Combined Oral Contraceptive Pill

• 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 COCP (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 COCP may be decreased by severe vomiting or diarrhoea and concurrent use of other enzyme-inducing medications.

Advantages

• Non-invasive method.
• Menses tend to become regular, lighter and less painful. The COCP has been shown to have similar efficacy to mefenamic acid for menorrhagia, and there is weak evidence for it as a treatment of dysmenorrhoea.
• Running packets together allows control of timing of menses for events such as holidays, exams, and sporting competitions.
• Some women find the COCP 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.
• The COCP 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 COCP for the primary prevention of ovarian cancer.
• 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 COCP should include discussion of alternative methods of contraception in order to allow the woman to make an informed choice.

Risks

• Venous thromboembolism (VTE)

There is a well-established small increase in risk of VTE for women on the COCP. 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 COCPs containing ethinylestradiol plus levonorgestrel, norgestimate or norethisterone.
• Risk is increased to 9-12 per 10,000 women in those COCPs 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 Health (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.

The 2014 Cochrane review suggests a pill with the lowest possible dose of ethinylestradiol along with levonorgestrel has the lowest risk of VTE.[13]

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 COCP. (Women with current breast cancer should not have the COCP 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 5 years of use of the COCP, 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

COCPs 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), triphasic (three different doses - eg, 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 COCPs come in calendar packs of 21 active pills. No tablet is taken in the pill-free interval of 7 days. However, some brands come with a "dummy" pill for 7 days to help concordance (eg, Microgynon 30 ED®, Logynon ED®). Zoely® has 4 inactive pills; Qlaira® has 2.
• 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 COCP may be prescribed as first-line. FRSH guidance does not suggest any one preparation over another.

Some of the more common conditions which confer a UKMEC Category 3 or 4 risk, meaning the COCP should probably not be prescribed, are:

• BMI of 35 kg/m2 or more.
• Breast-feeding up to 6 months postnatally.
• In smokers aged 35 or more.
• In those with multiple risks of cardiovascular disease (ie smoking, hypertension, obesity, smoking, diabetes, older age).
• Hypertension (systolics greater than 140 mm Hg and/or diastolics 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.
• Migraine with aura.
• Cardiac valvular disease with complications.
• Breast cancer.
• Primary liver cancers.
• Gallbladder disease and cholestasis.
• Systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies.
• Some types of secondary Raynaud's disease.
• Known thrombogenic mutations, such as factor V Leiden deficiency.
• Some medication which interacts, including some antiretroviral therapy, enzyme-inducing medication, and some anticonvulsants - especially lamotrigine. See the separate section 'Interactions', below.

Interactions

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 COCP with lamotrigine, and a risk of toxicity during the pill-free week, when levels rise. Therefore risk may outweigh benefit.
• 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 COCP 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.

When to start

• The COCP 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 9 days and 7 days respectively.)
• When started at any other time in the cycle, additional contraceptive precautions (eg, condoms) should be used for 7 days (9 days for Qlaira®.) The woman should be as certain as she can be that she is not pregnant.
• The COCP can be started immediately after emergency contraception, but women should use additional contraceptive precautions for 7 days after levonorgestrel, and 14 days after ulipristal acetate.

Administration

The COCP 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 7 pill-free days (or 7 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.

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.

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.

Missed pill advice

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 COCP.

Diarrhoea and 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.

Extended cycling

• Avoidance of bleeding can be managed by extended or continuous administration of the COCP:
• 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.

Side-effects

The majority will settle very quickly if they persevere for 2-3 months:

• Breakthrough bleeding. This can occur with the COCP, 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. 
• Weight gain. This is commonly thought to be a side-effect. The Cochrane reviews have consistently failed to show any evidence that significant weight gain is a side-effect of the COCP.
• Mood changes. Studies have not convincingly shown a causal relationship between the COCP 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 COCP or an alternative form of contraception may be tried.

References:

http://patient.info/doctor/combined-oral-contraceptive-pill-first-prescription

https://www.nlm.nih.gov/medlineplus/druginfo/meds/a601050.html

http://www.medicinenet.com/oral_contraceptives_birth_control_pills/article.htm

https://en.wikipedia.org/wiki/Oral_contraceptive_pill

https://en.wikipedia.org/wiki/Combined_oral_contraceptive_pill

http://www.ippf.org/our-work/what-we-do/contraception/oral-contraceptives-pill

http://www.familyplanning.org.nz/advice/contraception/combined-oral-contraceptive-pill

https://www.msdmanuals.com/professional/gynecology-and-obstetrics/family-planning/oral-contraceptives