The synthetic gonadotropin releasing hormone agonist [D-leu6, desgly-NH210, proethylamide9]-GnRH (leuprolide) was tested for its ability to inhibit androgen-sensitive R3327-G rat prostatic tumor growth in Copenhagen x Fischer F1 male rats. The chronic administration of leuprolide at 50 μg. per kg. body weight or 1000 μg. per kg. body weight significantly reduced serum testosterone levels and testis weights. Only chronic leuprolide administration at high concentration (100 μg. per kg.) compared with orchiectomy in reducing the rate of tumor growth, prolonging survival, and affecting changes in DNA content per cell as quantitated by flow cytometry. The DNA content changes and cell kinetic responses of R3327-G tumors to these treatments were related to the extent to which serum testosterone levels were reduced. The data suggest that for some prostatic cancers gonadotropin releasing hormone agonist administration must reduce serum testosterone levels to those achieved by orchiectomy for maximal growth rate inhibition.
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