Subcutaneous bioabsorbable pellets of norethindrone for contraception in women: Phase I. Clinical study

Ten healthy, normally menstruating female volunteers participated in a 1-year phase I clinical study in which subcutaneous pellet implants of norethindrone (NET) were employed as a low-dose and long-acting potential contraceptive. Two NET pellets were implanted subcutaneously by the aid of a trocar in the forearm of each volunteer on the fifth day after the start of menstrual bleeding. Serum levels of NET, follicle-stimulating hormone, luteinizing hormone, 17 beta-estradiol, and progesterone were determined weekly by radioimmunoassay. The daily NET release from the pellets, based on mean values (+/- standard error of the mean) in five subjects was 79.4 +/- 7.6 micrograms. The mean serum NET level was initially 1.0 +/- 0.34 ng/ml; thereafter, it gradually lowered during the 343 days of the study period to the level of 0.43 +/- 0.09 ng/ml. The ovarian response, days of bleeding, and cycle lengths with continuously sustained release of NET from the pellets were similar to those observed in women taking the daily oral "minipill" of 300 micrograms NET. The results of the phase I study suggest that NET pellet implants may provide a simple and acceptable approach to long-term contraception in women.