Subcutaneous implantation of pure crystalline estradiol pellets for conception control.

Objectives: Assessment of the contraceptive effectiveness of pure estradiol pellets implanted annually under the skin, thus avoiding the 'first passage phenomenon' through the liver, using a modification of Emperaire and Greenblatt's method.
Study Design: 228 women wishing birth control for 1 year or more were included. 5 pellets of estradiol (25 mg each) were implanted initially. At each subsequent annual treatment, 4 pellets were implanted. Withdrawal bleeding was induced monthly with oral norethindrone acetate 5 mg taken for 7 days. Our experience encompassed 8,136 cycles, or 678 women years. The study obtained approval of the local Ethical Committee.
Results: Annual continuation rates were 51 per 100 women in the second year, 65 in the third, 72 in the fourth and 84 +/- 10.1 annually over the next 6 years. Through 12 years of our study, 2 accidental pregnancies occurred. The annual net cumulative pregnancy rates were 0.44 and 0.48 per 100 women at 1 and 2 years, and reduced to 0.29 at the end of 10 years. Return of fecundity after discontinuing treatment was 53% after 12 months, 81% after 24 months and 89% after 36 months. The mean estradiol levels were 1,413 +/- 161 pmol/l one week following the pellet installation. The mean serum estradiol level of the 43 women who were assayed arbitrarily or a year following last insertion was 1,207 pmol/l (range 462-2,904 pmol/l); 22% had serum estradiol levels <1,000 pmol/l and 6.3% (3 women) had levels >1,750 pmol/l. A total of 28 endometrial biopsies were obtained -19 were proliferative, 6 showed slight simple hyperplasia, and three, benign cystic glandular hyperplasia.
Conclusion: Subcutaneous implantation of pure estradiol pellets offers excellent birth control, has minimal untoward effects, is simple to insert and can serve as a possible alternative for conception control. It could be considered for 3 indications: for women who have completed family planning; for women in older age group (above 35 years) who are approaching the climacteric; and for women at any age, who need prolonged periods of contraception.