Contraception with subdermal implants releasing levonorgestrel. A clinical and pharmacological study

Two methods for release of levonorgestrel from polydimethylsiloxane (Silastic) subdermal implants for contraception were studied. The first system consists of six 3 cm long Silastic capsules filled with levonorgestrel (NORPLANT). The second one consists of two 4 cm long rods made from Silastic and levonorgestrel, covered with thin Silastic tubing (NORPLANT-2). The contraceptive efficacy of NORPLANT implants was excellent during the four years of observation. That of NORPLANT-2 implants was very good during the first three years, but not acceptable during the fourth year. Both types of implants were well tolerated and the most common side effect experienced was bleeding disturbances such as irregular bleeding and periods of prolonged bleeding. The frequency of such disturbances decreased considerably after the first year of use. The plasma levels of levonorgestrel decreased throughout the study, and did not show any statistically significant difference between users of the two types of implants. The plasma levels of levonorgestrel in women who became pregnant did not differ from those in women who did not become pregnant. Levonorgestrel binds to sex hormone binding globulin (SHBG) with high affinity, and in the bound form is not biologically active. A "free levonorgestrel index" (FLI), i.e. the ratio of plasma level of levonorgestrel to SHBG capacity, was calculated. Women with NORPLANT had higher FLI than those with NORPLANT-2 and women who became pregnant had lower FLI than those who did not. It is suggested that NORPLANT-2 implants have a lower rate of release of levonorgestrel than NORPLANT implants. SHBG capacity, thyroid binding proteins and corticosteroid binding globulin decreased during treatment. Plasma total testosterone decreased during treatment, whereas free testosterone was unaltered. Thyroid function and plasma cortisol levels did not change during treatment. Treatment with phenytoin decreased the contraceptive effect. In a group of regularly menstruating women who had used NORPLANT-2 implants for more than three years, 40% showed anovulation, 20% luteinization of unruptured follicles and 40% apparent ovulation.