Antifertility effects of an aromatase inhibitor, 1,4,6-androstatriene-3, 17-dione.

1,4,6-Androstatriene-3,17-dione (ATD), previously reported by us to be an aromatase (estrogen synthetase) inhibitor, was found effective in inhibiting mating and ovulation in the rat. Mating did not occur for as long as treatment was continued (up to 13 days) in 68% of the rats. In the remainder, mating and ovulation were delayed for at least 4 days past the expected day of proestrus and for an average of 5.8 days. Five animals which had been treated for 6 days mated 2 days after treatment was discontinued and all were pregnant at autopsy on day 8 of pregnancy. In contrast, when treatment was continued after mating, implantation sites were absent when the animals were examined on day 8 of pregnancy, indicating ATD may also be effective postcoitally. ATD had no significant hormonal activity in bioassay but prevented the rise in ovarian estradiol secretion on the afternoon of proestrus. Estradiol benzoate counteracted the effect of ATD when administered concomitantly, so that mating occurred at the normal time in all eight rats and ovulation occurred in six of the eight rats. The above results suggest that the aromatase inhibitor, ATD, may act in vivo to inhibit fertility by inhibition of estrogen biosynthesis.