Synonyms: combined pill, 'The Pill'
The combined oral contraceptive (COC) pill is a highly effective form of contraception and used to control fertility by almost 20% of women aged 16-49 years in the UK.
Starting the COC pill is an important and complex consultation. It should include:
- Discussion and explanation:
- Mechanism of action.
- Advantages and disadvantages.
- Consideration of alternative forms of contraception.
- Types of COC pill. Choice of first-line options.
- Establish safety by using UK medical eligibility criteria (UKMEC).
- Exclude pregnancy.
- Advice on taking the pill:
- When/how to start.
- Missed pill advice.
- Diarrhoea and vomiting.
- Drug interactions.
- Verbal and written information.
All these elements are discussed in detail below.
Mechanism of action
The COC pill prevents conception by acting on:
- The hypothalamic-pituitary-ovarian axis to suppress synthesis and secretion of follicle-stimulating hormone and the mid-cycle surge of luteinising hormone, thus inhibiting the development of ovarian follicles and ovulation.
- Cervical mucus to prevent penetration of sperm.
- The endometrium to inhibit blastocyst implantation.
The efficacy of any contraceptive method depends on the protection afforded by the technique itself and how consistently and correctly it is used.
The failure rate for the COC pill (when used perfectly) is estimated to be only 3 pregnancies per 1,000 women per year. However, the typical failure rate is closer to 90 pregnancies per 1,000 women per year.
The efficacy of the COC pill may be decreased by severe vomiting or diarrhoea and concurrent use of other enzyme-inducing medications.
Advantages and disadvantages
- Non-invasive method.
- Menses tend to become regular, lighter and less painful. The COC pill has been shown to have similar efficacy to mefenamic acid for menorrhagia, and there is weak evidence for it as a treatment of dysmenorrhoea[4, 5].
- Running packets together allows control of timing of menses for events such as holidays, exams, and sporting competitions.
- Some women find the COC pill improves acne. There is evidence that this is the case, but it remains unsure whether one type of pill is better than another, and how effective it is in comparison to alternative treatments for acne.
- It may help symptoms of premenstrual syndrome (PMS). Trials are ongoing, particularly for those pills containing drospirenone which claim efficacy for this condition[7, 8].
- The COC pill has been shown to reduce the risk of ovarian, endometrial and colorectal cancer. The risk reduction is most significant for ovarian cancer. For every 5 years of use, there is a 20% reduction in the risk of ovarian cancer, and after 15 years of use a woman's risk is half that of a woman who has never taken the pill. (There is currently insufficient evidence to support or advise against the use of the COC pill for the primary prevention of ovarian cancer.)
- It may reduce risk of ovarian cysts.
- User-dependent method. Relies on remembering to take it regularly. Less effective than long-acting reversible methods of contraception (LARCs).
- There may be side-effects in some women. Discussed below.
- Risks - particularly venous thromboembolism (VTE). Discussed below.
- May cause an increase in blood pressure.
- Does not protect against sexually transmitted infections (STIs) so condoms should also be used.
- Breakthrough bleeding (BTB) may occur, particularly in the first few months of use.
Discussion of advantages, disadvantages and risks of the COC pill should include discussion of alternative methods of contraception in order to allow the woman to make an informed choice.
Venous thromboembolism (VTE)
There is a well-established small increase in risk of VTE for women on the COC pill. Risk increases with the dose of oestrogen. Latest evidence suggests the following:
- Risk in healthy non-pregnant women is 2 per 10,000.
- Risk is increased to 5-7 per 10,000 in women in COC pills containing ethinylestradiol plus levonorgestrel, norgestimate or norethisterone.
- Risk is increased to 9-12 per 10,000 women in those COC pills containing ethinylestradiol plus gestodene, desogestrel or drospirenone.
- The absolute risk is small and less than the risk conferred by pregnancy.
The Medicines and Healthcare products Regulatory Agency (MHRA) and the Faculty of Sexual and Reproductive Healthcare (FSRH) continue to advise that in most women the benefits outweigh the risk, but that each woman must be assessed for her individual risk of VTE so that prescribing for higher-risk women can be avoided. (See below for UKMEC.)
The 2014 Cochrane review suggests a pill with the lowest possible dose of ethinylestradiol along with levonorgestrel has the lowest risk of VTE.
Myocardial infarction and stroke
There is a very small increase in risk, increased in those with multiple risk factors for these conditions.
There is a possible very small increased risk of breast cancer in women taking the COC pill. (Women with current breast cancer should not have the COC pill and in those with known gene mutations such as the BRCA1 the risk may outweigh the benefits.)
There is thought to be a small increase of cancer of the cervix after five years of use of the COC pill, and a two-fold risk after 10 years. Cervical cancer is not a contra-indication to use.
Types of combined oral contraceptive pills and which to choose
COC pills differ from each other in the following ways:
- Dose variability over 28 days:
- Monophasic: the dose of oestrogen and progestogen is constant in the active tablets (majority of pills).
- Phasic: the amount of oestrogen and progestogen varies through the cycle. This may be biphasic (two different doses - eg, BiNovum®), triphasic (three different doses - eg, TriNovum®, Logynon®) or quadriphasic (four different doses - eg, Qlaira®).
- Strength and type of oestrogen. Most pills contain 30-35 micrograms of ethinylestradiol (may be higher in phased pills). Low-strength pills contain 20 micrograms of ethinylestradiol. The newer pills Qlaira® and Zoely® contain synthetic estradiol.
- Strength and type of progestogen. Commonly used progestogens are levonorgestrel, norgestimate, norethisterone (all associated with lower thrombotic risks), desogestrel, gestodene and drospirenone. Zoely® uses the new progestogen, nomegestrol. Co-cyprindiol products such as Dianette®, used primarily for acne, contain cyproterone. This has higher risks of VTE than the three lower-risk progestogen products, but no higher risk than the others.
- The pill-free interval. Most COC pills come in calendar packs of 21 active pills. No tablet is taken in the pill-free interval of seven days. However, some brands come with a "dummy" pill for seven days to help concordance (eg, Microgynon 30 ED®, Logynon ED®, and Femodene ED®). Zoely® has four inactive pills; Qlaira® has two.
A first-line choice would be a monophasic preparation with the lowest possible risk of VTE. This would usually be a preparation containing 20-35 micrograms of ethinylestradiol plus levonorgestrel or norethisterone. However a person's preference can be taken into account, as any COC pill may be prescribed as first-line. FRSH guidance does not suggest any one preparation over another.
Choice of pill-taking regimen
Dr Sarah Jarvis, 21st January 2019
New guidance from the Faculty of Sexual and Reproductive Healthcare (FSRH)on combined hormonal contraception makes the following statements and recommendations:
- There are no health benefits to patients of having a monthly withdrawal bleed. All women should therefore be advised of all CHC regimes, both standard and tailored, and allowed to choose the alternative they prefer.
- Women should be advised that while tailored regimes are out with the manufacturer’s licence, they are supported by the FSRH.
- Use of continuous-use CHC is associated with an increase in intermenstrual bleeding, but this usually settles with time.
- Most evidence suggests no association between weight/body mass index (BMI) and effectiveness of combined oral contraceptives (COCs). There is some evidence that patch effectiveness may be reduced in women ≥90 kg.
- Effectiveness of the COC may be reduced in women who have had bariatric surgery.
- Many women can safely be offered an initial prescription for 12 rather than 3 months’ supply of CHC.
- Online, rather than face-to-face, consultation for CHC provision is possible as long as the former includes the same checks and information provision to women.
Tailored regimes for CHC include:
- Tricycling - 3 x 21 active pills consecutively, followed by 4- or 7-day hormone-free interval (HFI).
- Continuous use - no HFI between 21-day packs
- Flexible extended use - continuous use of CHC with no gap between packs until breakthrough bleeding occurs for 3-4 days, followed by 4-day HFI.
- Shortened hormone-free interval - 4-day instead of 7-day HFI between packs.
UK Medical Eligibility Criteria (UKMEC)
The UKMEC was initially produced in 2006, adapted from the World Health Organization (WHO) medical eligibility criteria. In considering prescription and choice of the COC pill as contraception, an assessment regarding suitability and safety must be made. The COC pill can only be prescribed safely in consultation with UKMEC guidance. Conditions are classified into four categories, with increasing risk to users of contraception:
- Category 1: no restriction to use.
- Category 2: advantages of use of the method of contraception generally outweigh the risks.
- Category 3: risks generally outweigh advantages. Use is not usually recommended.
- Category 4: use of the contraceptive method would result in unacceptable risk to health.
For a complete list and for precise categories, refer to the full UKMEC guidance. All health professionals prescribing the COC pill, should be aware of, and have easy access to, the UKMEC, so they can refer to them where necessary. They are a comprehensive list of relevant medical conditions which can be excluded by a thorough history and assessment. Some of the more common conditions which confer a UKMEC Category 3 or 4 risk for the COC pill, meaning the COC pill should probably not be prescribed, are:
- Age over 50 years.
- BMI of 35 kg/m2 or more.
- In smokers aged 35 or more. Also those aged 35 or more who have smoked within the preceding year.
- Migraine with aura.
- Postnatal women who are breast-feeding up to six weeks.
- Postnatal women who are not breast-feeding up to three weeks if no other risk factors for VTE, up to six weeks if other risks.
- In those with multiple risks of cardiovascular disease (ie smoking, hypertension, obesity, diabetes, older age).
- Hypertension (systolic blood pressure greater than 140 mm Hg and/or diastolic blood pressure greater than 90 mm Hg, and controlled hypertension, are Category 3, whilst higher readings confer Category 4 risk).
- Vascular disease.
- History of VTE or current VTE.
- Family history of VTE in a first-degree relative under the age of 45.
- Prolonged immobility due to major surgery or disability.
- History of coronary heart disease or stroke.
- Diabetes with complications such as nephropathy, retinopathy, neuropathy or vascular disease.
- Valvular or congenital heart disease with complications. Also cardiomyopathy with impaired cardiac function.
- Atrial fibrillation.
- Breast cancer.
- Primary liver cancers and severe cirrhosis.
- Gallbladder disease and cholestasis.
- Systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies.
- Known thrombogenic mutations, such as factor V Leiden deficiency.
- Women taking liver enzyme-inducing medication which interacts, including some antiretroviral therapy, certain antibiotics (rifampicin, rifabutin), St John's wort and some anticonvulsants.
Assessment before starting the combined oral contraceptive pill
- A full clinical history must be taken:
- Current and previous medical conditions.
- Medication use, including prescription, over-the-counter and herbal remedies.
- Family history.
- Specifically enquire about:
- Previous VTE and family history of VTE.
- Record blood pressure and BMI.
- Check any past or current conditions/medication against UKMEC.
- Exclude pregnancy by history and pregnancy test if appropriate.
- Assess competence to decide, especially in teenage girls and women with special needs. For information on guidelines surrounding prescribing for girls under the age of 16, see the separate Contraception and Young People article.
There are many commonly used medications which can affect the efficacy of the pill:
- Antibacterials - enzyme inducers only - eg, rifampicin, rifabutin.
- Antidepressants - St John's wort (which can be bought over-the-counter).
- Anticonvulsants - carbamazepine, oxcarbazepine, eslicarbazepine, phenobarbital, phenytoin, primidone and topiramate due to their enzyme-inducing activity. Also lamotrigine which has a specific safety warning - there is an increased risk of seizure whilst taking the COC pill with lamotrigine, and a risk of toxicity during the pill-free week, when levels rise. Therefore risk may outweigh benefit (UKMEC Category 3).
- Antiretrovirals - in particular, ritonavir-boosted protease inhibitors.
- Ulipristal acetate (the "morning after pill" ellaOne®).
|Type of medication||Advice given|
|Non-enzyme-inducing antibacterial.||Women should be advised that no additional contraception is required.|
|Short course (two months or less) of enzyme-inducing antibacterials rifampicin or rifabutin.||Women are advised to continue taking the COC and use additional precautions. Monophasic 21-day pills should be taken either as an extended regimen (continue packets without a break until 3-4 days of BTB occurs, then have 4-day pill-free interval) or a tricycling regimen (three packets without a break then a 4-day pill-free interval). Additional contraception should be continued for 28 days after stopping the rifampicin/rifabutin.|
|Long-term course of enzyme-inducing antibacterials rifampicin or rifabutin.||Should be advised to use an alternative, non-hormonal method where possible (very potent enzyme inducers).|
|Other enzyme-inducing drugs, including anticonvulsants, St John's wort, etc.||Short course: advice is as per that above for rifampicin/rifabutin. Long course: women should be encouraged to use alternative methods of contraception. If, having considered alternatives, they still choose the COC, the patient should be advised of the increased risk of pregnancy. Should use a preparation containing at least 50 micrograms of oestrogen. Tricycling or extended regimens as above should be used. If BTB occurs on 50 micrograms, the dose should be increased to a maximum of 70 micrograms.|
|Lamotrigine.||Women should be advised not to take lamotrigine with the COC and should seek another form of contraception (unless also taking a non-enzyme-inducing anticonvulsant such as sodium valproate).|
|Antiretroviral therapies.||Those women on ritonavir-boosted protease inhibitors should be advised to use alternative methods of contraception.|
|Ulipristal acetate.||Women should use additional contraceptive precautions for 14 days after taking ulipristal acetate as ellaOne® for emergency contraception (16 days for Qlaira®). Those taking ulipristal in a higher dose as Esmya® for fibroids should not be advised to use alternative contraception.|
Women on medication which may interact with the contraceptive pill should be advised to carry out a pregnancy test and seek medical advice if there is a very light or no withdrawal bleed. They should also seek advice if they have BTB, which may indicate reduced efficacy in this situation.
Other medications may cause lack of efficacy of the contraceptive pill by causing side-effects such as diarrhoea or vomiting. Women on the anti-obesity pill, orlistat, who experience severe diarrhoea, for example, are advised to use additional contraceptive precautions, as there is a theoretical risk of lack of absorption.
Concomitant administration of the COC pill with some medications may increase levels. This may be the case with theophylline, and levels should be monitored. Tacrolimus levels may also be increased, and effect should be monitored.
The COC pill should be started on the first day of menstrual bleeding, but can be started up to day 5 without the need for extra protection. (For Qlaira® and Zoely®, unless it is started on Day 1, additional precautions should be used for nine days and seven days respectively.)
When started at any other time in the cycle, additional contraceptive precautions (eg, condoms) should be used for seven days (nine days for Qlaira®.) The woman should be as certain as she can be that she is not pregnant.
The COC pill can be started immediately after emergency contraception, but women should use additional contraceptive precautions for seven days after levonorgestrel, and 14 days after ulipristal acetate.
Take time to explain that the COC pill is usually taken for 21 consecutive days, at approximately the same time of day (mobile phones can also act as alerts/alarms). This is followed by seven pill-free days (or seven days of neutral tablets) to allow endometrial shedding and a withdrawal bleed. Contraception is still provided during the hormone-free interval. For preparations containing 28 pills there is no pill-free interval.
Explain that only the first pill is taken on the first day of the woman's period. Future packets will all be started on the same day of the week as the first packet, following a strict 28-day cycle.
Advise women to choose a time of day when they can consistently take their pill to help get into a habit, and make it easier to remember. If they take it more than 48 hours after the last pill (ie more than 24 hours late) it counts as a missed pill.
Clinical Editor's comments (October 2017)
Dr Hayley Willacy draws your attention to recent advice from family planning expert, Professor John Guillebaud. He told the RCGP annual conference in Liverpool last week that the recommendation to take the pill on a 21/7 regimen was made 60 years ago and was 'based arbitrarily on the calendar, and not on science'. A study published in 1990 in the British Journal of Family Planning (n=120) found that half of women aged 18 to 30 years taking a low-dose oral contraceptive with a pill-free interval had quiescent ovaries on the seventh pill-free day. However, in 23% of women, pre-ovulatory follicles were present. These follicles can readily reach sizes leading to ovulation if the pill-free interval is inadvertently lengthened by the woman forgetting to take the first or second pill of a new pack. Not only does this occur commonly but women are also more likely to have intercourse during this time, after abstaining during the withdrawal bleed. Taking pills continuously affords a greater margin of error as most women will be able to miss up to seven pills and still be protected against pregnancy, even if they had sex in that week, said Professor Guillebaud. Taking the pill in this way is an off-licence indication but does make the pill more effective as a contraceptive, and reduces problems such as period pain, PMS and migraine.
Missed pill advice
See the separate Missed Contraceptive Pills article for further information.
- Advise that the leaflet in the packet contains specific recommendations, but that missing one pill, at any time, does not compromise contraception.
- Pills missed at the beginning or end of the pack confer the most risk of pregnancy.
- Advise that if a woman misses two or more pills, she should refer to the information in her packet which will inform her of what to do.
- Advice for Qlaira® and Zoely® differs from the others types of COC pill.
Diarrhoea and vomiting
Give advice about what to do in the event of diarrhoea or vomiting:
- Vomiting within two hours of taking the pill, or very severe diarrhoea, can affect the absorption of the pill.
- A woman who vomits within two hours of taking a pill should ideally take another one as soon as possible.
- The advice for women who experience vomiting or diarrhoea for more than 24 hours is to follow the same advice as if they had missed pills.
- This advice is different for Qlaira® and Zoely®, and women should follow the advice in the packet.
The patient should be informed that avoidance of bleeding can be managed by extended or continuous administration of the COC pill:
- It has become popular for the treatment of endometriosis, dysmenorrhoea and menstrual-associated symptoms.
- Women may be given the option of "tricycling" packets of pills to avoid menstrual periods, for reasons of personal choice.
- Women are likely to report less and lighter bleeding with reduced menstrual pain and bloating.
- Similar rates of BTB are found with single or extended cycling.
Advise women about possible side-effects, and inform them that the majority will settle very quickly if they persevere for 2-3 months:
- Breakthrough bleeding. See the separate Breakthrough Bleeding with Combined Hormonal Contraception article. Women should be advised that this can occur with the COC pill, most commonly in the first few months. If there has been no vomiting or diarrhoea and there have been no missed pills, it has not been shown to indicate reduced efficacy. If it occurs, consider sexually transmitted infections, pregnancy, missed pills, and malabsorption as possible causes. However, BTB is a common side-effect.
- Weight gain. This is commonly thought to be a side-effect. Reassure women that Cochrane reviews have consistently failed to show any evidence that significant weight gain is a side-effect of the COC pill.
- Mood changes. Studies have not convincingly shown a causal relationship between the COC pill and mood changes. There is no evidence that it causes depression.
- Other temporary adverse effects may include breast tenderness, headaches and nausea.
- If side-effects do not settle over the first three months, an alternative COC pill or an alternative form of contraception may be tried.
Provide women with written information to read, as there is a lot to take in at a first pill prescription consultation. Family planning association (fpa) leaflets are extremely helpful, and these can be given to the woman or she can be directed to their website. Also direct the woman to the information that will be found within her pill packets, as this will be relevant to the individual pill she is taking.
- Ideally, follow-up should be after three months, but advise the patient to come sooner if she becomes concerned. Provide information on signs that should prompt medical opinion - eg, new headache or VTE.
- Women should be encouraged to persist for three months before considering an alternative.
- Repeat blood pressure measurement, and document the results.
- Enquire about adverse effects or problems.
Further reading and references
FSRH Clinical Guidance: Quick Starting Contraception; Faculty of Sexual and Reproductive Healthcare (Apr 2017)
Contraception and Sexual Health 2008/09; Office for National Statistics
Trussell J; Contraceptive failure in the United States, Contraception, 2011
Contraception - combined hormonal methods; NICE CKS, June 2012 (UK access only)
Farquhar C, Brown J; Oral contraceptive pill for heavy menstrual bleeding. Cochrane Database Syst Rev. 2009 Oct 7(4):CD000154. doi: 10.1002/14651858.CD000154.pub2.
Wong CL, Farquhar C, Roberts H, et al; Oral contraceptive pill for primary dysmenorrhoea. Cochrane Database Syst Rev. 2009 Oct 7(4):CD002120. doi: 10.1002/14651858.CD002120.pub3.
Arowojolu AO, Gallo MF, Lopez LM, et al; Combined oral contraceptive pills for treatment of acne. Cochrane Database Syst Rev. 2012 Jul 117:CD004425. doi: 10.1002/14651858.CD004425.pub6.
Lopez LM, Kaptein AA, Helmerhorst FM; Oral contraceptives containing drospirenone for premenstrual syndrome. Cochrane Database Syst Rev. 2012 Feb 152:CD006586. doi: 10.1002/14651858.CD006586.pub4.
Schindler AE; Non-contraceptive benefits of oral hormonal contraceptives. Int J Endocrinol Metab. 2013 Winter11(1):41-7. doi: 10.5812/ijem.4158. Epub 2012 Dec 21.
Davidson BA, Moorman PG; Risk-benefit assessment of the combined oral contraceptive pill in women with a family history of female cancer. Expert Opin Drug Saf. 2014 Oct13(10):1375-82. doi: 10.1517/14740338.2014.951327. Epub 2014 Aug 22.
Beral V, Doll R, et al; Collaborative Group on Epidemiological Studies of Ovarian Cancer. Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet. 2008 Jan 26371(9609):303-14.
Havrilesky LJ, Gierisch JM, Moorman PG, et al; Oral contraceptive use for the primary prevention of ovarian cancer. Evid Rep Technol Assess (Full Rep). 2013 Jun(212):1-514.
FSRH Healthcare Statement: Venous Thromboembolism (VTE) and Hormonal Contraception; Faculty of Sexual and Reproductive Healthcare, November 2014
de Bastos M, Stegeman BH, Rosendaal FR, et al; Combined oral contraceptives: venous thrombosis. Cochrane Database Syst Rev. 2014 Mar 33:CD010813. doi: 10.1002/14651858.CD010813.pub2.
Combined Hormonal Contraception; Faculty of Sexual and Reproductive Healthcare (2011 updated August 2012)
FSRH Clinical Guidance: Combined Hormonal Contraception; Faculty for Sexual and Reproductive Healthcare (January 2019)
UK Medical Eligibility Criteria for Contraceptive Use; Faculty of Sexual and Reproductive Healthcare (2016)
Drug Interactions with Hormonal Contraception; Faculty of Sexual and Reproductive Healthcare (January 2011 - updated January 2012)
British National Formulary (BNF); NICE Evidence Services (UK access only)
Edelman A, Micks E, Gallo MF, et al; Continuous or extended cycle vs. cyclic use of combined hormonal contraceptives for contraception. Cochrane Database Syst Rev. 2014 Jul 297:CD004695. doi: 10.1002/14651858.CD004695.pub3.
Gallo MF, Lopez LM, Grimes DA, et al; Combination contraceptives: effects on weight. Cochrane Database Syst Rev. 2014 Jan 291:CD003987. doi: 10.1002/14651858.CD003987.pub5.