Progestogen-only contraceptive pill

Synonym: mini pill

The progestogen only pill is a useful method for those who are unable to use combined hormonal contraception (CHC), for example due to contraindications to oestrogen, or adverse effects; it may also be chosen as a first-line method for those who could also use CHC.

Currently, the following POPs are available in the UK:

• Norethisterone 350 micrograms - Noriday.

• Levonorgestrel 30 micrograms - Norgeston.

• Desogestrel 75 micrograms - Cerazette, Desomono, Desorex, Zeletta and Cerelle.

• Drospirenone 4mg - Slynd.

Levonelle is a progestogen-only emergency contraception (EC) which is not discussed further in this article.

How does the progestogen-only contraceptive pill work?¹

• The cervical mucus becomes more viscous and impenetrable to sperm. This is the primary mode of action for norethisterone and levonorgestrel pills.

• Desogestrel and drospirenone pills work primarily by inhibition of ovulation.

Advantages of a progestogen-only contraceptive pill (compared with a combined oral contraceptive pill)^{2 3}

• It is an effective and safe form of contraception and can be used in many conditions where oestrogens are contra-indicated - for example in those with a past history or strong family history of venous thromboembolism (VTE), those who have migraine with aura, or those who have multiple relative contradindications which make their prescriber feel that CHC is unsafe. It is a suitable alternative for smokers over 35 years who need to be changed from a combined oral contraceptive (COC) pill and those with hypertension, valvular heart disease, diabetes mellitus, and migraine.

• It can be used during breastfeeding at any point, as opposed to CHC which can only be used from six weeks post-partum in breastfeeding women.

• 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)⁴

• The window for taking older pills (levonorgestrel and norethisterone) is just three hours after the time when the last pill was taken the day before - any later than that and the contraceptive efficacy may be reduced. However, very few women now take these older POPs, with most using a desogestrel pill for which the window is 12 hours; the newer drospirenone pill has a 24 hour window.

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

• It does not control the menstrual cycle as effectively as the COC pill - details of bleeding patterns are given in the side-effects section of this leaflet.

• 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; it is not always possible to tell if a cyst was due to the POP, as they are also not uncommon in the general population.

• There may be a small increased risk of breast cancer for women taking the POP, also discussed in more detail later in this leaflet.

Contra-indications⁵

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 current 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. It may however be the case that an experienced clinician might prescribe a contraceptive method that is UKMEC 3, after a full consideration of the alternatives and a discussion with the patient as to the risks and benefits, which is carefully documented in the notes. UKMEC 3 contraception cannot usually be given on a patient group directive. The UKMEC is due to be updated in late 2025.

UKMEC 3 conditions for the POP include:

• Past history of breast cancer.

• Severe cirrhosis.

• Liver tumours.

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

• 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 pill⁴

In all of the following paragraphs, where contraceptive precautions for 48 hours are referred to, this is for levonorgestrel, norethisterone and desogestrel pills. For the drospirenone pill, seven days should be substituted for the 48 hours.

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 (for example, 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 three weeks after the last episode of unprotected intercourse - this is usually bought by the woman and done at home.

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 levonorgestrel intrauterine device (LNG-IUD): 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 copper intrauterine contraceptive device (Cu-IUD): 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 IUD. Additional contraception is required for 48 hours if it is not started within the first five days of the menstrual cycle.

Most POPs are taken continuously, with an active pill every day and no break between packets. The drospirenone pill Slynd is also taken continuously, but the last four tablets in the pack are placebos. They are green, as opposed to the active pills which are white.

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 any type of POP is affected by weight.

Missed pills⁴

Pills must be taken at about the same time each day.

It is regarded as late if the POP is taken more than three hours after the usual time (for levonorgestrel/norethisterone), more than 12 hours after the usual time for desogestrel and more than 24 hours after the usual time for drospirenone. 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 (levonorgestrel, norethisterone and desogestrel pills) or for seven days for the drospirenone pill.

No more than two pills should be taken on the same day for levonorgestrel, norethisterone and desogestrel pills, but this may occur with the drospirenone pill if taking a missed pill more than 24 hours later and then taking the usual pill on the same day. If a drospirenone pill is missed in the last seven active (white) pills in the pack, the placebo pills should be omitted and the next pack of active pills started after the last active pill of the pack in which the pill was missed.

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) levonorgestrel, norethisterone and desogestrel pills) or seven days (drospirenone pills) afterwards.

Side-effects ¹³⁴

Irregular menstrual bleeding patterns are common and may settle with time - see the table below and the separate Breakthrough bleeding with combined hormonal contraception article for details. If not, consider a change to a different formulation or a different type of contraception. If irregular bleeding is persistent, or starts some time after the pill was started consider other causes of irregular menstrual bleeding and exclude where relevant.

There is no strong evidence that the POP causes weight gain, loss of bone density, headache or mood changes.^{6 7 8}

There is a small increased risk of breast cancer for women who take the POP - the evidence on this is limited and conflicting. The relative risk is around 1.26 -1.4; for most women of reproductive age, whose background risk of breast cancer is low, the absolute number of extra cases will be very small. For women with a family history of breast cancer, the POP is a UKMEC 1 - it is a UKMEC 2 for those who carry a gene associated with breast cancer, such as the BRCA 1 or 2 genes, and a UKMEC 3 for those with a past history of breast cancer. There is no known increased risk of ovarian, endometrial or cervical cancer for women taking POPs.

Interactions ⁹

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.

• The interactions between lamotrigine and hormonal contraception are complex:

  • Lamotrigine slightly reduces exposure to contraceptive progestogens, although the relevance of this in terms of risk of ovulation is not known.

  • It is possible that desogestrel may increase exposure to lamotrigine in some women, potentially putting them at risk of lamotrigine toxicity if the desogestrel is started after the woman is stable on lamotrigine. Symptoms of lamotrigine toxicity include dizziness, ataxia and diplopia.

  • Evidence relating to lamotrigine and drospirenone is very limited.

  • Any change in hormonal contraception which is planned in a woman who is stable on lamotrigine should first be discussed with her consultant, and it would be sensible for condoms to be used as well. The depot injection or an intrauterine device might be a safer option for this cohort.

• 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. Women who are taking the POP after use of ellaOne should start the POP at least five days after the ellaOne was taken and use additional contraceptive precautions for the first two days of use of levonorgestrel, norethisterone and desogestrel pills and the first seven days of use of the drospirenone pill.

Follow-up⁴

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 for those who have risk factors for chronic kidney disease (for example, age over 50, hypertension, diabetes or cardiovascular disease).

• 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).