PHARMACOLOGY OF 18-METHYL-MESTRANOL

This paper reports the hormonal activity and the contraceptive action of 18-methylmestranol.In immature female mice, 18-methyl-mestranol was estrogenic as shown by the marked stimulation of uterine development. When compared with mestranol, its estrogenic potency was approximately 1/50. Given simultaneously with estradiol, 18-methylmestranol did not affect the uterine development induced by the estrogen, indicating that 18-methyl-mestranol had no anti-estrogenic action.In Clauberg test 18-methyl-mestranol did not stimulate the development of the rabbit endometrium but markedly inhibited the endometrium stimulating activity of norgestrel. Deciduomas in rats was provoked by injection of estrogen and norgestrel and by passing a thread through one uterine horn. Simultaneous administration of 18-methyl-mestranol with the norgestrel inhibited the development of the deciduoma. These results show that 18-methyl-mestranol possesses no progestational activity but is antiprogestogenic.Oral administration of 18-methyl-mestranol on the 1st, 2nd and 3rd day of gestation at the dosage of 1 mg/kg/day, completely prevented pregnancy in mice. When administered on the 6～8th day of gestation, 80～90% of the mice had their pregnancy interrupted. These experiments indicate that 18-methyl-mestranol is able to prevent implantation and interrupts early pregnancy.18-Methyl-mestranol was administered to mice on the 1st and 2nd day of gestation. On the 4th day of gestation, fertile eggs were seen in the oviduct in 4 out of 10 animals, while no egg was seen in the control group. Thus egg transport in the oviduct was slowed in the treated group, This slowing of egg transport might play a role inthe prevention of implantation.18-Methyl-mestranol was administered orally to mice at a daily dosage of 2 mg/kg for 14 days. No noticeable changes of body weight and morphology of the main viscera were observed. Dogs were given daily oral doses of 1 mg/kg for 14 days. At the end of this period, the blood picture, heart, SGPT and blood urea nitrogen were normal.