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5-Alpha Reductase Inhibitors Don'tOffer Much Help In BPH

By David Jack
Special to DG News

GLASGOW, SCOTLAND -- June 23, 1999 -- Results of several clinical trials show that 5-alpha reductase inhibitors such as finesteride do not contribute much to the treatment of benign prostatic hyperplasia (BPH) when combined with alpha-1 blockers.


The findings were presented yesterday at the British Association of Urological Surgeons (BAUS) meeting in Glasgow, Scotland.


Dr. R. R. Kirby, St. George’s Hospital, London, England, presented the results of the PREDICT (Prospective European Doxazosin and Combination Therapy) trial. The randomised trial, sponsored by Pfizer, investigated the safety and efficacy of the alpha-1 blocker, doxazocin, the 5-alpha reductase inhibitor, finasteride, or a combination of doxazosin + finasteride, compared with placebo in patients with symptomatic BPH.


The researchers randomised 1,089 patients with BPH, 50 to 80 years of age, to receive one of the four treatments and monitored them for one year. The doxazosin dose was titrated up to a maximum of 8 mg daily while finasteride was maintained at 5 mg daily throughout the study.


The primary efficacy variables were the International Prostate Symptom Score (I-PSS) and the maximum urinary flow rate (Qmax), while safety was monitored by the incidence of acute urinary retention (AUR) and the need for TURP (transurethral resection of the prostate).


Both doxazosin and doxazosin + finasteride produced a statistically-significant improvement in both the Qmax and I-PSS. There was no difference in I-PSS between finasteride alone and placebo, while doxazosin and the doxazosin + finasteride combination were equally effective. Both AUR and TURP were more common in the placebo group than in the three drug-treated groups and both drugs were well tolerated. The 5-alpha reductase inhibitor, finasteride, on its own does not seem to be of significant benefit in treating symptoms of BPH, although both drugs seem able to reduce the need for surgery.

WTF???

:confused:
 
TITLE

Comparison of finasteride (Proscar), a 5 alpha reductase inhibitor, and various commercial plant extracts in in vitro and in vivo 5 alpha reductase inhibition.

AUTHOR

Rhodes L; Primka RL; Berman C; Vergult G; Gabriel M; Pierre-Malice M; Gibelin B

ORGANISATION

Department of Biochemistry, Merck Research Laboratories, Rahway, New Jersey 07065.

SOURCE

Prostate 1993; 22 (1): 43-51

LANGUAGE OF PUBLICATION

English

ABSTRACT

Human prostate was used as a source of 5 alpha reductase. Compounds were incubated with an enzyme preparation and [3H]testosterone. [3H]-dihydrotestosterone production was measured to calculate 5 alpha reductase activity. IC50 values (ng/ml) were finasteride=1; Permixon=5,600; Talso=7,000; Strogen Forte=31,000; Prostagutt=40,000; and Tadenan=63,000. Bazoton and Harzol had no activity at concentrations up to 500,000 ng/ml. In castrate rats stimulated with testosterone (T) or dihydrotestosterone (DHT), finasteride, but not Permixon or Bazoton, inhibited T stimulated prostate growth, while none of the three compounds inhibited DHT stimulated growth. These results demonstrate that finasteride inhibits 5 alpha reductase, while Permixon and Bazoton have neither anti-androgen nor 5 alpha reductase inhibitory activity. In addition, in a 7 day human clinical trial, finasteride, but not Permixon or placebo, decreased serum DHT in men, further confirming the lack of 5 alpha reductase inhibition by Permixon. Finasteride and the plant extracts listed above do not inhibit the binding of DHT to the rat prostatic androgen receptor (concentrations to 100 micrograms/ml). Based on these results, it is unlikely that these plant extracts would shrink the prostate by inhibiting androgen action or 5 alpha reductase. (AUTHOR)

MJTR: Androstenes PD. Azasteroids PD. Plant Extracts PD. Testosterone 5-alpha-Reductase AI.

MNTR: Animal. Comparative Study. Human. In Vitro. Male. Prostate DE. Prostate EN. Rats. Receptors, Androgen DE. Stanolone BL. Testosterone BL. CLINICAL TRIAL. CONTROLLED CLINICAL TRIAL. JOURNAL ARTICLE

RNUM: EC 1.3.99.5 (Testosterone 5-alpha-Reductase); 0 (Androstenes); 0 (Azasteroids); 0 (Permixon); 0 (Plant Extracts); 0 (Receptors, Androgen); 521-18-6 (Stanolone); 57-85-2 (Testosterone); 98319-26-7 (Finasteride)

GEOT: UNITED STATES

IDEN: ISSN: 0270-4137. JOURNAL-CODE: PB4. ENTRY-DATE: 930226. JOURNAL-SUBSET: M X. IM-DATE: 9305.

ACCE: 93149919
 
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