Long-term effects of finasteride on prostate tissue composition

Objectives. To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferent ial action on the transition zone. Methods. Nineteen men with symptomatic benign prostatic hyperplasia (BPH) w ho completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed toget her 70 times: at baseline(n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 t o 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone. Results. Decreases in symptom score, dihydrotestosterone and prostate-speci fic antigen levels, and prostate volume occurred at 6 months (P <0.01), sta bilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition ; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 c c, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, r espectively, P <0.01 for all). Percent epithelial contraction was similar i n the peripheral and transition zones (P = NS). The transition zone remaine d a relatively constant proportion (53% to 58%) of whole-prostate volume fr om baseline to long-term observation. Conclusions. Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithel ium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of fin asteride. (C) 1999, Elsevier Science Inc. All rights reserved.