12 Treatment of hirsutism with 5α-reductase inhibitors

Much of the evidence gathered from studies of 5α-reductase activity levels and androgen metabolism in the skin of hirsute women and the excretion of androgen metabolites by hirsute women indicates that 5α-reduced androgens are probably of primary importance in hirsutism. Unfortunately, until very recently, the lack of a suitable 5α-reductase inhibitor made it very difficult to adequately test the hypothesis that such an inhibitor might be useful in the treatment of hirsutism and certain other androgen-related diseases. No substance was available which had good, unambiguous activity in vivo as a 5α-reductase inhibitor.

A number of 4-azasteroids have now been found to possess excellent 5α-reductase inhibitory activity both in vitro and in vivo. Among other properties, several of these compounds show little or no affinity for the androgen receptor of rat prostate cytosol, they attenuate the growth promoting effect of T, but not DHT, on the ventral prostate of castrated male rats, they cause a marked reduction in prostatic DHT concentration in acutely treated rats and dogs and they bring about a significant decline in prostate size in chronically treated rats and dogs. It is expected that, in the near future, one or more of these highly active 5α-reductase inhibitors will be tested in the clinic as a treatment for hirsutism. The results of those studies will be awaited with a great deal of interest since they should considerably advance our understanding of this disease and possibly contribute to its control.