Choosing a Combined Pill
Selecting a combined formulation means matching eligibility, route, oestrogen dose and progestin to the patient. The oestrogen dose sets cycle control and a share of venous thrombosis risk. The progestin sets the thrombosis risk class and the non-contraceptive effects. The route sets adherence demands and oestrogen exposure. Eligibility categories do not change with formulation.
Progestin classes and venous thrombosis risk. Levonorgestrel, norethisterone and norgestimate carry the lowest risk, about 5 to 7 events in 10,000 woman-years. Desogestrel, gestodene and drospirenone carry about 9 to 12. Cyproterone acetate carries a risk at or over that range. The risk without hormones is about 2 in 10,000 woman-years.
Oestrogen dose. Ethinylestradiol 20 micrograms gives more breakthrough bleeding than 30 to 35 micrograms. Doses of 50 micrograms or more raise thrombosis risk and are avoided.
Route. Pill, patch, ring and monthly injection give first-year pregnancies of 8, 8, 8 and 3 in 100 women with typical use, and 0.3, 0.3, 0.3 and 1 in 100 with perfect use.
Return to fertility. Without delay after pill, patch or ring; about 5 months on average after the injectable.
Step 1: confirm eligibility. A combined method is not used with category 4 conditions:
- breastfeeding under 6 weeks
- blood pressure 160/100 or more
- ischaemic heart disease, stroke or complicated valvular disease
- migraine with aura
- current or past breast cancer
- current or past deep vein thrombosis or pulmonary embolism, or thrombogenic mutation
- diabetes with vascular disease or more than 20 years duration
- smoker 35 years or more with 15 or more cigarettes daily
- lupus with positive or unknown antiphospholipid antibodies
- decompensated cirrhosis
- liver adenoma or malignancy
- major surgery with prolonged immobilisation
Category 3 conditions need another method unless none is available or acceptable and follow up is certain: breastfeeding 6 weeks to under 6 months; not breastfeeding under 21 days postpartum; blood pressure 140/90 to 159/99; smoker 35 years or more under 15 cigarettes daily; symptomatic gall bladder disease on treatment; rifampicin; rifabutin; enzyme-inducing antiseizure medicines.
Step 2: choose the route.
| Need | Choice |
|---|---|
| Can take a daily tablet | Pill |
| Daily adherence difficult | Patch, ring or combined injectable |
| Weight 90 kg or more | Pill or ring rather than patch |
| Vomiting, chronic diarrhoea or malabsorptive bariatric surgery | Ring |
| Skin disease or adhesive allergy | Pill or ring |
| Reluctance to use the vagina | Pill, patch or injectable |
| Needs a clinician-given method for privacy | Combined injectable, where stocked |
Step 3: choose oestrogen and progestin.
| Clinical need | Choice | Caution |
|---|---|---|
| First prescription, no special need | Monophasic levonorgestrel 150 micrograms or norethisterone 1 mg with ethinylestradiol 30 to 35 micrograms | Most commonly stocked; lowest thrombosis risk class |
| Nausea or breast tenderness on 30 micrograms | Ethinylestradiol 20 micrograms, or the ring | More breakthrough bleeding on 20 micrograms |
| Breakthrough bleeding on 20 micrograms after 3 months of correct use | Ethinylestradiol 30 micrograms, or a different progestin | Check adherence and interactions first |
| Acne or hirsutism | Drospirenone 3 mg, dienogest, norgestimate, or cyproterone acetate 2 mg with ethinylestradiol 35 micrograms | Cyproterone: higher thrombosis risk, not for contraception alone. Drospirenone: potassium |
| Heavy menstrual bleeding | Extended monophasic pill, or oestradiol valerate with dienogest | Confirm availability |
| Dysmenorrhoea or endometriosis | Monophasic pill used continuously | Spotting in the first months |
| Premenstrual dysphoric symptoms | Drospirenone 3 mg with ethinylestradiol 20 micrograms, 24 active and 4 inactive tablets | Potassium with interacting medicines |
| Enzyme-inducing medicine | No combined method | Use an injectable progestin, copper device or levonorgestrel intrauterine system |
| Breastfeeding under 6 months | No combined method | Use a progestin-only method |
Investigations. Blood pressure and body mass index. Potassium for drospirenone users on potassium-sparing diuretics, angiotensin converting enzyme inhibitors, angiotensin receptor blockers or aldosterone antagonists.
Counselling points for the clinician. Explain the reason for the choice, the bleeding pattern, warning signs and condom use. Consent, no coercion, assent from under 18 years.
Special groups. Adolescents: all combined methods are eligible; adherence support decides the route. Perimenopause: category 2 from 40 years; reassess at each review, and at about 50 years a change to a progestin-only or non-hormonal method is usual practice.
HIV: dolutegravir, raltegravir, tenofovir, abacavir, zidovudine, lamivudine, emtricitabine, rilpivirine and etravirine are category 1; efavirenz, nevirapine and ritonavir-boosted regimens are category 2 with condoms. Epilepsy: lamotrigine and the enzyme inducers are category 3. Sickle cell disease, obesity: category 2. Postpartum: not breastfeeding, not before 21 days; breastfeeding, from 6 months.
Default regimen line. Levonorgestrel 150 micrograms with ethinylestradiol 30 micrograms, oral, one tablet daily at about the same time for 21 days, then 7 hormone-free days or inactive tablets. Start within 5 days of the start of menses with no backup; later starts need 7 days of backup. Grace: missing 1 or 2 pills carries little or no risk.
Missing 3 or more pills: take a pill now, continue, backup 7 days, consider emergency contraception if sex in the last 5 days; in week 3, finish the active pills, discard the inactive pills, start the next pack the next day and use backup for 7 days. Vomiting within 2 hours: take another pill. Vomiting or diarrhoea for more than 2 days: apply the rule for 3 or more missed pills. Enzyme inducers: do not use. Body weight does not change the dose.
Pregnancy exclusion at start. 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 test. When pregnancy cannot be excluded, start with 7 days of backup or issue packs to start at the next menses, and repeat the test in 2 to 4 weeks.
Supply. Up to 3 cycles at a visit. Review at about 3 months.
Changing formulation. Allow about 3 months of correct use before changing for bleeding, nausea or breast tenderness, unless the effect is severe. Between combined pills, start the new pack the day after the last active tablet or after the usual hormone-free interval, with no backup if the old pill was taken correctly. From a pill to a patch or ring, start within 7 days of the last active tablet or at the end of the hormone-free interval.
Follow up. Yearly: blood pressure, weight, smoking, medicines and new risk factors. Stop 4 weeks before major surgery with prolonged immobilisation.
Common prescribing errors. Combined method with migraine with aura; no blood pressure measurement; smoker 35 years or more; breastfeeding under 6 months; enzyme-inducing medicine; ethinylestradiol 50 micrograms or more; cyproterone acetate as a contraceptive alone; drospirenone with potassium-raising medicines and no potassium check; patch for a patient weighing 90 kg or more; confusing the combined injectable with a progestin-only injectable.
Expected effects. Spotting and nausea in the first 3 months, breast tenderness, mild headache.
Management of unscheduled bleeding. Exclude pregnancy, infection, missed doses and interactions; give ibuprofen 800 mg orally three times daily for 5 days with food (maximum 2.4 g daily; avoid in renal impairment, active peptic ulcer or significant liver disease; not used in pregnancy); after 3 months change dose, progestin or route.
Pregnancy while using a combined method. Stop the method, confirm the pregnancy and its location. Combined hormones are not known to harm the foetus. Suspect ectopic pregnancy with pain or bleeding.
Serious complications and red flags. Venous thromboembolism, stroke and myocardial infarction. Severe abdominal pain, chest pain or breathlessness, severe or new headache, eye problems and severe calf pain: stop the method and arrange urgent evaluation.
Referral and escalation. Emergency transfer for suspected thrombosis, stroke or myocardial infarction. Refer for persistent unexplained bleeding, undiagnosed breast lump, uncontrolled hypertension or a category 4 diagnosis.
