Delay of ovulation due to diets containing levonorgestrel in cynomolgus monkeys (Macaca fascicularis).

This study was undertaken to develop a simple and practical method to control the time of ovulation in cynomolgus monkeys. Diets containing a synthetic gestagen, levonorgestrel (LNG) were given daily to normally cycling female monkeys for 2 weeks, and plasma concentrations of estradiol-17β and progesterone were determined by EIA in order to estimate the time of ovulation. Doses of LNG (0, 3.2, 8, 20, 50, or 125 μg) were given from Day 2 (Day 0 =the first day of menstruation) through Day 15. The numbers of days from the last administration of LNG to the estimated ovulation in the groups treated with LNG at 20 μg and above were significantly greater than those in the controls, and the values in the group treated with LNG at 50 μg were within a narrow range. In a second experiment, LNG was administered at 50 μg in different phases of the menstrual cycle (Days 9-22, 16-29, and 23-36), and the results indicated that ovulation occurred more than 12 days after the last administration in all monkeys, and the number of days from the last administration of LNG to the estimated ovulation in the group treated on Days 16-29 (luteal phase) was significantly greater than that in the group treated on Days 23-36. These results indicate that daily provision of a diet containing 50 μg LNG could be applicable for delaying ovulation, and suggest that the total level of (exogenous and endogenous) progestins is critical for determining the length of ovulation delay in cynomolgus monkeys.