Structure, Pharmacology, Mechanism of Action & Effectiveness
The ENG implant is a single-rod, progestin-only contraceptive implant measuring 4 cm in length and 2 mm in diameter containing a total of 68 mg of progestin. The rod is composed of an ethylene vinyl acetate core that is embedded with ENG crystals. Surrounding this core is an additional (0.06 mm) ethylene vinyl acetate layer that controls the rate of hormone release.[10]
Pharmacokinetic studies show that the progestin is released initially at a rate of 60–70 µg/day. This decreases to 35–45 µg/day at the end of 1 year of use, 30–40 µg/day at the end of 2 years and 25–30 µg/day by the end of the third year. Bioavailability remains constant throughout the life of the device (95%), and there is no evidence to suggest accumulation over time. Half-life elimination time is approximately 25 h.[11] Previous literature suggests a serum ENG level of 90 pg/ml is required to maintain ovulation suppression.[12] After insertion, serum concentrations increase to levels associated with ovulation inhibition within 8 h. Maximum mean serum concentrations of approximately 800 pg/ml are reached by 4 days. At the end of the first year of use, ENG serum concentrations decline to approximately 196 and 156 pg/ml at the end of the third year (Figure 1).[13] These levels suggest the implant may be effective beyond the currently approved 3 years. ENG levels become undetectable within the first week following removal. There are several studies that suggest the serum concentration of ENG may be affected by body weight. Although plasma serum concentrations in obese implant users appear to be lower than their normal weight counterparts,[14] these lower levels do not appear to result in a higher rate of contraceptive failure in obese women compared with normal weight women.[15]
Figure 1.
Serum concentration of etonorgestrel (pg/ml) over time during 3 years of Nexplanon use. Reproduced with permission of Merck Sharp & Dohme B.V., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. All rights reserved.102
Through a continuous release of etonogestrel, the implant provides contraceptive protection through suppression of ovulation and thickening of the cervical mucus. Ovulatory suppression by the ENG implant was described in a study of 188 women within 20 months of ENG insertion. These women were evaluated for potential ovulation using serial ultrasound. Evidence of only one ovulation at 16 months was demonstrated.[16] A second smaller study of 16 women documented two ovulations: one at 30 months and the second at 33 months following insertion.[17] When ovulation does occur, the thickening of the cervical mucus enhances the overall effectiveness of the method.[2,16]
An analysis of 11 clinical trials evaluated 923 women contributing 22,888 cycles over the course of 3 years, and demonstrated no pregnancies while the ENG implant was in place. Six pregnancies occured during the first 14 days following the ENG implant removal. Any pregnancies occurring within 14 days after cessation of a hormonal contraceptive are considered method failures by the FDA. Even with these pregnancies included, the ENG implant failure rate is only 0.38 pregnancies per 100 women-years of use.[2,10] A Cochrane meta-analysis of clinical trials found no pregnancies with either the levonorgestrel system (Norplant) or the ENG implant in 45,000 women-months of use.[18] This indicates that the implant is as effective as permanent sterilization.[19]
Expert Rev of Obstet Gynecol. 2013;8(4):337-344. © 2013 Expert Reviews Ltd.
