contraceptives--postcoital and 17-beta-hydroxy-7-alpha-methyl-androst-5-en-3-one

RMI 12,936 (17 beta-hydroxy-7 alpha-methyl-5-androstene-3-one) exhibited postcoital contragestative activity at 10 mg/kg in hamsters. The endocrinological profile was determined for this steroid. This antifertility agent had significant antiprogestational, antiuterotrophic and gonadotropin-inhibiting activity. RMI 12,936 also exhibited weak uterotrophic and androgenic properties when given to immature gonadectomized rats. Hormonal antagonism and weak estrogen agonist properties would appear to contribute to the contragestative activity of RMI 12,936 in hamsters.

Topics: Androstenols; Animals; Contraceptives, Postcoital; Contraceptives, Postcoital, Synthetic; Cricetinae; Estradiol; Female; Genitalia, Female; Genitalia, Male; Gonadotropins; Male; Pregnancy; Progesterone; Rabbits; Random Allocation; Rats; Rats, Inbred Strains; Uterus; Vaginal Smears

A single sc injection of 1 mg 17-beta-hydroxy-7 alpha-methylandrost-5-en-3-one (RMI-12,936) given a few hours after mating interrupted pregnancy in all the treated rats. Circulating progesterone (delta 4P) levels were higher in RMI-12,936 treated females than in controls on the corresponding days during the course of termination of pregnancy. Higher levels of delta 4P were recorded on day-4 (P less than 0.01) and day-6 (P less than 0.05) of pregnancy. In addition to the changes in serum delta 4P, an acceleration of egg transport was encountered. The eggs were prematurely expelled from the uterus within 48 h of the treatment. Although the oestrous cycle of the RMI-12,935 treated females was disturbed, they were found sexually receptive. Successful matings resulting in normal gestation and morphologically normal foetuses were recorded 20-26 days after RMI-12,936 induced pregnancy termination. These results suggest that in addition to its mid-pregnancy terminating effect, RMI-12,936 is capable of interrupting early pregnancy when given soon after mating in the rat. The safety and efficacy of this compound as a post-coital contraceptive deserves further investigation.

Topics: Abortifacient Agents; Abortifacient Agents, Steroidal; Abortion, Induced; Androstenols; Animals; Contraceptives, Postcoital; Contraceptives, Postcoital, Synthetic; Estrus; Female; Pregnancy; Progesterone; Rats