The Effect of an Aromatase Inhibitor, 4-Hydroxy-4-Androstene- 3,17-Dione, On Estrogen-Dependent Processes in Reproduction and Breast Cancer11

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Abstract
Four hydroxy-4-androstene-3-17-dione (4-OH-A) when tested at various concentrations inhibited markedly the conversion of 4-androstene-3,17-dione to estrogens in human placental and rat ovarian microsomes. To obtain evidence that estrogen biosynthesis could also be reduced in vivo with 4-OH-A, rats were treated s.c. at a dose level of 50 mg/kg body weight. After 3 h the ovarian veins were cannulated and blood collected. Estradiol concentrations in the plasma were reduced by 80% compared to control values during the proestrous surge and on day 4 of pregnancy. Also, 4-OH-A was effective in controlling estrogen-dependent reproductive and neoplastic processes. In rats treated from day 2-7 of pregnancy, implantation of fertilized ova was completely prevented in some rats, while in others either implantation was delayed or the development of implants was retarded. The 4-OH-A treatment of rats having estrogen-dependent breast tumors induced by 7,12-dimethylbenz(a)anthracene caused 80% of the tumors to regress significantly in 4 wk of treatment; 42% of these regressed completely.