THE ANTIANDROGEN WITHDRAWAL SYNDROME

In 1989 the unanticipated agonist effect of antiandrogens on LNCaP pro state cancer cells was detected. A ''flutamide withdrawal syndrome'' w as first described by Kelly and Scher [15], who reported a decrease in serum prostate-specific antigen (PSA) levels after the removal of flu tamide from the treatment regimen. In the last few years the paradoxic al response to antiandrogens has also been reported for bicalutamide, chlormadinone acetate and others. Therefore the name of the syndrome h as changed to ''antiandrogen withdrawal syndrome.'' Several reasons su ch as mutations in the androgen receptor or a direct stimulatory effec t of the antiandrogen for this effect have been discussed, but the exa ct molecular mechanism remains unclear. However, in patients with horm onally relapsed prostate cancer, a trial of ''withdrawal therapy'' is required prior to the initiation of toxic therapies.