Prostate cancer and androgen deprivation: optimal castration? Prospects and developments

Prostate cancer (PCa) therapy has always been connected with the problem of what optimal male castration is and how to achieve and control it. Optimal medical castration should follow quite the same characteristics as surgical castration, then it should allow testosterone levels to be quickly and permanently reduced to levels ranging between 12 and 20 ng/dl. It should also be pointed out that using luteinizing hormone-releasing hormone (LHRH) agonists does not result in immediate castration; castration occurs 2-4 weeks after the first injection. Furthermore testosterone levels could also increase after subsequent injections if the depot formulation does not adequately cover the period between injections, as some LHRH receptors can remain free. This results in a new testosterone surge in conjunction with the following injections. Such episodes of increased testosterone levels in vicinity with injections are known as "miniflares". Yet, also persistently increased testosterone levels (> 50 ng/dl) might be shown, even under continuous treatment with LHRH analogues. Such increases are known as "late breakthrough escapes". A depot formulation of leuprolide acetate using a novel delivery system provides steady blood levels above the threshold of 0.1 mg/ml and completely suppresses pituitary gonadotropin secretion.