Side effects of contraception are usually transient, resolving within 3–5 months of use (Grossman Barr, 2010). However, while most individuals will find that any adverse effects resolve or lessen to the point of acceptability, side effects are the most common reason for individuals to discontinue a method of contraception (Grossman Barr, 2010).
Side effects can range in severity between individuals and can have different impacts on quality of life, depending on that individual's own circumstances. While one individual may find unpredictable bleeding entirely unacceptable because of their job or lifestyle, another may be happy with this bleeding pattern as it is preferable to their natural, heavy periods. Therefore, it is important to discuss the expected contraceptive side effects, so that users have realistic expectations and can make an informed decision about the most appropriate method of contraception for them. Patient education should be informative but concise, as intensive prolonged counselling has not been shown to improve rates of continuation (Modesto et al, 2014).
Contraceptives are associated with multiple side effects, although the evidence to prove causality is limited. Many studies show no statistically significant difference in the rates of side effects reported in those using hormonal contraception when compared to no contraception, non-hormonal contraception or the general population (Faculty of Sexual and Reproductive Healthcare [FSRH], 2015a; 2015b; 2019; 2021). There is also a lack of evidence-based guidance on effective management of side effects, meaning many clinicians rely on anecdotal evidence or theoretical ideas to guide management. Headache and changes in mood, skin and bleeding patterns are all commonly cited side effects of hormonal contraception, and the available evidence on managing these will be discussed below.
Headache
Headache is a reported side effect of all hormonal methods of contraception, but is also very common in women of reproductive age, particularly those age >35 years old (Grossman Barr, 2010). Because it is so common in the general population, the impact of contraception can be difficult to assess, with many studies finding that individuals in the placebo arm report headache as commonly as individuals using contraception (FSRH, 2019).
Headache is reported as a potential side effect of progestogen-only contraceptive methods (POC) in their summary of product characteristics (SPCs); however, there is insufficient evidence to confirm a causal effect or to understand the influence of POC on headache incidence.
From the limited evidence available, the progestogen-only pill (POP) does not appear to be associated with any increased risk of migraine. The desogestrel-containing POP appears to reduce the frequency and intensity of headaches in women with migraine, although the studies suggesting this evaluated only a small number of participants (FSRH, 2015b).
In an early study of the progestogen-only injectable contraception (POI), Depo Provera, 11% of users reported headache as a side effect, which, in contrast to combined hormonal contraception (CHC), increased over time (FSRH, 2014). The incidence of headache in progestogen-only subdermal implant (SDI) users has been reported as around 15%, with headache cited as the reason for removal in <2% of users (Darney et al, 2009).
There is insufficient evidence to recommend how to manage headache with progestogen-only (PO) methods.
For women that already experience headaches, CHC use may cause worsening or improvement or have no effect on the headaches (FSRH, 2019). For individuals who have migraine with aura, CHC should not be used for contraception as it is a United Kingdom Medical Eligibility Criteria (UKMEC) category 4 (risks outweigh the benefits) because of an unacceptable risk of stroke (FSRH, 2019). Individuals who develop migraine (with or without aura) while using CHC should be advised to stop and switch to a safer alternative, as risks generally outweigh benefits for continued use (UKMEC 3) (FSRH, 2019).
Approximately 10% of CHC users will report new onset of headache (Loder et al, 2005). This is most common in the first few months of use and usually settles with time (Loder et al, 2005). There is no evidence that the formulation of CHC, type and dose of progestogen, or dose of oestrogen affects the incidence of headache with CHC use (Loder et al, 2005; MacGregor, 2013) and therefore there is no recommendation that either switching between CHC types or prescribing diuretics or multivitamins will be beneficial (Loder et al, 2015). However, the patient can be reassured that the headache will likely resolve after the first few cycles.
Headaches can occur during active CHC days or during the hormone free interval (HFI). For individuals who have headache during the HFI, a tailored CHC regimen that reduces either the frequency and/or duration of HFI is usually beneficial (FSRH, 2019). Examples of tailored CHC regimens can be found in Table 1.
Table 1. Tailored regimens
| Traditional | 21 days of active combined hormonal contraception (CHC) then 7 day hormone-free interval |
| Shortened hormone free interval | 21 days of active CHC then 4 day hormone-free interval |
| Tricycling/extended | 63 days of active CHC then 4 or 7 day hormone-free interval |
| Flexible extended | At least 21 days of active CHC. If patient experiences 4 days of bleeding or spotting in a row, then stop for 4–7 day hormone-free interval |
| Continuous | Continuous active CHC with no hormone-free interval |
Skin changes
Although skin changes such as acne, hirsutism and oily skin are cited as side effects of POCs, there is insufficient evidence to prove causation. Acne is cited as a ‘common’ (≥1/100 to <1/10) or ‘very common’ (≥1/10) side effect in each of the summary of product characteristics for the POC, with new facial hair being reported in around 6% of Depo Provera users (Berenson et al, 2008). The synthetic progestogens used in contraceptives are structurally similar to testosterone and many are derived from testosterone. Theoretically, this could explain why they produce androgenic side effects.
Conversely, CHC is used as a treatment for acne and hirsutism (National Institute for Health and Care Excellence, 2020) and therefore would be a suitable alternative for medically eligible individuals. CHC stimulates the production of sex hormone binding globulin, which binds to testosterone and lowers the levels of circulating free testosterone, thus improving androgen-related symptoms. Modern CHC preparations contain progestogens that have been developed to have fewer androgenic effects or anti-androgenic effects but while many clinicians will opt for one of these newer preparations, any CHC preparation is likely to be beneficial for individuals with acne and hirsutism and there is currently insufficient evidence to recommend one preparation over another (FSRH, 2019). For those in whom CHC is contraindicated, or who prefer an alternative method of contraception to CHC, standard treatments for acne and hirsutism can be used alongside their PO method of contraception.
Depression
Depression and mood changes are classed as ‘common’ (≥1/100 to <1/10) side effects of hormonal contraception in the SPCs. Mood change is common in the general population and is often related to external events, making the effect of contraception on mood difficult to evaluate, with many studies being limited by bias, confounding factors and a lack of control group (Worley et al, 2018).
While numerous studies have sought to identify an association between depression and POC, a recent systematic review has concluded that the majority of studies do not support an association between PO contraception and depression (Worley et al, 2018).
Despite mood change being a commonly cited side effect of CHC, it is an infrequent cause of discontinuation (FSRH, 2019) and the significance of mood change is unknown. In addition, CHC is used as treatment for cyclical mood changes and premenstrual syndrome (Royal College of Obstetricians and Gynaecologists, 2016). However, while there is insufficient evidence to confirm CHC causes depression, the evidence does suggest that individuals can experience low mood with CHC (FSRH, 2019). The FSRH (2019) recommends that individuals who have negative mood changes but wish to continue CHC can try switching to a CHC containing an alternative progestogen. In particular, formulations that contain drospirenone could have a more beneficial effect on mood than those containing other progestogens (FSRH, 2019). If the negative mood change is premenstrual, or if it occurs during the hormone-free interval, then continuous CHC use may be beneficial (FSRH, 2019).
Changes in bleeding patterns
Unpredictable bleeding
Although the mechanism is poorly understood, unpredictable bleeding in individuals using POC is very common (FSRH, 2015a). Unpredictable bleeding is particularly common in the first few months of use, but bleeding with the desogestrel POP, the levonorgestrel intrauterine system (LNG IUS) and POI decreases with time (FSRH, 2015a). Bleeding with the SDI is less predictable and can change during the 3 years of use (FSRH, 2021).
For individuals with problematic bleeding on contraception, other causes of bleeding should be considered before assuming it is because of the contraception. It is therefore recommended that a medical history should be taken to identify or exclude an underlying cause; a drug history can check for potential interactions affecting contraceptive efficacy; a sexual history is required to assess the need for sexually transmitted infection screening; a cervical screening history +/- screening if due is required to exclude a cervical pathology; and a pregnancy test should be undertaken if indicated (Table 2) (FSRH, 2015b).
Table 2. Assessment of women with irregular bleeding on contraception
| Initial assessment | Other investigations that may be required depending on other risk factors |
|---|---|
|
|
For those who have been using contraception for less than 3 months and have no concerning features elicited from the clinical history, reassurance that a change in bleeding pattern is common and expected may be all that is required, but medical management can be offered (FSRH, 2015b). For individuals that have been using contraception for more than 3 months and have new or persistent bleeding (once sexually transmitted infection, pregnancy and drug interactions excluded) a speculum examination +/- bimanual examination is indicated. If this is normal and the patient has no other concerning symptoms, then reassurance or medical management would be advised (FSRH, 2015b). If the speculum/bimanual is normal but the patient has additional symptoms (pain, dyspareunia, heavy bleeding), or the patient is aged >45 years, or the patient is age <45 years but with risk factors for endometrial cancer then further investigation (ultrasound, endometrial biopsy, hysteroscopy) should be considered, depending on the likelihood of pathology (FSRH, 2015b).
For POP users, switching to a different POP may offer them a more acceptable bleeding pattern, as individuals may experience a different bleeding pattern with traditional POPs than the desogestrel POP (FSRH, 2015b). There is no evidence to support using two POPs per day to improve bleeding, and although the addition of oestrogen supplements or tranexamic acid may have short-term benefits for improving bleeding on the POP, the evidence does not support routine or long-term use (FSRH, 2015b).
For individuals using the POI whose bleeding problems occur in the weeks prior to their next injection, the interval between injections can be reduced to 10 weeks (FSRH, 2014). Although there is no evidence to support this, it is common in clinical practice and is of benefit for some individuals.
For medically eligible individuals using SDI, POI or IUS, a 3-month trial of a combined oral contraceptive pill (COC) can be offered. This would usually be a COC containing levonorgestrel or norethisterone and 30–35 mcg ethinylestradiol. The COC can be used continuously or in the traditional regimen of 3 weeks on, 1 week hormone-free interval (FSRH, 2015b). Mefenamic acid (500 mg up to three times per day) or tranexamic acid (1 g up to four times per day) have been shown to be useful in short-term management of problematic bleeding but do not appear to provide any long-term benefit (FSRH, 2015b).
Problematic bleeding with CHC is less common than with PO contraception and although irregular bleeding in the first 3 months of CHC use is common, this will usually settle with time and most individuals develop predictable bleeding during the hormone-free interval (FSRH, 2019). Individuals who use an estradiol containing COC are more likely to have shorter, lighter, or absent withdrawal bleeds than individuals using ethinylestradiol (EE)-containing COC (FSRH, 2019). For those individuals who take CHC continuously, bleeding is less predictable. Increasing the EE dose from 20 to 30 mcg per day does not reduce breakthrough bleeding when individuals are taking CHC continuously (Edelman et al, 2006).
Individuals who report unpredictable bleeding in the first few months of CHC use can be reassured this is likely to settle and there is no recommendation that switching pills at this time will be beneficial (FSRH, 2019). If unpredictable bleeding persists or starts after 3 months of use, and alternative causes such as pregnancy, sexually transmitted infection, drug interactions and cervical pathology are excluded, switching to an alternative CHC preparation can be tried. For individuals using a 20 mcg EE-containing pill, increasing the EE dose up to a maximum of 35 mcg may provide better cycle control (FSRH, 2015a). The lowest dose of EE that provides adequate cycle control should be used (FSRH, 2019). Many clinicians will also try switching progestogens and although there is no evidence to support this, it may be helpful on an individual basis (FSRH, 2019). The combined vaginal ring appears to give better bleeding control than COC and may be a good option for individuals with poor cycle control on COC (FSRH, 2019).
Amenorrhoea
Amenorrhoea is experienced by up to 50% of desogestrel POP (FSRH, 2015) users, >50% of POI users at 12 months (FSRH, 2014) and 13–24% of LNG-IUS users after 3 years of use (FSRH, 2015a).
While amenorrhoea is a desirable side effect of contraception for many individuals, it can be unwanted or unacceptable to others. For some individuals, explaining the mechanism of action causing amenorrhoea may be sufficient reassurance that this is not harmful and they will choose to continue using the method. For those who do wish to have regular bleeds, switching to a copper intrauterine device or a CHC with regular hormone-free intervals will re-establish bleeding. Amenorrhoea is less common with a 13 mg LNG-IUS than a 19 mg or 52 mg IUS (12.7%, 18.9% and 23.6% respectively, 12 months after insertion) (Gemzell-Danielsson et al, 2012) and therefore a lower dose IUS may be of benefit to individuals who wish an IUS but who do not want amenorrhoea.
Heavy menstrual bleeding and dysmenorrhoea
The copper IUD is associated with heavier, longer and/or more painful periods. Non-steroidal anti-inflamatory drugs (such as ibuprofen, diclofenac, naproxen) have been shown to be effective in both reducing menstrual blood loss and effectively treating dysmenorrhoea in IUD-users (Grimes et al, 2006). No significant differences in the efficacy of these drugs has been shown (Grimes et al, 2006). Tranexamic acid is an effective second-line treatment for heavy menstrual bleeding and dysmenorrhoea associated with IUD use (Grimes et al, 2006).
Conclusions
The evidence to prove causality and association of side effects and contraception is limited. However, with side effects being a common reason for cessation of contraception, it is important to discuss these fully with patients to allow them to make an informed decision around the most appropriate method of contraception for them. Evidence is also lacking in the management of these side effects and further studies would be welcomed to help direct evidence-based management.
From the evidence available, individuals using CHC who experience headache can be reassured that this will likely resolve within the first few months of use. If headache is experienced in the hormone-free interval of CHC, a continuous or extended regimen may be beneficial.
Although skin changes such as acne, hirsutism and oily skin are cited as side effects of POC, there is insufficient evidence to prove causation. For individuals who have new or worsening acne on POC, switching to CHC is likely to improve their skin.
There is insufficient evidence that contraception causes depression. CHC formulations that contain drospirenone could have a more beneficial effect on mood than those containing other progestogens and if the negative mood change is premenstrual, or if it occurs during the hormone-free interval, then continuous CHC use may be beneficial.
Unpredictable bleeding patterns on POC are common. Individuals using POP may find switching to an alternative POP improves their bleeding patterns. For individuals using the POI whose bleeding problems occur in the weeks prior to their next injection, the interval between injections can be reduced to 10 weeks. For medically eligible individuals using SDI, POI or IUS, a 3-month trial of a combined oral contraceptive pill (COC) can be offered. Individuals who report unpredictable bleeding in the first few months of CHC use can be reassured this is likely to settle, but if it persists, increasing the EE dose up to a maximum of 35 mcg, or switching to a CHC with an alternative progestogen, or switching to the combined vaginal ring may improve cycle control. Dysmenorrhoea or heavy menstrual bleeding associated with the IUD can be managed with CHC or non-steroidal anti-inflammatory drugs.
CPD reflective practice:
- Consider your contraception choices consultation. What information do you currently give individuals about the side effects of contraception? Having read the article, are there any gaps in the information that you give and how will you address these?
- Consider your contraception choices consultation. Do you provide any information about options to manage side effects or likely expected duration of side effects? Do you think this information would help inform individuals of their options and prevent them stopping contraception that they may have otherwise chosen to continue? How could you succinctly incorporate this into your consultation?
- Consider your contraception follow-up consultations. What questions would be helpful to illicit whether or not the individual is having any unwanted side effects, and if these are unacceptable to her?
- What questions about lifestyle, health beliefs and side effects would you wish to ask a woman, to help you advise her which methods might be most appropriate for her?
KEY POINTS:
- Side effects of contraception are common
- Individuals can be reassured that side effects of contraception usually resolve within the first few months
- Tailored CHC regimens that reduce or abolish the hormone free interval can be helpful for preventing side effects (such as headache or mood change) that occur during the hormone free interval
- CHC or non-steroidal anti-inflammatories can be used to manage problematic bleeding in those using progestogen-only contraception
- CHC is effective at treating acne and a good alternative for medically eligible individuals who experience worsening or new-onset acne with progestogen-only methods