Although the antiandrogenic treatment of metastatic prostate carcinoma is palliative, life expectancy is increased and thousands of patients have benefited. When distant metastases already are present, hormonal therapy becomes the primary treatment for prostate cancer. Pharmacological approaches to reduce the concentrations of endogenous androgens or inhibit their action include antiandrogens, or more commonly, the administration of gonadotropin-releasing hormone (GnRH) agonists or antagonists with or without antiandrogens (see below).
Among men with metastatic prostate cancer, >90% have an initial favorable response to primary hormonal therapy with androgen deprivation therapy (ADT). This is manifest as disease regression or stabilization and relief of cancer-related symptoms. The average time to progression is 18-36 months, making ADT one of the longest-lasting beneficial treatments in any advanced solid tumor. There is a survival benefit to ADT. Disease progression after ADT signifies an androgen-independent state, with subsequent median survival of only 12 months. However, many men will respond to secondary hormonal therapy even after failure of ADT. Secondary hormonal treatments include androgen receptor (AR) blockers, adrenal androgen synthesis inhibitors, and estrogenic agents. Responses are more variable than to primary hormonal therapy, but a substantial portion of men benefit from these well-tolerated forms of treatment. When patients become refractory to any form of hormonal therapy, their management usually involves chemotherapeutic agents.
Common side effects of all forms of antiandrogen hormonal therapy include vasomotor flushing, loss of libido, gynecomastia, increased weight, decreased bone mineral density (BMD), and loss of muscle mass. There is variability to these side effects. For example, AR blockers cause more gynecomastia compared with GnRH agonists but less vasomotor flushing and loss of BMD. Importantly, the increased cardiovascular toxicity observed with high doses of estrogen is not observed with other forms of ADT.
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