For patients with advanced prostate cancer, LHRH agonists have provided successful androgen deprivation therapy (ADT) for several years. However, following the administration of these agents, FSH and LH levels may briefly increase, causing an initial surge in testosterone levels that may worsen some conditions. LHRH antagonists, on the other hand, tend to reduce testosterone levels more quickly and do not cause flares, advocates E. David Crawford, MD.

In addition to a reduction in testosterone-induced flare, which may still occur despite complete androgen blockade, treatment with antagonists results in fewer joint-related, musculoskeletal, and urinary tract complications compared with agonists, notes Crawford. Moreover, antagonists appear to maintain castrate levels of testosterone for longer durations, suggesting an improvement in survival.

Studies have indicated that ADT with LHRH agonists could be associated with cardiovascular events and death, resulting in past FDA safety warnings. In general, Crawford notes, these warnings were made concerning agonists and not antagonists. For men with a prior history of cardiovascular disease, there is a 9% risk of cardiovascular death with an agonist compared with a 3% risk with antagonists, Crawford notes. The relationship between agonists and cardiovascular events may be related to increases in T cells, cytokines, and inflammation following treatment, which do not occur as frequently with antagonists, Crawford believes.