EFFECT OF NORETHANDROLONE ON 17-KETOSTEROID EXCRETION IN PROSTATIC CANCER PATIENTS

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Abstract
Norethandrolone (19-nortestosterone, 17α-ethyl) was administered to 5 men with histologically proven, actively progressing, disseminated prostatic cancer, after individual daily levels of urinary 17-ketosteroid excretion had been established. Each patient received 100 mg. of norethandrolone daily for periods varying from one to three months. The 17-ketosteroid determinations were repeated at intervals of three to four weeks. Norethandrolone provided palliation in 4 of the 5 patients, consisting chiefly of relief of pain, improved appetite, and significant gain in weight. No objective changes were noted in prostatic size and induration, in the number and size of osseous metastases, or in the levels of serum acid and alkaline phosphatase. As contrasted with the usual effect of testosterone, the administration of norethandrolone was consistently followed by significant reductions in urinary total neutral 17-ketosteroids. This response was observed in the 3 patients who hadpreviously been castrated as well as in the 2 who had not been castrated. The decrease affected all of the less polar 17-ketosteroids uniformly (androsterone, dehydroepiandrosterone and etiocholanolone). No consistent changes were noted in the levels of 11-keto-or 11β-hydroxysteroids. The results of this study tend to confirm earlier observations that the presence of an alkyl function at the 17-position interferes with the formation of 17-ketosteroids, perhaps by preventing the complete conversion of testosterone to 4-androstene,3,17-dione, or by interfering with the production of dehydroepiandrosterone. Supplementary animal experiments have also shown that norethandrolone partially inhibits the full effects of administered testosterone on the prostate of both intact and castrated male rats. In view of the fact that norethandrolone exerted no apparent effect on the course of the prostatic cancer in the presence of significant reductions in the excretory levels of androgenic 17-ketosteroids, it seems difficult to accept the hypothesis held by a number of investigators that androgenic 17-ketosteroid values constitute an index of prostatic cancer activity.