Combined hormonal contraception

What is combined hormonal contraception?

There are three types of combined hormonal contraception (CHC) currently available - the combined oral contraceptive (COC) pill, the contraceptive transdermal patch and the contraceptive vaginal ring. These contraceptive methods contain both oestrogen and progestogen.

Mechanism of action

The CHC methods all prevent 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.

All include a seven-day hormone-free part of each monthly cycle (other than Zoely® and Eloine®, which have four inactive days, and Qlaira, which has two®), during which oestrogen and progestogen levels fall, causing a shedding of the endometrium, so that the woman menstruates monthly.

Whilst this is the traditional way of using combined hormonal contraception, there is no evidence that a monthly bleed (or any bleed at all) is required for safety.¹ "Tailored" regimens are supported by the FSRH and may be preferred by some women; they eliminate or reduce the frequency of withdrawal bleeding, and, theoretically, may increase contraceptive efficacy.² Tailored regimes include:

• Shortening the hormone-free interval to 4 days.

• Extended use (tricycling) - taking combined hormonal contraception for 9 weeks continuously, followed by a 4 or 7 day hormone-free interval.

• Flexible extended use - taking combined hormonal contraception continuously until breakthrough bleeding occurs for 3-4 days, then taking a 4 day hormone-free interval.

• Continuous use.

These regimens are off-label.

Efficacy^{2 3}

Efficacy is dependent on consistency and correct method of use, but is similar between the three types of CHC. The failure rate (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.

A Cochrane review comparing the three methods found:⁴

• Similar efficacy.

• Women are more likely to discontinue the patch than the COC pill; however, there was better compliance with the patch than the COC pill.

• Users of the patch had more side-effects than those using the COC pill.

• Users of the ring had fewer side-effects overall than those using the COC pill, but more vaginal discharge and irritation.

Assessment⁵

In considering prescription and choice of contraception, an assessment regarding suitability and safety must be made. Whilst the woman's preference is critical, CHC can only be prescribed safely in consultation with the UK Medical Eligibility Criteria (UKMEC). 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. Some of the more common conditions which confer a UKMEC Category 3 or 4 risk for CHC, meaning CHC 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 venous thromboembolism (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.

Combined hormonal contraception risks⁶

Broadly, the risks of the different types of CHC are similar. However, there are limited long-term data for the ring and the patch. Results are mixed, but there is some evidence that the ring and patch may carry a slightly higher thrombosis risk.⁷

Venous thromboembolism (VTE) ^{8 2}

There is a well-established small increase in risk of VTE for women on the COC pill. The rsk increases with the dose of oestrogen. VTE risks are estimated as follows:

• Risk in healthy non-pregnant women is 2 per 10,000.

• Risk is increased to 5-7 per 10,000 women in pills containing ethinylestradiol plus levonorgestrel, norgestimate or norethisterone.

• Risk is increased to 6-12 per 10,000 in women using CHC containing etonogestrel (ring) or norelgestromin (patch).

• Risk is increased to 9-12 per 10,000 women in those pills containing ethinylestradiol plus gestodene, desogestrel or drospirenone.

• The absolute risk is small and less than the risk conferred by pregnancy. (Risk in pregnancy is 29 per 10,000 and 300-400 per 10,000 postnatally.)

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. (See above for UKMEC advice.)

The 2014 Cochrane review suggests a pill with the lowest possible dose of ethinylestradiol along with levonorgestrel has the lowest risk of VTE.⁹

Myocardial infarction and stroke

There is a very small increase in risk, increased in those with multiple risk factors for these conditions. The risk of stroke is the reason migraine with aura is a contra-indication to usage of CHC, as migraine increases the risk in these individuals.

Breast cancer

There is a possible very small increased risk of breast cancer in women taking CHC. (Women with current breast cancer should not have CHC 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 CHC, and a two-fold risk after 10 years. Cervical cancer is not a contra-indication to use.

Side-effects of combined hormonal contraception

The majority of side-effects settleafter 2-3 months of use. Potential side-effects of CHC include the following:

• Breakthrough bleeding (BTB). See separate Breakthrough Bleeding with Combined Hormonal Contraception article. Women should be advised that this can occur with CHC, 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.²

• Weight gain is commonly thought to be a side-effect. However, there is no clear evidence that use of CHC causes weight gain.¹⁰

• Mood changes. These are commonly reported. Evidence suggest that some women may experience negative mood changes during CHC use. However, there is an absence of clear, consistent evidence that CHC use causes depression.²

• Other temporary adverse effects may include breast tenderness, headaches and nausea.

• If side-effects do not settle over the first three months, an alternative CHC or an alternative form of contraception may be tried.

Generally the side-effects of all methods of CHC are fairly similar. A Cochrane review found that:

• The patch tends to cause more breast discomfort, dysmenorrhoea, nausea and vomiting when compared to the COC pill.

• The ring causes less nausea, acne, irritability and depression than the COC pill.

• The ring causes more vaginal irritation and discharge.

The combined oral contraceptive pill

For full information on the COC pill, including missed pill advice, choices of pill, disadvantages and advantages, see the following separate articles: Combined Oral Contraceptive Pill (First Prescription), Combined Oral Contraceptive Pill (Follow-up and Common Problems) and Missed Contraceptive Pills.

The contraceptive transdermal patch ^{112 6}

Currently the only combined hormonal patch available in the UK is Evra®, which contains ethinylestradiol 33.9 micrograms/24 hours and norelgestromin 203 micrograms/24 hours.

How the patch is used

A patch should be applied once weekly for three weeks. The first patch is ideally applied on day 1 of the cycle, then the patch changed on days 8 and 15. The third patch is removed on day 22 and a new patch applied after a seven-day patch-free interval to start the subsequent contraceptive cycle. Withdrawal bleeding occurs during the patch-free interval. Each subsequent course of three weeks is repeated after a seven-day patch free interval.

Patches should be applied to clean, dry, hairless areas of skin, such as upper outer arms, upper torso (not breast), buttock, or lower abdomen. They should not be applied to red, broken, or inflamed skin.

Make-up, creams, lotions, powders, or other products should not be used in the area where the patch is placed, as its stickiness can be affected. Patches usually remain adherent in water or during exercise; however, they should be checked daily.

Additional advice about starting:

• If the patch is started on days 2-5, the no additional contraception is required. However, if started later in the cycle, avoidance of sexual intercourse, or use of additional contraceptive measures (barrier methods), is required for seven days.

• If starting after the COC pill or ring, it should be applied the day after the last day of taking the pill, or the last day of the ring, and no additional contraception is required.

• If starting after the levonorgestrel emergency contraceptive pill, the patch can be started immediately but advise the use of additional contraception or to avoid sexual intercourse for seven days.

• If starting after using ulipristal acetate for emergency contraception, advise a wait of five days before starting the patch, and the use of additional contraception or avoidance of sexual intercourse during these five days and the subsequent seven days.

• If starting after any contraceptive progestogen-only pill (POP) other than those containing desogestrel, or the intrauterine system (IUS), the patch can be started at any point in the cycle, and additional contraception should be used, or sexual intercourse avoided, for seven days.

• If starting after any other progestogen-only method, the patch can be started on the first day after the previous method runs out/is removed, and no additional contraception is required.

• If changing to the patch after using a copper intrauterine contraceptive device (IUCD), remove the IUCD on day 1-5 and advise starting the patch the same day. No additional contraception is required. If the IUCD is removed at other times in the cycle, either start the patch seven days before, or start the patch on the day of removal and advise avoidance of sexual intercourse, or use of additional contraception, for seven days.

Advice if the patch comes off

• If the patch came off <48 hours ago, it can be reapplied and changed at the normal time. If it is not sticky enough, a new patch can be reapplied in its place but still changed on the original change day schedule.

• If the patch came off >48 hours ago, or if it is not known when the patch came off, then additional contraceptive measures should be used, or sexual intercourse avoided, for seven days. A new patch should be applied and the change day schedule adjusted accordingly so that this becomes day 1 of week 1. Consider emergency contraception if unprotected intercourse has occurred in the previous five days.

Advice if the patch change has been delayed

• Delayed change at the end of week 1 or week 2:

  • Delay <48 hours: replace with a new patch as soon as possible. It should be changed on the normal day. No additional contraception is required.

  • Delay >48 hours: a new patch should be applied and the change day schedule adjusted accordingly so that this becomes day 1 of week 1. Additional contraceptive measures should be used, or sexual intercourse avoided, for seven days. Consider emergency contraception if unprotected intercourse has occurred in the previous five days.

• Patch not removed at the end of week 3: the patch should be removed as soon as possible. No additional contraception is required. The new patch should be started at the usual time.

• Delay starting a new patch at the end of the cycle (ie after the patch-free week):

  • Delay <48 hours: a new patch should be applied as soon as possible. This is now day 1 and the patch change day for future patch changes. No additional contraception is required.

  • Delay >48 hours: a new patch should be applied as soon as possible. This is now day 1 and the patch change day for future patch changes. Advise additional contraceptive measures, or avoidance of intercourse, for the following seven days. Consider emergency contraception if unprotected intercourse has occurred in the previous five days.

Advantages

The patch is not affected by nausea or vomiting. It only needs changing weekly. As with other methods of CHC, it is effective contraception.

Disadvantages

In addition to the risk profile which is similar to other CHC methods, the patch may cause irritation or a rash. There may be a higher incidence of breast discomfort, dysmenorrhoea, nausea and vomiting than there is with the COC pill. Potential interaction with liver enzyme-inducing medication remains the same as for other CHC options.

It may be difficult to get into a weekly routine.

The contraceptive vaginal ring ^{2 6 11}

Currently the only contraceptive vaginal ring available in the UK is the NuvaRing®, a flexible, latex-free ring delivering etonogestrel 120 micrograms/24 hours and ethinylestradiol 15 micrograms/24 hours.

How the ring is used

The ring should be inserted high into the vagina and left in place for three weeks. There follows a seven-day ring-free interval and then another ring is inserted, starting another cycle. The ring may be left in place when using tampons, or during sexual intercourse. It may be removed (for no more than three hours) if preferred during sexual intercourse.

It should be initiated on day 1-5 of the menstrual cycle, in which case no additional contraceptive measures are required. If starting at any other time in the cycle, pregnancy should be excluded, and additional contraceptive measures and avoidance of sexual intercourse advised for seven days.

Additional advice about starting:

• If the ring is started on days 2-5, no additional contraception is required. (Note this is FRSH advice and differs from the NuvaRing® SPC advice which is to use additional measures if started after day 1.) However, if started later in the cycle, avoidance of sexual intercourse, or use of additional contraceptive measures (barrier methods), is required for seven days.

• If starting after the COC pill or patch, it should be inserted the day after the last day of taking the pill, or the last day of the patch, and no additional contraception is required.

• If starting after the levonorgestrel emergency contraceptive pill, the ring can be inserted immediately but advise the use additional contraception, or avoid sexual intercourse, for 7 days.

• If starting after using ulipristal acetate for emergency contraception, advise a wait of five days before inserting the ring, and the use of additional contraception or avoidance of sexual intercourse during these five days and the subsequent seven days.

• If starting after any POP other than those containing desogestrel, or the IUS, the ring can be inserted at any point in the cycle, and additional contraception should be used, or sexual intercourse avoided, for seven days.

• If starting after any other progestogen-only method, the ring can be inserted on the first day after the previous method runs out/is removed, and no additional contraception is required.

• If changing to the ring after using a copper IUCD, remove the IUCD on day 1-5 and advise inserting the ring the same day. No additional contraception is required. If the IUCD is removed at other times in the cycle, either insert the ring seven days before, or insert on the day of removal and advise avoidance of sexual intercourse, or use of additional contraception, for seven days.

Unscheduled removal or breakage of the ring

If the ring is out of the vagina for more than three hours, it may be less effective. If the ring has been used correctly for the previous seven days, and is replaced within 48 hours, then no additional contraceptive measures are needed.

If the ring has been out of the vagina for more than 48 hours, then it should be rinsed and replaced, and additional contraceptive measures, or avoidance of sexual intercourse, advised for seven days. Consider emergency contraception if unprotected sexual intercourse has taken place within the previous five days.

If a new ring insertion has been delayed by more than 48 hours, additional contraceptive measures should be used for seven days or sexual intercourse avoided. A new ring should be inserted as soon as possible and emergency contraception considered if unprotected sexual intercourse has taken place in the previous five days.

If the ring is not removed after three weeks, it should remain effective for up to four weeks. When the woman realises she has forgotten to remove it, she should take it out as soon as possible and have a ring-free week, then start a new ring. If it has been left in place for more than four weeks, it may not be effective and pregnancy should be excluded.

If a ring is found to be broken, it should be replaced with a new one as soon as possible. Sexual intercourse should be avoided, or additional contraceptive measures used, for seven days, and emergency contraception considered.

Advantages

• Some women may find a ring that lasts for three weeks more convenient than a daily pill or a weekly patch.

• The ring is not affected by diarrhoea or vomiting.

• Like the other CHC methods, it is effective contraception.

Disadvantages

• In addition to risks and adverse effects common to all methods of CHC, it may cause vaginal irritation or discharge. Headache may be more common.

• It may interfere with sexual intercourse.

• Some women may not be comfortable with placing a ring inside their vagina, or may find it difficult to remove.

• It may break or accidentally fall out.