Anti-uterotrophic and folliculostatic activities of anordiol (2α, 17α-diethynyl -A-nor-5α-androstane-2β, 17β-diol)

The estrogenicity and antiestrogenlcity of the biologically active metabolite of the contraceptive anordrin was investigated for its actions on both the uterus and ovary. Anordiol (30 μg), administered s.c. to ovariectomized mice did not significantly increase wet weight, soluble protein content, or DNA content of uteri 72 hours after a single dose. By comparison, 3 μg of estradiol-17β under the same conditions significantly increased all three parameters of uterine growth. The increments in uterine wet weight, soluble protein content, and DNA content that were induced by estradiol-17β were reduced by 50, 71, and 81%, respectively, when 30 μg of anordiol was administered with estradiol-17β. A 60 μg dose of anordiol did not decrease further any of the three parameters. In further evaluation of the uterine response to anordiol an increase in uterine wet weight and soluble protein was observed with both 30 and 90 μg doses of anordiol at 12, 24, 36, and 48 hours, but not at 6 or 72 hr after a single s.c. injection. No significant increase in uterine DNA content was observed with either dose at any time. We conclude that anordiol in this assay is an antiestrogen with weak estrogenic activity. Anordiol was further tested to determine its effect on the estrous cycle of the rat. When given on the afternoon of the first day of diestrus in a dose of 0.8 mg/kg body weight in rats with 5-day estrous cycles, it caused an average lengthening of the cycle to 9.1 ± 2.1 (S.D.) days. Estradiol given at the same time of the estrous cycle in a dose of 0.024 mg/kg resulted in a shortening of the cycles of similar rats to 2.8 ± 0.4 (S.D.) days. When anordiol was given on the the afternoon of diestrus day 2 of rats with 5-day cycles or on diestrus day 1 of rats with 4-day cycles, no effect on the length of the estrous cycle was seen.