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New
releases from the AUA meeting in
Orlando, Fl:
AN
INVESTIGATION INTO THE "IN
VIVO" EFFECT
OF PERMIXON, AN EXTRACT OF THE AMERICAN
DWARF PALM, SERENOA REPENS, ON HUMAN
BENIGN PROSTATIC HYPERPLASIA
Alfred C Buck*,
Vinay Mahendra, Glasgow, UK; Colin
W Bayne, Margaret Ross, Fouad Habib,
Edinburgh, UK,2002
Introduction and Objectives:
The extract of the American dwarf palm, Serenoa repens, is the commonest phytoceutical
used world-wide for the medical treatment of symptomatic BPH. PERMIXON, a
lipido-sterolic extract of Serenoa repens, is a mixture of long chain free
fatty acids. "In vitro" studies have suggested multiple mechanisms
of action including inhibition of 5 alpha reductase and the interference
with DHT-receptor binding. The aim of this study was to determine whether
treatment with PERMIXON results in changes in prostate tissue androgen activity
or alterations in the biochemical and hormonal profile which could explain
its clinical effects
Methods:
Prostate tissue obtained by TUR from 32 patients with BPH was studied. Of these,
16 patients had been treated with PERMIXON (320 mgs daily) for three months
prior to operation and the prostate tissue analysed for testosterone, DHT (dihydrotestosterone)
and androstenedione. The results were compared with the tissue hormone levels
in prostate tissue from 16 control patients undergoing TUR of the prostate
who had not received any treatment. In addition, the plasma hormone profile
and PSA was studied before the start of and following the end of treatment.
Results:
There was an 112% increase in tissue testosterone and a 36% decrease in DHT
in the PERMIXON treated group compared with controls. These differences, however,
did not reach statistical significance (p=0.173 and 0.226 for T and DHT respectively).
There was a significantly higher concentration of androstenedione in the prostate
of the PERMIXON treated patients. A discriminant analysis which measured the
testosterone/DHT ratio showed that the T/DHT ratio in the tissue of the PERMIXON
treated patients was almost twice that of the controls (p=0.03). No differences
were observed in the plasma hormone levels or PSA concentrations before or
after treatment, or in comparison with the controls.
Conclusions:
This study has shown that PERMIXON treatment alters the hormone profile of
the prostate with a tendency to decrease DHT and concomitantly to increase
testosterone and androstenedione levels. Wide variations in individual patients
in these small groups obviated statistically significant differences, but the
trend was in accord with the results of others. The absence of changes in PSA
and plasma hormone values would indicate that PERMIXON affects androgen metabolism
in the prostate by a mechanism different from the conventional inhibition of
5 alpha reductase
EFFECT OF DUTASTERIDE
ON THE RISK OF ACUTE URINARY RETENTION
AND THE NEED FOR SURGICAL TREATMENT Peter Boyle*,
Milan, Italy, Italy; Paul Siami,
Evansville, IN; Barton H Wachs,
Long Beach, CA; Claus G Roehrborn,
Dallas, TX; Gerald L Andriole,
St Louis, MO; Curtis Nickel, Ontario,
Canada
The dual 5 a-reductase
inhibitor dutasteride lowers the
risk of AUR and BPH related surgery
by 48 - 57% compared
with placebo over 24 months. Differences
between treatment groups increase
over time.
THE EFFECT OF FINASTERIDE ON THE EXPRESSION
OF VASCULAR ENDOTHELIAL GROWTH FACTOR AND MICROVESSEL DENSITY:
A MECHANISM FOR DECREASED PROSTATIC BLEEDING OBSERVED IN TREATED
PATIENTS
Decreased expression of VEGF by
finasteride inhibits angiogenesis
and significantly decreases MVD in
prostatic suburethral tissue. This
sequential relationship provides
histochemical insight into the mechanism
by which finasteride may reduce prostatic
urethral bleeding
PROSTATE VOLUME
AT BASELINE PREDICTS THE MARGIN OF
THERAPEUTIC RESPONSE WITH THE 5a-
REDUCTASE INHIBITOR, DUTASTERIDE Claus G Roehrborn*,
Dallas, TX; Joe Ramsdell, Lajolla,
CA; Paul Siami, Evansville, IN;
Barton H Wachs, Long Beach, CA;
Sidney Rosenblatt, Irvine, CA
LONG-TERM TREATMENT
WITH FINASTERIDE IN MEN WITH SYMPTOMATIC
BENIGN PROSTATIC HYPERPLASIA: 10-YEAR
FOLLOW-UP John S Lam*, Nicholas
A Romas, Frank C Lowe, New York,
NY
EFFECT OF THE DUAL
5a-REDUCTASE
INHIBITOR DUTASTERIDE ON ENDOCRINE
PARAMETERS
Claus G Roehrborn*,
Dallas, TX; Gerald L Andriole,
St Louis, MO; Curtis Nickel, Ontario,
Canada; Peter Boyle, Milan, Italy
Introduction and Objectives:
Inhibition of the 5a-reductase type II isoenzyme
causes a reduction in circulating levels of dihydrotestosterone (DHT). Effects
on other hormones such as testosterone (T) and luteinizing hormone (LH) have
not been well characterized. Our objectives were to study the impact of dutasteride
(D), a dual inhibitor of 5a-reductase types I and
II, on circulating androgenic hormones.
Methods:
Three 2-year multi-center, double-blind, placebo-controlled studies were conducted
(n = 4325);D was administered at a dose of 0.5 mg/day. Inclusion criteria were:
moderate to severe symptoms (AUA-SI ³ 12); prostate
volume ³ 30 ml; PSA ³ 1.5
ng/ml to £ 10.0 ng/ml; and maximum flow rate (Qmax) £ 15
ml/sec. DHT and T were measured in the 3 studies in a subset of the total patient
population at baseline, 1, 3, 6, 12, 18 and 24 months and in all patients at
baseline, month 12 and 24. LH was measured in all patients in 1 of the 3 studies
at months 6, 12, 18 and 24.
Results:
The table shows the median % change from baseline
for DHT, T and LH at each timepoint. The overall median%change
from baseline in D-treated subjects for DHT at month 24 was -93.7% (SD=17)
and for T 19.6% (SD=40); LH increased by 21.2% (SD=161).
The decrease in DHT for D-treated subjects was predictable with 97% of
the subjects achieving at least a 70% reduction,
95% achieving at least an 80% reduction,
and 81% achieving at least a 90% reduction
at month 24. The changes in LH and T were small and not regarded as clinically
significant.
Conclusions:
The new dual 5a-reductase inhibitor D induces early
hormonal changes with a near total reduction in serum DHT as early as 1 month.
The overall reduction in DHT is much greater than that usually observed with
finasteride (~70%) and is less variable. Serum testosterone
increases early and remains constant over the 24-month treatment period.
| 1 mo |
3
mo |
6
mo |
12
mo |
18
mo |
24
mo |
| DHT/D (n=195) |
-91
(15) |
-92.7
(12) |
-93.6
(14) |
-94.4
(7) |
-94.7
(16) |
-94.1
(14) |
| DHT/Plc (n=195) |
9.2
(51) |
10.4
(52) |
13.0
(48) |
4.3
(39) |
3.9
(44) |
6.1
(60) |
| T/D (n=195) |
18.1
(37) |
18.4
(36) |
19.3
(36) |
22.7
(33) |
13.9
(39) |
16.1
(38) |
| T/Plc(n=195) |
3.4
(28) |
8.1
(27) |
5.2
(36) |
0.6
(25) |
2.7
(27) |
5.2
(34) |
| LH/D (n=770) |
NA |
NA |
11.8
(248) |
20.2
(310) |
22.6
(57) |
21.2
(161) |
| LH/Plc (n=753) |
NA |
NA |
4.2
(66) |
5.1
(110) |
9.7
(79) |
5.7
(73) |
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