Clinical assessment of subdermal implants of megestrol acetate, d-norgestrel, and norethindrone as a longterm contraceptive in women

Megestrol acetate (MA), d-norgestrel (d-Ng), and norethindrone (NET) contained in Silastic capsules were implanted under the skin for clinical evaluation as a longterm contraceptive in women. 1509 woman-months of exposure and 4 pregnancies were recorded within the first twelve months of use in 135 women who received 6 MA implants. 1049 woman-months and 19 pregnancies were recorded within the first twelve months of use in 131 women who received 4 d-Ng implants. After twelve months use, the implants were replaced with a new set of capsules. The contraceptive effectiveness of the second and subsequent set of implants was similar to that of the first. Five NET implants failed completely to prevent pregnancy and 4 MA implants combined with 2 d-Ng implants were as effective as 6 MA implants. Other doses tested were: 5 MA, 3 d-Ng, and 4 MA plus 1 d-Ng. They were significantly less effective than the higher doses. No adverse effect upon the outcome of unplanned pregnancies was noted and prompt recovery of fertility was observed after termination of treatment. Ovulation took place in most cycles of women treated with 5 or 6 MA implants, as judged from the occurrence of LH peak in urine, pregnanediol excretion, changes of cervical mucus, BBT, and endometrial biopsy. Intermenstrual bleeding was by far the most common side effect recorded. Initially, it occurred in about 30 % of the cycles, but the incidence decreased gradually and by the end of the second year, it was below 10 %. Adnexal complications were observed in some of the treatment groups.