Managing side effects of contraception

It could be said that no contraception is free of side effects. While some side effects could be argued to be beneficial, most attention is placed on perceived negative side effects. Side effects may be cited by women as the reason for discontinuing or changing contraception. This article will discuss common side effects and strategies for management.

A side effect is defined as ‘any effect of a drug, chemical, or other medicine that is in addition to its intended effect, especially an effect that is harmful or unpleasant’ (dictionary.com, 2023).

Side effects and the meanings associated with them matter; with experience of side effects being predictive of early discontinuation, and the presence of three side effects increasing the likelihood of discontinuation by 320% (Rosenburg et al, 1995). Women report changing their contraception due to side effects, with non-contraceptive side effects cited as the main reason for this (Wigginton et al, 2016). Wigginton et al (2016) argue that it is not only side effects themselves that lead to discontinuation or change of method, but also the social meanings attached to side effects, with the example given of a negative sociocultural context of weight gain as a side effect.

Contraceptive counselling on side effects and their management, provided in a setting with respect for choice and the knowledge that change of method is possible if wanted, can improve contraceptive continuation rates (Cavallaro et al, 2020).

Methods of contraception

There are 14 methods of contraception, and side effects are usually associated with hormonal and intrauterine methods. These methods will now be considered individually by method, exploring the current recommended management.

Combined hormonal contraception

Combined hormonal contraception (CHC) preparations contain estrogen (usually in the form of the synthetic form of ethinylestradiol) and a progestogen (synthetic form of progesterone). CHC is available in three forms: combined oral contraceptive (COC), combined transdermal patch (CTP) and combined vaginal ring (CVR). Most commonly used is COC, with the National Survey of Sexual Attitudes and Lifestyle indicating that one third of women age 16–44 had used oral contraception in the last year (Clifton et al, 2012).

CHC is associated with many non-contraceptive benefits. These should be discussed with women, along with other non-beneficial or harmful side effects to provide a balanced view. Beneficial side effects include reduction in heavy menstrual bleeding and pain, improvement in premenstrual symptoms, possible improvement in acne and improvement of vasomotor symptoms in perimenopausal women. (FSRH, 2019). In addition, evidence shows that use of CHC for 10 years or more reduces the risk of endometrial cancer by 34% and ovarian cancer by 50%. Ever users of CHC have a reduced risk of colorectal cancer of 19% (FSRH, 2019). However, it is reported that 25% of women discontinue the COC due to negative side effects (Westoff et al, 2007). Understanding and effective management of this is an important aspect of contraceptive care.

Management of side effects of CHC

Headaches

Headache is a commonly cited side effect of CHC. Headache is, however, common in all women of reproductive age, regardless of contraceptive use. Migraine is often associated with the menstrual cycle (so called menstrual migraine) and may also occur due to withdrawal of exogenous hormones, as occurs in women who have a hormone-free interval (HFI) of their CHC (Sacco et al, 2016). Although headache is common, women who suffer from or develop migraine with aura must discontinue CHC.

Migraine with aura is associated with an increased risk of ischaemic stroke, and represents an unacceptable health risk if CHC is used (FSRH, 2016). McGregor (2016) offers useful methods of diagnosing migraine with aura, and suggests asking, ‘Have you ever had visual disturbance lasting 5–60 minutes followed by headache?’ Although aura may be sensory only, visual aura is present in 98% of cases and is classically described as a scotoma with zig-zag margins or fortification spectra, which persists when the eyes are closed. In 1% of cases, aura may occur without the subsequent headache, especially with increasing age.

Where there is doubt about the diagnosis, it is safer to provide a progestogen only contraceptive until the woman can be reviewed (McGregor, 2016). Headache that increases during the initial months of taking CHC often does not persist, and women can be encouraged to continue. Headache that occurs during the HFI can be helped by using CHC with a continuous or extended regimen, thereby avoiding the HFI (FSRH, 2019). Continuous CHC use requires taking the CHC with no HFI. Extended regimen may involve taking 3 months continuously and stopping for a 4- or 7-day HFI, or taking CHC continuously until bleeding occurs for 3 or 4 days and then having a HFI of 4 days.

Unscheduled bleeding

Bleeding that is unexpected and occurs on the hormone taking days is common and has been estimated to occur in 10–18% of cycles, which is similar to the incidence of intermenstrual bleeding in natural cycles (FSRH, 2019). As with headaches, it is most common in the first few months of hormone use and does often improve with time.

Other causes of bleeding should be excluded, including incorrect method use, pregnancy, sexually transmitted infections, interacting medications and gynaecological pathology. It is reasonable to reassure and encourage new CHC users to continue for 3 months before making any changes to the choice of CHC.

Options for management of unscheduled bleeding include:

• Change of preparation. There is evidence that CVR may produce better cycle control than CHC, including with extended regimens (FSRH, 2013). Use of CTP is less clear, and does not appear to reduce bleeding
• Increasing the dose of ethinylestradiol (EE) may help. For example, if using a 20 mcg EE COC, it is reasonable to try increasing to a 30 mcg EE COC (FSRH, 2019). This sometimes needs some patience and trial and error to find the right formulation for the woman
• Extended or continuous regimes may reduce unscheduled bleeding.

Persistent or new bleeding on CHC

If bleeding persists, is a new symptom or change in bleeding pattern, other causes of bleeding should be considered. Exclusion of causes mentioned above should be carried out, including checking participation in the national cervical screening programme and a speculum examination to assess the cervix. The FSRH (2013) advises examination and/or referral if bleeding persists or changes beyond the first 3 months of use for users of hormonal contraception. Findings should be managed appropriately, with consideration of referral for further assessment depending on age and likelihood of pathology (FSRH, 2013).

Mood changes

While mood change is a common complaint, it is less likely to lead to discontinuation of CHC (Rosenburg and Waugh, 1998, cited in FSRH, 2019). It can be difficult to assess the impact of CHC on mood. Studies are conflicting and, although most are reassuring, a recent Danish study reported a significant association with CHC use and depression (Skovlund et al, 2016).

There is no clear, consistent evidence of a causative effect of CHC on depression, but mood changes are common and may be related to external events (FSRH, 2016). Management may include:

• Continuous CHC use if mood change is associated with HFI
• Change of preparation to one containing a different progestogen
• Consider a COC containing drospirenone, as this may possibly have a beneficial effect on mood (Kelly et al, 2010).

CHC does have some health risks, which can rarely increase risk of adverse events such as venous thromboembolism and arterial thromboembolic disease. These have not been considered here as a management process. Women should be evaluated for risk factors for these using the UK Medical Eligibility Criteria for Contraceptive Use (FSRH, 2016) before starting during use of CHC and a minimum of annually during use.

Progestogen only contraception

Progestogen only contraception (POC) is available as three methods: orally as progestogen only pill (POP), injectable and subdermal implant. Although side effects might be assumed to be similar, there are some differences between these methods of administration, and so will be considered separately.

Progestogen only pill (POP)

There are currently three types of POP:

• Traditional POP containing levonorgestrel or norethisterone
• Desogestrel POP (DSG POP)
• Drospirenone POP (DRSP POP) – not in the UK at the time of writing.

Traditional POP works primarily by the effect of thickening of cervical mucous and the thinning of the endometrium, with an interference with ovulation. DSG POP and DRSP POP inhibit ovulation.

Management of side effects of POP

Change in bleeding pattern

Bleeding patterns with all POP can be unpredictable, and can include amehorrhoea, or frequent or prolonged bleeding (FSRH, 2022). There is weak evidence that POP can help with heavy menstrual bleeding and dysmenorrhea (FSRH, 2022).

Irregular or problematic bleeding is a common reason for discontinuation of POP. Bleeding patterns are unpredictable and dependent on the type of POP as well as circulating estrogen levels and whether or not ovarian suppression is achieved.

Studies of bleeding patterns can be difficult to interpret due to lack of consistency in categorisation of bleeding patterns. However, traditional POP users are more likely to experience normal, or mostly regular bleeding with amenorrhoea uncommon.

Bleeding with DSG POP tends to become less frequent and prolonged over the first 12 months of use, with most users reporting amenorrhoea or infrequent bleeding. DRSP POP users may experience scheduled bleeding in the HFI but unscheduled bleeding and spotting is also common. This may reduce over the first year of use with low rates of prolonged or frequent bleeding (FSRH, 2022). The challenge is how to manage bleeding problems. Often, women are using POP because CHC use is not suitable for them due to medical or personal characteristics. As with management of bleeding on CHC, other potential causes for bleeding should be considered and excluded. A change of POP; for example, from DSG POP to traditional, or the DRSP POP (when available), may help and women could try this (FSRH, 2013). Explanation should be given that bleeding patterns often improve over time.

Other reported side effects

Women report side effects of mood change, headache, acne (less than 1:10), weight gain and loss of libido. However, evidence is either absent or limited as to any causative effect of POP. It is recommended that other contributing factors are explored, but that if women feel POP is adversely affecting these factors, then alternative contraception should be explored (FSRH 2022).

Progestogen only implant (etonorgestrel implant (ENG-IMP))

The ENG-IMP is a single rod implant containing the progestogen etonorgestrel 68 mg which is released over 3 years. The primary effect is the prevention of ovulation.

Management of side effects of ENG-IMP

Unpredictable bleeding

Unacceptable bleeding is a common side effect of the ENG-IMP. Bleeding patterns commonly change throughout the 3 years of use and may prove to be unacceptable. Bleeding patterns may be irregular and prolonged, although amenorrhea is also possible (FSRH, 2021).

While the ENG-IMP is a highly cost effective method of contraception, with early removal rates between 16–20% in the first 2 yeas of use, early discontinuation of the method reduces cost effectiveness (FSRH, 2021).

Although it is not possible to predict the bleeding pattern for an individual woman, evidence suggests that women who have favourable bleeding patterns in the first few months of use are more likely to continue to do so. Where women have unfavourable bleeding patterns initially, there is a 50% change that the pattern will improve (FSRH, 2021).

Women should be carefully counselled and informed about potential bleeding. Some studies have shown that women were not prepared for, or did not absorb, information about bleeding patterns and were often advised to persevere with bleeding in the hope of improvement.

However, this could mean that the therapeutic window for intervention was missed, and the so-called ‘tipping point’ was reached in tolerability of the method. Recognition of the impact of bleeding is important and early intervention to manage bleeding recommended (Dickson et al, 2013). After exclusion of other causes of bleeding, options for management are:

• Where women are medically eligible, a 3-month course of CHC can be given. Dickson et al (2013) advise a preparation containing ethinylestradiol 30 mcg and levonorgestrel 150 mcg. This can be taken continuously or cyclically. This is an off-licence use of CHC
• If CHC is contraindicated, medically eligible women can a try a 5-day course of mefenamic acid 500 mg three times daily, which will usually arrest the current bleeding episode (FSRH, 2021)
• Although use of an additional progestogen has been used in practice, there is no available evidence to evaluate the effectiveness of this (FSRH, 2021)
• Good pre-insertion counselling, including bleeding patterns and an accessible approach to facilitate early management of problems.

Acne

Some users report new or worsening acne, while others report an improvement. Women may report side effects of headache and depression or mood changes. Evidence is too limited to confirm or exclude ENG-IMP as causation (FRSG, 2021).

Progestogen only injectables (DMPA)

Depo medroxyprogestogen acetate (DMPA) is available for intramuscular injection as DMPA 150 mg in 1 ml (DMPA-IM) or 104 mg in 0.65 ml subcutaneous injection (DMPA-SC) for self-administration. Side effect profile is similar for both methods of administration. The primary contraceptive effect is by inhibition of ovulation.

Management of side effects of DMPA

Altered bleeding patterns

Amenorrhoea is common with DMPA use, and becomes more common with increased duration of use, with 47% women experiencing this at 1 year of use (FSRH, 2020).

This is often seen as a beneficial side effect; with DMPA being licensed for management of heavy menstrual bleeding as well as contraception. However, some women experience irregular or problematic bleeding. Management suggested by FSRH (2013) is:

• Use of CHC for 3 months (if medically eligible)
• Mefenamic acid 500 g three times a day for 5 days or tranexamic acid 1 g four times a day. There is no evidence that these will have a long-term effect on bleeding patterns.

Weight gain

DMPA does have an association with weight gain. Women who gain more than 5% of their starting weight are more likely to continue to gain weight. A high initial BMI in under 18 year olds is predictive of weight gain, although this is not found in adult women (FSRH, 2013).

Injection site reactions

Lipoatrophy or dimpling at injection site of SC-DMPA has been reported, in up to 8% of women (Jodicke et al, 2017). It is advised that women are informed of this potential, and should it be noticed, be made aware that further site reactions could occur.

Side effects have been reported of acne, reduced libido, mood swings, headache, vaginitis and hot flushes, but there is little evidence as to causation (FSRH, 2013). Other potential areas for concern should be discussed before initiation of DMPA. There can be a delay in return to fertility of up to 1 year. DMPA is associated with a small loss of bone mineral density, which is largely recovered after discontinuation (FSRH, 2013).

Intrauterine contraception (IUC)

There are two methods of intrauterine contraception: copper intrauterine device (CU-IUD) and levonorgestrel releasing intrauterine device (LNG-IUD). LNG-IUD contains either 52 mg, 19.5 mg or 13.5 mg of levonorgestrel.

Some IUC problems are common to both types of device, but mode of action and side effects differ. The CU-IUD works primarily by preventing fertilisation due to toxic effects of the copper on sperm and ovum. The LNG-IUD works by thinning of endometrium, thereby preventing implantation, and prevents sperm penetration by the effects of progestogen on the cervical mucous.

Bleeding pattern

Users of CU-IUD will have a menstrual pattern similar to their normal cycle. However, periods can be heavier, longer and more painful, with intermenstrual bleeding or spotting possible. Heavy bleeding may improve over time (FSRH, 2023). Bleeding disturbance is the most common reason for discontinuation of CU-IUD with 41% of women citing this (Saloranta et al, 2020).

LNG-IUD users often experience frequent or prolonged bleeding at first, but the number of bleeding days reduces over time, with amenorrhoea or infrequent bleeding more likely at the end of the first year. Likelihood of amenorrhoea is dose dependent and more common in users of 52 mg LNG-IUD (FSRH, 2023). Discussion of possible bleeding patterns prior to fitting of the device is an important aspect of counselling.

Managing bleeding problems with CU-IUD

Heavy bleeding can be managed with use of tranexamic acid or non-steroidal anti inflammatory drugs. Consider and discuss change to LNG-IUD if medically eligible.

Managing bleeding problems with LNG-IUD

Evidence for management of problematic bleeding with LNG-IUS is limited. Women can be reassured that initial bleeding usually lessens. After exclusion of other causes, a 3-month trial of CHC (if medically eligible) can be tried, although bleeding often resumes once this is stopped (FSRH, 2023).

Hormonal side effects with LNG-IUD

Acne, breast tenderness and mood changes have been reported. However, there is insufficient evidence to establish any causative effect. If they do occur, women can be advised that they usually decrease over time (FSRH, 2023).

New onset pelvic pain

Pelvic pain may be due to other causes, which should be considered. A full clinical history should be taken and vital signs checked. Management should include:

• Pregnancy test (be mindful of possibility of ectopic pregnancy)
• Abdominal and pelvic examination
• Screening for sexually transmitted infections
• Pelvic ultrasound.

Missing IUC threads

Although not a side effect of IUC, this is a common problem experienced by 18% of women who have had a standard insertion of IUC, and 30–50% if fitted immediately post partum or at caesarian section (FSRH, 2023). Often, the threads are in the cervical canal or uterus, but it is important to exclude pregnancy, expulsion or perforation of the device. Management should consist of:

• Pregnancy test
• Emergency contraception, if sex has occurred in the previous 120 hours
• Provide alternative contraception
• Pelvic ultrasound – if device is seen it can be left in situ, unless the woman wants removal
• If no device is seen at ultrasound, abdominal X-ray, to exclude perforation.

Weight gain and contraception

Women commonly raise the possibility of weight gain as a concern when discussing contraception. Perceived weight gain is a common factor in discontinuation of a method. With the exception of DMPA, there is no evidence for a causal association between the method and weight gain (FSRH, 2019).

Conclusion

Side effects are a common reason for discontinuation of contraception. Some reported side effects have little or no evidence for causation by the method but they remain a concern for women. Discussion of possible side effects, and what to expect with methods, should be an integral part of pre-contraception counselling. Contraception consultations are different to most medical consultations in that women are not unwell, but are making a positive choice about controlling their fertility. Evidence suggests that a patient-centred approach with an evidence-based discussion of side effects, facilitating a shared decision-making process, is associated with continuation of the method.

Providing honest discussion about side effects and having a respectful approach to addressing women’s concerns has been show to improve outcomes of contraceptive use (Dehlendorf et al, 2014). During the consultation, an awareness that efficacy is not always the only consideration for the woman, and that social and relational factors will also influence continuation is important. Many common side effects decrease with time but if unacceptable, good management may increase acceptability and continuation rates of the method.

Key Points

• Side effects are a common reason for discontinuation of contraception
• Contraceptive counselling can improve continuation rates
• Bleeding patterns are likely to be unpredictable with progestogen only contraception
• Early intervention and management of side effects, such as bleeding, may improve continuation rates

CPD reflective questions

• How can I improve my contraceptive counseling regarding expected bleeding patterns on ENG-IMP?
• What is the best way to discuss a woman’s concern about weight gain on contraception?
• How can I facilitate easy access for women to allow early intervention and management of bleeding problems with contraception?
• How can I introduce a protocol for management of women presenting with missing IUC threads?