Aromatase inhibitors—iv. Regression of hormone-dependent, mammary tumors in the rat with 4-acetoxy-4-androstene-3,17-dione

An aromatase (estrogen synthetase) inhibitor, 4-acetoxy-4-androstene-3,17-dione (4-acetoxy-A)‡, was effective in causing regression of DMBA (7,12-dimethylbenz(a)anthracene)-induced, hormone-dependent, mammary tumors in the rat. At a similar dose (15 mg/day), treatment was more effective when 4-acetoxy-A was administered by silastic wafer supplemented with injections than by injections alone. When 4-acetoxy-A was administered by wafers to 7 rats for 4 weeks, 64% of the tumors completely regressed. The mean ovarian estradiol secretion rate measured at the end of treatment with 4-acetoxy-A was reduced to 28% of the control value. Estrone and progesterone secretion rates were reduced but not significantly. Gonadotropin levels were unchanged. Tumor regression with 4-acetoxy-A was counteracted when estradiol-17β was administered concomitantly. The above finclings indicate that 4-acetoxy-A probably acts to cause tumor regression by reducing estrogen production via aromatase inhibition.