Combined oral contraceptive pill- first prescription

Synonyms: combined pill, 'The Pill'

The combined oral contraceptive (COC) pill is a highly effective form of contraception and used to control fertility by approximately 20% of women aged 16-49 years in the UK¹ .

Starting the COC pill is an important and complex consultation. It should include:

• Discussion and explanation:

  • Mechanism of action.

  • Efficacy.

  • Advantages and disadvantages.

  • Risks.

  • Consideration of alternative forms of contraception.

  • Types of COC pill. Choice of first-line options.

• Assessment:

  • Establish safety by using UK medical eligibility criteria (UKMEC)² .

  • History.

  • Examination.

  • Exclude pregnancy.

• Advice on taking the pill:

  • When/how to start.

  • Missed pill advice.

  • Diarrhoea and vomiting.

  • Drug interactions.

  • Side-effects.

  • Verbal and written information.

  • Follow-up.

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.

Efficacy

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 year³ .

The efficacy of the COC pill may be decreased by severe vomiting or diarrhoea and concurrent use of other enzyme-inducing medications.

Advantages and disadvantages⁴

Advantages

• 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^{5 6} .

• 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 acne⁷ .

• It may help symptoms of premenstrual syndrome (PMS). Trials are ongoing, particularly for those pills containing drospirenone which claim efficacy for this condition^{8 9} .

• The COC pill has been shown to reduce the risk of ovarian, endometrial and colorectal cancer¹⁰ . The risk reduction is most significant for ovarian cancer. For every five 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 pill¹¹ . (There is currently insufficient evidence to support or advise against the use of the COC pill for the primary prevention of ovarian cancer¹² .)

• It may reduce risk of ovarian cysts.

Disadvantages

• 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.

Risks⁴

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 VTE¹³ .

Myocardial infarction and stroke

There is a very small increase in risk, increased in those with multiple risk factors for these conditions.

Breast cancer

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.)

Cervical cancer

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 choose⁴

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 another¹⁴ .

UK Medical Eligibility Criteria (UKMEC)²

The UKMEC were 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 guidance¹⁵ . 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 breastfeeding up to six weeks.

• Postnatal women who are not breastfeeding 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 pill¹⁶

To ensure that the woman fulfils the criteria of eligibility for use:

• 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:

  • Migraine.

  • Smoking.

  • Hypertension.

  • Thrombophilia.

  • Previous VTE and family history of VTE.

  • Hyperlipidaemia.

• 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.

Interactions

There are many commonly used medications which can affect the efficacy of the pill¹⁷

• 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®).

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.

Advice

When to start¹⁴

If the woman is not currently using a regular method of contraception or using a barrier method (such as condoms):

• She can start the COC pill on day 1 of the menstrual cycle and no additional contraception is required.

• If the COC pill is started on days 2-5 of the menstrual cycle:
  

  • No additional contraception is required unless the woman is starting Qlaira® or Zoely®:
    

    • If the woman is starting Qlaira®, advise her to avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 9 days.

    • If the woman is starting Zoely®, advise her to avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days.

• If the COC is started at any other time in the menstrual cycle, provided a barrier method has been used consistently and correctly and/or it is reasonably certain that the woman is not pregnant:
  

  • Advise the woman to avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days (9 days for Qlaira®).

  • Inform the woman that medical advice may differ from that included in the packet of pills, but it is based on good medical practice.

• If pregnancy cannot be excluded and the woman wishes to start hormonal contraception without delay:
  

  • Prescribe the COC pill and advise the woman to take a pregnancy test no sooner than three weeks after the last episode of unprotected sexual intercourse (UPSI).

If the woman is starting a COC after oral emergency contraception:

• For levonorgestrel, advise the woman to start the COC immediately and avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days (9 days if taking Qlaira®).

• For ulipristal acetate, advise the woman to start the COC 5 days after taking ulipristal acetate, and to use a barrier method of contraception (such as condoms) for this time and the next 7 days (9 days if taking Qlaira®).

If the woman is switching from another combined hormonal method such as the combined contraceptive patch, or the combined vaginal ring:

• Start the COC pill on the day after the last active pill, patch, or vaginal ring. There is no need to wait for the next menstrual period. No additional contraception is required.

• If the woman decides to take a 7-day hormone-free interval (or a 4-day hormone-free interval for Zoely®) before starting the new COC pill, assess the need for additional contraception and emergency contraception.

If the woman is switching from a progestogen-only pill (except desogestrel) or levonorgestrel intrauterine system (LNG-IUS):

• Start the COC pill at any time in the menstrual cycle provided it is reasonably certain that the woman is not pregnant. There is no need to wait for the next menstrual period.

• Advise the woman to avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days (9 days for Qlaira®).

If the woman is switching from the progestogen-only injection or desogestrel-only pill:

• Start the COC pill at any time up to when the repeat of injectable is due, or the next day after the progestogen-only pill. No additional contraception is required.

If the woman is switching from a progestogen-only implant that has been in situ:

• For 3 years or less - advise the woman to start the COC pill immediately and that no additional contraception is required.

• For between 3-4 years and has not had UPSI within the last 3 weeks and the current pregnancy test is negative - advise the woman to start the COC pill immediately and avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days.

• For between 3-4 years and has had UPSI within the last 3 weeks and the current pregnancy test is negative - advise the woman to start the COC pill immediately and avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days, and take a pregnancy test at 3 weeks.

If the woman is switching from a copper intrauterine device (Cu-IUD):

• Remove the IUD on day 1-5 of the menstrual cycle and start the COC pill on the same day (except if starting Qlaira®). No additional contraception is required.

• If starting Qlaira®, remove the IUD on day 1 of the menstrual cycle and start the COC pill on the same day. No additional contraception is required.

• If the IUD is removed at any other time in the menstrual cycle, advise the woman to avoid sexual intercourse or use a barrier method of contraception (such as condoms) for the first 7 days of pill taking (9 days for Qlaira®).

• If the COC pill is started 7 days before removal of the IUD (9 days for Qlaira®) no additional contraception is required.

Excluding pregnancy

Health professionals can be reasonably certain that a woman is not pregnant if there are no signs or symptoms of pregnancy and one or more of the following criteria are met.

• Has not had sexual intercourse since the last normal menses.

• Has used a reliable method of contraception correctly and consistently.

• Is within the first 7 days of the onset of a normal menstrual period.

• Is within 4 weeks postpartum for non-breastfeeding women.

• Is within the first 7 days post-termination of pregnancy, or miscarriage.

• Is fully or nearly fully breastfeeding, amenorrhoeic, and less than 6 months postpartum.

• A pregnancy test is performed no sooner than 3 weeks since the last episode of UPSI and is negative.

Administration

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.

The FSRH guidance¹⁴ now states there are no health benefits to patients of having a monthly withdrawal bleed. All women should therefore be advised of all combined hormonal contraception (CHC) regimes, both standard and tailored, and allowed to choose the alternative they prefer.

Tailored regimes for CHC

The patient should be informed that avoidance of bleeding can be managed by extended or continuous administration of the COC pill, as above:

• It has become popular for the treatment of endometriosis, dysmenorrhoea and menstrual-associated symptoms but can be chosen for personal preference.

• 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.

Possible regimes 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.

Women should be advised that while tailored regimes are out with the manufacturer’s licence, they are supported by the FSRH.

Missed pill advice

See the separate Missed Contraceptive Pills article for further information.

Essentially:

• 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 having 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.

Side-effects

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 STIs, pregnancy, missed pills, and malabsorption as possible causes.

• 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 pill¹⁸ .

• 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.

Written information

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.

Follow-up

• 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.