5-ALPHA-REDUCTASE INHIBITORS AND PROSTATIC DISEASE

5α-Reductase inhibitors are a new class of substances with very specific effects on type I and type II 5αR which may be of use in the treatment of skin disease, such as male pattern baldness, male acne and hirsutism, as well as prostatic hyperplasia and prostate cancer. At least two types of 5αR inhibitors with a different pH optimum have been described. cDNA encoding for both the type I and the type II enzyme has been cloned. Most of the orally effective 5αR inhibitors belong to the class of 4-azasteroids. The radical substituted in the 17 position of the steroid ring seems to be related to species specific variations and to the types of 5αR enzymes in different species and organ systems. 5αR inhibitors lead to a decrease of plasma DHT by about 65% while there is a slight rise in plasma testosterone. The decrease of tissue DHT in the ventral prostate of the intact rat, the dog and in humans is more pronounced and amounts to about 85%. There is a reciprocal rise of tissue T in these systems. The application of an inhibitor of 5αR type II leads to a shrinkage of BPH in men by about 30%. In the rat a similar shrinkage accompanied by a significant decrease of total organ DNA occurs. This decrease, however, is not as pronounced as can be achieved with castration. As regards the application of 5αR type II inhibitors to human BPH, most experience has been gained with Finasteride. This substance leads to a 20-25% volume decrease of the prostate, roughly a 30% improvement of total symptom score and of maximal urinary flow rate. These improvements are clinically considered to be moderate in comparison to the functional results achieved with standard prostatic surgery. As far as prostate cancer goes, the role of 5αR inhibitors still needs to be determined. It is uncertain whether testosterone stimulates prostate cancer to a greater degree than BPH. The decrease of serum PSA under Finasteride treatment does not seem to match the decrease seen with castration or total androgen blockade. It has not been determined whether 5αR inhibitors applied very early on in the development of prostate cancer may have a preventive effect.