Optimal testosterone concentration for the treatment of prostatic cancer

In order to determine the effects of the absolute concentration of circulating androgens on normal and malignant androgen dependent tissue, normal adult male rats and rats bearing the Dunning R3327H prostatic adenocarcinoma were castrated and implanted with testosterone filled silastic pellets of 1, 3, 5, 10, 20 and 30 mm. designed to release constant amounts of testosterone, or placebo pellets. After 1 month the weights of the ventral prostate and seminal vesicles, serum testosterone and luteinizing hormone levels and the sexual activity of the normal rats were determined. The volume of the prostatic tumor was determined twice weekly for 9 weeks. Serum testosterone increased directly with the length of the implant (r = 0.986). Ventral prostate and seminal vesicle weight increased with increasing serum testosterone (r = 0.984 and r = 0.975 respectively). Changes in prostatic tumor volume did not vary with increasing serum testosterone concentration. In animals with implants of greater than 5 mm. (sig. greater than than castrate value) tumor volume increased markedly and similarly over castrate controls at 9 weeks. Animals with implants of less than or = 5 mm. had tumor volume changes identical to the castrate controls. Sexual activity was relatively normal in animals with implants of greater than 3 mm. A threshold of serum testosterone exists below which the Dunning R3327H tumor is inhibited from growing. This level is higher than the castrate level but is compatible with relatively normal sexual activity. Were there methods to determine the threshold of human tumors, therapy might be individualized to minimize side effects such as the loss of sexual activity.