Clinical trial with Nestorone ™ subdermal contraceptive implants

Abstract

The clinical performance and the in vivo release rate of a single 4-cm Nestorone ™ 1 1 Nestorone ™ is the Population Council trademark for 16-methylene-17-alpha-acetoxy-19 norprogesterone, previously known as ST 1435. subdermal implant were investigated. Implants manufactured by two different procedures were compared. Volunteers were 70 healthy women of proven fertility. Forty women provided blood samples twice a week in the pretreatment cycle and for 5–6 weeks at 6-month intervals during treatment. Additional control cycles (n = 31) were studied in 19 Copper T users. No pregnancy occurred in 1570 woman-months. Nesterone ™ plasma levels (X ± S.E.) declined from 112 ± 8 to 86 ± 3 pmol/L (Implant A) and from 145 ± 8 to 57 ± 5 pmol/L (Implant B) from the first to the 24th month. Progesterone levels were <9.5 nmol/L in 166 (93%) of 178 blood samplings taken during treatment. Progesterone levels >16 nmol/L were found in only 7 sampling periods (3.9%) in treated women and in 70 (98.6%) out of 71 control cycles. No ovulation occurred with Nestorone ™ plasma levels above 105 pmol/L. No abnormal changes were observed in plasma lipoproteins or other clinical chemistry parameters during treatment. The implants were well tolerated. The most frequent complaint was the occurrence of irregular bleeding. Enlarged follicles found during pelvic examination in 8 subjects (11.4%) disappeared spontaneously in 10 days to 6 weeks. Implants were removed because of medical (n = 10, 14.3%) or personal reasons (n = 6, 8.6%) or at the 24th month of treatment (n = 54, 77.1%). The estimated average daily in vivo release rate of Nestorone ™ was 45–50 μg/day. A single Nestorone ™ subdermal implant affords efficient contraceptive protection during two years.