Results

Case study 50: Individualising hormonal contraception

December 2007

NPS is an independent, non-profit organisation for Quality Use of Medicines funded by the Australian Government Department of Health and Ageing. ABN 61 082 034 393 | Level 7/418A Elizabeth Street Surry Hills 2010 | PO Box 1147 Strawberry Hills 2012 Phone: 02 8217 8700 | Fax: 02 9211 7578 | email: info@nps.org.au | web: www.nps.org.au

NPSCS0442

Inside
Case study 50: Individualising hormonal contraception Scenario and questions Summary of results page 3 page 4

Results in detail Oral contraceptive use when migraine occurs Suitability of long-term contraception Family history of venous thromboembolism and contraceptive choice Commentaries Dr Deirdre ODea Dr Terri Foran References page 11 page 13 page 16 page 6 page 8 page 9

The information contained in this material is derived from a critical analysis of a wide range of authoritative evidence. Any treatment decision based on this information should be made in the context of the clinical circumstances of each patient. Declarations of interest have been sought from all commentators.

Case study 50: Individualising hormonal contraception

Scenario
Sandra is a 34-year-old non-smoker who recently moved to Australia from the United Kingdom. She is newly married and has a daughter from a previous relationship. Sandra struggles to control her weight and is anxious about potential weight gain from any new medicine. As there are no plans to have any children in the next few years, Sandra started on a combined oral contraceptive pill, ethinyloestradiol 35 micrograms/norethisterone 1 mg (Brevinor-1 or Norimin-1) 6 months ago. She is not using any other medicines. Her blood pressure is 118/75 mmHg and BMI 26 kg/m2. There is no family or personal history of diabetes, hepatic disease, migraine, cardiovascular disease or cancer. Sandra presents with a history of several episodes of a persistent, throbbing headache which started when she commenced the new pill. On probing, she mentions that she has experienced the headache at least 5 times in the last 6 months when she has a period (i.e. during the inactive pill / pill-free week). It did not occur to her that this was due to her oral contraceptive until you mentioned it. There has been no weight gain or any other oestrogenic/progestogenic effect. Further questioning and examination do not suggest another diagnosis and the symptoms are consistent with migraine without aura associated with oral contraceptive use.

1. a) Given Sandras migraines, would you recommend any changes to her oral contraceptive? Yes No Please state why OR why not. b) If yes, please list Sandras new regimen (include existing drug if continuing). Drug Dose Frequencyiiiiii

2. a) Do you think Sandra would be a good candidate for long-term contraception (i.e. implant, depot injection or intrauterine device)? Yes No Please state why OR why not. b) If yes, please list Sandras new contraceptive regimen. Drug Dose Frequencyiiiiii

3. a) Would you recommend a different contraceptive to ethinyloestradiol 35 micrograms /norethisterone 1 mg (Brevinor-1 or Norimin-1) if Sandra had a family history of venous thromboembolism (i.e. if her mother had suffered from a spontaneous deep vein thrombosis 10 years ago) and no personal history of migraine? Yes No Please state why OR why not. b) If yes, please list Sandras new contraceptive regimen. Drug Dose Frequencyiiiiii

Summary of results
At the time of publication, 820 responses had been received. This report summarises responses from 200 general practitioners.

Case synopsis
Sandra, a 34-year-old non-smoker presented with migraine without aura associated with oral contraceptive use (migraine occurs during the pill-free week). She started on ethinyloestradiol 35 microgram / norethisterone 1 mg (Brevinor-1 or Norimin-1) six months ago. She is not using any other medicines. Her blood pressure is 118/75 mmHg and BMI 26 kg/m2. There has been no weight gain or any other oestrogenic or progestogenic effect. There is no family or personal history of diabetes, hepatic disease, migraine, cardiovascular disease or cancer. (See page 3 for more details.)

Impact of migraine on contraceptive choice

99.0% of respondents reported that they would change Sandras oral contraceptive after presentation of migraine without aura to stop or reduce the headaches. The main changes recommended were: tricycling the original contraceptive (i.e. having a pill-free interval of 37 days only once every 3 months)1 (30.3%) reducing the oestrogen and progestogen component of the contraceptive (i.e. low-dose combined oral contraceptive) (17.7%) adding an oestrogen during the pill-free week (9.5%) using a progestogen-only pill (9.1%) using a triphasic oral contraceptive (8.6%). Many respondents advised that they would discuss the options with the patient before deciding on the management plan.

Suitability of long-term contraception*

76.5% of respondents considered that long-term contraception would be suitable, 21.0% did not and 2.5% of respondents thought the decision depended on additional factors. Main reasons for using a long-term contraceptive were: no plans for having a child in the next few years (38.6%), no risk of oestrogenic adverse effects (22.2%), to reduce migraine/headache (19.0%), to reduce risk of weight gain (7.8%), because the patient was parous (7.2%) and because there were no contraindications (6.5%). Of those who thought that long-term contraception was suitable, 60.1% selected etonorgestrel implant (Implanon) and 32.1% selected levonorgestrel-releasing intrauterine device (Mirena). Respondents who felt that long-term contraception was inappropriate did so because the patient may want further pregnancies (45.2%), because of potential weight gain (28.5%) and because there were no cardiovascular risk factors to warrant a change in her oral contraceptive.

* Long-term contraception options include etonogestrel implant (Implanon), levonorgestrel-releasing intrauterine device (Mirena),
copper intrauterine devices, depot medroxyprogesterone acetate (Depo-Provera) and ethinyloestradiol/etonorgestrel-releasing vaginal ring (NuvaRing).

Family history of venous thromboembolism and contraceptive choice

72.0% of respondents would recommend a different contraceptive from the monophasic combined oral contraceptive if there was a family history of venous thromboembolism and no history of migraine, while 27.0% would not. Most respondents would select a progestogen-only pill to decrease the risk of venous thromboembolism, while 19.4% were satisfied with a low-dose combined oral contraceptive. Interestingly, 16.8% of respondents indicated that they would not make a treatment decision until Sandra was screened for thrombogenic mutations (i.e. factor V Leiden).

Results in detail
Oral contraceptive use when migraine occurs
99.0% of respondents reported that they would change Sandras oral contraceptive after presentation of migraine without aura. Several respondents acknowledged that there were many different options to manage this condition; 5.5% of respondents provided a second choice of oral contraceptive. Table 1 groups the responses according to reason for the recommended changes, while table 2 analyses the medicines recommended by respondents and the rationale behind these recommendations.

Table 1
Reason for changing/regimen recommended
To stop or reduce migraine/headache Oestrogen withdrawal during pill-free week may be the cause of the headaches Tricycling pills will avoid the pill-free week To avoid the pill-free week by adding oestrogen during pill-free week or by tricycling her pills Lower oestrogen dose as higher oestrogen content triggered the adverse effect
*Respondents may have more than one response

% of respondents* (n = 198)
38.8 14.5 13.1 9.1 7.1

Table 2
% of respondents* (n = 198)
30.3 17.7

Medicine/regimen
Tricycle the original contraceptive Change to a low-dose oral contraceptive (mostly ethinyloestradiol 20 microgram / levonorgestrel 100 microgram [Microgynon 20]) Add an oestrogen during the pill-free week Use a progestogen-only pill (mostly levonorgestrel 30 microgram [Microlut]) Use a triphasic oral contraceptive (mostly ethinyloestradiol 30/40/30microgram / levonorgestrel 50/75/125 microgram [Triphasil])
*Respondents may have more than one response

Rationale

Avoid withdrawal headaches Reduce the oestrogen and progestogen component of the contraceptive to reduce headache Decrease hormonal fluctuation thus reducing headache Stop the oestrogen content to decrease headache and risk of stroke Mimic the cyclical pathway of endogenous hormones to reduce headache

9.5 9.1 8.6

Duration for tricycling ranged from 6 weeks to 4 months Oestrogen type and dose ranged from conjugated oestrogens (0.30.625 mg) to ethinyloestradiol (1030 microgram) Rationale may not have been explicit in responses

Practice points
There is a 24-fold increased risk of stroke in women who experience migraine (with or without aura) while using combined oral contraceptives (COCs) compared with those who experience migraine but do not use COCs.2 Besides use of COCs, additional risk factors for stroke are noted in the summary table below. 2,3 Contraindications for use of COCs in women with migraine are based on limited evidence and expert opinion.3 For women who develop migraine without aura after starting a COC, the risks of continuing the COC may outweigh the benefit.2,4 As Sandra is < 35 years old and did not have the migraines until she started the new COC, the risk of stroke outweigh the advantages (strong relative contraindication). Other options for patients with migraine without aura after starting a COC include the progestogenonly preparations (progestogen-only pill, etonorgestrel implant [Implanon], depot medroxyprogesterone acetate (DMPA) injection [Depo-Provera, Depo-Ralovera], levonorgestrel-releasing intrauterine system [Mirena]), copper intrauterine device (copper IUD), barrier and natural methods.4 Currently there is no evidence to suggest that the effects of non-oral combined contraception (i.e. vaginal ring) are any different from those of COCs. Table 3 summarises COC use in women with migraine or headache.

Table 3: Migraine, headache and hormonal contraception

Diagnosis
Migraine with aura before starting COC Migraine with aura during use of COC No history of migraine before starting COC AND migraine without aura develops during use of COC (i.e. Sandras case) In women > 35 years, stop the combined oral contraceptive (COC). Consider progestogen-only contraceptive or non-hormonal methods2 In women < 35 years, the risks generally outweigh the advantages. (Strong relative contraindication) 5 Exercise clinical judgement if other risk factors for cardiovascular disease are present (i.e. smoking, diabetes) 2 History of migraine without aura before starting COC In women < 35 years, if no other risk factors, the advantages of COC generally outweigh the disadvantages2 If 1 additional risk factor for stroke, the disadvantages of COC generally outweigh the advantages but the COC may be used with caution.2 Risk factors for stroke include age > 35 years, smoking, hypertension, diabetes mellitus, hyperlipidaemia, BMI > 30 kg/m2, and family history of arterial disease before age 452 If more than 1 additional risk factor for stroke, stop the COC. Consider progestogen-only contraceptive or non-hormonal methods2 Headache in the pill-free week (no migraine) Add oestrogen daily during pill-free week (e.g. 100 microgram oestrogen patch or equivalent) Tri-cycle pills to avoid the pill-free week2
*NPS would like to thank Dr Christine Read (Family Planning NSW) for her assistance in putting this table together

Recommendation
Stop COC. Consider progestogen-only contraceptive or non-hormonal methods2

Suitability of long-term contraception

76.5% of respondents felt that long-term contraception would be suitable, 21.0% did not and 2.5% of respondents thought the choice depended on other factors.

Reasons long-term contraception is suitable

No plans on having children in the next few years No risk of oestrogenic adverse effects Reduce occurrence of headache/migraine May reduce risk of weight gain Parous No contraindication to long-term contraceptive use

% of respondents* (n = 153)
38.6 22.2 19.0 7.8 7.2 6.5

Reasons long-term contraception is unsuitable

May want further pregnancies Increased risk of weight gain from long-term contraception No cardiovascular risk factors to warrant a change
*Respondents may have more than one response

% of respondents* (n = 42)
45.2 28.5 9.5

9.5% specifically referred to depot medroxyprogesterone acetate (Depo-Provera, Depo-Ralovera)

Of those who thought long-term contraception was suitable, 60.1% selected etonorgestrel implant (Implanon) and 32.1% selected levonorgestrel-releasing intrauterine device (Mirena).

Practice points
Bone mineral density loss has been reported in users of depot medroxyprogesterone acetate (DMPA). It is important that risk factors for osteoporosis are evaluated, especially in women aged < 18 years or those at risk of osteoporosis (> 45 years).2 Encourage adequate calcium and vitamin D intake, and recommend weight-bearing exercise and smoking cessation.1 There are limited studies on the effects of long-term contraception on weight gain. DMPA has the most effect on weight gain (23 kg increase in 1 year) while there is no evidence of significant weight change among users of copper IUDs or levonorgestrel-releasing IUD (Mirena) in European studies. There is insufficient evidence to suggest weight gain with the etonorgestrel implant (Implanon).6

Family history of venous thromboembolism and contraceptive choice

72.0% of respondents would recommend a different contraceptive from the monophasic combined oral contraceptive if there was a family history of venous thromboembolism and no history of migraine; 27.0% would not.

Reasons for changing from the original contraceptive

Lower oestrogen dose may reduce deep vein thrombosis (DVT) risk Decreased risk of venous thromboembolism (including DVT) Family history may increase risk of DVT Removes oestrogenic adverse effects Sandra is approaching 35 years of age, which may increase her DVT risk

% of respondents* (n = 144)
24.3 23.6 18.8 9.1 9.0

Reasons for continuing the original contraceptive

No evidence that current contraceptive has a higher risk of venous thromboembolism compared with other contraceptives Consider screening for thrombogenic mutation (i.e. factor V Leiden) before making treatment decision The absolute risk of venous thromboembolism is very small for combined oral contraceptives Not a smoker
*Respondents may have more than one response

% of respondents* (n = 54)
26.0 16.8 13.0 7.4

4.9% said they would screen for factor V Leiden mutation as well

Alternative drugs
Progestogen-only pill [mostly levonorgestrel 30 microgram (Microlut)] Levonorgestrel-releasing intrauterine device (Mirena) Etonorgestrel implant (Implanon) Low-dose combined oral contraceptive [mostly ethinyloestradiol 20 microgram / levonorgestrel 100 microgram (Microgynon 20)]
*Respondents may have more than one response

% of respondents* (n = 144)
26.5 20.8 21.5 19.4

Practice points
All combined oral contraceptives may increase the risk of venous thromboembolism (VTE). Be wary of increased risk of DVT and pulmonary embolism, especially in the first 4 months of COC use.2 Provide written information and encourage patients to read consumer medicine information, which provide information on warning signs of VTE. There is limited evidence on the risk of venous thromboembolism associated with etonorgestrel implant (Implanon) or levonorgestrel-releasing IUD (Mirena). Routine thrombophilia screening is not recommended before prescribing COC. If a woman has a family history of VTE in a 1st-degree relative under age 45 who, having considered other contraceptive methods, still wishes to use a COC, a thrombophilia screen should be performed. It is good practice to consult with a haematologist or other expert when interpreting a thrombophilia screen.7

There is limited data on the cardiovascular effects of progestogen-only pills. Progestogen-only pills may be suitable for women who want to use an oral contraceptive but who have risk factors for cardiovascular complications with the COC, such as age, moderate to severe hypertension, diabetes, migraine with aura, obesity, a history of VTE or heavy smoking. At the same time, these women should be closely screened and monitored.8 Other options to consider in women at high risk of VTE are barrier methods and natural family planning.

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Commentary 1
Key points
Contraception and possible side effects of contraception are common GP consultations. Migraine without aura developing during combined oral contraceptive (COC) use is a relative contraindication to the use of COC. Thrombophilia screening in COC users is indicated with a family history of idiopathic venous thromboembolism in a parent or sibling under 45 years of age. Screening in other situations is not cost-effective.

Dr Deirdre ODea General Practitioner Sydney NSW

A small number of respondents suggested changing to a triphasic pill. These are not usually recommended for women who get headaches, as the fluctuations in hormone levels may act as a trigger. The first option (tricycling or adding oestrogen in the pill-free week) was suggested by nearly 40% of respondents and is consistent with the advice in Table 2 of NPS News 54.9 The theoretical disadvantage of this would be that more oestrogen is ingested per year of COC use. Almost 20% of respondents suggested reducing the oestrogen and progesterone component of the contraceptive, and this low-dose pill could be tricycled. The challenges in Sandras case are her age and her new-onset migraines. There is dispute over whether migraine without aura is truly a risk factor for thrombotic stroke.10 Despite this, Contraception: an Australian Clinical Practice Handbook1 states that if migraine without aura develops during COC use it is automatically a World Health Organization category 3 (Strong relative contraindication) regarding COC use and, if you are over 35, it is WHO category 4, (Absolute contraindication). The reason for this caution is that risk of thrombotic stroke rises with age. The background annual risk of thrombotic stroke for women aged 20 years is 2 in 100,000.10 With more than 1 migraine per month and COC use, this rises to 10 in 100,000. But at age 40 the background risk is 20 in 100,000. This rises to 56 for women who experience more than 1 migraine per month. Adding the COC increases the annual risk to 100 in 100,000, or 1 in 1000. If the management plan we developed with Sandra was to tricycle the COC at present, there would need to be a clear understanding that this was not her ideal long-term contraceptive option.

Impact of migraine on contraceptive choice

Two of our core GP skills are developing a shared management plan with our patients and being available to review this over time. I imagine that Sandra would be keen to review her oral contraceptive after making the link that her migraines were occurring during the pill-free week. It would be interesting to know if she hopes for children from this new relationship. If she does, I would encourage her not to put it off for the next few years, as the scenario suggests. Respondents clearly recognised that Sandras migraines were linked to the drop in oestrogen levels during the pill-free week. Sandras options are: Limit the fluctuation in oestrogen levels, either by tricycling* the COC to avoid the pill-free week or by taking oestrogen during the pill-free week. Stop the COC and use another form of contraception.

*Tricycling the original contraceptive (i.e. having a pill-free interval of 37 days only once every 3 months)

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Would Sandra be a good candidate for long-term contraception?

More than 75% of respondents considered long-term contraception to be suitable, and almost all these recommended either Implanon or Mirena. A copper IUD would be another option. Sandra is worried about potential weight gain, so Depo-Provera is out. The ethinyloestradiol/ etonorgestrel-releasing vaginal ring (NuvaRing) would have the same disadvantages as the COC. Among those who felt that long-term contraception was unsuitable, almost half cited concerns about a possible delayed return to fertility. However, there is no evidence of a delay in return to fertility for Implanon or IUD users 10.

of respondents would not recommend the COC. As Sandra is approaching age 35, this conservative approach is reasonable. Family history of VTE in a parent or sibling aged > 45 years is classified as WHO 2 (generally safe to use)10. Idiopathic VTE in a parent or sibling aged < 45 years is an indication for thrombophilia screening if available. Screening in other situations is not cost-effective and a negative thrombophilia screen cannot be entirely reassuring. About 15% of respondents suggested screening for the most common thrombophilia, factor V Leiden. Each year there are only 3 extra cases of VTE among 1000 pill takers with factor V Leiden mutation, compared with pill uses without this predisposition.10 For GPs looking for a user friendly reference about Contraception I would recommend Sexual Health and Family Planning Australias Contraception: an Australian Practice Handbook2 and John Guillebauds comprehensive Contraception, your questions answered.10

Family history of venous thromboembolism and contraceptive choice

If Sandra had a family history of venous thromboembolism (VTE), almost three-quarters

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Commentary 2
Key points
Migraine occurring exclusively in the pill-free week of the combined contraceptive pill appears to be triggered by falling levels of oestrogen. Such attacks are usually migraines without aura and typically start a couple of days after the active pills are stopped. Combined contraceptive methods are generally considered safe to use in women with migraine without aura who are under 35 years of age, provided there are no other risk factors present. Migraine arising for the first time with initiation of a COC is more concerning. Migraine with aura remains an absolute contraindication to combined oral contraceptive pill use, as it increases the risk of ischaemic stroke. Though lower in dosage, the vaginal ring is also contraindicated in women with migraine with aura. Progestogen-only hormonal contraception is considered generally safe to use in women with migraine with aura, except in rare cases when the first attack occurs after starting the 5 regimen. A family history of VTE in one 1st-degree relative would generally still make the COC generally safe to use, although some clinicians might wish to order a screen for the known thrombogenic mutations before starting the pill. A history of spontaneous thromboembolism in several relatives would be even more compelling. A past history of DVT or pulmonary embolus, or the presence of a known thrombogenic mutation, remain absolute contraindications to combined 5 contraceptive use. Progestogen-only hormonal contraception is generally safe to use even in those with a past history of DVT or pulmonary embolism 5 or a known thrombogenic mutation.

Dr Terri Foran Sexual Health Physician University of NSW

Management of migraine in the pill-free week

Sandra gives a typical history of headache triggered by oestrogen withdrawal during the pill-free week of the combined pill. In people who experience migraine without hormonal contraception there is often an increase in the frequency and severity of attacks in the latter half of the cycle, which is believed to be due to a relative oestrogen deficiency at this time.11 Many women with common migraine report an improvement in symptoms on the pill but, when attacks do occur, they are more likely in the hormone-free week.12,13 The background risk of stroke in all women aged 30-34 years on the COC is 5 in 100,000, but a history of common migraine doubles this risk. For those with migraine with aura this risk increases to 29 in 100,00014 , which is generally considered unacceptable.15 Age is also a factor, and use of combined contraception in women with migraine, even without aura, becomes less advisable after age 35, particularly if there are any other risk factors present for stroke or heart disease.5 The most conservative approach in Sandras case, in which her migraines appear to have arisen for the very first time at initiation of hormonal contraceptive use, would be to recommend stopping combined contraception. However, since these migraines occur exclusively during the pill-free week, and there is a good physiological explanation for their occurrence, I am not surprised that only a minority of respondents suggested this. In Sandras case simply changing to a combined pill with a lower dose of oestrogen, or to a triphasic, is unlikely to be effective because she will still experience an inevitable drop in oestrogen levels during the pill-free week. If, after discussion of the possible risks, Sandra was keen to persist with a combined pill, I would be inclined to explore

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strategies that would mitigate the sudden fall in oestrogen during the pill-free week. As identified by some respondents, I would discuss both the possibility of running cycles of the pill together and the use of a low-dose oestrogen preparation in the pill-free week. Combining these two strategies is also possible. The progestogen in the pill Sandra is taking suppresses endometrial proliferation particularly well and it may in fact be possible to run packets together for many months perhaps indefinitely without the problem of breakthrough bleeding. As this will mean fewer periods it may be necessary to reassure Sandra that such manipulation of her cycle will not involve any risks to her future fertility. If she prefers to have regular withdrawal bleeds or finds that she needs to take scheduled breaks with extended pill use, I would suggest that she consider use of a natural oestrogen preparation during the pill-free week.16 This provides protection from hormonally triggered migraines while still allowing for withdrawal bleeding. A weekly oestradiol patch is probably the most convenient option. Though 50-100 micrograms is the usual recommended dose16, some women find that their headaches settle with dosages as low as 25 micrograms/24 hours. If patches are unacceptable, oestradiol gel 1 mg, or 12 mg oral oestradiol valerate, daily during the pill-free week are possible alternatives. It should be noted that all the above preparations would require a private prescription, as migraine prevention is not a PBS indication for their use. Sandras presentation provides an opportunity to review her contraceptive options generally. As a more convenient alternative she might consider the use of a vaginal contraceptive ring. Though the oestrogen dose is lower it is presently considered to have the same risks as the combined pill and it is likely that she would need to employ similar strategies to avoid oestrogenwithdrawal migraines. It would be important to monitor Sandra closely if she chooses to continue with combined contraception.

Role of progestogen-only contraception

After discussing the potential risks related to oestrogen use Sandra may wish to explore the possible benefits of progestogen-only contraception (progestogen-only pill, contraceptive implant, progestogen IUD, depot medroxyprogesterone acetate [DMPA] injection). This would also be advisable if she continued to experience migraines on the extended pill regimen described above. In making this choice she would need to be carefully counselled about other potential side effects, in particular the possibility of irregular bleeding. The higher failure rate of the progestogen-only pill and its strict dosing regimen mean that few modern women consider it a viable option except during lactation. In view of Sandras concerns regarding weight gain it would be important to discuss that, although significant weight gain may be a problem for some DMPA users, as identified by the respondents, it is much less likely in users of the other progestogen-only methods. A copper IUD would be another option, as Sandra appears to be at low risk of sexually transmitted infections, but she should be warned that she could experience heavier menstrual bleeding while using it. As there are no immediate plans for a pregnancy, the convenience and effectiveness of these longer-acting methods may well appeal to her. I would, however, gently advise her that at 34 years of age she should not push her plans for further children too far into the future. For this reason the long delay in the resumption of fertility after DMPA use would make it a less appealing option, while the other long-acting contraceptive methods are all rapidly reversible. Sandra could also consider other non-hormonal contraceptive methods such as condoms, diaphragms and fertility awareness, although she may not consider these effective enough considering her desire to avoid pregnancy in the next few years.

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VTE risk and combined oral contraception

The last issue raised in this case is that of a family history of spontaneous DVT in a 1st-degree relative. Sandra is using a pill that contains one of the older progestogens. This increases her risk of VTE to about 3 times her background rate. The risk is higher with the newer progestogens. WHO guidelines5suggest that for someone with a 1st-degree relative with a history of VTE but no other risk factors, the advantages of oestrogen-containing contraception usually outweigh the risks. However, as the risk of VTE increases with age, this consultation may be an ideal opportunity to discuss the various alternative contraceptive options available to Sandra as she moves into her late 30s and 40s. This would be even more important if she develops any other risk factors for cardiovascular disease. Although evidence is limited, progestogen-only contraception is generally considered safe to use in those with a personal or family history of

thromboembolism. If Sandra was keen to remain on the combined pill there would be a case for arranging a thrombophilia screen (factor V Leiden, prothrombin mutation, protein S, protein C, antithrombin deficiency). If any of these results indicated an increased risk of thrombophilia it may be prudent to arrange a consultation with a haematologist and to recommend an alternative to combined contraception. Even if the results are negative Sandra may wish to consider a lower-dose combined method such as a 20 microgram pill or a vaginal ring. It is also important to remember that Sandra is planning a pregnancy in the next few years. Her family history of DVT may be even more important in this situation, as pregnancy itself represents a 12-fold increase in the risk of VTE. In summary, Sandras case illustrates that the choice of a contraceptive method is an extremely personalised one in which all risks and benefits must be carefully weighed up by both the user and the clinician.

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References
1. 2. 3. 4. Australian Medicines Handbook. January 2007. http://www.amh.hcn.net.au/ (accessed 26 July 2007). Read C, McNamee K, Harvey C. Contraception: an Australian Clinical Practice Handbook. Sydney: Sexual health and Family Planning Australia, 2006. MacGregor E. Hormonal contraception and migraine. J Fam Plan Reprod Health Care 2001;27:4952. Clinical Knowledge Summaries. Contraception http://cks.library.nhs.uk/DRAFT_Contraception/In_depth/Management_issues (accessed 12 October 2007). WHO. WHO Medical Eligibility Criteria for contraception use. 2004. http://www.who.int/reproductive-health/publications/mec/mec.pdf (accessed 8 August 2007). NICE. Long-acting reversible contraception. October 2005. http://www.nice.org.uk/nicemedia/pdf/CG030fullguideline.pdf (accessed 9 November 2007). Royal College of Obstetricians and Gynaecologists. Venous thromboembolism and hormonal contraception. 2004. http://www.rcog.org.uk/resources/Public/pdf/VTE_hormonal_contraception.pdf (accessed 21 November 2007). Consumers' Association. Oral contraceptives and cardiovascular risk. Drug Ther Bull 2000;38. National Prescribing Service Ltd. NPS News 54. Hormonal contraceptives: tailoring for the individual. 2007. http://www.nps.org.au/site.php?content=/html/news.php&news=/resources/NPS_News/news54 (accessed 29 November 2007).

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8. 9.

10. Guillebaud J. Contraception Your Questions answered. 4th ed: Elsevier Health Services, 2004. 11. MacGregor EA, Frith A, Ellis J, et al. Incidence of migraine relative to menstrual cycle phases of rising and falling estrogen. Neurology 2006;67:21548. 12. Kudrow L. The relationship of headache frequency to hormone use in migraine. Headache: The Journal of Head and Face Pain 1975;15:3640. 13. Ryan RE. A Controlled Study of the Effect of Oral Contraceptives on Migraine. Headache: The Journal of Head and Face Pain 1978;17:2502. 14. Becker WJ. Use of oral contraceptives in patients with migraine. Neurology 1999;53:S1925. 15. Etminan M, Takkouche B, Isorna FC, et al. Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies. BMJ 2005;330:636. 16. MacGregor EA, Hackshaw A. Prevention of migraine in the pill-free interval of combined oral contraceptives: A double-blind, placebo-controlled pilot study using natural oestrogen supplements. J Fam Plan Reprod Health Care 2002;28:2731.

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