Combined Oral Contraceptive Pills

Combined oral contraceptive pills contain an oestrogen, almost always ethinylestradiol, and a progestin in each active tablet. They prevent pregnancy mainly by suppressing ovulation and by thickening cervical mucus. They are taken daily and do not disrupt an existing pregnancy.

Dose classes. High dose: ethinylestradiol 50 micrograms or more, now rarely used because of higher thrombosis risk. Low dose: 30 to 35 micrograms, the most commonly stocked group. Ultra-low dose: 20 micrograms.

Pack designs. 21 tablets, all active, followed by 7 days without tablets. 28 tablets, with 21 active and 7 inactive (often iron). Some 28 tablet packs contain 24 active and 4 inactive tablets.

Common combinations. Levonorgestrel 100 to 150 micrograms with ethinylestradiol 20 to 30 micrograms; norethisterone 0.5 to 1 mg with ethinylestradiol 20 to 35 micrograms; desogestrel 150 micrograms with ethinylestradiol 20 or 30 micrograms; norgestimate 250 micrograms with ethinylestradiol 35 micrograms; drospirenone 3 mg with ethinylestradiol 20 or 30 micrograms.

Pharmacokinetics. Ethinylestradiol is absorbed quickly and undergoes extensive first-pass metabolism, giving oral bioavailability of about 40%. Levonorgestrel is almost completely bioavailable. Both are cleared by hepatic and gut enzymes, so enzyme inducers lower levels. Vomiting within 2 hours of a dose and prolonged diarrhoea reduce absorption.

Effectiveness. First-year pregnancies: 8 in 100 women with typical use, 0.3 in 100 with perfect use. The risk is greatest when a new pack starts 3 or more days late or when 3 or more pills are missed near the start or end of a pack.

Return to fertility. Without delay after stopping.

Non-contraceptive benefits. Lighter, shorter menses; less dysmenorrhoea; improvement in endometriosis and polycystic ovary syndrome symptoms; less iron-deficiency anaemia; improvement in acne and hirsutism; lower ovarian and endometrial cancer risk.

Limits. No protection against HIV, hepatitis B or other sexually transmitted infections. Milk volume falls in breastfeeding women.

Suitable candidates. Patients from menarche to 40 years who can take a tablet daily and have no category 3 or 4 condition. Age alone, parity, previous pelvic surgery, varicose veins, fibroids, endometriosis, benign breast disease, family history of breast cancer, HIV, tuberculosis, malaria, schistosomiasis, thyroid disease, compensated mild cirrhosis, iron-deficiency anaemia and thalassaemia are category 1 or do not restrict use.

History and examination. Ask about thrombosis, stroke, heart disease, migraine with aura, smoking, hypertension, diabetes, liver and gall bladder disease, breast cancer, postpartum status and medicines. Measure blood pressure and body mass index. No pelvic or breast examination is required to start. Do a pregnancy test only when pregnancy cannot be excluded.

Category 2 conditions.

• Age 40 years or more
• breastfeeding 6 months or more
• not breastfeeding 21 days or more postpartum with no thrombosis risk
• unexplained vaginal bleeding awaiting evaluation
• efavirenz, nevirapine or ritonavir-boosted regimens
• hypertension in pregnancy with normal blood pressure now
• diabetes without vascular disease
• body mass index 30 or more
• asymptomatic gall bladder disease or cholecystectomy
• undiagnosed breast lump
• sickle cell disease
• smoker under 35 years
• superficial venous thrombosis
• first-degree family history of deep vein thrombosis
• major surgery without prolonged immobilisation
• migraine without aura
• focal nodular hyperplasia
• uncomplicated valvular heart disease
• cervical neoplasia awaiting treatment

Category 3 conditions. Breastfeeding 6 weeks to under 6 months; not breastfeeding under 21 days postpartum; 21 to 42 days postpartum with thrombosis risk factors; blood pressure 140/90 to 159/99; smoker 35 years or more under 15 cigarettes daily; symptomatic gall bladder disease on treatment; acute viral hepatitis (3 or 4 by severity); rifampicin or rifabutin; phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine or lamotrigine.

Category 4 conditions.

• Breastfeeding under 6 weeks
• blood pressure 160/100 or more
• ischaemic heart disease, stroke or complicated valvular disease
• diabetes with vascular disease or over 20 years duration
• smoker 35 years or more with 15 or more cigarettes daily
• current or past breast cancer
• current or past deep vein thrombosis or pulmonary embolism, or thrombogenic mutation
• major surgery with prolonged immobilisation
• lupus with positive or unknown antiphospholipid antibodies
• migraine with aura
• decompensated cirrhosis
• hepatocellular adenoma or malignancy

Interactions. Rifampicin, rifabutin, enzyme-inducing antiseizure medicines, griseofulvin and St John’s wort reduce effectiveness; an alternative method is used. Efavirenz, nevirapine and ritonavir-boosted regimens need added condoms. Non-rifamycin antibiotics, antifungals other than griseofulvin and antiparasitic medicines do not reduce effectiveness. Lamotrigine levels fall.

Counselling points for the clinician. Daily timing, the missed-pill rules, warning signs, bleeding changes in the first 3 months, condoms for sexually transmitted infection protection, and what to do after unprotected sex. Assent from under 18 years, consent in line with the law, and no coercion.

Regimen line. Ethinylestradiol 20 to 35 micrograms with a progestin, orally, one tablet daily at about the same time. Cycle: 21 active tablets then 7 hormone-free days (or 7 inactive tablets). Protection continues while tablets are taken correctly; 7 consecutive active tablets are needed before protection is reliable after a start or a long break. Grace: missing 1 or 2 pills, or starting a new pack 1 or 2 days late, carries little or no risk.

Backup: condoms or abstinence for 7 days after a late start or 3 or more missed pills. Adjust for postpartum and breastfeeding status, category 2 age from 40 years, and liver disease; body weight does not change the dose. Enzyme inducers: do not use.

Start timing.

Pregnancy exclusion. Reasonably certain when there has been no intercourse since the last menses, a reliable method has been used correctly, menses began within the past 7 days, the patient is within 7 days of abortion, or within 4 weeks of childbirth and not breastfeeding. Otherwise do a pregnancy test. If pregnancy cannot be excluded and the patient is otherwise eligible, give packs to start with the next menses, or start at once with 7 days of backup and repeat the test in 2 to 4 weeks.

Missed pills.

Switching. From another hormonal method used correctly: start at once. From an injectable: start when the next injection is due. From a non-hormonal method: start within 5 days of menses, or at any time if pregnancy is excluded, with 7 days of backup after day 5. From an intrauterine device: start within 5 days of menses and remove the device then; if later, start with pregnancy excluded and remove the device at the next menses.

Supply and follow up. Up to 3 cycles at each visit; trained non-clinical providers use an eligibility checklist and refer category 3 and 4 conditions. Review at about 3 months and then yearly for blood pressure, weight, smoking, new medicines, bleeding and adherence. Stop 4 weeks before major surgery with prolonged immobilisation. At 40 years reassess, and at about 50 years a change to a progestin-only or non-hormonal method is usual practice.

Serious complications. Venous thromboembolism, stroke, myocardial infarction, hypertension, liver tumours and gall bladder disease.

Red flags. Severe abdominal pain, chest pain or breathlessness, severe or new headache, eye problems and severe calf pain. Stop the pill and arrange urgent evaluation.

When to change method. New category 4 condition; migraine with aura; blood pressure of 160/100 or more; need for rifampicin, rifabutin or an enzyme-inducing antiseizure medicine; persistent unacceptable bleeding.

Referral and escalation. Suspected thrombosis, stroke or myocardial infarction: emergency transfer. Unexplained bleeding that persists or an undiagnosed breast lump: evaluate and refer. Poorly controlled blood pressure: stop and refer.