The combined oral contraceptive pill (COCP) contains a combination of oestrogen and progesterone. The combined pill is more than 99% effective with perfect use, but less effective with typical use (91%). The pill is licensed for use up to the age of 50 years.
Mechanism of Action
The COCP prevents pregnancy in three ways:
- Preventing ovulation (this is the primary mechanism of action)
- Progesterone thickens the cervical mucus
- Progesterone inhibits proliferation of the endometrium, reducing the chance of successful implantation
Oestrogen and progesterone have a negative feedback effect on the hypothalamus and anterior pituitary, suppressing the release of GnRH, LH and FSH. Without the effects of LH and FSH, ovulation does not occur. Pregnancy cannot happen without ovulation.
The lining of the endometrium is maintained in a stable state while taking the combined pill. When the pill is stopped the lining of the uterus breaks down and sheds. This leads to a “withdrawal bleed“. This is not classed as a menstrual period as it is not part of the natural menstrual cycle. “Breakthrough bleeding” can occur with extended use without a pill-free period.
There are two types of COCP to be aware of:
- Monophasic pills contain the same amount of hormone in each pill
- Multiphasic pills contain varying amounts of hormone to match the normal cyclical hormonal changes more closely
Everyday formulations (e.g. Microgynon 30 ED) are monophasic pills, but the pack contains seven inactive pills, making it easier for women to keep track by simply taking the pills in order every day.
Different formulations vary in the amount of oestrogen (ethinylestradiol) and the type of progesterone they contain. Examples of monophasic combined contraceptive pills are:
- Microgynon contains ethinylestradiol and levonorgestrel
- Loestrin contains ethinylestradiol and norethisterone
- Cilest contains ethinylestradiol and norgestimate
- Yasmin contains ethinylestradiol and drospirenone
- Marvelon contains ethinylestradiol and desogestrel
The NICE Clinical Knowledge Summaries (2020) recommend using a pill with levonorgestrel or norethisterone first line (e.g. Microgynon or Leostrin). These choices have a lower risk of venous thromboembolism.
Yasmin and other COCPs containing drospirenone are considered first-line for premenstrual syndrome. Drospirenone has anti-mineralocorticoid and anti-androgen activity, and may help with symptoms of bloating, water retention and mood changes. Continuous use of the pill, as opposed to cyclical use, may be more effective for premenstrual syndrome.
Dianette and other COCPs containing cyproterone acetate (i.e. co-cyprindiol) can be considered in the treatment of acne and hirsutism. Cyproterone acetate has anti-androgen effects, helping to improve acne and hirsutism. The oestrogenic effects mean that co-cyprindiol has a 1.5 – 2 times greater risk of venous thromboembolism compared to the first-line combined pills (e.g. Microgynon). It is usually stopped three months after acne is controlled, due to the higher risk of VTE.
The combined pill can be taken in different regimes to suit the individual. These regimes are equally safe and effective. Three common options are:
- 21 days on and 7 days off
- 63 days on (three packs) and 7 days off (“tricycling“)
- Continuous use without a pill-free period
Side Effects and Risks
- Unscheduled bleeding is common in the first three months and should then settle with time
- Breast pain and tenderness
- Mood changes and depression
- Venous thromboembolism (the risk is much lower for the pill than pregnancy)
- Small increased risk of breast and cervical cancer, returning to normal ten years after stopping
- Small increased risk of myocardial infarction and stroke
The benefits of the combined pill include:
- Effective contraception
- Rapid return of fertility after stopping
- Improvement in premenstrual symptoms, menorrhagia (heavy periods) and dysmenorrhoea (painful periods)
- Reduced risk of endometrial, ovarian and colon cancer
- Reduced risk of benign ovarian cysts
When starting any form of contraception, it is essential to consider the contraindications for the individual. There are specific risk factors that should make you avoid the combined contraceptive pill (UKMEC 4):
- Uncontrolled hypertension (particularly ≥160 / ≥100)
- Migraine with aura (risk of stroke)
- History of VTE
- Aged over 35 and smoking more than 15 cigarettes per day
- Major surgery with prolonged immobility
- Vascular disease or stroke
- Ischaemic heart disease, cardiomyopathy or atrial fibrillation
- Liver cirrhosis and liver tumours
- Systemic lupus erythematosus (SLE) and antiphospholipid syndrome
It is worth noting that a BMI above 35 is UKMEC 3 for the combined pill (risks generally outweigh the benefits).
TOM TIP: The UKMEC guidelines have helpful tables that allow you to compare risk factors quickly and assess which form of contraception is most suited to the individual. It is worth looking these up and getting familiar with them, then using them when counselling patients if required.
Starting the Pill
Start on the first day of the cycle (first day of the menstrual period). This offers protection straight away. No additional contraception is required if the pill is started up to day 5 of the menstrual cycle.
Starting after day 5 of the menstrual cycle requires extra contraception (i.e. condoms) for the first 7 days of consistent pill use before they are protected from pregnancy. Ensure the woman is not already pregnant before starting the pill (i.e. they have been using contraception reliably and consistently).
When switching between COCPs, finish one pack, then immediately start the new pill pack without the pill-free period.
When switching from a traditional progesterone-only pill (POP), they can switch at any time but 7 days of extra contraception (i.e. condoms) is required. Ensure the woman is not already pregnant before switching (i.e. they have been using contraception reliably and consistently).
When switching from desogestrel, they can switch immediately, and no additional contraception is required. This differs from a traditional POP because desogestrel inhibits ovulation.
There are several things to check and discuss when prescribing the combined pill:
- Different contraceptive options, including long-acting reversible contraception (LARC)
- Adverse effects
- Instructions for taking the pill, including missed pills
- Factors that will impact the efficacy (e.g. diarrhoea and vomiting)
- Sexually transmitted infections (this pill is not protective)
- Safeguarding concerns (particularly in those under 16)
Screen for contraindications by discussing and documenting:
- Weight and height (BMI)
- Blood pressure
- Smoker or non-smoker
- Past medical history (particularly migraine, VTE, cancer, cardiovascular disease and SLE)
- Family history (particularly VTE and breast cancer)
Missed pill rules are commonly tested in exams, either in MCQs or by having to council a patient in an OCSE scenario. It is worth understanding the theory as this makes it easier to work out what to do. In reality, always double-check the rules with guidelines or product literature to make sure you get it right.
The best way to understand the rules is to consider that theoretically women will be protected if they perfectly take the pill in a cycle of 7 days on, 7 days off. This will prevent ovulation.
Missing one pill is when the pill is more than 24 hours late (48 hours since the last pill was taken).
Missing one pill (less than 72 hours since the last pill was taken):
- Take the missed pill as soon as possible (even if this means taking two pills on the same day)
- No extra protection is required provided other pills before and after are taken correctly
Missing more than one pill (more than 72 hours since the last pill was taken):
- Take the most recent missed pill as soon as possible (even if this means taking two pills on the same day)
- Additional contraception (i.e. condoms) is needed until they have taken the pill regularly for 7 days straight
- If day 1 – 7 of the packet they need emergency contraception if they have had unprotected sex
- If day 8 – 14 of the pack (and day 1 – 7 was fully compliant) then no emergency contraception is required
- If day 15 – 21 of the pack (and day 1 – 14 was fully compliant) then no emergency contraception is needed. They should go back-to-back with their next pack of pills and skip the pill-free period.
Theoretically, additional contraception is not required if more than one pill is missed between day 8 – 21 (week 2 or 3) of the pill packet and they otherwise take the pills correctly, although it is recommended for extra precaution.
Vomiting, diarrhoea and certain medications (e.g. rifampicin) can all reduce the effectiveness of the pill, and additional contraception may be required. A day of vomiting or diarrhoea is classed as a “missed pill” day, as the illness may affect the absorption.
NICE Clinical Knowledge Summaries (January 2019) recommends stopping the combined pill four weeks before a major operation (lasting more than 30 minutes) or any operation or procedure that requires the lower limb to be immobilised. This is to reduce the risk of thrombosis.
Last updated August 2020