QUALITATIVE AND QUANTITATIVE-EVALUATION OF PROSTATIC HISTOMORPHOLOGY IN RATS FOLLOWING CHRONIC TREATMENT WITH FINASTERIDE, A 5-ALPHA-REDUCTASE INHIBITOR
Sr. Prahalada et al., QUALITATIVE AND QUANTITATIVE-EVALUATION OF PROSTATIC HISTOMORPHOLOGY IN RATS FOLLOWING CHRONIC TREATMENT WITH FINASTERIDE, A 5-ALPHA-REDUCTASE INHIBITOR, Urology, 43(5), 1994, pp. 680-685
Objective. To determine any potential direct and/or indirect effects o
f elevated intraprostatic T levels on the prostates of rats chronicall
y (1-2 years) exposed to high doses (160 mg/kg/day) of finasteride, a
selective inhibitor of 5-alpha reductase. Methods. Sprague-Dawley male
rats were administered daily finasteride by oral gavage. Prostates fr
om all rats were weighed, fixed in 10% neutral buffered formalin, and
processed for light microscopic examination. The volume fractions of t
he prostatic glandular and stromal compartments were quantitated by mo
rphometric analysis. Results. Administration of finasteride at doses o
f 20, 40, and 80 mg/kg/day for one year resulted in a significant (P l
ess-than-or-equal-to 0.05) decrease in prostatic weight; prostatic atr
ophy was evident by light microscopy. Morphometric analysis of the pro
state showed that chronic finasteride administration resulted in a sig
nificant (P less-than-or-equal-to 0.001) decrease in the absolute volu
me of both glandular (-65.2%) and stromal (-57.1 %) compartments of th
e prostate. Furthermore, the total number of epithelial and stromal ce
lls per gland were significantly (P less-than-or-equal-to 0.002) decre
ased in finasteride-treated rats compared with vehicle controls; the m
agnitude of mean decrease was 69.8 percent and 50.6 percent of control
s in epithelial and stromal cells, respectively. In addition, prostate
s from all two hundred fifty rats in a two-year study were qualitative
ly evaluated by light microscopy. Administration of finasteride at dos
es ranging from 2.5 mg/kg/day to 160 mg/kg/day for two years did not r
esult in an increase over the background incidence of prostatic focal
hyperplasia or adenoma. No malignant tumors of the prostate were seen
in any of the groups. Conclusions. These studies have demonstrated tha
t the expected pharmacologic effects of finasteride on the prostate ar
e maintained following chronic treatment and that there was no evidenc
e of a direct and/or an indirect effect of elevated intraprostatic T o
n prostatic morphology in rats.