Treatment of rhesus monkeys (Macaca mulatta) with intravaginal rings loaded with levonorgestrel.

The effects of levonorgestrel-releasing intravaginal rings were investigated in 15 rhesus monkeys for 52 weeks. The intravaginal rings were designed to provide a sustained release of either three or ten times the human dose level of the hormone. Untreated placebo rings were used as a control. The devices were well retained. After insertion of the vaginal rings, a dose-related decrease in vaginal bleeding was observed. The vaginal microbial flora were assessed qualitatively and semi-quantitatively and although all groups including controls showed some changes in microbial populations, by the end of the study nearly all animals returned to a normal balanced microflora. Terminal studies showed that, at the high dose level, ovulation was suppressed and widespread atrophy of the uterine mucosal and glandular epithelium had occurred. A dose-related increase in mucus within the lumen of the endocervical canal was observed. Focal or diffuse atrophy of the vaginal mucosal epithelium was seen in the majority of levonorgestrel-treated animals.