A patient is being treated for metastatic prostate cancer

A patient is being treated for metastatic prostate cancer. Which of the following agents is used parenterally in prostate cancer to reduce luteinizing hormone (LH) release from the pituitary even though it initially increases LH release?

(A) diethylstilbestrol
(B) finasteride
© flutamide
(D) ketoconazole
(E) leuprolide

Explanation:

(E) Leuprolide is a GnRH agonist that when given in pulsatile fashion stimulates pituitary LH release, but when given continuously, or in a depot preparation, suppresses LH release and reduces plasma testosterone levels to castration levels. Because it is a peptide, it must be given parenterally. It is used extensively in the
treatment of metastatic prostate cancer. Diethylstilbestrol (choice A) is an oral nonsteroidal synthetic estrogen that is now rarely used in the treatment of prostate cancer. Use of this agent produces undesirable feminization and is reserved for cases unresponsive to other agents. Finasteride (choice B) is an orally active inhibitor of the 5-alpha-reductase that converts testosterone to dihydrotestosterone in the prostate. Because conversion of testosterone to dihydrotestosterone is essential for the androgenic effects in the prostate, inhibition of the 5-alpha-reductase decreases the stimulation of the prostate. Unfortunately, the drug has limited efficacy in prostate malignancy. Finasteride is used for the treatment of benign prostatic hyperplasia because it produces a moderate decrease in prostate size and improvement in urinary flow. It is also used for the treatment of androgenic hair loss. Flutamide (choice C) is a nonsteroidal antiandrogen occasionally used in the treatment of prostate cancer that is unresponsive to leuprolide. It is active orally. Ketoconazole (choice D) is an oral antifungal agent that has the property of inhibiting the cytochrome P450 isoforms involved in steroid biosynthesis. It has been used in the treatment of prostate cancer with mixed results.