Norethisterone
progestins
Progestogens (progestins)Pregnancy: contraindicated
Not used in pregnancy; it is stopped if pregnancy is confirmed.
A 19-nortestosterone progestin used for endometriosis, abnormal bleeding and amenorrhoea, in contraceptive pills and in menopausal hormone therapy.
Also called: Norethindrone, Norethisterone acetate
Quick facts
- Group
- Progestogens (progestins)
- Target
- Progesterone receptor (PR), a nuclear receptor
- Used for
- Endometriosis · Secondary amenorrhoea · Contraception
- Key effects
- Irregular bleeding or spotting · Breast tenderness
- Monitor
- Bleeding pattern · Blood pressure · Mood
- ATC
- G03DC02
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows norethisterone itself in the ligand-binding domain of the human progesterone receptor.
Norethisterone is a progestin derived from 19-nortestosterone. It activates the progesterone receptor: it makes the endometrium secretory and then atrophic, so bleeding becomes controlled and endometriotic implants regress; at the hypothalamus and pituitary it reduces gonadotropin release. The acetate ester is converted to norethisterone in the body. It also has mild androgenic activity, which explains acne or facial hair in some women.
- Norethisterone activates the progesterone receptor
- The endometrium turns secretory, then thin and inactive
- Gonadotropins fall and ovulation is suppressed
- Bleeding is controlled and endometriosis shrinks
Indications
- Endometriosis Endometriosis →
- Abnormal uterine bleeding from hormonal imbalance Abnormal uterine bleeding →
- Secondary amenorrhoea
- Contraception (progestin-only pill and combined pills)
- With estradiol, menopausal hormone therapy in women with a uterus Menopause and climacteric syndrome →
Adverse effects
Common
- Irregular bleeding or spotting
- Breast tenderness
- Nausea, bloating
- Weight change
- Acne, facial hair, hair loss
Contraindications
- Current or past breast cancer
- Undiagnosed abnormal genital bleeding
- Active or past thrombosis, stroke or heart attack
- Liver disease
- Pregnancy
Key interactions
- CYP3A4 inducers (St John's wort, rifampicin, carbamazepine, phenobarbital)
- Lower norethisterone levels; contraceptive failure is possible
- CYP3A4 inhibitors (azole antifungals, ritonavir, some macrolides)
- Higher levels
What is monitored
- Bleeding pattern
- Blood pressure
- Signs of thrombosis and severe headache
- Mood
- Liver symptoms
Administration and safety
- Oral tablet at about the same time each day
- Regimens differ: daily for months in endometriosis, a few days per cycle in amenorrhoea or bleeding
- A missed dose is not doubled
Pregnancy and breastfeeding
Not used in pregnancy; it is stopped if pregnancy is confirmed.
Nursing care
- Teach to take it at the same time each day
- Explain irregular bleeding in the first months
- Teach the warning signs of a clot and of liver problems
- Ask about smoking, migraine and previous clots
- Ask about St John's wort and enzyme-inducing drugs
Pharmacokinetics
- Absorption
- Oral; the acetate is converted to norethisterone in the body
- Metabolism
- In the liver by CYP enzymes, so inducers and inhibitors change its levels
Test yourself
Think of the answer, then tap the question to see it.
From which steroid is norethisterone derived, and what side effects does that explain?
From 19-nortestosterone; its mild androgenic activity explains acne, oily skin and facial hair in some women.
How does norethisterone help endometriosis?
By making the endometrium and implants secretory and then atrophic, and by suppressing gonadotropins, so the implants regress and pain falls.
Which herbal product can make norethisterone pills fail?
St John's wort, an inducer of CYP3A4 that lowers norethisterone levels.
Connections
← Back to the class: Progestogens (progestins)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Norethindrone: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2022); DailyMed - ESTRADIOL AND NORETHINDRONE ACETATE tablet (DailyMed (U.S. National Library of Medicine), 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025).
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Representative model, for educational purposes only.