Steroid hormone withdrawal syndromes. Pathophysiology and clinical significance.

The steroid withdrawal syndrome has brought a new dimension to the treatment of advanced prostate cancer not only in the way we treat androgen-independent disease but also in terms of insights into the development of hormonal resistance. The data now confirm that 30% of cases have a meaningful subjective, biochemical, and objective response to the withdrawal of a steroid hormone as the first maneuver after primary hormonal therapy failure. Larger studies are needed to define further the withdrawal effect related to the other steroid hormone family members and to determine the objective response proportions. Although controversy surrounds the cause of the steroid withdrawal phenomenon, studies suggest that the androgen receptor plays a pivotal role. Molecular studies of the androgen receptors involving larger number of patients are paramount if we are going to develop a better understanding of the evolution of the withdrawal effect and hormone resistance.