Abstract
The contraceptive efficacy of norethindrone (NET) fused pellets was evaluated over 12 months in a Phase II clinical study with three and four pellets, each pellet containing 35 mg of NET. Volunteers were healthy, fertile, sexually active women. The release rate of NET from three and four pellets, respectively, was 150.3±7.2μg and 212.5±8.6μg NET/day. Following the implantation of NET pellets, serum NET levels did not show any ‘burst effect’ and were sustained at levels between 0.4 and 0.6 ng NET/ml serum with three pellets and 0.6–0.7 ng NET/ml serum with four pellets. With three and four pellets, respectively, 40% and 27% of the women had normal menstrual cycles; 20% and 14% were amenorrheic; 27% and 37% had mid-menstrual spotting or bleeding; and 13% and 22% had prolonged episodes of bleeding. Cardiovascular, hepatic, and renal functions were normal throughout the study. Ovulation was inhibited in 85% and 92% of the cycles with three and four pellets, respectively. In women using three pellets, two pregnancies occurred, one at the 6th cycle and another at the 12th cycle. In women using four pellets, no pregnancies occurred during the entire period of study.
Resumé
L'efficacité anticonceptionnelle des implantations de pellets à fusion de noréthindrone (NET) a été évaluée sur une période de 12 mois dans une étude clinique à II Phases avec trois et quatre pellets, chacun contenant 35 mg de NET. Les volontaires étaient des femmes saines, fertiles avec une activité sexuelle. Le taux d'émission de la NET provenant de trois et de quatre pellets respectivement était de 150,3±7,2μg et de 212,5±8,6μg de NET par jour. A la suite de l'implantation des pellets de NET, les niveaux sériques de NET n'ont pas montré un ‘effet d'éclatement’ et ont présenté un effet prolongé à des niveaux entre 0.4 et 0.6ng de NET/ml de sérum avec trois pellets et de 0,6 à 0,7 ng de NET/ml de sérum avec quatre pellets. Avec trois et quatre pellets respectivement, 40% et 27% des femmes présentaient des cycles menstruels normaux; 20% et 14% présentaient une aménorrhée; 27% et 37% avaient des tachetures ou pertes intermenstruelles et 13% et 22% avaient des périodes d'hémorragies prolongées. Les fonctions cardiovascualires, hépatiques et rénales ont été normales tout au long de l'étude. Il y a eu inhibition de l'ovulation dans 85% et 92% des cycles avec trois et quatre pellets respectivement. Chex les femmes utilisant trois pellets, il y a eu deux grossesses, l'une au 6ème cycle et l'autre au 12ème cycle. Chez les femmes utilisant quatre pellets, il n'y a eu aucune grossesse pendant toute la durée de l'étude.
Resumen
La eficacia anticonceptiva de los pellets fundidos de norethindrone (NET) fué evaluada durante 12 meses en la Fase II de un estudio clínico con tres y cuatro pellets de 35mg de NET por pellet. Las voluntarias eran mujeres sanas, fértiles y sexualmente activas. La tasa de liberación de NET para tres y cuatro pellets respectivamente, fué 150.3±7.2μg y 212.5±8.6μg NET/día. Luego de la implantación de los pellets NET, los niveles de suero NET no mostraron ningun ‘efecto explosivo’ y se mantuvieron a niveles entre 0.4–0.6ng NET/ml con tres pellets y 0.6–0.7ng NET/ml con cuatro pellets. Con tres y cuatro pellets respectivamente, 40% y 27% de los ciclos menstruales fueron normales; 20% y 14% fueron amenorreicos; 27% y 37% tuvieron manchado o sangrado en mitad del ciclo y 13% y 22% tuvieron episodios prolongados de sangrado. Las funciones cardiovascular, hepática y renal fueron normales durante todo el estudio. La ovulación fué inhibida en 85% y 92% de los ciclos con tres y cuatro pellets respectivamente. Con tres pellets hubo dos embarazos, uno en el 6° ciclo y otro en el 12° ciclo. Con cuatro pellets no hubo ningún embarazo durante el período total del estudio.
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Singh, M., Saxena, B.B., Landesman, R. et al. Contraceptive efficacy of bioabsorbable pellets of norethindrone (NET) as subcutaneous implants: Phase II clinical study. Adv Contracept 1, 131–149 (1985). https://doi.org/10.1007/BF01849794
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DOI: https://doi.org/10.1007/BF01849794