Norethisterone contraceptive microspheres
Rivera, R.; Alvarado, G.; Flores, C.; Aldaba, S.; Hernandez, A.
Journal of Steroid Biochemistry 27(4-6): 1003-1007
1987
ISSN/ISBN: 0022-4731 PMID: 3695501 DOI: 10.1016/0022-4731(87)90181-6Document Number: 380976
At the Institute of Scientific Investigation of Juarez University of Durango State in Mexico, clinical researchers compared three delivery systems of norethisterone (NET) contraceptive microspheres (biodegradable polymers [e.g., polyglycolic or polylactic acid] containing micronized crystals of NET). In the 6-month system, they injected 800 mg of microspheres containing 200 mg NET intramuscularly into 19 women and then monitored the women for various effects and side effects. Soon after injection, the mean NET level in serum rose to a peak value of about 3 ng/ml and then fell gradually until it was below 0.5 ng/ml at 25 weeks. No pregnancies occurred during this period. Estradiol levels remained well below 100 pg/ml, suggesting inhibition of follicular activity. However, one patient showed an elevation in estradiol at week 16. By 24 weeks, 4 of the 19 women showed signs of the return of follicular activity. Rises in progesterone levels, indicative of ovulation, were not seen in most women during the 6-month period. However, 4 women showed progesterone peaks followed by menstruation in weeks 4, 7, 17, and 23, suggesting that their cycles had begun to return before the end of the 6-month period. 35% of women reported dizziness and nausea. 26% reported nausea. A more serious concern was the disruption seen in the menstrual pattern. 13 women had bleeding and spotting, which continued for 8-30 days in 8 women. In the 3-month system, microspheres containing either 75 or 100 mg NET were injected, each into 5 women. NET levels rose to between 1 and 2 ng/ml and fell to 0.5 ng/ml by week 15. At week 25, they were undetectable. Levels of estradiol remained low for at least 15 weeks as did serum progesterone. No pregnancies occurred. One woman ovulated in week 17. Although no headache, dizziness, and nausea were reported, many of the same disruptions in the menstrual cycle reported in the 6-month study were observed, particularly prolonged cycles, amenorrhea, and spotting. Based on these findings, the researchers deemed the 100 mg for 3 months to be the most safe and effective formulation.