Levonorgestrel has an inhibitory effect on sex hormone binding globulin (SHBG). This decrease in SHBG leads to an increase in the free levonorgestrel index (FLI), which has a stronger biological effect. The interaction between serum levels of levonorgestrel and SHBG in long-term users of Norplant implants has been described. This study was designed to understand the same interaction immediately after the insertion of the implants, in a group of 16 women, sampled at 0 and 6 h and at 1, 3, and 7 days after Norplant implant insertion. Peak serum levonorgestrel levels were achieved at 24 h after insertion, remaining stable on day 3 and decreasing by > 10% by day 7. SHBG did not change during the first 24 h, but decreased by 19% and 60% on days 3 and 7, respectively. FLI more than doubled from day 1 to day 7 after insertion. The large decrease in SHBG and doubling of FLI is not followed by a similar reduction in levonorgestrel, which is hard to explain without an increase in the release rate of the steroid from the capsule.
PIP: It has been documented that levonorgestrel (LNG) administration by any route induces a significant reduction in circulating levels of sex hormone binding globulin (SHBG), which, in turn, leads to an increase in the free LNG index (FLI). A previous study found a pronounced reduction in SHBG levels as early as 7 days after insertion of the LNG-releasing Norplant contraceptive implants. The present study investigated the same interaction 1-7 days after Norplant insertion in 16 women recruited from a family planning clinic in Santo Domingo, Dominican Republic. Mean SHBG level at insertion was 75.9 nmol/l and was essentially unchanged 24 hours later. On postinsertion day 3, however, a 19% reduction over baseline was recorded. This decrease in SHBG was even more marked between days 3 and 7. By day 7, the mean SHBG serum level was only 40% of that found at the time of implant insertion. 6 hours after implant insertion, LNG levels were already above 700 pg/ml and peaked at over 1000 pg/ml at 24 hours, remained stable at this level until day 3, and then showed a moderate and nonsignificant decline of about 10%. The FLI was 5.1 at 24 hours postinsertion, remained at this level until day 3, and reached 11.9 by day 7. The lack of a significant reduction in LNG between postinsertion days 1 and 7 was unexpected given the 60% drop in SHBG and the doubling in the FLI. Two possible explanations for this finding are an increase in the amount of LNG entering the circulation or a large cross-reaction of the LNG assay with LNG metabolites in serum.