Comparison of various hormonal therapies for prostatic carcinoma.

The goals of hormonal therapy for prostatic cancer are to decrease circulating plasma testosterone to castration levels; prevent a rise in or reduce circulating prolactin; and block residual androgen at the cell level. Orchiectomy is very effective but does not prevent residual adrenal androgens from being converted to dihydrotestosterone (DHT); also, it has no effect on plasma prolactin. Estrogen has no known effect on androgen-receptor concentration or DHT binding to receptor and raises plasma prolactin. It also has significant side effects. Megestrol acetate, the only antiandrogen currently available for use in the United States, has been shown to block androgen from all sources. It produces a transient reduction in plasma testosterone to levels somewhat higher than those in castrated men, and it has no effect on plasma prolactin. When used in a dose of 120 mg/day in combination with 0.5 to 1.5 mg of estradiol per day, it acts synergistically to suppress pituitary gonadotropins and maintain plasma testosterone at castration levels for periods of up to 1 year. Newer therapies being studied include flutamide, a nonsteroidal antiandrogen, and luteinizing hormone-releasing hormone (LHRH). Data on these agents are limited and comparisons with standard therapies are needed.