Norethindrone
Norethindrone is a first-generation oral progestin in clinical use since 1957. It is used in progestin-only contraceptive 'mini-pills', combined with ethinyl estradiol in many combined oral contraceptives, and as monotherapy at higher dose for abnormal uterine bleeding and endometriosis.
- Chemical formula
- C20H26O2
- CAS number
- 68-22-4
- ATC code
- G03DC02
- Molecular weight
- 298.42 g/mol
- Drug class
- Progestin
- Also known as
- Aygestin, Camila, Errin, Norethisterone, Nor-QD
What is it?
Norethindrone (norethisterone in international naming) is one of the oldest synthetic progestins, in clinical use since 1957. It is on the WHO Essential Medicines List and is the active progestin in many combined oral contraceptives, the progestin-only 'mini-pill' (Camila, Errin, Nor-QD), and in higher-dose monotherapy products such as Aygestin (norethindrone acetate 5mg) for non-contraceptive gynaecological indications. Authorised generic norethindrone is widely available across all formulations.
Mechanism of action
Norethindrone binds to progesterone receptors and exerts progestational effects: thickening cervical mucus, suppressing the LH surge, thinning the endometrium and inhibiting ovulation (at sufficient doses). It also has weak androgenic activity that distinguishes it from newer progestins like drospirenone or progesterone. In combined contraception, it works alongside ethinyl estradiol; in progestin-only pills, the contraceptive effect is primarily through cervical mucus changes with variable ovulation suppression.
Pharmacokinetics
Norethindrone is well absorbed orally with peak plasma at 1–2 hours. Bioavailability is ~64% with substantial first-pass metabolism. The terminal half-life is 8–10 hours, supporting once-daily dosing. Hepatic metabolism is via CYP3A4, with conjugation and partial conversion to ethinyl estradiol at high doses. The relatively short half-life requires strict adherence with progestin-only pills, where missing a dose by more than 3 hours reduces contraceptive efficacy.
Indications
Norethindrone is approved for prevention of pregnancy (progestin-only and combined formulations), secondary amenorrhoea, abnormal uterine bleeding, endometriosis-associated pain, and as part of menopausal hormone replacement therapy. Norethindrone acetate at higher doses (5–15mg) is preferred for endometriosis and abnormal uterine bleeding. According to current contraceptive guidelines, norethindrone-based pills are reasonable first-line options though newer progestins are often preferred for skin-related conditions.
Safety profile
Common adverse effects include breakthrough bleeding, breast tenderness, nausea, mood changes and headache. Compared with older progestins like medroxyprogesterone, norethindrone has more androgenic activity, which may worsen acne and weight gain in susceptible women. Compared with newer progestins like drospirenone, it has lower VTE risk. According to current guidelines, norethindrone-containing combined contraceptives have lower thrombotic risk than third- and fourth-generation progestin pills.
Products containing this ingredient
Frequently asked questions
What is the difference between norethindrone and progesterone? ▾
Progesterone is the natural hormone; norethindrone is a synthetic progestin with progesterone-like activity but different pharmacology. Norethindrone has higher oral bioavailability (because of structural modifications that block first-pass metabolism), modest androgenic activity, and a different metabolic profile. Progesterone is preferred when bioidentical replacement is the goal (HRT); norethindrone is preferred for contraception and high-dose gynaecological indications.
Why is the 'mini-pill' more dose-strict than combined pills? ▾
Progestin-only pills like norethindrone work primarily by thickening cervical mucus, an effect that wears off within hours. Missing a progestin-only pill by more than 3 hours can reduce contraceptive efficacy. According to the prescribing information, mini-pills require strict timing — same time each day within a 3-hour window — while combined pills tolerate up to 12-hour delays before backup contraception is needed.
Is norethindrone safe in breastfeeding? ▾
Yes — progestin-only contraceptive pills containing norethindrone (Camila, Errin, Nor-QD) are considered safe and are commonly preferred during breastfeeding because they do not affect milk supply, unlike estrogen-containing combined pills. According to current contraceptive guidelines, progestin-only pills can be started immediately postpartum in breastfeeding women.
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.