A comparative study of coagulation and fibrinolytic factors in users of etonogestrel and levonorgestrel implants showed no significant changes from baseline, with the exception of a modest increase in antithrombin III (ATIII)and a small decrease in factor VII activity, changes that might reduce coagulability. Lipid levels and liver function studies were not changed, with the exception of small elevations of bilirubin, with somewhat more observed in levonorgestrel users than etonogestrel users (259). Another study of hemostatic factors found modest decreases in many measurements, within the range of normal, and a modest reduction in the generation of thrombin in users of the etonogestrel implant (260). Taken together these studies provide considerable reassurance that the progestin implants do not increase thrombosis risk. With several million women now using the implants, there are no published studies linking either implant to venous thrombosis or myocardial infarction. Strokes were reported in users of Norplant™, but case reports do not allow calculation of whether risk is increased from baseline. Attempts to determine stroke risk of users compared to nonusers was inconclusive because so few stroke patients or controls were using the implant (261).
Postcoital use of sex steroids to prevent pregnancy began in the 1960s with high-dose estrogen taken daily for 5 days (262). This was replaced with the combination OC containing EE and levonorgestrel for greater convenience (263). More recently levonorgestrel alone became the method of choice after the World Health Organization showed its superiority in a large randomized trial with 1,998 women. The pregnancy rate was 3.2% with the EE/levonorgestrel method and only 1.1% with levonorgestrel alone (RR for pregnancy, 0.32; 95% CI, 0.18–0.70) for women treated within 72 hours of intercourse. Nausea and vomiting occurred much less frequently with levonorgestrel alone (23.1% vs. 50.5%, and 5.6% vs. 18.8%, respectively) (264). The efficacy of both methods declined as the time after intercourse increased. But even after 72 hours, the pregnancy rate with the levonorgestrel treatment was only 2.7% (Fig. 10.9) (265). A single dose of 1.5 mg levonorgestrel is just as effective as two doses of 0.75 mg, has no more side effects, and is more convenient for the patient. Both dosing regimens are FDA approved. Because levonorgestrel is almost as effective at 3 to 5 days after intercourse,
Figure 10.9 Emergency contraception: pregnancy rates by treatment group and time since unprotected coitus. LNG, levonorgestrel, 0.75 mg × 2. Yuzpe method is ethinyl estradiol, 0.100 mg plus levonorgestrel 0.50 mg × 2, 12 hours later. (From Randomized controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation. Lancet 1998;352:430 [modified from Table 3], with permission.) the World Health Organization recommends 1.5 mg of levonorgestrel as a single dose, given up to 120 hours after intercourse (266). Research suggests that the main mechanism of action is delay of ovulation. Noe and colleagues established that levonorgestrel works only if it is administered prior to the day of ovulation (267). No pregnancies occurred to 87 women who received levonorgestrel from 1 to 5 days prior to the day of ovulation. Seven pregnancies occurred to 35 women treated on the day of ovulation or later. Postcoital levonorgestrel is not an abortifacient because it is effective only when taken before ovulation.