Key Learning Points: Progestogen-only Pills

Dr Rebecca Mawson Offers Nine Key Learning Points From the Updated Faculty of Sexual & Reproductive Healthcare Guidance on Progestogen-only Pills, Including Advice on Drospirenone

In the UK, approximately 26% of women aged 16–49 years use hormonal methods of contraception, and 59.1% of women obtain their contraception in general practice.^1,2 A 2021 study on trends in contraceptive prescribing in the UK showed that the number of prescriptions issued for combined hormonal contraception almost halved between 2000 and 2018 (from 26.2% to 14.3%), whereas there was a more than two-and‑a‑half‑fold increase in progestogen‑only pill (POP) prescriptions (from 4.3% to 10.8%).³ This trend likely reflects the introduction of desogestrel (DSG)‑containing POPs to the UK in 2002, and may have been influenced by an increase in nonmedical prescribers, who are more inclined to issue medications with fewer contraindications and risks.^3,4

Navigating the Updated Guidance

In August 2022, the Faculty of Sexual & Reproductive Healthcare (FSRH) updated its POP guideline, and both the updated guidance⁵ and a quick reference guide⁶ (only accessible to FSRH members) are available on the FSRH website. Much of the new information relates to the new drospirenone (DRSP)‑containing POP, which will soon be available in the UK.⁵ This article provides nine key learning points for primary care practitioners from the updated guideline.

1. Get to Know the Types of POP Available in the UK

Because the DRSP POP will come to market imminently, there will soon be four types of POP available in the UK: two traditional POPs containing levonorgestrel (LNG) or norethisterone (NET), and two newer POPs containing DSG or DRSP.⁵ Table 1 outlines the regimens and modes of action of these four POPs.

The Atypical Regimen of the DRSP-containing POP

The DRSP-containing POP is taken every day, and consists of 24 active pills followed by four hormone-free placebo pills.⁵ This difference in regimen from the other POPs available may cause issues for any practices using standardised POP advice leaflets, so it is important that all practices update these in future.

Patients may or may not experience bleeding during the hormone-free interval.⁵ There is no evidence supporting the continuous use of DRSP-containing pills without a hormone-free interval, so this is not recommended. 

2. Understand That UKMEC Guidance Applies to all POPs

All four types of POP can be used from menarche to 55 years of age in medically eligible individuals,⁵ but the FSRH’s UK medical eligibility criteria for contraceptive use (UKMEC) guidance⁷ still applies to all POPs (including the DRSP-containing POP). In addition, there are some specific considerations around use of the DRSP-containing POP, outlined in the following sections, because of the risk of high potassium levels (hyperkalaemia) in susceptible individuals.⁵

All POPs

Medical conditions that are UKMEC3 or UKMEC4 for use of the POP—that is, in which POPs should be avoided or used only in exceptional circumstances—include:⁵

• current and past ischaemic heart disease, or history of stroke—UKMEC3 for continuation (UKMEC2 for initiation)
• current breast cancer—UKMEC4
• past breast cancer—UKMEC3
• severe (decompensated) cirrhosis (associated with, for example, ascites, jaundice, encephalopathy, or gastrointestinal haemorrhage)—UKMEC3
• hepatocellular adenoma or carcinoma—UKMEC3.

For further information, clinicians should consult the full guideline;⁵ see Box 1 (online) for an explanation of UKMEC categories as applied to POP use.^5,7,8

Special Considerations Around Eligibility for the DRSP POP

DRSP is a spironolactone derivative and an aldosterone antagonist, which means that its use confers a risk of hyperkalaemia in certain individuals.⁵ Furthermore, the potential for drug interactions may be higher in these individuals, so it is essential to know precisely what a patient is taking before prescribing.⁵

The FSRH guidance also recommends that urea and electrolytes (U&E) and blood pressure should be checked in individuals at significant risk of chronic kidney disease, such as those with diabetes or hypertension, especially if they are aged 50 years or older.⁵ This assessment of U&E may also be required for individuals with mild or moderate renal insufficiency or treated hypoaldosteronism.⁵

The DRSP POP should not be used by individuals with severe renal insufficiency or acute renal failure, as it is contraindicated.⁵ The FSRH also recommends that it should be avoided by:⁵

• individuals with known hyperkalaemia or untreated hypoaldosteronism (for example, Addison’s disease)
• individuals currently using potassium-sparing diuretics, aldosterone antagonists, or potassium supplements.

Furthermore, the DRSP POP should be used with caution by:⁵

• individuals with mild or moderate renal impairment
• individuals with treated hypoaldosteronism (for example, treated Addison’s disease)
• individuals using angiotensin‑converting enzyme inhibitors and angiotensin II receptor antagonists—the FSRH recommends checking U&E during the first cycle of concurrent use.

Ectopic Pregnancy and Ovarian Cysts

It is a common misconception that individuals with a history of ectopic pregnancy or ovarian cysts cannot use POPs, but they can use all forms of POP (UKMEC1; see Box 1, online).⁵ The use of all effective contraceptive methods, including the POP, reduces the risk of pregnancy (including ectopic) when compared with not using any method.⁵

3. Be Aware That Advice on Initiation Differs Between POPs

The DRSP POP has different starting and switching advice from the LNG, NET, and DSG POPs. Traditional and DSG POPs can be started on days 1–5 of a natural cycle without the need for additional contraceptive precautions and will be effective; however, the DRSP POP must be started on day 1 of the cycle.⁵ Traditional and DSG POPs will also be effective immediately when started up to 5 days after an abortion, a miscarriage, or an ectopic pregnancy and up to 21 days postpartum.⁵ The DRSP POP will also be effective if started up to 21 days postpartum, but must be started the day after an abortion, a miscarriage, or an ectopic pregnancy to be immediately effective.⁵ Furthermore, if the patient wants to take the POP immediately (a quick start), LNG, NET, and DSG POPs will require additional contraception use for 2 days after initiation, whereas the DRSP POP will require additional contraception use for 7 days after initiation.⁵

The newly updated guideline contains comprehensive tables to help clinicians decide what advice to give individuals switching between methods.⁵

4. Appreciate the Potential Benefits of the DRSP-containing POP

Evidence suggests that, like the DSG POP, the DRSP-containing POP can reduce dysmenorrhoea; it may also have beneficial effects on blood pressure, acne, and hirsutism because it is an antiandrogen, although data in support of these effects have not yet been published.⁵ It may also be helpful for women with polycystic ovary syndrome, who could benefit from its antiandrogenic effects; however, there is no published evidence to support this, as the DRSP-containing POP is a relatively new method of contraception.⁵ The 24-hour window for taking the DRSP‑containing POP is also an advantage of this new medication, as it gives individuals a better chance of taking it correctly.

5. Advise Patients on the Common Side Effects of POPs

Individuals wishing to start any POP should be advised that changes to bleeding pattern are common and unpredictable.⁵ For individuals using the new DRSP-containing POP, clinicians should advise patients that they may have ‘scheduled’ spotting when taking the hormone-free pills, but that they may also experience ‘unscheduled’ bleeding or spotting outside that time.⁵ Over the first year of using the DRSP-containing POP, unscheduled and scheduled bleeding may reduce in frequency.⁵ Table 2 details the frequency of bleeding-related side effects.

The evidence is too limited for there to be a clear causative relationship between POPs and other symptoms such as headache, acne, libido change, weight gain, or mood change.⁵ However, this does not mean that a side effect a patient experiences is not related to the POP, just that the research in this area is limited. It is important for clinicians to empower their patients to change to a different medication rather than to continue living with potential side effects.

6. Recognise Factors That can Affect the Efficacy of POPs

The efficacy of POPs is reliant on compliance and correct use: when used perfectly, they can be more than 99% effective.⁵ The typical success rate is significantly lower than this, however, with a risk of pregnancy of around 9% in the first year with typical use.⁵ There does not appear to be significant difference in effectiveness between the four kinds of POP, but the available evidence is limited.⁵

Drug Interactions

The use of enzyme-inducing drugs can make POPs less effective,⁹ and the FSRH recommends that individuals taking enzyme‑inducing drugs are provided with an alternative contraceptive method.⁵ Enzyme‑inducing drugs include:

• certain antiepileptics (for example, carbamazepine, eslicarbazepine acetate, oxcarbazepine, phenobarbital, phenytoin, rufinamide, topiramate)¹⁰
• certain antibacterials (for example, rifabutin, rifampicin)¹¹
• certain antiretrovirals (for example, efavirenz,¹² nevirapine¹³)
• St John’s wort.¹⁴

Other Considerations

Body weight and body mass index do not seem to impact the effectiveness of POPs.⁵ However, there is some concern that conditions causing malabsorption may reduce the effectiveness of POPs; these include vomiting, severe diarrhoea, use of certain weight‑management drugs, bariatric surgery, and active inflammatory bowel disease.⁵ As bariatric surgery may lead to malabsorption and decrease the absorption of oral contraceptives, an alternative nonoral contraceptive method is recommended in this scenario.⁵

7. Know How to Act When a Patient Misses a Pill

One of the most significant changes to the FSRH POP guidance concerns missed pills. Missed-pill recommendations relating to the new DRSP-containing POP have also been added to the guideline—there is a need for extra caution with this POP, in part because of the use of placebo pills. These are the timings that constitute a missed POP:⁵

• LNG and NET POP—more than 3 hours late
• DSG POP—more than 12 hours late
• DRSP POP—more than 24 hours late.

Tables 3 and 4 outline the FSRH’s recommendations following the incorrect use of POPs.

I recently assisted in the production of a missed pill calculator,¹⁵ which is based on FSRH guidelines and endorsed by the FSRH.¹⁶ It may be useful for patients trying to determine what to do if they have forgotten to take a POP.

8. Note That There is No Evidence to Support Double Dosing of the DSG POP

The guideline discusses double dosing of the DSG POP for problematic bleeding (giving patients 150 mcg rather than 75 mcg daily).⁵ The FSRH states there is no robust evidence to suggest that this is effective for reducing unscheduled or heavy bleeding.⁵ Pragmatically, however, it is worth noting that this double dose is the same as in certain combined oral contraceptives.⁵

9. Consider POP initiation advice when choosing emergency contraception

There are various important considerations when choosing an individual’s emergency contraceptive (EC), and practical algorithms can be found in the FSRH guideline on the topic.⁸ The copper intrauterine device is the most effective EC, but if oral preparations are chosen, there are two options: ulipristal acetate (UPA) and LNG.⁸ When using UPA, it is essential to delay starting or restarting a POP until 5 days after the UPA EC was taken; this is because of a potential interaction that can reduce the ability of UPA to delay ovulation.⁵ For the traditional POPs (NET/LNG) and DSG POPs, the individual would need to take extra contraceptive precautions for 7 days (5 days without a POP, plus 2 days after starting one) to prevent the risk of pregnancy.⁵ For the DRSP-containing POP, the individual would need this extra protection for 12 days (5 days without the POP, plus 7 days after starting it).⁵

Summary

As POP prescribing continues to increase, it is important that clinicians understand the different progestogens and how they should be used. Increasing the availability of different contraceptive progestogens can only be a good thing, as it increases choice and allows tailored switching to achieve the least side effects for individuals. Nevertheless, DRSP has more contraindications than other POPs, and prescribers need to be aware of a patient’s concurrent medication and medical history before issuing a script.