hirsutism, but flutamide was more effective than finasteride.
====================================================================
38.) Validation of a population pharmacokinetic/pharmacodynamic model for
5alpha-reductase inhibitors.
====================================================================
Eur J Pharm Sci 1999 Aug;8(4):291-9
Olsson Gisleskog P, Hermann D, Hammarlund-Udenaes M, Karlsson MO
Clinical Pharmacology, GlaxoWellcome Research and Development, Greenford
Road, Middlesex UB6 0HE, UK.
A population pharmacokinetic/dynamic model describing the conversion of
testosterone to dihydrotestosterone (DHT) by 5alpha-reductases and the
irreversible inhibition of 5alpha-reductase(s) by finasteride and
dutasteride was validated. The model had been developed using data from a
single dose study in healthy volunteers and was validated against data from
a 28-day repeat dose study in patients with benign prostatic hyperplasia.
Validation was carried out by comparing results of Monte Carlo simulations
to the observed data, fitting the model to the repeat dose data and
comparing with previously derived parameter values, and examining
individual predictions of the model for the individuals in the repeat dose
study for any bias. Simulations closely predicted the outcome of the repeat
dose study, estimated parameters of the pharmacodynamic modelling were
generally close to within 88 to 116% of those from the original model and
the individual predictions did not indicate any bias. Thus the model
derived from single dose data from healthy volunteers was considered to be
valid for the prediction of DHT levels in the patient population after
repeated dosing of dutasteride and finasteride.
====================================================================
39.) Benign prostatic hyperplasia. A review of diagnostic and treatment options.
Adv Nurse Pract 1999 Apr;7(4):31-6; quiz 37-8
====================================================================
Pfeiffer GM, Giacomarra M
Philadelphia Veterans Affairs Medical Center, USA.
Benign prostatic hyperplasia (BPH) is a noncancerous enlargement of the
prostate gland caused by histologic hyperplasia that produces an inward
transmission of pressure on the urethra and an increased resistance to
urine flow. The dominant risk factors for the disease are age and male
gender. Weak urine stream and hesitancy are the cardinal obstructive
features in BPH. Other signs and symptoms include inability to terminate
micturition abruptly, sensation of incomplete emptying and occasionally,
urinary retention. Many men with prostate enlargement can be successfully
treated with lifestyle modification and medication. But if symptoms
persist, with no significant improvement after 6 months of finasteride or 2
to 3 months of an alpha-1 blocker, consider a urology consultation. Several
surgical options are available.
====================================================================
40.) Finasteride treatment for one year in 35 hirsute patients.
====================================================================
Exp Clin Endocrinol Diabetes 1999;107(3):195-7
Bayram F, Muderris II, Sahin Y, Kelestimur F
Department of Endocrinology, Erciyes University, Faculty of Medicine,
Kayseri, Turkey.
This study was performed to confirm the favourable therapeutic effects of
finasteride in hirsute women as described by previous publications of
different research groups. Our study was a non-randomized, prospective
clinical trial. Thirty five patients with hirsutism were included in the
study. The patients received 5 mg finasteride orally once per day over a
period of 12 months. Hirsutism score, FSH, LH, E2, total T, free T,
androstenedione (A), DHEAS, 17-hydroxyprogesterone (17-OHP) and sex
hormone-binding globulin (SHBG) levels were determined in all the patients
before treatment and every 6 months during treatment. The modified
Ferriman-Gallwey score decreased from a mean of 19.06 +/- 6.12 to 11.31 +/-
4.93 during the study. Clinical improvement in the degree of hirsutism was
observed in 26 of 35 patients. The percent reductions in hirsutism scores
(mean% +/- SD) at 6 and at 12 months were 25.8 +/- 11.3 and 41.3 +/- 18.5,
respectively. During the finasteride therapy E2 and SHBG were increased
significantly while DHEAS was decreased significantly at 12 months. There
were no significant changes in the values of the other hormones and no
serious side effects were observed in the study. In conclusion, finasteride
is a well tolerated therapeutic agent without significant side pathological
laboratory findings and can be used in the treatment of hirsutism.
====================================================================
41.) Impact of drug therapy on benign prostatic hyperplasia-specific quality of
life.
====================================================================
Urology 1999 Jun;53(6):1090-8
Rhodes PR, Krogh RH, Bruskewitz RC
Department of Surgery, Madison Medical Center, Wisconsin, USA.
Quality of life (QOL) is an important issue when assessing medical
treatment of benign prostatic hyperplasia (BPH). There are many QOL
questionnaires available, and disease-specific questionnaires are being
developed. Currently, most patients undergoing treatment for BPH receive
alpha-blockers or finasteride. To determine which QOL measures are being
used, we did a Medline search covering the past 10 years and found 11
studies in which BPH-QOL was investigated. The wide variety of
questionnaires used made comparison between drug studies difficult. When
comparing studies that used at least one similar questionnaire to that of
another drug study, we found alpha-blocker treatment excelled over
finasteride in improving BPH-QOL in the areas of earlier response, larger
decreases in mean changes, and reduced sexual side effects. QOL assessment
should be a routine part of BPH treatment, and more standardized and
validated measures should be used to allow for comparative, meaningful
analyses.
====================================================================
42.) Finasteride in the treatment of men with frontal male pattern hair loss.
====================================================================
J Am Acad Dermatol 1999 Jun;40(6 Pt 1):930-7
Leyden J, Dunlap F, Miller B, Winters P, Lebwohl M, Hecker D, Kraus S,
Baldwin H, Shalita A, Draelos Z, Markou M, Thiboutot D, Rapaport M, Kang S,
Kelly T, Pariser D, Webster G, Hordinsky M, Rietschel R, Katz HI,
Terranella L, Best S, Round E, Waldstreicher J
University of Pennsylvania School of Medicine, Philadelphia, USA.
BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase,
decreases serum and scalp dihydrotestosterone and has been shown to be
effective in men with vertex male pattern hair loss. OBJECTIVE: This study
evaluated the efficacy of finasteride 1 mg/day in men with frontal
(anterior/mid) scalp hair thinning. METHODS: This was a 1-year,
double-blind, placebo-controlled study followed by a 1-year open extension.
Efficacy was assessed by hair counts (1 cm2 circular area), patient and
investigator assessments, and global photographic review. RESULTS: There
was a significant increase in hair count in the frontal scalp of
finasteride-treated patients (P < .001), as well as significant
improvements in patient, investigator, and global photographic assessments.
Efficacy was maintained or improved throughout the second year of the
study. Finasteride was generally well tolerated. CONCLUSION: In men with
hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day
slowed hair loss and increased hair growth.
====================================================================
43.) Effect of finasteride and/or terazosin on serum PSA: results of VA
Cooperative Study #359.
====================================================================
Prostate 1999 Jun 1;39(4):234-9
Brawer MK, Lin DW, Williford WO, Jones K, Lepor H
Northwest Prostate Institute and Pacific Northwest Cancer Foundation,
Seattle, Washington 98133, USA.
BACKGROUND: Medical management of benign prostatic hyperplasia (BPH) giving
rise to lower urinary tract symptomatology (LUTS) has emerged as the
mainstay for first-line therapy. Prostate-specific antigen (PSA) is the
most important method of detecting prostate carcinoma. The effect of
finasteride on PSA has been widely reported. Little data exist with respect
to alpha-adrenergic blocking therapy in men treated for BPH. In the present
investigation we set out to evaluate the effect of these two forms of
therapy. METHODS: Patients enrolled in the VA Cooperative Study #359 trial
were evaluated. This study evaluated men with moderate LUTS owing to BPH in
four treatment groups: placebo (P), finasteride (F), terazosin (T), and
combination of finasteride plus terazosin (C). Men were recruited at 31 VA
medical centers and had a baseline in 52-week PSA determination at the
respective sites. RESULTS: There was no significant difference in baseline
PSA between four groups (mean range, 2.0-2.9 ng/ml). Statistically
significant reduction in PSA levels was observed at 52 weeks in the F and C
arms (P < 0.001), whereas significant increases were observed in the T and
P arms (P < 0.01). Additionally, there was no significant difference in PSA
response between the T and P arms. Thirty percent of men in the C or F arms
had more than 40-60% reduction of PSA. In contrast, the majority of men on
T or P had less than 40% change in PSA. Only 35% of men on F or C had the
expected 40-60% reduction in PSA level. CONCLUSIONS: These data demonstrate
no clinically significant effect of T on PSA level. The heterogeneity of
PSA response to F may make monitoring patients for the development of
prostate cancer problematic.
====================================================================
44.) Androgenetic alopecia in men: the scale of the problem and prospects for
treatment.
====================================================================
Int J Clin Pract 1999 Jan-Feb;53(1):50-3
Rushton DH
School of Pharmacy and Biomedical Sciences, University of Portsmouth, Hants.
While the precise incidence of androgenetic alopecia is unknown, it is
universally acknowledged to be the most common hair problem in men. Balding
is generally associated with ageing; consequently, the desire to prolong a
youthful appearance inevitably leads to demands for effective treatments.
Further, changing attitudes in modern society have resulted in people
becoming concerned about their appearance and less tolerant about
conditions that might be alleviated by medical intervention. The importance
of hair loss upon quality of life has been underestimated by the medical
profession. Clinicians failing to accept hair loss as an important medical
problem ignore the real distress suffered by a significant proportion of
those affected. New options for treatment that selectively target the
metabolic pathways involved in the balding process are showing promise. The
first generation of such drugs, Propecia, is now available in some
countries and other molecules are currently under development.
====================================================================
45.) Inhibition of androgen synthesis in human testicular and prostatic
microsomes and in male rats by novel steroidal compounds.
====================================================================
Endocrinology 1999 Jun;140(6):2891-7
Nnane IP, Kato K, Liu Y, Long BJ, Lu Q, Wang X, Ling YZ, Brodie A
Department of Pharmacology and Experimental Therapeutics, University of
Maryland School of Medicine, Baltimore 21201, USA.
The C(17,20)-lyase and 5alpha-reductase are key enzymes in the biosynthesis
of androgens. The effects of novel steroidal compounds were evaluated as
inhibitors against both human C(17,20)-lyase and 5alpha-reductase in vitro.
The concentrations of testosterone (T) and dihydrotestosterone (DHT) in the
prostate, testis and serum and changes in the tissue weights were also
determined in rats treated with the novel inhibitors. L-12 and L-26 showed
potent inhibition of human testicular C(17,20)-lyase with IC50 values of 50
and 25 nM, respectively. L-12, L-38, and I-47 showed moderate inhibition of
human testicular C(17,20)-lyase with IC50 values of 75, 108, and 70 nM,
respectively similar to ketoconazole (78 nM). Interestingly, L-6, L-26, and
L-38 also showed some inhibitory activity against 5alpha-reductase with
IC50 values of 75, 125, and 377 nM, respectively. Finasteride, an inhibitor
of 5alpha-reductase had an IC50 value of 33 nM. However, ketoconazole did
not inhibit 5alpha-reductase nor did finasteride inhibit C(17,20)-lyase.
Treatment of normal male rats with several of these novel inhibitors (50
mg/kg x day, s.c., for 14 consecutive days) caused about 45-91% decrease in
serum, testicular and prostatic T concentration. Similarly, serum and
prostatic DHT concentration were significantly decreased in rats treated
with these novel compounds by 50-90% compared with controls. Surgical
castration caused almost complete elimination of circulating T and DHT
concentration in rat tissues. L-6 and L-12 were the most effective and
reduced the wet weight of the prostate by 50%. Although future improvements
in their bioavailability are necessary, these novel steroidal compounds
show promise as potential agents for reducing T and DHT levels in patients
with androgen dependent diseases.
====================================================================
46.) Finasteride: an update of its use in the management of symptomatic benign
prostatic hyperplasia.
====================================================================
Drugs 1999 Apr;57(4):557-81
Wilde MI, Goa KL
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
[email protected]
Finasteride inhibits type 25alpha-reductase activity, significantly
reducing dihydrotestosterone levels. Consequent reductions in prostate
volume, increases in urinary flow rates and improvements in symptoms
compared with placebo have been observed in trials of up to 4 years'
duration and in noncomparative extensions (for up to 6 years). Results from
the 4-year placebo-controlled PLESS trial show finasteride to significantly
reduce the risk of benign prostatic hypertrophy (BPH)-related acute urinary
retention and the requirement for surgical intervention. Finasteride has
significantly greater efficacy in patients with a large prostate (> or = 40
ml) than in patients with a small prostate. However, the predictive value
of prostate size has been questioned. Results of an earlier comparative
1-year trial show terazosin monotherapy and terazosin plus finasteride
therapy to be significantly more effective than both finasteride
monotherapy and placebo in reducing symptom scores and improving maximum
urinary flow rates. Prostatic volume was significantly reduced by
finasteride monotherapy and combination therapy only. The overall efficacy
of finasteride in patients with mild to moderate symptomatic BPH tended to
be greater than that of serenoa repens (Permixon) in a 6-month trial. A US
cost analysis model indicates that finasteride and terazosin are less
expensive than transurethral resection of the prostate (TURP) during the
first 2 years of initiation. Canadian cost-effectiveness and cost-utility
analyses using decision analysis modelling have shown primary intervention
with finasteride to provide more quality-adjusted life years (QALYs) at
lesser cost than watchful waiting or TURP in patients with moderate
symptoms who receive the drug for < or = 3 years and < or = 14 years,
respectively, but fewer QALYs at a higher cost in patients with severe
symptoms needing therapy for > or = 4 years. Confirmatory prospective
economic studies are required. Finasteride appears to improve overall
quality of life to a similar extent to serenoa repens; patient satisfaction
appears similar with finasteride and TURP. Finasteride is generally well
tolerated. Most commonly reported adverse effects are sexually related (1
to 2.1 %). Gynaecomastia has been reported in 0.4% of patients.
CONCLUSIONS: Despite modest improvements in maximum urinary flow rates and
symptom scores, finasteride is a first-line treatment option in those with
moderate uncomplicated BPH, especially in patients with a large prostate (>
or = 40 ml). It is also an option in patients with more severe symptoms who
are unable or unwilling to undergo surgery and in those awaiting surgery.
Importantly, finasteride appears to reduce disease progression,
significantly decreasing the incidence of acute urinary retention and the
requirement for surgical intervention; to date, no other pharmacological
agent has been shown to reduce these outcomes.
====================================================================
47.) Efficacy of finasteride is maintained in patients with benign prostatic
hyperplasia treated for 5 years. The North American Finasteride Study Group.
====================================================================
Urology 1999 Apr;53(4):690-5
Hudson PB, Boake R, Trachtenberg J, Romas NA, Rosenblatt S, Narayan P,
Geller J, Lieber MM, Elhilali M, Norman R, Patterson L, Perreault JP, Malek
GH, Bruskewitz RC, Roy JB, Ko A, Jacobsen CA, Stoner E
Tampa Bay Urological Institute, Seminole, Florida, USA.
OBJECTIVES: The purpose of this open-label study extension was to assess
the long-term safety and efficacy of finasteride in the treatment of men
with benign prostatic hyperplasia (BPH). METHODS: A Phase III North
American BPH trial originally enrolled 895 men, 297 of whom were randomized
to receive finasteride 5 mg. An enlarged prostate gland by digital rectal
examination, symptoms of urinary obstruction, and a maximal urinary flow
rate of less than 15 mL/s were required for entry. Patients who completed
the initial 12-month, double-blind, placebo-controlled study were invited
to participate in an open-label extension for 4 additional years. RESULTS:
Of the 297 patients initially randomized to receive finasteride 5 mg, 259
completed 12 months in the double-blind period and 186 completed 48 months
of open-label therapy. Prostate volume reached a nadir of -24.6% at month
24, and the effect was maintained through month 60. Compared with baseline
values, month 60 prostate volume was decreased by 22.7% (P<0.001), the
quasi-American Urological Association symptom score was decreased by 4.3
points, and maximal urinary flow was increased by 2.3 mL/s (P<0.001) on
average. Finasteride was well tolerated, with no significant increase in
the prevalence of sexual adverse events over time. CONCLUSIONS: Patients
treated with finasteride 5 mg maintained an initial decrease in prostate
volume and improvement in symptom score and maximal urinary flow rate over
5 years.
====================================================================
48.) Long-term effects of finasteride on prostate tissue composition.
====================================================================
Urology 1999 Mar;53(3):574-80
Marks LS, Partin AW, Dorey FJ, Gormley GJ, Epstein JI, Garris JB, Macairan
ML, Shery ED, Santos PB, Stoner E, deKernion JB
Department of Urology, University of California, Los Angeles School of
Medicine, USA.
OBJECTIVES: To determine the long-term effects of finasteride treatment on
prostate tissue composition; to relate these effects to clinical outcomes;
and to test the hypothesis that finasteride exerts a selective or
preferential action on the transition zone. METHODS: Nineteen men with
symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month
double-blind trial of finasteride were enrolled in a 24-month open-label
extension study of drug responders. Magnetic resonance imaging and prostate
biopsy for morphometric analysis were performed together 70 times: at
baseline (n = 19), after treatment periods of intermediate duration (6 to
18 months, n = 32), and after long-term drug treatment (24 to 30 months, n
= 19). At baseline, prostate volume averaged 51 cc, of which 57% was
transition zone. RESULTS: Decreases in symptom score, dihydrotestosterone
and prostate-specific antigen levels, and prostate volume occurred at 6
months (P <0.01), stabilized, and were maintained without further long-term
decreases. Prostate epithelium contracted progressively from baseline
(19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to
intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment
(6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial
contraction was similar in the peripheral and transition zones (P = NS).
The transition zone remained a relatively constant proportion (53% to 58%)
of whole-prostate volume from baseline to long-term observation.
CONCLUSIONS: Long-term finasteride treatment (24 to 30 months) results in a
marked involution of the prostate epithelium, which continues to progress
for many months after clinical effects stabilize. The effect on the
epithelium is similar in the peripheral and transition zones for both
morphometric and volumetric changes. Progressive contraction of the
prostate epithelium appears to constitute the underlying mechanism for
sustained action of finasteride.
===================================================================
DATA-MEDICOS/DERMAGIC-EXPRESS No (77) 06/10/99 DR. JOSE LAPENTA R.
===================================================================
|
