Etonogestrel contraceptive implant
- Philip D Darney, MD, MSc
Philip D Darney, MD, MSc
- University of California, San Francisco
The etonogestrel implant is a single-rod progestin contraceptive placed subdermally in the inner upper arm for long-acting (three years) reversible contraception in women (figure 1). It was originally marketed under the brand name Implanon, but was subsequently modified and marketed as Nexplanon (figure 2). Implanon and Nexplanon are bioequivalent.
Accumulating evidence supports the safety, efficacy, and acceptability of this contraceptive method [1,2]. In 2009, 0.8 percent of current contraceptors used an etonogestrel implant, up from 0.4 percent in 2002 . Contraception is the only approved indication for the etonogestrel implant, although it has been studied for use in progestin-responsive disorders, such as endometriosis .
STRUCTURE AND PHARMACOKINETICS
The implant consists of a 40 mm by 2 mm semi-rigid plastic (ethylene vinyl acetate) rod containing 68 mg of the progestin etonogestrel (the 3-keto derivative of desogestrel). Etonogestrel is slowly released over at least three years (figure 3), initially at 60 to 70 mcg/day, decreasing to 35 to 45 mcg/day at the end of the first year, to 30 to 40 mcg/day at the end of the second year, and then to 25 to 30 mcg/day at the end of the third year .
Unlike Implanon, the Nexplanon rod is radio-opaque so it can be detected by x-ray and thus does not require magnetic resonance imaging (MRI) for locating an impalpable implant. In addition, the redesigned applicator makes subdermal insertion easier and failed insertion unlikely because the new cap will not open if the implant is not in the needle and a finger pressure activated lever ensures that the trocar completely discharges the contraceptive implant under the skin.
MECHANISM FOR CONTRACEPTION
Progestins cause changes in cervical mucus and tubal motility that are unfavorable to sperm migration, thus inhibiting fertilization. At high doses, progestins also inhibit gonadotropin secretion, thereby inhibiting follicular maturation and ovulation. This dual effect allows contraceptive efficacy to be maintained even though ovulation is not consistently inhibited in implant users toward the end of the three-year period of use. Although progestins suppress endometrial activity, which makes the endometrium unreceptive to implantation, this is less important since the major mechanisms of contraceptive action prevent fertilization.
- Tocce KM, Sheeder JL, Teal SB. Rapid repeat pregnancy in adolescents: do immediate postpartum contraceptive implants make a difference? Am J Obstet Gynecol 2012; 206:481.e1.
- Winner B, Peipert JF, Zhao Q, et al. Effectiveness of long-acting reversible contraception. N Engl J Med 2012; 366:1998.
- Finer LB, Jerman J, Kavanaugh ML. Changes in use of long-acting contraceptive methods in the United States, 2007-2009. Fertil Steril 2012; 98:893.
- Walch K, Unfried G, Huber J, et al. Implanon versus medroxyprogesterone acetate: effects on pain scores in patients with symptomatic endometriosis--a pilot study. Contraception 2009; 79:29.
- Wenzl R, van Beek A, Schnabel P, Huber J. Pharmacokinetics of etonogestrel released from the contraceptive implant Implanon. Contraception 1998; 58:283.
- Cardiovascular disease and use of oral and injectable progestogen-only contraceptives and combined injectable contraceptives. Results of an international, multicenter, case-control study. World Health Organization Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Contraception 1998; 57:315.
- Heinemann LA, Assmann A, DoMinh T, Garbe E. Oral progestogen-only contraceptives and cardiovascular risk: results from the Transnational Study on Oral Contraceptives and the Health of Young Women. Eur J Contracept Reprod Health Care 1999; 4:67.
- Gomes MP, Deitcher SR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med 2004; 164:1965.
- Darney P, Patel A, Rosen K, et al. Safety and efficacy of a single-rod etonogestrel implant (Implanon): results from 11 international clinical trials. Fertil Steril 2009; 91:1646.
- ACOG Committee on Practice Bulletins-Gynecology. ACOG practice bulletin. No. 73: Use of hormonal contraception in women with coexisting medical conditions. Obstet Gynecol 2006; 107:1453.
- Lidegaard Ø, Løkkegaard E, Jensen A, et al. Thrombotic stroke and myocardial infarction with hormonal contraception. N Engl J Med 2012; 366:2257.
- Hennessy S, Berlin JA, Kinman JL, et al. Risk of venous thromboembolism from oral contraceptives containing gestodene and desogestrel versus levonorgestrel: a meta-analysis and formal sensitivity analysis. Contraception 2001; 64:125.
- Bouquier J, Fulda V, Bats AS, et al. A life-threatening ectopic pregnancy with etonogestrel implant. Contraception 2012; 85:215.
- Leticee N, Viard JP, Yamgnane A, et al. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception 2012; 85:425.
- Suherman SK, Affandi B, Korver T. The effects of Implanon on lipid metabolism in comparison with Norplant. Contraception 1999; 60:281.
- Levine JP, Sinofsky FE, Christ MF, Implanon US Study Group. Assessment of Implanon insertion and removal. Contraception 2008; 78:409.
- US Selected Practice Recommendations for Contraceptive Use, 2013. http://www.cdc.gov/mmwr/pdf/rr/rr62e0614.pdf. (Accessed on June 14, 2013).
- Mascarenhas L. Insertion and removal of Implanon: practical considerations. Eur J Contracept Reprod Health Care 2000; 5 Suppl 2:29.
- Bensouda-Grimaldi L, Jonville-Béra AP, Beau-Salinas F, et al. [Insertion problems, removal problems, and contraception failures with Implanon]. Gynecol Obstet Fertil 2005; 33:986.
- Ismail H, Mansour D, Singh M. Migration of Implanon. J Fam Plann Reprod Health Care 2006; 32:157.
- Wechselberger G, Wolfram D, Pülzl P, et al. Nerve injury caused by removal of an implantable hormonal contraceptive. Am J Obstet Gynecol 2006; 195:323.
- Singh M, Mansour D, Richardson D. Location and removal of non-palpable Implanon implants with the aid of ultrasound guidance. J Fam Plann Reprod Health Care 2006; 32:153.
- James P, Trenery J. Ultrasound localisation and removal of non-palpable Implanon implants. Aust N Z J Obstet Gynaecol 2006; 46:225.
- Shulman LP, Gabriel H. Management and localization strategies for the nonpalpable Implanon rod. Contraception 2006; 73:325.
- STRUCTURE AND PHARMACOKINETICS
- MECHANISM FOR CONTRACEPTION
- General population
- Overweight and obese women
- Drug interactions
- SIDE EFFECTS AND ADVERSE EVENTS
- Preinsertion examination and testing
- - Back-up contraception
- Position the patient
- Administer anesthesia
- Verify placement
- Post insertion care and follow-up
- Complications related to insertion
- REMOVAL AND RETURN OF OVULATION
- Difficult removals
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS