Endocrine therapy: where do we stand and where are we going?

Endocrine management is the best palliative management available for patients with carcinoma of the prostate. It is based on androgen withdrawal by castration or other means. Endocrine management was introduced into clinical medicine by Huggins and his associates in the early 1940s on the basis of careful clinical and experimental research establishing the biological effects of androgen withdrawal in animal systems and in humans. It was believed for a long time that endocrine treatment would prolong life. This, however, in spite of extensive clinical research, remains unproven. The possibility that the life span of prostate cancer patients is determined by the hormone independent cell populations within virtually all prostate cancers still remains a possibility. Endocrine treatment has, however, been shown to have a significant impact on symptoms related to prostate cancer, especially on bone pain, urethral and ureteral obstruction. It has also been shown to prolong time to progression and to death from prostate cancer. Although castration and the application of exogenous oestrogens with the purpose of interfering with pituitary testicular feedback have been standard treatment of prostate cancer for more than 30 years, new treatment methods have recently become available. Luteinizing hormone releasing hormone agonists allow suppression of plasma testosterone to castration levels without exerting the side effects associated with oestrogens (eg cardiovascular incidents, gynaecomastia). Also, the application of pure or steroidal anti-androgens allows direct counteraction of circulating androgens at the target cell. The possibility that initial suppression of adrenal androgen production, which contributes about 10% of circulating androgens in males, may be more beneficial than suppression of testicular androgens alone has been subject to intense clinical research recently. Simultaneous suppression of testicular and adrenal androgens in primary management of prostate cancer is called total androgen blockade or total androgen suppression. Up to now, however, no convincing advantages of total androgen suppression regimens above castration have been shown. Total androgen suppression seems to produce significantly better survival when compared with daily injections of LHRH alone. The use of pure anti-androgens or of 5 alpha-reductase inhibitors could potentially prevent the most significant side effect of all androgen withdrawal regimens, loss of libido and impotence. However, neither the use of pure anti-androgens as monotherapy nor the use of 5 alpha-reductase inhibitors as monotherapy has been shown to produce clinical results that are equal to castration.(ABSTRACT TRUNCATED AT 400 WORDS)