Biodegradable norethindrone (NET:cholesterol) contraceptive implants: phase II-A: a clinical study in women

Safety, contraceptive efficacy and biodegradability of subdermal norethindrone (NET)-cholesterol implants (Anuelle) were investigated in 19 healthy, sexually active women. Mean serum NET levels in women with four and five pellets, containing 174 mg and 266.5 mg NET, showed a "burst-effect" of 3.17 and 3.71 ng/ml, respectively, within 24 h post implantation. Subsequently, for the four- and five-pellet groups, respectively, the levels declined from 0.75 to 0.40 ng/ml and 1.05 to 0.61 ng/ml during the months 12-15, from 0.40 to 0.11 ng/ml and 0.61 to 0.25 ng/ml up to month 36. The serum NET levels were undetectable at 36 months and beyond, indicating complete biodegradability of NET pellets. Serum E2 levels remained within normal limits (> 50 pg/ml), whereas serum P indicated anovulatory cycles in 78% of the four-pellet group and 99% of the five-pellet group. FSH and LH levels were subnormal and acyclic. Plasma lipids showed reduced total and LDL cholesterol and triglycerides. HDL cholesterol remained unchanged. Drug-related adverse effects were essentially limited to irregular bleeding. There were no pregnancies in either group.