Hormonal therapy: historical perspective to future directions

Prostate cancer is second only to lung and bronchial cancer as the leading cause of cancer death in men. Local treatment, surgery, and radiation remain the mainstay of treatment for early-stage disease. However, in locally advanced and advanced disease, there has been considerable evolution in the hormonal therapies. Suppression of testosterone production, the primary goal of hormonal therapy, may be accomplished with the use of estrogens, antiandrogens, and agonists and antagonists of luteinizing hormone-releasing hormone (LHRH). This article provides an overview of the primary hormonal therapies currently used in prostate cancer. Estrogen therapy was initially the predominant medical form of hormone manipulation and an alternative to orchiectomy. However, serious thrombogenic side effects were associated with its use, which decreased after the introduction of LHRH agonists in the 1980s. Many of the side effects occurring with oral estrogen therapy may be modulated by parenteral administration, and thus estrogen use is being revisited. LHRH agonists effectively reduce testosterone levels to castration levels (<50 ng/mL) within 2 to 4 weeks, although their use is associated with tumor flare. Antiandrogen monotherapy may offer quality-of-life benefits over treatment with androgen deprivation. The additive benefit of combined androgen blockade is yet to be determined. Recent evidence suggests that hormonal therapy may offer a survival benefit when initiated in earlier stages of prostate cancer. Future investigations will be directed to determining the most efficacious regimens.