Combined oral contraceptives: Issues for current users

In this article

• Medical conditions that affect the suitability of COC use
• Important drug interactions
• Minor adverse effects
• UK Medical Eligibility Criteria (UKMEC) for combined oral contraceptive use ²
• References

In this article

Approximately 147,000 women in New Zealand take oral contraceptives. About 80% of these women take combined oral contraceptives (COC) containing oestrogen and a progestogen.¹

This article offers guidance for managing situations when women who are currently using COCs:

• Develop conditions which affect their suitability for COC use.
• Require other medicines that interact with COCs.
• Experience adverse effects.

A follow up visit is appropriate to measure blood pressure and assess any problems, three months after a first prescription of an oral contraceptive, and then at least yearly thereafter. Women should also be advised to return if any problems arise.²

Medical conditions that affect the suitability of COC use

The use of COCs must be carefully considered in certain medical conditions. The UK Medical Eligibility Criteria (UKMEC) for combined oral contraceptive use provides guidance on suitability of COCs in particular conditions (view tables here).²

Conditions that may require review of COC use

Women whose clinical condition changes while using hormonal contraception require assessment on an individual basis. It may be appropriate to discuss risks and benefits and offer alternative contraceptive methods that pose less risk.

COCs are contraindicated in migraine with aura
Combined oral contraceptives increase the risk of stroke in women who suffer from migraines with aura. COCs should therefore not be started by women of any age who suffer from migraine with aura. They should also be discontinued in women who develop migraine with aura whilst already on COC.³ Progestogen only or non hormonal methods can be considered for these women.³

COCs are best discontinued if migraine without aura develops
It is usually recommended that women who develop migraine without aura following initiation of COC should discontinue use, especially women over 35 years. Progestogen only or non hormonal methods can also be considered for these women.³

Pre-existing migraine without aura in women less than 35 years old is not a contraindication to COC initiation.

COCs increase the risk of venous
thromboembolism
Combined oral contraceptive users have a higher risk of venous thromboembolism (VTE) than non-users (see table below).

COCs are contraindicated for women with a current or past history of VTE and best avoided for those at high risk. Risk factors include obesity, smoking, or a family history of VTE in a first degree relative younger than 45 years old.³ Progestogen only or non hormonal methods can be used.

COC use in heavy smokers substantially increases cardiovascular risk³
COCs can generally be used in women younger than 35 years who smoke, however their use is not advised in women over 35 years who smoke. Progestogen only or non hormonal methods can be used in women who smoke.

Get a PDF of VTE, Table 2 and table 3

COCs may increase the risk of MI or stroke in the presence of multiple cardiovascular risk factors
There is weak evidence that COCs increase the risk of myocardial infarction and ischaemic stroke, however the absolute risk is still low.³

In women with multiple cardiovascular risk factors (e.g. older age, smoking, diabetes, hypertension, obesity or a family history of cardiovascular disease before age 50) the risk may be increased further.

COCs are best avoided in these women, however progestogen only or non hormonal methods can be used.⁸

Important drug interactions

Ethinyloestradiol and progestogens are metabolised by liver enzymes. Induction of these enzymes by certain drugs may affect the plasma concentration of contraceptive hormones. Some anti-epileptics and antibiotics are examples of drugs that may reduce the concentration of hormonal contraceptives and decrease their efficacy. Table 1 provides a list of drugs that interact with oral contraceptives. The list is not comprehensive.

Practice points for oral contraceptive interactions

Liver enzyme inducing drugs:
COCs and POPs are both affected; alternative methods of contraception may be a better choice for women using enzyme inducers long-term.

For short-term use of enzyme inducers, women taking COCs should use a 50 microgram daily dose of ethinyloestradiol and use additional precautions for the duration of treatment and for four weeks afterwards.

Antibiotics:
The antibiotics listed in the table as liver enzyme inducers should be dealt with as above. Although other antibiotics are not liver enzyme inducers, they may temporarily decrease colonic bacteria and therefore inhibit the enterohepatic circulation of ethinyloestradiol.⁷ Progestogen is not affected.

Generally the evidence for this interaction is weak and often based on anecdotal reports, however because the consequences of an unwanted pregnancy can be serious the following advice is provided for all antibiotics:

Women on short courses (less than three weeks) of antibiotics should be advised to use additional precautions during the course and until seven consecutive active pills have been taken after antibiotics have been discontinued. This may require missing the inactive pills or the pill-free week.

It is thought that gut flora develop resistance to non-enzyme inducing antibacterials after three weeks of treatment and for this reason additional precautions are not required after this time.⁶

Minor adverse effects

Most COCs contain the same oestrogen (ethinyloestradiol) and for that reason the properties of individual products are based on the amount of ethinyloestradiol in the tablet along with the varying properties of the progestogen (Table 2).

The activity of various progestogens is largely based on animal experiments and how this applies to humans is largely unknown. The dose is often adjusted to make different progestogens approximately equivalent in terms of their activity and for these reasons there is some debate about whether different progestogens are better or worse in terms of side effects or clinical responses.⁹

There is limited clinical evidence to guide pill changes when women experience adverse effects on a particular pill; however there are some principles that may guide choice (Table 3). Often a change in COC type can help to improve some adverse effects as long as it does not increase the risk of more serious medical conditions. Many side effects are commonly experienced in the first three months and may subside after this time therefore it is best to try a particular pill for at least three cycles before switching.^{5, 9}

Get a PDF of VTE, Table 2 and table 3

Get a PDF of VTE, Table 2 and table 3

Level of oestrogen affects side effect profile

COCs contain 20–50 micrograms of ethinyloestradiol; 20 micrograms being considered low-strength, 30–40 micrograms standard-strength and 50 micrograms high strength.

Generally, advice at present is to start with a standard dose pill and a first or second generation progestogen (lower VTE risk) e.g. Levlen, Monofeme or Norimin. These pills are fully funded and cost $3 for six months supply.

GPs may favour using the lowest effective dose of ethinyloestradiol as it would theoretically carry a lower risk of adverse effects associated with oral contraceptive use such as thrombosis or myocardial infarction.

Authors of a Cochrane review compared lower- versus higher-dose oestrogen for contraception. While they could not detect differences in rare adverse effects or contraceptive effectiveness they found lower-dose oestrogen COCs resulted in higher rates of bleeding pattern disruptions and early trial discontinuation.¹⁰

High-strength preparations containing 50 micrograms of ethinyloestradiol are generally used only in situations where the bioavailability of ethinyloestradiol will be reduced, for example in women who are concomitantly taking enzyme-inducing drugs.²

Type of progestogen may affect side effect profile

A Cochrane review that compared various progestogens in COCs found that second and third generation progestogens were preferred to norethisterone (first generation) across all acceptability indices they measured including; effectiveness (pregnancy rates), discontinuation rates, reasons for discontinuation, cycle control, and side effects. It also found that gestodene has comparable contraceptive effectiveness to levonorgestrel and desogestrel and that drospirenone is similar to desogestrel.¹²

The newer progestogens, gestodene and desogestrel are associated with a slightly increased absolute risk of VTE compared with levonorgestrel or norethisterone. Cyproterone acetate has a higher risk and is not generally recommended unless the woman has androgenic features such as acne and hirsutism or polycystic ovary syndrome (see article).

Switching COCs

When switching COCs containing different progestogens, the new COC should be started the day after the last active pill has been taken from the previous COC. For 28 day packs, this will mean missing out the seven inactive pills. If a seven-day break is taken before starting the new brand then additional precautions will be required until seven active pills have been taken.

Summary

COCs are generally safe, however their use may need review in some situations. Medical conditions may arise where a COC is no longer suitable and is best discontinued or the experience of adverse effects may require a trial of a different COC. Drug interactions may affect COC efficacy and additional precautions may be required.

UK Medical Eligibility Criteria (UKMEC) for combined oral contraceptive use ²