Etonogestrel Implant

The etonogestrel implant is a single flexible rod, 4 cm long and 2 mm in diameter, containing 68 mg etonogestrel in an ethylene vinyl acetate copolymer core with a rate-controlling membrane. It is placed subdermally in the inner upper arm and provides contraception for 3 years. Etonogestrel is the active metabolite of desogestrel.

Classification. Progestin-only, long-acting reversible, single-rod implant.

Formulations. A radiopaque rod containing barium sulfate, supplied in a preloaded single-use applicator, and an earlier non-radiopaque rod with a different applicator. The radiopaque rod can be located by plain X-ray; the non-radiopaque rod cannot.

Mechanism. Inhibition of ovulation is the main action and occurs in almost all cycles through the 3-year lifespan. Thickened cervical mucus and endometrial thinning add to the effect.

Pharmacokinetics. Bioavailability is close to complete. Release is about 60 to 70 micrograms daily at weeks 5 to 6, falling to about 35 to 45 micrograms daily at the end of year 1, 30 to 40 micrograms at the end of year 2, and 25 to 30 micrograms at the end of year 3. Serum levels sufficient to inhibit ovulation are reached within the first day. Etonogestrel is metabolised by hepatic cytochrome P450 3A4, which explains the effect of enzyme inducers, and has an elimination half-life of about 25 hours.

Effectiveness. About 0.05 pregnancies per 100 women in the first year with typical and with perfect use.

Duration of action. 3 years from insertion.

Return to fertility. Etonogestrel becomes undetectable within about 1 week of removal, and most patients ovulate within 3 to 6 weeks.

Ideal candidates. Patients wanting the most effective reversible method without daily action, including adolescents, nulliparous and postpartum patients. Its consistent ovulation suppression makes it useful in dysmenorrhoea and endometriosis-associated pain.

History and examination. Last menstrual period, intercourse since then, current method, breastfeeding status, current medicines, liver disease, breast cancer, current venous thromboembolism, and unexplained vaginal bleeding. Inspect the non-dominant arm.

Investigations. None routinely. Pregnancy test only when pregnancy cannot be reasonably excluded on history.

Eligibility categories.

• Category 1: adolescents from menarche, smoking, obesity, hypertension with blood pressure under 160/100 mm Hg, sickle cell disease, HIV infection, dolutegravir or raltegravir-based antiretroviral therapy, epilepsy without enzyme inducers.

• Category 2: breastfeeding under 6 weeks postpartum, past venous thromboembolism, migraine without aura, uncomplicated diabetes, irregular or heavy bleeding, efavirenz, nevirapine, ritonavir-boosted protease inhibitors, rifampicin, rifabutin, carbamazepine, phenytoin, phenobarbital, primidone, topiramate, oxcarbazepine.

• Category 3: current deep vein thrombosis or pulmonary embolism, severe cirrhosis, hepatocellular adenoma or malignant hepatoma, unexplained vaginal bleeding before evaluation, ischaemic heart disease, stroke or worsening migraine with aura during use.

• Category 4: current or past breast cancer.

Interactions. Enzyme inducers lower etonogestrel levels and pregnancies have occurred. Efavirenz lowers etonogestrel exposure markedly, with the effect increasing after the first year. Advise consistent condom use with the implant for the whole period of inducer use and for 28 days after stopping, or offer a method not affected (DMPA, copper IUD or levonorgestrel IUD).

Counselling points. Bleeding pattern is unpredictable: about one in five users becomes amenorrhoeic and a similar proportion has frequent or prolonged bleeding. The pattern in the first 3 months broadly predicts later bleeding. The implant does not protect against STIs or HIV.

Regimen line. Etonogestrel 68 mg single radiopaque rod.

• Subdermal, inner aspect of the non-dominant upper arm, about 8 to 10 cm proximal to the medial epicondyle and 3 to 5 cm posterior to the groove between biceps and triceps.
• Inserted once with the preloaded applicator after local anaesthesia with lidocaine 1%, 2 mL.
• Protection immediate if inserted within 7 days of the start of bleeding, otherwise backup 7 days.
• Replace at 3 years; no grace window after expiry.
• With enzyme inducers or efavirenz add condoms throughout and for 28 days after stopping, or switch.
• No adjustment for breastfeeding, adolescence, perimenopause or body weight.
• Avoid in severe liver disease.

Start timing.

• Within 7 days of the start of menstrual bleeding: insert, no backup.

• Any other day: insert if reasonably not pregnant; backup 7 days.

• Non-breastfeeding postpartum: insert immediately or at any time up to 21 days without backup; from 21 days without menses, exclude pregnancy and use backup 7 days.

• Breastfeeding: may be inserted immediately postpartum; if amenorrhoeic, insert at any time, with backup 7 days if 6 months or more postpartum.

• After abortion or miscarriage: insert immediately.

• After levonorgestrel emergency contraception: insert within the first 7 days of the next menses and use condoms or oral contraceptives until then.

Switching.

• From combined pill, patch, ring, progestin-only pill or another implant used correctly: insert immediately, no backup.

• From DMPA or norethisterone enanthate: insert on or before the date the next injection is due, no backup.

• From IUD: insert within 7 days of bleeding and remove the IUD the same day; after day 7, insert and leave the IUD in until the next period.

• From a nonhormonal method: within 7 days of bleeding no backup; after day 7, exclude pregnancy and use backup 7 days.

Verification after insertion. Both clinician and patient palpate the full length of the rod immediately after insertion. If it cannot be felt, the rod may not have been inserted or may be deep; use backup and arrange localisation before relying on the method.

Follow up. No scheduled visit. Card records the type, insertion date and removal date at 3 years. Return for site problems, rod not palpable, suspected pregnancy, new red flag symptoms, or wish to remove.

Discontinuation. Removal through a 2 mm incision over the distal tip after local anaesthesia. A replacement rod may be inserted through the same incision, with no gap in protection.

Bleeding changes. Amenorrhoea, infrequent bleeding, frequent or prolonged bleeding. Exclude pregnancy, STI and pelvic pathology when bleeding is new or heavy. For bothersome bleeding with no cause: ibuprofen 800 mg orally three times daily for 5 days, or mefenamic acid 500 mg twice daily for 5 days, or, if oestrogen is eligible, a combined pill with ethinylestradiol 30 micrograms and levonorgestrel 150 micrograms daily for 21 days. Remove if bleeding stays unacceptable.

Other effects. Acne may improve or worsen. Headache, breast tenderness, mood change and modest weight change occur; a causal link with weight gain is not established. Enlarged ovarian follicles resolve without treatment and do not require removal.

Insertion and removal complications. Bruising, haematoma, infection, scarring, failed insertion, deep insertion, migration and, rarely, intravascular placement with migration to the pulmonary artery. Deep placement near the neurovascular bundle risks medial antebrachial cutaneous or ulnar nerve injury.

Red flags. No palpable rod, hand numbness or weakness, signs of venous thromboembolism, pregnancy symptoms with pelvic pain, new breast lump, jaundice.

Management of a non-palpable rod. Use backup until located. Locate with high-frequency linear ultrasound first; use plain X-ray of the arm for the radiopaque rod; if not found in the arm, image the chest. Measure serum etonogestrel where available to confirm presence. Remove under imaging by an experienced provider. Never explore the arm blind.

Pregnancy. Exclude ectopic pregnancy. If the pregnancy continues, remove the implant. No teratogenic effect is known.

Referral and escalation. Refer non-palpable or deep rods, suspected nerve injury, suspected chest migration, suspected ectopic pregnancy and suspected venous thromboembolism.