Progestogen-only contraceptive pill

Synonym: mini pill

Approximately 6% of women aged 16-49 years in the UK use the contraceptive progestogen-only pill (POP).¹ It is particularly used when combined hormonal contraception is contra-indicated - eg, breastfeeding mothers.

Currently, the following POPs are available in the UK:

• Norethisterone 350 micrograms - Micronor® and Noriday®.

• Levonorgestrel 30 micrograms - Norgeston®.

• Desogestrel 75 micrograms - Cerazette®, Aizea®, Cerelle® and Nacrez®.

Levonelle® is progestogen-only emergency contraception (EC).

Mode of action

• The cervical mucus becomes more viscous and impenetrable to sperm.¹ This is the primary mode of action for traditional POPs.

• Ovulation has been shown to be inhibited in about 60% of cycles (although it does not occur in 100% of cycles normally).² With desogestrel, ovulation is inhibited in 97% of cycles. Thus, suppression of ovulation is not the prime mechanism of action for traditional POPs, whereas it is for those containing desogestrel.

Advantages of a progestogen-only contraceptive pill (compared with a combined oral contraceptive pill)³

• It is an effective and safe form of contraception and can be used in many conditions where oestrogens are contra-indicated - eg, venous thromboembolism (VTE), past history of VTE, or migraine with aura. It is a suitable alternative for those aged over 35 years who need to be changed from a combined oral contraceptive (COC) pill, heavy smokers, and those with hypertension, valvular heart disease, diabetes mellitus, and migraine. There is, however, very little evidence regarding cardiovascular risk and the POP.

• It contains an even lower dose of progestogen than low-dose combined contraceptives and no oestrogen.

• It can be used during breastfeeding.⁴

• It is suitable for women about to undergo major surgery or surgery on their legs.

• There is no evidence that the POP is associated with an increased risk of VTE.

Disadvantages of a progestogen-only contraceptive pill (compared with a combined oral contraceptive pill)⁵

• It has to be taken meticulously at the same time each day. The error for forgotten pills is just three hours late for traditional POPs. Newer POPs contain desogestrel which has a licence for 12 hours.

• It is just as susceptible to substances that cause enzyme induction, like rifampicin, many anticonvulsants and St John's wort.

• It does not control the menstrual cycle as effectively as the COC pill.

• It may produce irregular menstruation or amenorrhoea. This may be severe enough for some that it leads to cessation of using the POP. Generally, around 2 in 10 women become amenorrhoeic, 4 in 10 have regular menses and 4 in 10 have irregular menses.

• There may be minor side-effects such as breast tenderness, skin changes and headaches. These usually improve with time.

• There is an increased risk of ovarian cysts, perhaps up to 30%. They are usually reversible and do not require operation.

• There may be a small increased risk of breast cancer for women taking the POP.

Contra-indications⁶

The UK Medical Eligibility Criteria (UKMEC) should be used to determine safety of prescribing the POP for individual women. These recommendations divide conditions into four categories:

• Category 1: no restriction to use.

• Category 2: advantages of use of the method of contraception generally outweigh the risks.

• Category 3: the risks generally outweigh the advantages. Use not usually recommended.

• Category 4: use of the contraceptive method would result in unacceptable risk to health.

The only condition for the POP which comes into UKMEC Category 4, and therefore is contra-indicated, is breast cancer.

However, there are a number of conditions which are classed as UKMEC 3, in which risks usually outweigh benefits, and therefore the POP would not usually be an appropriate choice of contraception. These include:

• Past history of breast cancer.

• Severe cirrhosis.

• Liver tumours.

• Stroke and coronary heart disease (UKMEC 3 for continuation, 2 for initiation).

• Systemic lupus erythematosus (SLE) with positive antiphospholipid antibodies.

• Those on medication, including antiretroviral therapy, enzyme-inducing anticonvulsants (but not lamotrigine which is contra-indicated with the COC pill), and enzyme-inducing antibiotics such as rifampicin and rifabutin.

Starting the progestogen-only contraceptive pill⁵

Women not currently using any contraception: it is usually started on the first day of menstruation, in which case contraceptive cover is immediate. If started any day up to the fifth day from the start of menstruation, no additional contraceptive precautions are required. If started at any other time in the cycle, pregnancy should be excluded first, and additional contraceptive precautions should be used for 48 hours (eg, condoms or abstinence).

After childbirth: it can be started on day 21, irrespective of whether the woman is breastfeeding. There is no need for contraception before then. If started after 21 days, additional contraceptive precautions should be used for 48 hours.

Following miscarriage or termination of pregnancy: it can be started immediately after miscarriage or termination of pregnancy up to 24 weeks of pregnancy, and it is immediately effective. If started after five days after the miscarriage or termination, additional contraceptive precautions should be used for 48 hours.

Changing from the COC pill: when changing from the COC pill to a POP, start at the end of a COC pill pack, moving straight on from the last COC pill to the POP the following day. If the COC pill is an every day (ED) pack then start after the last active pill. No additional contraception is required.

Starting after emergency contraception: start the POP immediately after levonorgestrel and five days after ulipristal. Women should use additional contraceptive precautions for two days following the EC. A pregnancy test should be done after three weeks.

Changing from injectable progestogen-only contraception: start the POP on the day the injection is due. No additional contraception is required.

Changing from the implant: start the POP immediately. No additional contraception is required.

Changing from the intrauterine system (IUS): start the POP on the day of removal (ideally removal should be within five days of the start of menstruation). No additional contraception is required.

Changing from the intrauterine contraceptive device (IUCD): start the POP on the day of removal (ideally removal should be within five days of the start of menstruation). No additional contraception is required. It can also be started at least two days before removal of the IUCD. Additional contraception is required for 48 hours if it is not started within the first five days of the menstrual cycle.

Weight

It has been thought in the past that the POP may be less effective in women weighing more than 70 kg, and that they may need a higher dose. However, the current position is that evidence does not support the unlicensed use of two traditional POPs in women weighing more than 70 kg. There is no evidence that efficacy of desogestrel pills is affected by weight.

Missed pills⁵

Pills must be taken at about the same time each day. This should be within three hours of the time taken the previous day. For desogestrel pills, this can be up to 12 hours.

It is regarded as late if the POP is taken more than three hours after the usual time (or 12 hours with desogestrel-containing pills). The missed pill should be taken as soon as possible. The subsequent pills should be taken as usual but additional contraception should be used until pills have been taken correctly for two days. No more than two pills should be taken on the same day. If unprotected sexual intercourse has taken place during the time when the POP cover is doubtful, consider the need for emergency contraception.

Vomiting or severe diarrhoea may impair absorption of the hormone. Additional contraception should be used during this phase and for two days afterwards.

Side-effects⁵

Irregular menstrual bleeding patterns are common and may settle with time. If not, consider a change to a different formulation or a different type of contraception. (There is no evidence that changing the dose or the type of POP improves bleeding, however.) On the POP, generally around 2 in 10 women become amenorrhoeic, 4 in 10 have regular menses and 4 in 10 have irregular menses. If irregular bleeding is persistent, consider other causes of irregular menstrual bleeding and exclude where relevant - see the separate Breakthrough Bleeding with Combined Hormonal Contraception article.

There is no strong evidence that the POP causes weight gain, loss of bone density, headache or mood changes.^{7 8 9}

Interactions

Liver enzyme-inducing drugs may interfere with efficacy of the POP. Women should normally be advised to use alternative forms of contraception. For short courses of enzyme-inducing medication, consider a one-off injection of progestogen-only injectable contraception. If continuing the POP, advise use of additional precautions (such as condoms or abstinence) during use of the enzyme-inducing medication, and for 28 days afterwards. Enzyme-inducing medication includes:

• Anticonvulsants such as carbamazepine, oxcarbazepine, phenytoin, barbiturates, primidone and topiramate. Lamotrigine does not affect the POP.

• Antibiotics - rifabutin and rifampicin (potent enzyme inducers).

• St John's wort.

• Antiretrovirals - particularly ritonavir-boosted protease inhibitors.

Progesterone receptor modulators - such as ulipristal acetate which is available as ellaOne® in a 30 mg dose for EC, and Esmya® in a 5 mg dose for fibroids. Use of the POP is not recommended for women taking Esmya®, or for 12 days after finishing it.¹¹ Women who are taking the POP after use of ellaOne® should use additional contraceptive precautions until the start of the next menstrual period or for nine days if amenorrhoeic.

Follow-up⁵

Review 10-12 weeks after starting. After this, follow-up should be at least every 12 months.

At follow up appointments:

• Consider checking blood pressure. (This is not mandatory and does not affect prescribing, but is considered good practice.)

• Ensure the woman is taking the pill correctly, and knows what to do in the event of missing pills.

• Check the POP is still the most appropriate form of contraception. Consider the use of long-acting reversible contraception (LARCs). Offer verbal and/or written advice about LARCs.

• Check there is no change in medication which might affect the efficacy of the POP, including over-the-counter preparations.

• Check there has been no change in eligibility (ie no new medical conditions).

Desogestrel¹²

Desogestrel is a newer progestogen that is converted in the body to the active form of etonogestrel. There are four contraceptive pills containing desogestrel, currently licensed in the UK: Cerazette®, Aizea®, Cerelle® and Nacrez®. The feature of this formulation that is likely to have the greatest impact is the 12-hour window in which to remember to take it, rather than just three hours.

Amenorrhoea is more likely to occur than with older POPs, as is irregular menstrual bleeding. The overall failure rate for the desogestrel-only pill has not been shown to be significantly different to other POPs. There are insufficient data to compare types of POP with each other.