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  • Title: Sex hormone binding globulin and free levonorgestrel index in the first week after insertion of Norplant implants.
    Author: Alvarez F, Brache V, Tejada AS, Cochon L, Faundes A.
    Journal: Contraception; 1998 Oct; 58(4):211-4. PubMed ID: 9866001.
    Abstract:
    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. 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.
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