Pharmacology · Hormonal contraceptives
Ethinylestradiol + levonorgestrel !
The classic combined contraceptive pill (estrogen plus progestin): it stops ovulation. Risk of blood clots; not for smokers over 35.
Updated 2026-11-01
Crystal structure of the ligand-binding domain of the human progesterone receptor with levonorgestrel, the progestin of this combination.
Mechanism of action
Levonorgestrel activates the progesterone receptor and ethinylestradiol the estrogen receptor. Together they suppress GnRH, LH and FSH by negative feedback, so no follicle matures and ovulation does not happen. The progestin also thickens cervical mucus and changes the endometrium.
- Estrogen and progestin act on hypothalamus and pituitary
- LH and FSH fall, and the LH surge does not occur
- No ovulation; cervical mucus thickens and blocks sperm
Pharmacokinetics
- Absorption
- Levonorgestrel: about 100% by mouth, no first pass; ethinylestradiol: about 38–48% after first pass
- Metabolism
- Ethinylestradiol mainly through CYP3A4 in the liver; levonorgestrel by reduction, hydroxylation and conjugation
- Half-life
- About 34 hours (levonorgestrel) and about 17 hours (ethinylestradiol)
Indications
- Prevention of pregnancy (oral contraception)
- Heavy or irregular periods Abnormal uterine bleeding →
- Irregular periods in polycystic ovary syndrome Polycystic ovary syndrome →
Adverse effects
Common
- Headache and nausea
- Spotting between periods or missed periods
- Breast tenderness and mood changes
- Acne and vaginal yeast infection
Contraindications
- Smoking in women over 35
- Previous or current deep vein thrombosis, pulmonary embolism or inherited clotting disorder
- Cerebrovascular or coronary artery disease, and uncontrolled hypertension
- Migraine with aura (or any migraine over 35)
- Liver tumours or liver disease, and current or past breast cancer
- Undiagnosed abnormal uterine bleeding and pregnancy
- Use with ombitasvir, paritaprevir and ritonavir hepatitis C regimens
Key interactions
- Enzyme inducers (rifampicin, carbamazepine, phenytoin, barbiturates, St John's wort)
- Lower hormone levels and contraceptive failure; a backup method is needed
- Some HIV and hepatitis C antivirals
- Change hormone levels; some combinations are contraindicated
- Lamotrigine
- Ethinylestradiol lowers lamotrigine levels; seizure control may change
- Thyroid hormone replacement
- The dose of thyroid hormone may need adjustment
What is monitored
- Blood pressure before starting and during use
- Smoking status, migraine type and personal or family history of thrombosis
- Warning signs of thrombosis: leg pain or swelling, chest pain, sudden breathlessness
- Glucose and lipids in women with diabetes or high lipids
Administration and safety
- Taken daily at the same time; missed pills follow the product's written rules.
- Stopped before major surgery with long immobilisation, as the label states, and restarted later after birth (thrombosis risk).
- Some packs include inactive or iron tablets: explain which are which.
Nursing care
- Before starting: blood pressure, smoking, migraine with aura, thrombosis history, liver disease and breast cancer.
- Teach the warning signs of clots and stroke (leg pain, chest pain, breathlessness, sudden headache, vision change, weakness).
- Review new medicines for enzyme inducers and advise a backup method when needed.
- Explain that it does not protect against sexually transmitted infections.
- While breastfeeding: it can reduce milk supply; other methods are preferred.
Pregnancy and breastfeeding
Contraindicated and stopped if pregnancy occurs; accidental use in early pregnancy shows little or no increase in birth defects.
Test yourself
Think of the answer, then tap the question to see it.
Which patient group has the boxed warning for combined oral contraceptives?
Women over 35 who smoke: higher risk of heart attack, stroke and other cardiovascular events.
Which migraine type contraindicates combined oral contraceptives?
Migraine with aura, because estrogen raises the risk of ischaemic stroke.
Which antiepileptic has its levels lowered by ethinylestradiol?
Lamotrigine.
What is the main mechanism of combined oral contraceptives?
Suppression of ovulation by negative feedback on GnRH, LH and FSH.
Related drugs
Related conditions
← Back to the class: Hormonal contraceptives
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - LEVONORGESTREL AND ETHINYL ESTRADIOL kit (DailyMed (U.S. National Library of Medicine), 2026); Polyendocrine metabolic ovarian syndrome (PMOS) - NHS (NHS, 2026); eEML - Electronic Essential Medicines List (World Health Organization, 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.