A comparative evaluation of the safety and contraceptive effectiveness of 65 mg and 100 mg of 90-day norethindrone (NET) injectable microspheres: a multicenter study.

The first of a second generation of slow-release injectable contraceptives is the norethindrone (NET) microspheres with a 90-day duration of action. It was evaluated at 65-mg and 100-mg doses for safety and contraceptive effectiveness in two randomized, single-blind trials among 131 women: 94 women for 12 months and 37 women for 6 months. The 6-month trial included additional evaluations of ovarian function and serum NET values. In the 6-month trial, no indication of ovulation was detected in the 100-mg dose group, while 3 of the 19 women in the 65-mg group showed signs of ovulation (progesterone greater than 3 ng/ml). No pregnancies were reported in the 100-mg group and one pregnancy in the 65-mg group resulted in a life-table pregnancy rate for that dose of 2.6 per 100 woman-years (95% confidence interval, 0 to 7.5). Days of vaginal bleeding were analyzed for 30 days before treatment and in 90-day reference periods after treatment. The mean number of vaginal bleeding and spotting days increased initially after the first injection in both dose groups, but decreased to below baseline in both dose groups after 6 months. The two doses appear comparable in clinical safety, side effects, vaginal bleeding patterns, and laboratory measures. With the preliminary estimate of efficacy, the 65-mg dose would be the minimally effective dose for the NET 90-day injectable contraceptive.