Release of norethisterone from a bioabsorbable implant in female bonnet monkeys (Macaca radiata)

Bioabsorbable implants prepared by fusion of 85% norethisterone (NET) and 15% cholesterol were inserted subdermally in four cycling bonnet monkeys (Macaca radiata). No skin reaction or inflammation was observed at the site of implantation. Plasma concentration of norethisterone (NET) measured by radioimmunoassay were monitored for 14 to 16 months at monthly intervals. In the first month weekly samples were analysed. NET was released into circulation within 24 hours after insertion of the implant. In all the monkeys, except one, a sharp rise in NET (1.9 to 20 ng/ml) occurred immediately after insertion. Levels then remained between 1.7 and 0.6 ng/ml for about 4 months. Thereafter they remained steady up to about 9 months in two monkeys and gradually declined to about 0.4 ng/ml in the remaining two. In all except one, there was a sudden burst of NET release between the 10th and 11th month. The hormone almost cleared out of circulation by the 14th to 16th month. Initial menstrual cycles after pellet insertion were disturbed, leading to spotting and irregular bleeding. Regular cycles appeared from 5 to 8 months after the insertion of the implant. These cycles were ovulatory, as determined by the progesterone levels.