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To the Editor:
An underlying hypothesis in the study by Eisenberger et al. (Oct. 8 issue) (1) is that bilateral orchiectomy is equivalent to treatment with a gonadotropin-releasing hormone agonist (e.g., leuprolide or goserelin) in the management of advanced prostate cancer. This is probably not the case. Whereas the addition of an antiandrogen to a gonadotropin-releasing hormone agonist was beneficial in extending survival as compared with the agonist alone, a similar degree of benefit was not demonstrated when an antiandrogen was added to bilateral orchiectomy. The addition of an antiandrogen to a gonadotropin-releasing hormone agonist may address deficiencies intrinsic to this method of treatment and thus enhance its clinical effectiveness; bilateral orchiectomy does not have such shortcomings.
Specifically, in addition to the substantial surge of testosterone (and hence exacerbation of disease) that accompanies the initial administration of a gonadotropin-releasing hormone agonist in all patients, (2) there are manifestations of an inadequate gonadotropin reserve. One such manifestation is the "acute-on-chronic" phenomenon, whereby, after castration, subsequent injections of a gonadotropin-releasing hormone agonist may cause microsurges of both testosterone and luteinizing hormone, which can last from hours to days. (3) With depot formulations of gonadotropin-releasing hormone agonists, a small percentage of patients "escape" (4) a castrated state between scheduled injections, and a further small percentage of patients never have post-castration levels of testosterone. In all these circumstances, an antiandrogen would be expected to ameliorate the deficiency, with resulting clinical benefit.
Castration by bilateral orchiectomy is not associated with any of these deficiencies, and hence an antiandrogen would add little, if any, benefit, as shown by Eisenberger et al. (1) Thus, the conclusion of their study, that the benefit of combined androgen blockade is negligible, is perhaps true in the case of orchiectomy but may not be applicable to antiandrogen therapy combined with a gonadotropin-releasing hormone agonist.
Marc B. Garnick, M.D.
Beth Israel Deaconess Medical Center
Boston, MA 02215
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