Phase I comparative clinical trial with subdermal implants--bioabsorbable levonorgestrel or norethisterone pellet fused with cholesterol.

The potential for antifertility effect of two bioabsorable pellets, one containing norethisterone (NET) and the other containing levonorgestrel (LNG) fused with cholesterol, was studied in a group of healthy, menstruating but sterilised women. The pellets weighed approximately 30 mg and contain 85% steroid and 15% cholesterol. A single NET pellet was inserted in 4 subjects, out of which 2 were also studied for steroid pattern in blood. After reaching peak levels within 48 hours, the plasma NET levels declined gradually within a fortnight's time, and thereafter, ranged between 200 to 700 mg/ml up to 90 days post-insertion. After this period, occassional spurts of NET release were seen. Bleeding pattern was studied in 37 cycles; mid-luteal progesterone (P) estimation was done in 16 cycles, mid-cycle cervical mucus was studied in 27 cycles and post-coital test (PCT) in 7 cycles. Cycle length with pellet insertion was of 25 to 37 days duration except one cycle of 55 days duration. All cycles studied during the treatment were ovulatory (P greater than 5 ng/ml) and no consistent effect was observed on cervical mucus as well as on PCT. Thus, a single NET pellet does not seem to have a reliable contraceptive potential. A single LNG pellet was inserted in 8 subjects, and steroid patterns were studied in 6 women. Peak levels of LNG were reached within 24 hours of pellet insertion and the levels fell gradually in a week's time. Thereafter, LNG levels ranged between 100-400 pg/ml up to 8 months. In contrast to the observation with NET pellets, only one subject showed frequent spurts of LNG release until the 4th month of treatment. Bleeding pattern was studied in 90 cycles, P was estimated in 52 cycles, mid-cycle cervical mucus studied in 55 cycles and PCT done in 26 cycles. Breakthrough bleeding (BTB) occurred on 15 occasions, 11 episodes being in 2 subjects. Cycle length varied between 21 to 42 days. The LNG pellet did not exert a consistent effect either on ovulation inhibition or cervical mucus or PCT. In their present form, therefore, a single LNG pellet also does not appear to have a reliable contraceptive effect.