The antiandrogen withdrawal syndrome.

In 1989 the unanticipated agonist effect of antiandrogens on LNCaP prostate cancer cells was detected. A "flutamide withdrawal syndrome" was first described by Kelly and Scher [15], who reported a decrease in serum prostate-specific antigen (PSA) levels after the removal of flutamide from the treatment regimen. In the last few years the paradoxical response to antiandrogens has also been reported for bicalutamide, chlormadinone acetate and others. Therefore the name of the syndrome has changed to "antiandrogen withdrawal syndrome." Several reasons such as mutations in the androgen receptor or a direct stimulatory effect of the antiandrogen for this effect have been discussed, but the exact molecular mechanism remains unclear. However, in patients with hormonally relapsed prostate cancer, a trial of "withdrawal therapy" is required prior to the initiation of toxic therapies.