In the rat, pregnancy was affected by androstane derivatives (including three 9\g=a\-fluoro-4-androsten-3-one, 11-and 17-substituted), given orally in doses of 5 mg/100 g body weight from Days 3 to 10. Fluorohydroxyandrostenedione (FHA) and fluoxymesterone appeared to be 100% effective in suppressing fertility, while steroid U-6596 seriously disturbed gestation though not in all cases. Under similar experimental conditions, the abortifacient activity of FHA, fluoxymesterone and steroid U-6596 was respectively abolished, decreased or left unaltered after substitution of 9\g=a\-fluorine by hydrogen. The 5\ g=b\saturated homologues of FHA and fluoxymesterone, as well as 9\g=a\fluoro-17\g=a\-methyl-5\g=b\-androstane-3\g=a\,11\g=b\,17-triol, were totally ineffective in interrupting pregnancy. The relative antifertility potency of the fluorosteroids in rats roughly paralleled their uterotrophic activity in immature mice. Comparative studies showed that FHA (administered at the 5-mg dose level but from the 3rd to the 7th day of pregnancy) was more effective than the other two fluoroandrostenes tested. The abortifacient action of FHA was reduced when the dosage was decreased, the minimum 100% effective oral dose being 2\m=.\5 mg/100g body weight. In addition, this fluorosteroid also exerted some interceptive activity. Progesterone abolished the abortifacient effect of 2\m=.\5, but not of 5 mg, of FHA. Under identical conditions, prolactin had no such protective influence.
In rats, CS-1 (5 mg) totally prevents implantation when administered by mouth during the first 8 days post coitum, but has no influence on pregnancy if treatment is initiated after the 13th day of gestation. The antifertility effect of this compound is abolished by the simultaneous injection of progesterone or prolactin. CS-1 might depress the production of pituitary luteotrophic hormone, thereby interfering with the secretory function of the corpus luteum and diminishing the supply of progesterone below the level required to maintain pregnancy.
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