Levonorgestrel concentrations during 7 years of continuous use of Jadelle contraceptive implants.

Serum levonorgestrel concentrations were assayed in a multicenter, 7-year study of 199 users of Jadelle rod implants. We examined drug levels, patterns of changes, factors affecting drug levels, and concentrations at which pregnancies occurred. Mean levonorgestrel concentrations declined from 435 pg/mL at 1 month of use to 64% of that value (280 pg/mL) at the end of 3 years. Between the end of the third and fifth years neither mean nor median serum levels varied markedly. At 5 years the mean concentration was again 64% of the first month's mean. Declining levels were observed thereafter through the end of 7 years when the mean, 224 pg/mL, was 52% of the 1-month value. Last measured drug concentrations of women who became pregnant during Jadelle use had mean and median values of 152 and 144 pg/mL, respectively, and a maximum value of 180 pg/mL. Analyses indicated ponderal index, body weight, duration of use, and a single clinical center were the most important variables affecting measured levonorgestrel levels. Approximately one-third of assays in the sixth and seventh years were found to be below 180 pg/mL, suggesting that Jadelle levonorgestrel implants would not maintain sufficiently high levels of effectiveness against pregnancy after 5 years and that heavier women would then be at greater risk of pregnancy.

Clinical performance of a new two-rod levonorgestrel contraceptive implant: a three-year randomized study with Norplant implants as controls.

In a randomized three-year clinical trial at seven clinics, the performance of levonorgestrel rod (LNG ROD) implants used by 600 women was compared with that of soft tubing NORPLANT implants used by 598 women. No pregnancies occurred in either group of women and, accordingly, body weight did not affect the efficacy of either type of implant. There were neither statistically significant nor important differences in termination rates for any reason over the three years. Complaint and illness rates during use of either of the two implant types were statistically indistinguishable and were attributable to the same set of conditions. Seventy-one per 100 of the women using each implant regimen continued to the three-year point, for an average annual continuation rate of 89 per 100. Removals of LNG ROD implants were accomplished in about half the time required for removal of Norplant capsule implants (p < 0.001).

The performance of levonorgestrel rod and Norplant contraceptive implants: a 5 year randomized study.

A new contraceptive (LNG rod implants, Jadelle, Leiras Oy's registered trademark for rod implants) was prospectively evaluated in randomized 5 year comparison with Norplant (Population Council's registered trademark for contraceptive implants releasing levonorgestrel) capsule implants. The study involved 1198 women at seven centres. No pregnancies occurred in the first 4 years. At 5 years, the cumulative pregnancy rate was 1 per 100 users or less for each regimen. Annual discontinuation rates averaged 11-12 per 100 users (P > 0.05), corresponding to 5 year continuation rates of 55.1 for rods and 53.0 per 100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5 and 4.2 per 100 for rod and capsule implants respectively (P > 0.05), and mean annual removal rates for medical problems were 3.5 and 3.0 per 100 (P > 0.05) respectively. Apart from menstrual problems, headache, weight gain and acne were the principal medical reasons for removal. In proportional hazard analyses, family formation variables, age, parity and desire/non desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant (P < 0.01); complications of rod removal were at a lower rate. With these contraceptives indistinguishable in performance except for ease and speed of removal, LNG rod implants appear to be preferable to Norplant for use through 5 years by virtue of relative ease of removal.

PIP: This paper presents the 5-year randomized study on the performance of levonorgestrel rod (LNG) and Norplant contraceptive implants in 1198 women in 7 centers. In the first 4 years, no pregnancies occurred. At 5 years, the cumulative pregnancy rate was 1/100 users or less for each regimen. Annual discontinuation rates averaged 11-12/100 users, corresponding to a 5-year continuation rate of 55.1/100 for rods and 53.0/100 for capsules. Mean annual discontinuation rates for menstrual disturbances were 3.5/100 for rod and 4.2/100 for capsule implants. Reasons for discontinuation of use were vaginal spotting or bleeding, irregular bleeding, headache, weight gain and acne. Proportional hazard regression models established that family formation variables, age, parity, and desire for another child, recorded at admission, significantly affected discontinuation rates for major decrement categories and for all reasons combined. Mean rod removal time was half that of Norplant. Complications of rod removal were at a lower rate. This study concludes that there is an extremely high contraceptive effectiveness for LNG rod and Norplant implants; however, LNG rod implants were more preferable than Norplant for its relative ease in removal.