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Efficacy and acceptability of tadenan (Pygeum
africanum extract) in the treatment of benign prostatic
hyperplasia ( BPH): a multicentre trial in central
Europe.
Breza J; Dzurny O; Borowka A; Hanus T; Petrik R; Blane G;
Chadha-Boreham H
Department of Urology, University Hospital, Bratislava,
Slovak Republic.
Curr Med Res Opin (England) 1998, 14 (3) p127-39
Pygeum africanum extract is available as Tadenan in many
countries, including those in central and eastern Europe, for
the treatment of mild to moderate BPH. Its efficacy and
acceptability have been demonstrated in numerous open and
placebo-controlled studies in large populations. The present
open three-centre efficacy and safety study was conducted
according to common protocol at urology clinics in the Czech
and Slovak Republics and in Poland, in order to confirm the
therapeutic profile of Pygeum africanum in conditions of daily
practice, using International Prostate Symptom Score (IPSS)
and flowmetry assessments. Men aged 50-75 years and in
compliance with the selection criteria (including IPSS > or
= 12, quality of life (QoL) score > or = 3, and maximum
urinary flow < or = 15 ml/s) were first examined then
recalled after two weeks during which no treatment was
provided (washout and check of stability). If still compliant,
they were entered at this point into a two-month period of
treatment with Pygeum africanum extract 50 mg twice daily.
There followed a further one-month period without treatment,
the objective being to evaluate the persistence of any effects
observed during the previous two months of Pygeum africanum
administration. The primary efficacy parameter investigated
was IPSS; the other efficacy parameters were QoL, nocturnal
frequency, maximum urinary flow, average urinary flow,
post-voiding residual volume and prostatic volume, after one
and two months of Pygeum africanum treatment and one month
after stopping treatment. A total of 85 patients were evenly
distributed between the three centres and completed the entire
study. At inclusion their mean IPSS was 16.17, QoL was 3.60
and nocturia was 2.6 times per night. The changes in
subjective scores, IPSS and QoL after the two-month treatment
period were highly statistically significant with mean
improvements of 40% and 31%, respectively. Nocturnal frequency
was reduced by 32% and the mean reduction was again highly
statistically significant. Mean maximum urinary flow, average
urinary flow and urine volume were also statistically
significantly improved, but the modest improvement in
post-voiding volume did not reach statistical significance.
The improvements, which exceeded those observed with placebo
in earlier studies, were maintained after one month without
treatment indicating an interesting persistence of clinically
useful activity. Prostatic volume and quality of sexual life
remained unchanged throughout. No treatment-related adverse
effects were observed. In conclusion, under conditions of
daily practice, Pygeum africanum extract induces significant
improvement in IPSS and uroflowmetry parameters. These
positive effects are accompanied by a very satisfactory safety
profile with the overall result of a substantial improvement
in QoL.
Review of recent placebo-controlled trials
utilizing phytotherapeutic agents for treatment of BPH.
Lowe FC; Dreikorn K; Borkowski A; Braeckman J; Denis L;
Ferrari P; Gerber G; Levin R; Perrin P; Senge T
Department of Urology, St. Luke's-Roosevelt Hospital, New
York, New York 10019, USA.
Prostate Nov 1 1998, 37 (3) p187-93
BACKGROUND: In order to assess the efficacy of
phytotherapeutic agents for the treatment of benign prostatic
hyperplasia (BPH), a review of recently published double-blind
placebo-controlled trials was undertaken.
METHODS: Only those studies reviewed by the Other Medical
Therapies Committee of the Fourth International Consultation
on BPH were included.
RESULTS: These studies suggest a possible benefit for the
use of phytotherapeutic preparations in the treatment of
BPH.
CONCLUSIONS: These studies need to be confirmed in larger
long-term placebo-controlled studies in order to ascertain the
true efficacy of these agents. (32 Refs.)
Genistein inhibits the growth of human-patient BPH
and prostate cancer in histoculture.
Geller J; Sionit L; Partido C; Li L; Tan X; Youngkin T;
Nachtsheim D; Hoffman RM
AntiCancer, Inc., San Diego, California 92111, USA.
Prostate Feb 1 1998, 34 (2) p75-9
BACKGROUND: There is strong epidemiological evidence that
prostate disease is significantly less prevalent in the
Orient, where the intake of soy products is very high, than in
the United States. We therefore undertook a study of the
effects of genistein, a major component of soy, on growth of
human-patient benign prostatic hypertrophy (BPH) and prostate
cancer tissue in three-dimensional collagen gel-supported
histoculture.
METHODS: Surgical specimens of human BPH and cancer were
histocultured for 5 days to study the effects of genistein on
growth, as measured by inhibition of 3H-thymidine
incorporation per microgram protein on day 5.
RESULTS: Genistein in doses of 1.25-10 micrograms/ml
decreased the growth of BPH tissue in histoculture in a
dose-dependent manner, with little additional effect at higher
doses. Prostate cancer tissue in histoculture was similarly
inhibited by these doses of genistein.
CONCLUSIONS: Genistein decreases the growth of both BPH and
prostate cancer tissue in histoculture. The data suggest that
genistein has potential as a therapeutic agent for BPH and
prostate cancer.
Efficacy and acceptability of Tadenan (R) (Pygeum
africanum extract) in the treatment of benign prostatic
hyperplasia ( BPH): A multicentre trial in central
Europe
Breza J.; Dzurny O.; Borowka A.; Hanus T.; Petrik R.; Blane
G.; Chadha-Boreham H.; Autet W.
Dr. W. Autet, Medical Affairs, Groupe Fournier, 153 rue de
Buzenval, 92380 Garches France
Current Medical Research and Opinion (United Kingdom), 1998,
14/3 (127-139)
Pygeum africanum extract is avialable as Tadenan (R),
including those in central and eastern Europe, for the
treatment of mild to moderate BPH. Its efficacy and
acceptability have been demonstrated in numerous open and
placebo-controlled studies in large populations. The present
open three-centre efficacy and safety study was conducted
according to common protocol at urology clinics in the Czech
and Slovak Republics and in Poland, in order to confirm the
therapeutic profile of Pygeum africanum in conditions of daily
practice, using International Prostate Symptom Score (IPSS)
and flowmetry assessments. Men aged 50-75 years and in
compliance with the selection criteria (including IPSS less
than or equal to 12, quality of life (QoL) score less than or
equal to 3, and maximum urinary flow less than or equal to 15
ml/s) were first examined then recalled after two weeks during
which no treatment was provided (washout and check of
stability). If still complaint, they were entered at this
point into a two-month period of treatment with Pygeum
africanum extract 50 mg twice daily. There followed a further
one-month period without treatment, the objective being to
evaluate the persistence of any effects observed during the
previous two months of Pygeum africanum administration. The
primary efficacy parameter investigated was IPSS; the other
efficacy parameters were QoL, nocturnal frequency, maximum
urinary flow, average urinary flow, post-voiding residual
volume and prostatic volume, after one and two months of
Pygeum africanum treatment and one month after stopping
treatment. A total of 85 patients were evenly distributed
between the three centres and completed the entire study. At
inclusion their mean IPSS was 16.17, QoL was 3.60 and nocturia
was 2.6 times per night. The changes in subjective scores,
IPSS and QoL after the two-month treatment period were highly
statistically significant with mean improvements of 40% and
31%, respectively. Nocturnal frequency was reduced by 32% and
the mean reduction was again highly statistically significant.
Mean maximum urinary flow, average urinary flow and urine
volume were also statistically significantly improved, but the
modest improvement in post-voiding volume did not reach
statistical significant. The improvements, which exceeded
those observed with placebo in earlier studies, were
maintained after one month without treatment indicating an
interesting persistence of clinically useful activity.
Prostatic volume and quality of sexual life remained unchanged
throughout. No treatment-related adverse effects were
observed. In conclusion, under conditions of daily practice,
Pygeum africanum extract induces significant improvement in
IPSS and uroflowmetry parameters. These positive effects are
accompanied by a very satisfactory safety profile with the
overall result of a substantial improvement in QoL.
Phytotherapy of BPH with pumpkin seeds - A
multicentric clinical trial
Schiebel-Schlosser G.; Friederich M.
G. Schiebel-Schlosser, SmithKline Beecham GmbH and Co. KG,
Hermannstrasse 7, 77815 Buhl Germany
Zeitschrift fur Phytotherapie (Germany), 1998, 19/2
(71-76)
Therapeutic use and safety of a pumpkin seed extract were
tested in a multicentric clinical triol with 2,245 patients
suffering from benign prostatic hyperplasia (Stage I to II
according to Alken). Urinary symptoms were recorded by the
International-Prostate-Symptom-Score according to the American
Urological Association (I-PSS), the influence on quality of
life has been recorded by a quality of life questionnaire
(LQ-Index). Patients were treated for 12 weeks with 1-2
capsules per day containing 500 mg of a pumpkin seed extract
(15-25:1). The I-PSS decreased by 47,4%, life quality improved
by 46,1% during therapy. More than 96% of the patients had no
undesired side effects under the treatment with Prosta Fink
Forte (R).
Multicenter open trial for phytotherapy in benign
prostate hyperplasia stage I and II. Sabal fruit and urtica
reduces the residual urine and increases the urinary
flow
Jenner R.; Haertel S.
Dr. R. Jenner, Urologie Abteilung, Kaiserstrasse 15, 76131
Karlsruhe Germany
Therapie und Erfolg Urologie Nephrologie (Germany), 1998,
10/1-2 (48-51)
102 patients with benign prostatic hyperplasia stage I-II
(Alken) were treated with a combined preparation of Sabal
fruit and Urtica root extracts (PRO 160/120, Prostagutt (R)
forte) in a 12-week multicenter open trial. The primary
outcome variable of the study, the maximal urinary flow rate,
was increased by a statistically highly significant mean value
of 4,2 ml/s at the end of therapy. Almost all secondary
outcome variables showed a statistically significant
improvement after 12 weeks, too. Particularly the reduction of
the residual urine volume by 26,3 ml on average is clinically
relevant. Moreover, a clear improvement of the subjective
condition of the patients was observed. Besides its good
efficacy, the investigational drug was excellently tolerated
by the patients, thus confirming its therapeutic suitability
in the treatment of benign prostatic hyperplasia stage I-II
(Alken).
Saw Palmetto, African prune and stinging nettle for
Benign Prostatic Hyperplasia ( BPH)
Awang D.V.C.
Canadian Pharmaceutical Journal (Canada), 1997, 130/9
(37-44+62)
No abstract.
[Benign prostatic hyperplasia--the outcome of
age-induced alteration of androgen-estrogen balance]?
Weisser H, Krieg M
Institut fur Klinische Chemie, Transfusions- und
Laboratoriumsmedizin, Berufsgenossenschaftliche Kliniken
Bergmannsheil, Universitatsklinik der Ruhr-Universitat,
Bochum.
Urologe A 1997 Jan;36(1):3-9
Although human benign prostatic hyperplasia (BPH) is the
most common tumor in men, its etiology is still unclear. At
present, it is only widely accepted that BPH is under the
endocrine control of the testes and strongly associated with
aging. Therefore, in the human prostate we describe the impact
of aging on the activity of various androgen metabolizing
enzymes as well as on the endogenous androgen and estrogen
levels. Moreover, the inhibition of 5 alpha-reductase by
finasteride (Proscar) will be reported. Among all androgen
metabolizing enzymes, within the human prostate 5
alpha-reductase is the most powerful one. Most of the androgen
metabolizing enzymes undergo a significant age-dependent
alteration. For distinct enzymes, the correlation with age is
either negative (e.g. 5 alpha-reductase), or positive. Despite
a complex pattern of age-dependent alterations, the dominance
of 5 alpha-reductase among all androgen metabolizing enzymes
is always maintained. This is underlined by a strong
accordance between the age-dependent 5 alpha-reductase
activity and the corresponding age-dependent endogenous DHT
level. In epithelium, both the 5 alpha-reductase activity and
the DHT level decrease with age, whereas in stroma not only
the 5 alpha-reductase activity is rather constant over the
whole age range but the DHT level as well. In contrast to the
relatively unaltered DHT content in the stroma of the human
prostate, the estrogen content follows an age-dependent
increase. On the other side, in epithelium such a positive
correlation between the estrogen level and age is not found.
Thus, the age-dependent decrease of the DHT accumulation in
epithelium and the concomitant increase of the estrogen
accumulation in stroma will lead to a tremendous increase with
age of the estrogen/androgen ratio in the human prostate. This
could be of pathogenetic importance for BPH development if in
fact a balanced androgen/estrogen synergism is necessary for
the integrity of the normal human prostate. Finally, it is
remarkable that the inhibition of 5 alpha-reductase activity
by finasteride (Proscar) is significantly stronger in
epithelium than in stroma. Therefore, it is conceivable that
the global size-reduction of BPH under finasteride treatment
is primarily due to the regression of BPH epithelium.
[Androgen and estrogen metabolism in human benign
prostatic hyperplasia].
Krieg M, Weisser H, Tunn S
BG-Kliniken Bergmannsheil-Universitatsklinik-Institut fur
Klinische Chemie und Laboratoriumsmedizin, Bochum.
Verh Dtsch Ges Pathol 1993;77:19-24
Among all androgen metabolizing enzymes within the human
prostate 5 alpha-reductase is the most powerful one. In the
epithelium its activity decreases with age, while in the
stroma it remains constant over the whole age range. Thus, in
older prostates with benign hyperplasia the activity of 5
alpha-reductase is almost the same in both compartments. The
same holds true for the DHT content, being highest in the
epithelium of prostates from young men. With age it decreases
to levels similar to those in the stroma. In contrast to DHT,
estrogens are increasingly accumulated in the stroma with
advancing age, while in the epithelium the estrogen level
remains constant over the whole age range. The age-dependent
decrease of the DHT level in the epithelium and the increase
of the estrogen level in the stroma lead to a significant
increase of the estrogen/androgen ratio. This could be of
pathobiological importance for BPH development.
Effect of aging on endogenous level of 5
alpha-dihydrotestosterone, testosterone, estradiol, and
estrone in epithelium and stroma of normal and hyperplastic
human prostate.
Krieg M, Nass R, Tunn S
Institute of Clinical Chemistry and Laboratory Medicine,
University Clinic Bergmannsheil, Bochum, Germany.
J Clin Endocrinol Metab 1993 Aug;77(2):375-81
It is widely believed that benign prostatic hyperplasia
(BPH) is associated with aging. Thus, the question arises
whether or not a correlation exists between the well known
prostatic androgen and estrogen accumulation and aging. To
address this question, we measured 5 alpha-dihydrotestosterone
(DHT), testosterone, estradiol, and estrone in epithelium and
stroma of six normal (NPR) and 19 BPH and correlated the
values with the age of the donors (26-87 yr). The mean DHT
level in NPR epithelium was significantly higher than in NPR
stroma, and also significantly higher than in epithelium and
stroma of BPH. The epithelial DHT level of NPR and BPH
decreased with age, the correlation being statistically
significant. The stromal DHT level of NPR and BPH showed no
correlation with age. Concerning testosterone, generally
rather low values were found which showed no correlation with
age. The mean levels of estradiol and estrone were
significantly higher in BPH stroma as compared to BPH
epithelium as well as to NPR epithelium and stroma. In NPR,
the mean levels of estradiol and estrone were significantly
higher in epithelium than stroma. In NPR and BPH, the stromal
estradiol and estrone levels increased significantly with age.
In epithelium such a correlation between the estrogen levels
and age was not found. Our results indicate that the prostatic
accumulation of DHT, estradiol, and estrone is in part
intimately correlated with aging, leading with increasing age
to a dramatic increase of the estrogen/androgen ratio
particularly in stroma of BPH.
The effect of androgen and estrogen on secretory
epithelial cells and basal cells of the rat ventral prostate
after long-term castration.
Kawamura H, Kimura M, Ichihara I
Department of Anatomy, Aichi Medical University, Japan.
Anat Anz 1993 Dec;175(6):569-75
After long-term castration, rats were injected with cotton
seed oil, testosterone- and estradiol-17 beta-cypionate (CS,
TC and EC). The height of the epithelial cells of the ventral
prostates from the castrated rats increased after TC and
EC-injection. The secretory and basal cells formed two layers
of epithelium, an inner layer near the lumen with pale nuclei
and another layer with dark nuclei. These two layers could
result from a reduction of secretory epithelial cells.
Castration decreased the ratio of secretory cells to basal
cells (S/B). TC-injection increased the ratio of S/B because
of the secretory epithelial cell growth. Longer dark cells may
be transient cells, appearing during the differentiation of
basal cells into secretory epithelial cells. A sheet branching
off from the basal lamina was observed. Androgen may stimulate
the synthesis of the lamina, but whether it induces the
synthesis or turnover of the basal lamina has not been
established. EC increased the ventral prostatic weight and
secretory epithelial cell height and induced the appearance of
crystalline granules. Increase in S/B ratio may result from an
increase in the secretory epithelial cells, but not from basal
cell multiplication due to squamous metaplasia. The ratio is
significantly correlated to the weight of the ventral
prostate, but not to the secretory epithelial cell height. Its
value could indicate the multiplication of secretory
epithelial cells, differentiation of basal cells into
epithelial cells, or both. It is probable that basal cells do
not change in number, but control the size of the rat ventral
prostate in response to the hormone level.
Obesity and benign prostatic hyperplasia.
Giovannucci E, Rimm EB, Chute CG, Kawachi I, Colditz GA,
Stampfer MJ, Willett WC
Channing Laboratory, Department of Medicine, Harvard Medical
School, Boston, MA.
Am J Epidemiol 1994 Dec 1;140(11):989-1002
Abdominal obesity increases the estrogen-to-androgen ratio
and may increase sympathetic nervous activity, both
hypothesized to influence the development of benign prostatic
hyperplasia and the severity of urinary obstructive symptoms.
In 1986 and 1987, men aged 40-75 years who were participants
in the Health Professionals Follow-up Study and who were
without prior diagnosis of cancer or prostatectomy provided
data on weight, height, and waist and hip circumferences. The
men were followed for incidence of prostatectomy for benign
prostatic hyperplasia up to January 1992. In addition, the
frequency and severity of symptoms of urinary obstruction were
assessed among respondents to a questionnaire in 1992. Among
25,892 men who provided complete information for both surgery
and symptoms, 837 men had surgery for benign prostatic
hyperplasia, and 2,581 of those without surgery reported
frequent urinary symptoms. After adjustment for age, smoking,
and body mass index, abdominal obesity was related to
prostatectomy (odds ratio (OR) = 2.38, 95% confidence interval
(CI) 1.42-3.99, for those with a waist circumference > or =
43 inches (109 cm) relative to those with a waist
circumference < 35 inches (89 cm); p trend < 0.0001) and
with frequent urinary symptoms among those without
prostatectomy (OR = 2.00, 95% CI 1.47-2.72; p < 0.0001).
Body mass index, hip circumference, and waist-to-hip ratio
were not associated with benign prostatic hyperplasia
independently of waist circumference. These results suggest
that abdominal obesity in men may increase the frequency and
severity of urinary obstructive symptoms and may increase the
likelihood that such obese men will undergo a
prostatectomy.
Effect of obesity on prostatic hyperplasia: its
relation to sex steroid levels.
Soygur T, Kupeli B, Aydos k, Kupeli S, Arikan N, Muftuoglu
YZ
Department of Urology, University of Ankara, School of
Medicine, Turkey.
Int Urol Nephrol 1996;28(1):55-9
In 68 men with benign prostatic hyperplasia, we evaluated
the association between obesity and prostatic enlargement, as
well as changes in serum levels of oestradiol, testosterone,
dihydroepiandrosterone and dihydroepiandrosterone sulphate.
Despite the larger adenomas, no increase in the symptom score
for BPH was observed with increasing obesity. Average specimen
weights increased with increasingly obesity and increasing
host age from 46 to 80 g. We also found the serum oestradiol
level significantly elevated in obese men who were 140% or
over recommended weight compared to underweight men younger
than 60 years (51.3 pg/ml versus 26.8 pg/ml, p < 0.01).
This pattern was present in all age groups. These results
indicate that obesity is a risk factor for prostatic
enlargement but not for obstruction. Also the degree of
obesity appears to have a direct effect on oestradiol levels
through transformation of androgens in adipose tissue to
oestrogens. In conclusion, further studies to evaluate the
pathogenesis, pathophysiology, natural history and
symptomatology of BPH would be of great interest and should
help to define better the associations that we have
recognized.
Larger prostatic adenomas in obese men with no
associated increase in obstructive uropathy.
Daniell HW
Department of Family Practice, University of California
Medical School, Davis.
J Urol 1993 Feb;149(2):315-7
In 379 men less than age 75 years who underwent initial
transurethral prostatectomy for benign prostatic hypertrophy
specimen weights were compared with host ages, obesity,
smoking habits and the presence of incidental cancer. Among
334 men 60 to 74 years old average specimen weights increased
with increasing obesity from 20.3 to 36.6 gm. Underweight men
in comparison with men at least 30% overweight demonstrated
more small specimens (10 gm. or less, 24% versus 2%, p <
0.001) and fewer large specimens (50 gm. or more, 5% versus
26%, p < 0.005). This pattern was present in smokers and
nonsmokers. Adenoma weights increased with increasing host age
and were larger in nonsmokers of all age groups. Body habitus
was similar in the prostatectomy patients and 290 office
patients of similar age, suggesting no increase in obstructive
uropathy among obese men despite the larger adenomas. These
observations are compatible with different risk factors for
the obstructing and nonobstructing components of benign
prostatic enlargement.
Clinical, anthropometric, metabolic and insulin
profile of men with fast annual growth rates of benign
prostatic hyperplasia.
Hammarsten J, Hogstedt B
Urological Section, Department of Surgery, Varberg Hospital,
Sweden.
Blood Press 1999;8(1):29-36
The purpose of this study was to test the hypothesis of a
causal relationship between high insulin levels and the
development of benign prostatic hyperplasia (BPH) and to
determine the clinical, anthropometric, metabolic and insulin
profile in men with fast-growing BPH compared with men with
slow-growing BPH. The present study was designed as a risk
factor analysis of BPH in which the estimated annual BPH
growth rate was related to components of the metabolic
syndrome. Two hundred and fifty patients referred to the
Urological Section, Department of Surgery, Central Hospital,
Varberg, Sweden, with lower urinary tract symptoms with or
without manifestations of the metabolic syndrome were
consecutively included. The prevalences of atherosclerotic
disease manifestations, non-insulin-dependent diabetes
mellitus (NIDDM) and treated hypertension were obtained. Data
on blood pressure, waist and hip measurement, body height and
weight were collected and body mass index (BMI) and waist/hip
ratio (WHR) were calculated. Blood samples were drawn from
fasting patients to determine insulin, total cholesterol,
triglycerides, HDL and LDL cholesterol, uric acid, alanine
aminotransferase (ALAT) and prostate-specific antigen (PSA).
The prostate gland volume was determined using ultrasound. The
median annual BPH growth rate was 1.04 ml/year. Men with
fast-growing BPH had a higher prevalence of NIDDM (p = 0.023)
and treated hypertension (p = 0.049). These patients were also
taller (p=0.004) and more obese as measured by body weight
(p<0.001), BMI (p=0.026), waist measurement (p <0.001),
hip measurement (p = 0.006) and WHR (p=0.029). Moreover, they
had elevated fasting plasma insulin levels (p = 0.018) and
lower HDL cholesterol levels (p = 0.021) than men with
slow-growing BPH. The annual BPH growth rate correlated
positively with diastolic blood pressure (rs = 0.14; p =
0.009), BMI (rs = 0.24; p < 0.001) and four other
expressions of obesity and fasting plasma insulin level (rs =
0.18; p = 0.008), and negatively with the HDL cholesterol
level (rs = -0.22; p = 0.001). In conclusion, the data suggest
that NIDDM, hypertension, tallness, obesity, high insulin and
low HDL cholesterol levels constitute risk factors for the
development of BPH. The results also suggest that BPH is a
component of the metabolic syndrome and that BPH patients may
share the same metabolic abnormality of a defective
insulin-mediated glucose uptake and secondary
hyperinsulinaemia, as patients with the metabolic syndrome.
The findings support the hypothesis of a causal relationship
between high insulin levels and the development of BPH, and
give rise to a hypothesis of increased sympathetic nerve
activity in men with BPH.
Effect of postnecrotic and alcoholic hepatic
cirrhosis on development of benign prostatic
hyperplasia.
Cetinkaya M, Cetinkaya H, Ulusoy E, Baz S, Memis A, Yasa H,
Yanik B, Ozturk B, Uzunalimoglu O
Department of Urology, Ankara Numune Hospital, Turkey.
Prostate 1998 Jul 1;36(2):80-4
BACKGROUND: The object of this study was to investigate the
effects of hepatic cirrhosis on the development of benign
prostatic hyperplasia and consequent effects on prostatic
volume, serum prostate-specific antigen (PSA), and prostatism
symptoms.
METHODS: Sixty patients with postnecrotic cirrhosis and
alcoholic cirrhosis at age 40 and over, and 20 voluntary
subjects in the same age group with normal hepatic functions,
were evaluated with prostatic volume calculation by
transrectal ultrasound, symptom scoring according to American
Urology Association (AUA) criteria, measurement of serum
prostate-specific antigen (PSA), serum total testosterone
(TT), free testosterone (FT), estradiol (E2), and calculation
of E2/FT ratios, and the results were analyzed statistically
by the Mann-Whitney U-test.
RESULTS: Serum FT and TT levels were significantly lower in
the hepatic cirrhosis group compared to the control group (P =
0.0000 and P = 0000, respectively). Though mean serum E2 level
was a little higher in cirrhotic patients compared to
controls, the difference was not significant; however, the
higher E2/FT ratio in the cirrhotic group was statistically
significant (P = 0.27 and P = 0.0002, respectively). In the
cirrhotic group, the decrease in FT and TT levels was greater,
as the disease advanced. While E2 and E2/FT ratio increase,
correlate with poor prognosis, no statistically significant
differences were found. Mean prostatic volume, serum PSA
level, and total symptom score were significantly higher in
the control group, compared to the cirrhotic group (P =
0.0001, P = 0.0006, and P = 0.002, respectively). Prostatic
volume decreased parallel to severity of disease in cirrhotic
patients.
CONCLUSIONS: The main reason for the decrease in mean
prostatic volume in cirrhotic patients compared to subjects in
the same age group with normal hepatic functions was the
decrease in serum FT and TT levels, and the secondary cause
was the increase in E2/FT ratio, indicating estrogenic
predominance
Estrogen suppression as a pharmacotherapeutic
strategy in the medical treatment of benign prostatic
hyperplasia: evidence for its efficacy from studies with
mepartricin.
Boehm S, Nirnberger G, Ferrari P
Department of Neuropharmacology, University of Vienna,
Austria
Stefan.Boehm@univie.ac.at
Wien Klin Wochenschr 1998 Dec 11;110(23):817-23
Estrogen suppression has been introduced as a
pharmacotherapeutic strategy in the medical treatment of
benign prostatic hyperplasia. Recent negative results obtained
in placebo-controlled trials with the aromatase inhibitor
atamestane raised doubts about the efficacy of estrogen
reduction. However, inhibition of aromatase not only reduces
estrogens but also increases androgens which promote prostatic
growth. In order to reevaluate the therapeutic efficacy of
estrogen suppression, we summarize clinical trials
investigating the therapeutic effects of mepartricin in the
treatment of uncomplicated benign prostatic hyperplasia.
Mepartricin has been reported to lower the levels of
circulating estrogens without causing changes in other
hormones such as androgens. By applying stringent inclusion
criteria, 23 studies (including 7 placebo-controlled trials, 3
post-marketing surveillance studies, and 13 open trials)
published between 1982 and 1996 were selected to be included
in this report. In 79.9% of 4635 patients treated with
mepartricin, its therapeutic effect was rated "good" or
"excellent". In 6 out of 7 placebo-controlled trials, the
therapeutic efficacy of mepartricin was significantly superior
to that of placebo. Comparison of these data with results
obtained with alpha 1-adrenoceptor antagonists or with the 5
alpha-reductase inhibitor finasteride indicates that
mepartricin is as efficient as these widely accepted medical
treatments for benign prostatic hyperplasia. Since mepartricin
acts selectively upon estrogens, the present results show that
estrogen suppression may be considered an efficient
pharmacotherapeutic strategy in the medical treatment of
uncomplicated benign prostatic hyperplasia.
Chlormadinone acetate pellet implantation plus
short-term oral administration in dogs with benign prostatic
hypertrophy.
Kawakami E, Shimizu M, Orima H, Fujita M, Hori T, Tsutsui
T
Department of Reproduction, Nippon Veterinary and Animal
Science University, Tokyo, Japan.
Int J Androl 1998 Apr;21(2):67-73
Eight beagles with benign prostatic hypertrophy (BPH) were
treated by subcutaneous implantation of pellets containing 10
mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen,
plus daily oral administration of CMA at 2 mg/kg per day for 7
days as a therapy for BPH. Prostatic and testicular size were
measured and prostatic and testicular biopsies were performed
by laparotomy before and after CMA treatment. Plasma levels of
luteininzing hormone (LH), testosterone and oestradiol were
also measured. The clinical signs of BPH, for example
haematuria and dysuria, resolved within 1 week of treatment.
Mean prostatic volume decreased to 56% of the pretreatment
value. At 40 weeks after treatment, prostatic volume had
decreased by 36%. Histological examination of the prostate 1
week after treatment revealed reduction in diameter of the
alveoli and in height of the glandular epithelium.
Degeneration and atrophy of the glands were marked 4-12 weeks
after treatment. In the testis, the diameter of seminiferous
tubules and the number of germ cells in the seminiferous
tubules had decreased markedly at 12 and 24 weeks after
treatment. Although plasma LH concentrations did not undergo
any marked fluctuations after CMA treatment, levels of
testosterone and oestradiol were lower than before treatment.
The results indicate that implantation of 10 mg/kg CMA, , plus
7-day oral administration of 2 mg/kg CMA, bring about
resolution of the clinical signs and marked reduction in
prostatic volume within 1 week of treatment.
Effects of the aromatase inhibitor testolactone on
human benign prostatic hyperplasia.
Schweikert HU, Tunn UW
Department of Internal Medicine, University of Bonn,
FRG.
Steroids 1987 Jul-Sep;50(1-3):191-200
The aromatase inhibitor testolactone was used for endocrine
treatment of benign prostatic hyperplasia (BPH). Thirteen
patients (mean age 79 years) with complete urinary retention
(BPH stage IV) without improvement after 4 weeks of bladder
drainage by suprapubic catheter were treated with testolactone
100 mg, b.i.d., for 6 months. Nine men (mean age 80 years)
with identical conditions who did not receive hormonal therapy
served as controls. Results, treatment group: In 7 patients
spontaneous micturation reoccurred after an average treatment
period of 8 weeks (group A); 6 patients continued to need the
catheter (group B). Prostatic volume decreased in all
patients, and an average volume reduction of 26% was found in
group A, whereas in group B the decrease averaged 15%.
Finally, the testosterone/estradiol ratio significantly
increased in all patients during treatment. Control group:
Prostatic volume did not change nor did spontaneous
micturation occur during the whole observation period.
[Drug therapy of benign prostatic
hyperplasia]
Vahlensieck W Jr, Fabricius PG, Hell U
Fortschr Med 1996 Nov 10;114(31):407-11
PH patients with Vahlensieck stage II or III disease are
suitable for drug treatment. The points of attack are
reduction of testosterone, conversion of testosterone to
dihydrotestosterone, conversion of testosterone to estrogen
using GnRH analogues, antiandrogens and alpha reductase
inhibitors or aromatose inhibitors. Furthermore a reduction in
obstruction is achieved through the use of
phytopharmaceuticals containing 5-lipoxygenase and
cyclooxygenase inhibitors. At present, Curcurbitae pepo seeds,
Urtica dioica root, Pollinis siccae extract and Sabal
serrulata seed extract are approved for the treatment of
prostatic diseases in Germany. The use of
alpha-1-sympathicolytic treatment may reduce muscular tone in
the prostate. Combination of the various modes of action may
also offer an effective form of treatment.
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