A seminal paper published by Charles Huggins, MD, in 1941 on castration and the effects of androgen deprivation on prostate cancer has continued to influence the treatment of prostate cancer to this day. Oliver Sartor, MD, notes that the use of LHRH analogues in the treatment of prostate cancer has been a major advance, because with LHRH therapy, men can avoid castration while still benefiting from androgen deprivation.

Although the older anti-androgens, such as bicalutamide and flutamide, may have benefits in non-metastatic disease, they do not produce the level of androgen deprivation necessary to control metastatic disease, Sartor states. He comments that newer antiandrogen agents are superior to older agents, and newer agents have advantages, such as libido- and bone-sparing effects; however, a disadvantage is that the newer agents are associated with gynecomastia. Clinicians may consider anti-androgen monotherapy with a newer agent for patients with metastatic disease.

Kenneth Kernen, MD remarks that the use of diethylstilbestrol (DES) has declined due to the thromboembolic risk associated with its use and the introduction of newer agents. Neal Shore, MD, comments that increased estradiol levels can have beneficial effects. In the United Kingdom, transdermal estrogen is currently being evaluated in clinical trials.