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Hair Loss Study Abstract: Comparison of the effects of new specific azasteroid inhibitors of steroid 5
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Title
Comparison of the effects of new specific azasteroid inhibitors of steroid 5
alpha-reductase on canine hyperplastic prostate: suppression of prostatic DHT correlated
with prostate regression.
Author
Cohen SM; Werrmann JG; Rasmusson GH; Tanaka WK; Malatesta PF; Prahalada S; Jacobs JG;
Harris G; Nett TM
Address
Merck Research Laboratories, Rahway, New Jersey.
Source
Prostate, 26: 2, 1995 Feb, 55-71
Abstract
Four new azasteroid inhibitors of steroid 5 alpha-reductase were compared to the
benchmark compound finasteride, each at a dose level of 1 mg/kg/day, as well to placebo
and to castration, in seven groups of mature male beagle dogs with enlarged prostates.
Prostate volumes were measured repetitively by a volume MRI method over 15 weeks of
treatment. The study probed the obverse of the familiar relation between DHT and prostate
growth, and provides the first documentation of a tight negative correlation between
prostate regression and the prostatic concentration of DHT across a range of treatment
regimens (r = -0.982). In this first direct comparison study of structure vs. in vivo
activity for several azasteroids in the dog model of BPH, relative efficacy for induction
of shrinkage of the dog prostate did not correlate at all with the inhibitor's relative
activity against the dog 5 alpha-reductase in vitro. On the basis of the relative IC50
values it would not have been predicted that, at the dose tested, the analogue MK-434 (17
beta-benzoyl-4-aza-5 alpha-androst-1-en-3-one) was distinguished from the other inhibitors
with respect to the induction of faster and more complete regression (69%) as well as
greater reduction in prostatic DHT (95%), both of which approached the castrated dog
levels of 75% prostatic shrinkage and > 98% reduction in DHT. Treatment with any one of
the five azasteroids induced two- to five-fold increases in prostatic testosterone.
However, total androgen was conserved at the placebo control level. Despite the
differences noted, each azasteroid tested induced a highly significant decrease in
prostatic volume that correlated tightly with a decreased prostatic DHT level in canine
spontaneous BPH.
Language of Publication
English
Unique Identifier
95158244
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