Norethisterone Enanthate Injection

Norethisterone enanthate is a progestin-only injectable containing norethisterone enanthate 200 mg as an oily solution, given by deep intramuscular injection every 8 weeks (2 months). It contains no oestrogen. It has a shorter interval and shorter grace period than DMPA and must not be used interchangeably with it.

Mechanism. Ovulation suppression, thickened cervical mucus and endometrial thinning.

Effectiveness. Class estimates apply: typical use 4 and perfect use 0.2 pregnancies in 100 women in the first year. Risk is highest when an injection is late.

Onset and return to fertility. Immediate protection if given within 7 days of menses; otherwise backup is needed for 7 days. Return of fertility may be delayed for four months or longer.

Ideal candidates. Patients who want a private method and can attend every 8 weeks, breastfeeding women from 6 weeks, and those wishing to avoid oestrogen.

Assessment. Menstrual, obstetric and medicine history and blood pressure. No pelvic or breast examination or laboratory test is needed. Exclude pregnancy by the usual criteria, with a test if none applies. Offer HIV testing.

Eligibility.

• Category 1: BMI 30 or more; smoking; HIV; sickle cell disease; mild compensated cirrhosis; breastfeeding from 6 weeks.
• Category 2: under 18 or over 45 years; controlled hypertension; past deep vein thrombosis; high HIV acquisition risk; rifampicin or rifabutin; phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine; efavirenz, nevirapine or ritonavir-boosted regimens.
• Category 3: breastfeeding under 6 weeks; ischaemic heart disease or stroke; blood pressure 160/100 mm Hg or more; acute deep vein thrombosis or pulmonary embolism; severe cirrhosis or liver tumour; unexplained bleeding before evaluation; lupus with positive or unknown antiphospholipid antibodies; past breast cancer.
• Category 4: current breast cancer.

Interactions. Enzyme inducers may reduce effect, so the injection must be given on time; DMPA is preferred where available because it is category 1 with these medicines.

Counselling. Consent, confidentiality, absence of coercion; assent for adolescents under 18 years. Explain bleeding change, possible delayed fertility, and condoms for infection protection.

Regimen.

• Norethisterone enanthate 200 mg oily solution, deep intramuscular injection into the gluteal muscle, every 8 weeks.
• Start within 7 days of menses without backup; later, backup for 7 days.
• Grace window: up to 2 weeks early and up to 2 weeks late without backup.
• Over 2 weeks late: exclude pregnancy, inject, and use backup for 7 days.
• Switching from another hormonal method used correctly: inject at once. From DMPA, inject when the repeat injection is due.
• Postpartum: breastfeeding women from 6 weeks; non-breastfeeding women at once or within 21 days, later with pregnancy excluded and backup for 7 days. After abortion within 7 days, or later with backup for 7 days.
• No dose change for body weight or liver disease.
• Use a new disposable syringe and needle, and do not rub the site.

Switching between DMPA and norethisterone enanthate. Not interchangeable. If switching is necessary, for example during a stockout, give the new injectable at the time the repeat injection was due.

Special groups.

• Adolescents: use is allowed; assent under 18 years, consent in line with the law.
• Rifampicin, rifabutin or enzyme-inducing antiseizure medicines: category 2; punctual reinjection is essential and DMPA is preferred where available.
• HIV: can be used; add condoms.

Follow up. Reinject every 8 weeks. Review each visit for bleeding, blood pressure and weight; full review at least yearly. Stockouts and missed visits need an agreed plan: arrange condoms and early reinjection.

Expected effects. Irregular bleeding, heavy or prolonged bleeding, spotting, amenorrhoea, weight change, headache, dizziness, mood swings, bloating, acne, breast tenderness.

Bleeding management.

• Persistent spotting with no pathology: ibuprofen 400 to 800 mg orally three times daily with food for 7 to 14 days, maximum 2400 mg in 24 hours; avoid in peptic ulcer, renal impairment, severe liver disease and NSAID-sensitive asthma.
• Heavy or prolonged bleeding (over 8 days or twice usual length): exclude gynaecological disease, then ibuprofen 400 to 800 mg orally three times daily with food for 7 to 14 days (maximum 2400 mg in 24 hours) or a combined oral contraceptive, one active tablet daily for 1 to 3 cycles, if oestrogen is not contraindicated and not breastfeeding under 6 months.
• Persistent unacceptable bleeding: stop and offer another method.

Other problems. Reassure amenorrhoea; test for pregnancy if in doubt. Check blood pressure for headache; refer severe headache. Breast tenderness: test for pregnancy, reassure, give analgesia, refer any lump.

Red flags. Severe lower abdominal pain (exclude ectopic pregnancy), jaundice, chest pain, calf swelling, severe headache.

Referral and escalation. Refer unexplained bleeding for examination and cervical screening. Refer pregnancy for antenatal care after stopping.