Abstract: | 6 healthy women aged 25-38 years, attending a family planning clinic in the Dominican Republic, participated in an experiment to determine blood levels of levonorgestrel (1Ng) resulting from daily vaginal placement of contraceptive pills containing .5 mg dl-norgestrel and .05 mg ethinyl estradiol and to evaluate the effect on ovulation. Subjects were observed for 3 cycles. Blood samples were taken on days 14, 18, 23 and 27 following the 1st day of menses on a pretreatment cycle. In 1 cycle the pill was taken daily for 21 days by the oral route, and in another it was placed in the vagina on the same schedule. Blood samples were taken frequently during the 1st 24 hours and subsequently on days 5, 8, 12, 15, 18, and 21 of experimental cycles. Plasma levels of 1Ng reached a peak of 3-4 ng/ml 1-4 hours after oral administation of dl-norgestrel and fell slowly thereafter to a level slightly over 1 ng at 24 hours after ingestion. Plasma concentrations of 1Ng rose at a slower rate and reached a lower peak value after vaginal placement. After 4 hours the 2 curves were approximately parallel. The mean 1Ng plasma concentration 24 hours after vaginal insertion was less than 1/2 the value after oral administration. The differences in plasma levels were statistically significant for each of the times studied. Differences were most pronounced in the 1st 2 weeks. In each pretreatment cycle, progesterone levels reached a peak above 4 ng/ml, indicating ovulation. All but 1 treatment cycle by either route had progesterone values suggesting anovulation; the exception was a vaginal administration cycle. 4 of the 6 women maintained low estradiol levels, mostly between 20-40 pg/ml, during treatment cycles by either route. The lower plasma levels of 1Ng after vaginal insertion of pills may reflect inefficient absorption of steroids within the vagina, or a difference in metabolic degradation when the drug is administered parenterally via the vaginal blood supply. It was still possible to suppress ovulation in 5 of the 6 vaginal cycles without attempting to adjust the dose. |