text: Antiandrogens that are currently on the market are particularly useful for the treatment of prostate cancer during the early stages. However, prostate cancer often progresses to a hormone-refractory state in which the cancer progresses in the presence of continued androgen ablation or antiandrogen therapy. This suggests that long term use of these antiandrogens during prostate cancer can lead to the development of androgen-independent prostate cancer cells or the ability of adrenal androgens to support tumor growth. This phenomenon is called antiandrogen withdrawal syndrome (AWS) and is one of the major drawbacks of existing antiandrogens. AWS is defined as tumor regression or symptomatic relief observed upon discontinuation of the antiandrogen therapy. The mechanism for this is not fully understood but current theories include alterations of the AR gene, coregulator proteins and/or signal transduction pathways. This antiandrogen resistance may also be linked to the relative weakness of current antiandrogens as they have an affinity 50 times or more lower than that of DHT for the AR. This may also explain why compensatory AR overexpression is often observed.