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]. From 2011 to 2013, 0.8 percent of women using contraception used an etonogestrel implant, up from 0.3 percent from 2006 to 2010 . Contraception is the only approved indication for the etonogestrel implant, although it has been studied for use in progestin-responsive disorders, such as endometriosis .
This topic will review the etonogestrel contraceptive implant. Information on related contraceptive topics can be found separately. (See "Contraceptive counseling and selection" and "Overview of the use of estrogen-progestin contraceptives" and "Progestin-only pills (POPs) for contraception" and "Intrauterine contraception: Devices, candidates, and selection" and "Contraception: Overview of issues specific to adolescents" and "Postpartum and postabortion contraception".)
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 . Data from a prospective study indicate the mean etonogestrel serum concentration is maintained at a level to provide contraception at least through the fifth year of implant use .
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.
- 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.
- Branum AM, Jones J. Trends in long-acting reversible contraception use among U.S. women aged 15-44. NCHS Data Brief 2015; :1.
- 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.
- McNicholas C, Maddipati R, Zhao Q, et al. Use of the etonogestrel implant and levonorgestrel intrauterine device beyond the U.S. Food and Drug Administration-approved duration. Obstet Gynecol 2015; 125:599.
- 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.
- Abraham M, Zhao Q, Peipert JF. Young Age, Nulliparity, and Continuation of Long-Acting Reversible Contraceptive Methods. Obstet Gynecol 2015; 126:823.
- Steinauer JE, Upadhyay UD, Sokoloff A, et al. Choice of the levonorgestrel intrauterine device, etonogestrel implant or depot medroxyprogesterone acetate for contraception after aspiration abortion. Contraception 2015; 92:553.
- Morrell KM, Cremers S, Westhoff CL, Davis AR. Relationship between etonogestrel level and BMI in women using the contraceptive implant for more than 1 year. Contraception 2016; 93:263.
- Leticee N, Viard JP, Yamgnane A, et al. Contraceptive failure of etonogestrel implant in patients treated with antiretrovirals including efavirenz. Contraception 2012; 85:425.
- Vieira CS, Bahamondes MV, de Souza RM, et al. Effect of antiretroviral therapy including lopinavir/ritonavir or efavirenz on etonogestrel-releasing implant pharmacokinetics in HIV-positive women. J Acquir Immune Defic Syndr 2014; 66:378.
- Guiahi M, McBride M, Sheeder J, Teal S. Short-Term Treatment of Bothersome Bleeding for Etonogestrel Implant Users Using a 14-Day Oral Contraceptive Pill Regimen: A Randomized Controlled Trial. Obstet Gynecol 2015; 126:508.
- Villas-Boas J, Vilodre LC, Malerba H, et al. Metabolic safety of the etonogestrel contraceptive implant in healthy women over a 3-year period. Eur J Obstet Gynecol Reprod Biol 2016; 202:51.
- 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/preview/mmwrhtml/rr6205a1.htm (Accessed on March 04, 2016).
- Han L, Teal SB, Sheeder J, Tocce K. Preventing repeat pregnancy in adolescents: is immediate postpartum insertion of the contraceptive implant cost effective? Am J Obstet Gynecol 2014; 211:24.e1.
- Gariepy AM, Duffy JY, Xu X. Cost-Effectiveness of Immediate Compared With Delayed Postpartum Etonogestrel Implant Insertion. Obstet Gynecol 2015; 126:47.
- 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.
- Chen MJ, Creinin MD. Removal of a Nonpalpable Etonogestrel Implant With Preprocedure Ultrasonography and Modified Vasectomy Clamp. Obstet Gynecol 2015; 126:935.
- STRUCTURE AND PHARMACOKINETICS
- MECHANISM FOR CONTRACEPTION
- General population
- Women at high risk of unintended pregnancy
- 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