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Luteinising hormone-releasing hormone antagonists in prostate cancer therapy

The introduction of androgen blockade therapy using luteinising hormone-releasing hormone (LHRH)/gonadotropin-releasing hormone analogues alone or in combination with non-steroidal antiandrogens has a major impact in both survival and quality of life of patients with locally advanced and metastatic prostate cancer. The effect of LHRH agonists is based on the continuous binding to the LHRH receptor (LHRH-R) on the gonadotrope cells of the pituitary, which although initially stimulate LH release, consequently downregulates the LHRH-R, thereby suppressing serum LH, testosterone levels and 5α-dihydrotestosterone levels. Because this initial surge of LH and testosterone can cause adverse consequences in these patients (the so-called flare-up symptoms), immediate inhibition of LH release and testosterone production is desirable and this can be achieved with the use of the LHRH antagonists. In addition, there exist data to support a direct anticancer effect of LHRH antagonists on prostate cancer cells. This review summarises the potential clinical use of the LHRH antagonists in prostate cancer patients.