Etonogestrel contraceptive implant

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Etonogestrel contraceptive implant
Implanon 03.jpg
Type Hormonal
Progestin-only implant
First use

1998  Indonesia

2008, over 61 countries.
Failure rates (first year)
Perfect use 0.05%[1]
Typical use 0.05%[1]
Duration effect 3 years (4 years off-label)
Reversibility Yes
User reminders Requires removal after the 3–4 years
Advantages and disadvantages
STD protection No
Weight May cause weight gain
Period disadvantages May cause irregular or prolonged bleeding
Period advantages Minimizes pain. 20% of women will stop having their period.
Benefits Long-term contraception.

Etonogestrel contraceptive implant, sold under the brandnames Nexplanon and Implanon, is a single-rod subdermal contraceptive implant made by Merck & Co. that is inserted just under the skin of a woman's upper arm and contains etonogestrel. Nexplanon/Implanon are a type of long-acting reversible contraception, the most effective form of birth control.[2] Nexplanon and Implanon NXT are essentially identical to Implanon except Nexplanon and Implanon NXT have 15 mg of barium sulphate added to the core, so it is detectable by x-ray.[3] Nexplanon / Implanon NXT also has a pre-loaded applicator for easier insertion.[4] Implanon was first approved for use in Indonesia in 1998, then approved for use in the United States in 2006. Subdermal contraceptive implants are now used by 11 million women around the world and approved for use in over 60 countries as of 2003.[5]


Nexplanon and Implanon are a type of long-acting reversible contraception, which has been shown to be the most effective form of birth control available.[2] The failure rate of Implanon is .05% for both perfect use and typical use because the method requires no user action after insertion.[6] Prospective follow-up studies of Implanon, which include over 2,467 women-years of exposure, have found no pregnancies.[5][7][8][9][10][11][12] Other studies have found some failures with this method, some attributed to failures of the method itself and others to improper placement, drug interactions, or conception prior to method insertion.[13]

In comparison, tubal sterilization has a failure rate of 0.5% and IUDs have a failure rate of 0.2–0.8%.[6] These statistics suggest that Implanon and Nexplanon are almost ten times more effective at preventing pregnancy than tubal sterilization. Also, tubal sterilization is permanent, whereas the subdermal implant is completely reversible, required to be replaced every three years.

Side effects[edit]

Irregular bleeding and spotting may occur: Many women will experience some type of irregular, unpredictable, prolonged, frequent, or infrequent bleeding when using Nexplanon or Implanon.[14] Some women also experience amenorrhea. For some women, prolonged bleeding will decline after the first three months of use. However, other women may experience this bleeding pattern through all three years of use. While these patterns are not dangerous, they are the most common reason that women give for discontinuing the use of the implant. After removal, bleeding patterns return to previous patterns in most women.[5][7][8][9][10][11][12]

Insertion Complications: Some minor side effects such as bruising, skin irritation, or pain around the insertion site are common.[5] However, there are some rare complications that can occur, such as infection or expulsion.[5][15] In some cases, a serious complication occurs when the provider fails to insert, and the rod is left in the inserter. An Australian study reported 84 pregnancies as a result of such failure.[13]

Migration: Although very rare, the rod can sometimes move slightly within the arm. This can make removal more difficult. It is possible that insertion of an Implanon or Nexplanon in the same site as a previous implant increases the likelihood of migration.[15] Implanon rods can be located only through high-frequency ultrasound or magnetic resonance imaging (MRI).[5] Nexplanon can be located using traditional X-ray or CT-scan because of the inclusion of barium sulphate. There have been rare reports of Nexplanon implants having reached the lung via the pulmonary artery.[16] Correct subdermal insertion reduces the risk of these events.

Possible weight gain: Some women may experience slight weight gain when using the implant.[5] However, current studies are not conclusive because they do not compare the weight of women using Implanon/Nexplanon with a control group of women not using the implant. The average increase in body weight in studies was less than 5 pounds (2,25 kg) over 2 years.[7][8][12]

Ovarian cysts: A small portion of women using Implanon/Nexplanon and other contraceptive implants develop ovarian cysts.[5] Usually these cysts will disappear without treatment.[17]

Drug interactions: It is possible that the implant has similar drug interactions as combined oral contraceptives.[5] However, drug interactions with Implanon/Nexplanon have not been systematically studied.

Pregnancy: it is recommended that Implanon or Nexplanon be removed if a pregnancy does occur. However, there is no evidence to suggest that the implant has a negative effect on pregnancy or a developing fetus.[5]

Acne: Acne has been self-reported to be a side effect of Implanon, and is listed as a side effect by the FDA. However, a study of Implanon users found that a majority of users with acne before their insertion reported that their acne had decreased, and only 16% of those who did not have acne before insertion developed acne.[8]

Other possible symptoms: Other symptoms that have been reported in clinical trials of Implanon or Nexplanon include headache, emotional lability, abdominal pain, loss of libido, and vaginal dryness.[5] However, there have been no studies that conclusively determine that these symptoms are caused by the implant.[8][9]


Women should not use Implanon or Nexplanon if they:[18][19]

  • Are, or think they are, pregnant
  • Are allergic to etonogestrel
  • Have vaginal bleeding that has not been explained
  • Are breastfeeding in the first 6 weeks postpartum (see note)
  • Have severe liver disease
  • Are using an IUD

There is some concern about women who develop ischemic heart disease, migraines with aura (spots or zig zag lines in vision), or stroke while using progestogen only contraception such as progestogen-only pills (POP), the depo medroxyprogesterone acetate (DMPA) injection, and the implant.[18] However, these concerns are less for the implant and POP and more for DMPA injection.

Implanon has also been shown to induce mild insulin resistance though the effects are not clinically relevant for healthy women.[20]

Note: There have been no studies to provide direct evidence that progestogen only contraception such as the implant has a negative effect on breast milk production or infants.[19] The WHO and CDC lists breastfeeding under 4 weeks as a category 2 concern in which the benefits outweigh the risks, and cites no risk after 4 weeks postpartum.[19]

Unlike the combinded oral contraceptive pill etonogestrel contraceptive implant is not contraindicated in women with past history of breast cancer as the pill does not contain estrogen (the driver of metaplastic change in some breast cancers).

A full list of contraindications can be found in the WHO Medical Eligibility Criteria for Contraceptive Use 2009 and the CDC United States Medical Eligibility Criteria for Contraceptive Use 2010

Device description[edit]

A removed rod

Nexplanon/Implanon consists of a single rod made of ethylene vinylacetate copolymer that is 4 cm long and 2mm in diameter.[14] It is similar to a matchstick in size. The rod contains 68 mg of etonogestrel (sometimes called 3-keto-destrogestrel), a type of progestin.[5] Peak serum etonogestrel concentrations have been found to reach 781–894 pg/mL in the first few weeks, gradually decreasing to 192–261 pg/mL after 1 year, 154–194 pg/mL after 2 years, and 156–177 pg/mL after 3 years, maintaining ovulation suppression and contraceptive efficacy.[21] Serum levels maintain relatively stable through 36 months, which implies that the method may be effective for longer than 3 years.[22]

Although not formally approved by the manufacturer for more than 3 years, none of the 240 women in the 3 studies became pregnant in the 4th year.[7][23][24]

Insertion and removal[edit]

Implantation of Implanon

An experienced clinician must perform the insertion of Nexplanon or Implanon to ensure proper insertion and minimize the risk of nerve damage or misplacement, which could result in pregnancy.[25] Before insertion, the arm is washed with a cleaning solution and a local anesthetic is applied to the upper arm around the insertion area.[5] A needle-like applicator is used to insert the rod under the skin into the subdermal tissue on the inner side of the arm between the biceps and triceps muscles.[5] The average time for insertion is 0.5 to 1 minute.[8][9] A bandage should be kept on the insertion site for 24 hours afterwards. Bruising and mild discomfort are common after insertion.[5] Serious insertion site complications such as infection can occur very rarely, in less than 1% of patients. If a woman receives an implant outside the first five days of her period, she should wait to have sex or use a backup method of contraception (such as a condom, female condom, diaphragm, sponge, or emergency contraception) for the following week after insertion to prevent pregnancy. However, if the implant is inserted during the first five days of a woman's period, she is protected for that cycle and beyond.[26]

Removal of Implanon

Nexplanon and Implanon should be removed after three years; however, they can be removed at any time if pregnancy is desired. The rod must also be removed by an experienced clinician. At removal, a local anesthetic is again used around the implant area at the distal end.[5] If the provider cannot feel the implant, imaging tests may be necessary to locate the rod before it can be removed. A small incision is made in the skin over the end of the implant site. In some cases, a fibrous sheath may have formed around the implant, in which case the sheath must be incised.[5] The implant is removed using forceps. The removal procedure lasts, on average, 3 to 3.5 minutes.[8][9]

Fertility after removal[edit]

Within a week of removal, the hormones from the device leave the body and etonogestrel is undetectable in most users.[5] Most women will begin to ovulate within six weeks of removal.[22][27] Fertility levels will return to what they were before Nexplanon or Implanon insertion.

Mechanism of action[edit]

The mechanism of action of progestin only contraceptives depends on the progestin activity and dose.[28] Intermediate dose progestin-only contraceptives, like Nexplanon or Implanon (and the progestin-only pill Cerazette) allow some follicular development but inhibit ovulation in almost all cycles as the primary mechanism of action. Ovulation was not observed in studies of Implanon in the first two years of use and only rarely in the third year with no pregnancies. A secondary mechanism of action is the progestogenic increase in cervical mucus viscosity which inhibits sperm penetration.[29] Hormonal contraceptives also have effects on the endometrium that theoretically could affect implantation, however no scientific evidence indicates that prevention of implantation actually results from their use.[30]


The possibility of the subdermal contraceptive implant began when silicone was discovered in the 1940s and found to be bio-compatible with the human body.[31] In 1964, Folkman and Long published the first study demonstrating that such a rod could be used to deliver drugs.[32] In 1966 Dziuk and Cook published a study that looked at release rates and suggested that the rods could be well suited for contraception.[33] After a study that used implants with progestogens for contraception, the Population Council developed and patented Norplant and Jadelle.[34] Norplant has six rods and is considered a first generation implant. Jadelle (Norplant II) and other single rod implants that followed were developed because of complications resulting from Norplants 6 rod system. The Jadelle system contains two silicone rods mixed with levonorgestrel. In 1990 De Nijs patented a co-axial extrusion technique of ethylene vinylacetate copolymers and 3-keto-desogestrel (etonogestrel) for the preparation of long-acting contraceptive devices, such as Implanon, Nexplanon and Nuvaring.[35] The single rods were less visible under the skin and used etonogestrel as opposed to levonorgestrel in the hopes that it would reduce side effects.[31]

Norplant was used internationally beginning in 1983 and was marketed in the United States and the United Kingdom in 1993. There were many complications associated with Norplant insertion and removal in the United States and it was taken off the market in 2002. Although Jadelle was approved by the FDA, it has never been marketed in the United States, but it is widely used in Africa and Asia.[34] Implanon was first used in Indonesia in 1998 and approved for use in the United States in 2006. Nexplanon was developed to eliminate the problem of non-insertion and localization of Implanon by changing the inserter device and making the rod radiopaque.[3] Nexplanon has replaced Implanon in the UK because of cases of incorrect insertion. As of January 2012, Implanon is no longer being marketed in the US, and Nexplanon is the only available single-rod implant.

See also[edit]


  1. ^ a b Trussell, James (2011). "Contraceptive efficacy". In Hatcher, Robert A.; Trussell, James; Nelson, Anita L.; Cates, Willard Jr.; Kowal, Deborah; Policar, Michael S. Contraceptive technology (20th revised ed.). New York: Ardent Media. pp. 779–863. ISBN 978-1-59708-004-0. ISSN 0091-9721. OCLC 781956734.  Table 26–1 = Table 3–2 Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception, and the percentage continuing use at the end of the first year. United States.
  2. ^ a b Winner, B; Peipert, JF; Zhao, Q; Buckel, C; Madden, T; Allsworth, JE; Secura, GM. (2012), "Effectiveness of Long-Acting Reversible Contraception", New England Journal of Medicine, 366 (21): 1998–2007, doi:10.1056/NEJMoa1110855, PMID 22621627 
  3. ^ a b Mansour, J (2010), "Nexplanon: What Implanon Did Next", J Fam Plann Reprod Health Care, 36: 187–189, doi:10.1783/147118910793048629 
  4. ^ Ormsby, Avril (5 Jan 2011). "Contraceptive alert after women fall pregnant". Reuters. Archived from the original on 10 May 2011. Retrieved 10 May 2011. 
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