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What you need to know about oral contraception

Reproductive healthcare specialist Dr Anne MacGregor answers GP Dr Mandy Fry’s questions on side-effects, mini-pills and the latest COCs

Reproductive healthcare specialist Dr Anne MacGregor answers GP Dr Mandy Fry's questions on side-effects, mini-pills and the latest COCs

1. Is there still a large role for the traditional ‘mini-pills'? In which circumstances would you use an older progestogen-only pill (POP) in preference to Cerazette?

41231412Cerazette's primary mode of action is to inhibit ovulation. This means it is as effective as the combined oral contraceptive, with the same 12-hour rule for late pills, but with the added advantage of being oestrogen-free.

The older POPs are generally less effective because their main effect is to thicken the cervical mucous, creating an effective barrier to sperm. In a few women, more often in long-term or older users, ovulation is also inhibited but this is unreliable and can vary from cycle to cycle.

In practical terms, this means that older POPs are less effective than COCs in younger women, although both are of similar efficacy in women over 35.

So older POPs are a good choice for women over 35 provided that they are good pill-takers, as the cervical mucous effect is lost if a pill is taken more than 27 hours since the last one.

Cerazette is preferred for women who want to take a pill, need the efficacy of a COC or the benefit of a method that inhibits ovulation, but for whom oestrogen is contraindicated.

2. How should we manage the issue of amenorrhoea in perimenopausal women using the mini-pill?

Amenorrhoea is not uncommon in women using older POPs. In the absence of pregnancy, this is likely to reflect inhibition of the hypothalamic-pituitary-ovarian axis by the POP and consequently suppression of ovulation – similar to the mode of action of the COC and Cerazette.

The POP does not affect FSH so check levels – if it is clinically indicated. FSH does not automatically go up in amenorrhoeic women taking the POP because many still produce follicles and so maintain adequate amounts of oestrogen – hence the increased risk of functional ovarian cysts in POP users.

But repeated FSH levels greater than 30IU/l – combined with amenorrhoea and hot flushes in a woman over age 50 – are very suggestive of ovarian failure.

The woman can be counselled that although the risk of later ovulation cannot be completely excluded, it is unlikely and she may consider discontinuing contraception. Make sure this is documented.

If she does not wish to take this small risk, alternative contraception should be continued for a further year and then discontinued provided that menstruation has not resumed.

3. I understand there has been a new combined oral pill launched that contains an alternative oestrogen to the ethinylestradiol that we find in current combined pills. What theoretical advantages might this bring? What place, if any, do you think it will have in practice?

It has been a challenge to produce a COC that contains natural oestrogen but we now have Qlaira, a new COC that contains estradiol valerate, which is metabolised to 17ß-estradiol, the same hormone produced by the ovaries.

Qlaira also contains dienogest, a progestogen with antiandrogenic activity of approximately one-third of that of cyproterone acetate. One pill is taken daily for 28 days, with the first 26 pills delivering hormones in an oestrogen step-down and a progestogen step-up sequence followed by two placebo pills. The next pack is then started immediately, without a break.

This four-phase regime of estradiol valerate/dienogest provides users with a good bleeding cycle and a short, light withdrawal bleed.

A potential advantage is that the combination appears to have less effect on some of the clotting factors. So it's hoped, but not yet proven, that the increased risk of arterial and venous thrombosis will be less than for contraceptives containing ethinylestradiol.

But Qlaira is so new that it will take some time to assess all its pros and cons. From a practical perspective, the missed

pill advice is different from standard pills and if one pill is missed in the first 24 days, additional precautions are necessary for the next nine days. Fortunately, missed pill instructions are printed on every pack.

4. Can you tell me about the associated increased risk of stroke in women who get migraine if they are using the COC? Is the risk similar for migraine with and without aura? What about women who only get migraine during their pill-free week?

An increasing body of evidence suggests that migraine with aura – and not migraine without aura – is associated with increased risk of ischaemic stroke, particularly in young women. Contraceptive methods containing ethinylestradiol further increase this risk.

As a consequence, pre-existing migraine with aura is an absolute contraindication to use of COCs (UK Medical Eligibility Criteria level 4 – a condition which represents an unacceptable health risk if the contraceptive method is used).

If a woman develops her first attack of migraine with aura when using COCs, she should stop the pill immediately, using emergency contraception if indicated (UKMEC4).

Progestogen-only methods do not increase risk of ischaemic stroke so can be a good choice for women with migraine with aura.

Migraine without aura does not appear to be associated with increased risk of ischaemic stroke. But current UK guidelines contraindicate COCs in women with migraine without aura over age 35.

Migraine without aura can occur when oestrogen levels drop, such as during the pill-free interval. Typically, migraine starts two to three days into the break.

Using three packs consecutively, without a break, or even continuous pill use with no breaks, can resolve this – but bear in mind this is an unlicensed indication.

5. It's relatively easy to remember the advice about additional contraceptive precautions for women on short-term antibiotics who use oral contraception. But I've got some women taking longer-term antibiotics for acne – what should I be telling them?

Broad-spectrum antibiotics that affect the enterohepatic circulation of oestrogen reduce the efficacy of COCs. For short courses of antibiotics, additional contraceptive precautions should be used for the duration of treatment, and for seven days after stopping. The pill-free interval should be omitted if fewer than seven pills remain in the pack at the end of the antibiotic course.

Beyond two weeks, gut flora become resistant to antibiotics. So if a woman taking COCs starts long-term antibiotics, extra barrier methods are required only for the first three weeks. But if a woman already taking long-term antibiotics starts the COC, additional precautions are unnecessary as the gut flora will already have developed resistance.

The advice for short-term courses of antibiotics is slightly different for Evra as interaction studies show that there is no need for additional precautions in women taking tetracycline. Women using NuvaRing do not need to use additional precautions when taking amoxicillin or doxycycline.

For any other antibiotic, barrier methods should be used during treatment and for seven days after stopping, skipping the patch-free or ring-free interval.

6. I still have women who come in with articles from women's magazines asking for Yasmin as they've read it's not associated with weight gain. What's the real situation regarding the COC and weight gain? Is any particular brand better than any other in this regard?

Many women worry about gaining weight with the Pill. It's true that weight gain can result from fluid retention, which tends to be shed during the pill-free interval.

Yasmin is a monophasic combined oral contraceptive containing 3.0mg drospirenone and 30µg of ethinylestradiol.

Drospirenone has diuretic properties ‘comparable to a 25mg dose of spironolactone', according to the summary of product characteristics. This may help to oppose the salt- and fluid-retaining effects of the Pill and so reduce weight gain due to fluid retention. Certainly, studies show statistically lower body-weight changes in the early months of taking Yasmin when compared with Marvelon. But this difference is not sustained – after two years of use, the mean weight of the users had returned to their starting weight.

So is any particular brand better than another with respect to weight gain? Not really. Results from clinical trials show that most women stay much the same weight after years of Pill use, with fewer than one in five women gaining more than 2kg and one in eight experiencing similar weight loss. Most of those who gained weight were under 20 years old so the weight gain may reflect normal development.

7. I still sometimes find the whole concept of Pill ladders confusing. Can you clarify which side-effects are likely to be progestogen-related and which are likely to be oestrogenic? Which pills would you choose in each situation?

Several different progestogens are available in current COC formulations. These are often known as second- and third-generation progestogens.

Second-generation progestogens include norethisterone and levonorgestrel and these tend to ‘oppose' the action of oestrogen, resulting in pills that have comparatively less oestrogenic activity. Typical side-effects of these pills include vaginal dryness, depression, acne and loss of libido. Think of symptoms typical of premenstrual syndrome.

Third-generation progestogens include desogestrel, gestodene and norgestimate, although the latter acts mostly, but not exclusively, through conversion to levonorgestrel. These progestogens have a neutral effect on oestrogen, resulting in comparatively greater oestrogenic activity. Symptoms of nausea, fluid retention and increased non-infective vaginal discharge can indicate a relative excess of oestrogen. Think of symptoms typical of pregnancy.

Progestogenic symptoms often resolve by changing to a more oestrogen-dominant combined pill. Oestrogenic symptoms usually resolve by changing to a less oestrogen-dominant combined pill (see diagram, right).

8. I understand that the COC is associated – though not necessarily in a causative way – with abnormalities on cervical screening. Should we be advising women with abnormal smears to switch their form of contraception? Is a progestogen-only form of oral contraception a reasonable alternative?

The major risk factor for cervical cancer is infection with high-risk strains of human papillomavirus (HPV), particularly types 16, 18 and 31. As HPV is passed through sexual contact, cervical cancer can be considered to be a sexually transmitted disease.

Most women infected with HPV do not develop cervical cancer, so other factors – including COC use – are important in disease development. Compared with women using IUDs, cervical cancer risk is doubled in women using COCs for at least five years. Risk reduces if COCs are stopped and by 10 years after stopping, the risk is no greater than in those who have never used a COC.

For most women using COCs who are diagnosed with cervical intraepithelial neoplasia (CIN), the benefits of continuing COCs outweigh the risks, as the absolute risk of cervical cancer is small.

Of utmost importance is that women should participate in the national screening programme so that CIN is monitored and treated appropriately.

It's worth noting that COCs reduce the risk of endometrial and ovarian cancer, which are less easy to detect in the early stages. Smoking is an important counselling point as it also doubles the risk of CIN and cervical cancer. But if the woman stops smoking, mild precancerous changes can revert back to normal without the need for additional treatment.

From the limited data, use of injectable progestogens appears to be associated with a small increase in risk but less than the risk associated with COCs. There is no information about the risk with use of other progestogen-only methods.

9. Women still sometimes ask me if they need to have a period off oral contraception after they've been on it for several years. Is there any evidence to support this? What side-effects of the COC are related to duration of use? Does having a short pill-free period affect these?

Intermittent breaks from the Pill are of no proven benefit for health and all too often lead to unplanned pregnancies. Modern COCs contain such low doses of hormones that any benefit from stopping the Pill, even for the usual pill-free interval, has become a matter of debate.

Women worry that long-term use might affect their fertility but the evidence is that if there have been no issues with fertility before starting COCs, it is highly unlikely that the Pill will affect fertility adversely. Indeed, the Pill can help protect fertility in women with conditions such as PCOS and endometriosis.

The pill-free interval is the Achilles heel of contraceptive efficacy as protection against pregnancy during this time is dependent on a new pack being started at the right time. Dispensing with the pill-free week offers additional advantages over improved efficacy as symptoms associated with fluctuating hormone levels, such as headaches and epilepsy, can also improve. Although we don't yet have continuous pills in the UK, they are licensed in the US. If it is appropriate to prescribe COCs continuously, it will be off-licence.

10. Is it true that the conception rate is higher in the first month following cessation of oral contraception than might be expected statistically? Is this true and, if so, why?

We generally advise women that there may be a slight delay in return to fertility when they discontinue COCs, although absolute fertility is not impaired. But this advice may be relevant only to COCs containing at least 50µg ethinyloestradiol. Studies of women who discontinued pills containing less than 50µg ethinyloestradiol versus those discontinuing non-hormonal methods in order to become pregnant, showed no difference between the two groups in the mean time it took the women to conceive.

Another factor often considered to delay return to fertility is duration of use. However, a study of nearly 8,500 planned pregnancies found that women who had used COCs for at least five years were more likely to conceive within a year of stopping the Pill, compared with women who had used COCs for a shorter duration and never-users. The reasons for this remain unclear but COCs have several mechanisms that could benefit future fertility, particularly reduced risk of pelvic inflammatory disease, ectopic pregnancy, reduced risk of anaemia and treatment of endometriosis.

11. We're all familiar with the potential for drug interactions to decrease the efficacy of the COC. Are there any other common herbal or alternative preparations that we should be aware of, apart from the well-known effect of St John's wort?

St John's wort is considered to reduce the effectiveness of the COC as it induces liver enzymes, accelerating the metabolism of ethinylestradiol and progestogens and reducing steroid blood levels by around 15%. There is no evidence that any other widely available herbal and alternative preparations have a similar effect. In contrast, there is some evidence that levels of ethinylestradiol are increased if the COC is taken with a drink of grapefruit juice. It is not known whether this is of any clinical importance but some specialists recommend that women take the COC at least four hours before or after drinking grapefruit juice.

Dr Anne MacGregor is associate specialist in sexual and reproductive healthcare at Barts Sexual Health Centre, St Bartholomew's Hospital, London

Competing interests None declared

Dr MacGregor is co-author of The Pill and other forms of hormonal contraception: The Facts, one of series of titles containing informative and practical advice for patients. Along with other The Facts titles, it is available to Pulse readers at a 20% discount from Oxford University Press. For more information about these books and how to order, click here

Oral contraceptives thps oc What I will do now What I will do now

Dr Mandy Fry considers the responses to her questions

It seems that using Cerazette probably does accrue additional benefits that offset the additional cost, so I think I'll continue using it in preference to the older POPs in younger women who prefer an oral form of contraception and are unable to take oestrogens.
It's also helpful to know FSH can be useful as a decision adjunct for some women who are perimenopausal and amenorrhoeic on the POP.
It's very useful to have the actual statistics to put to women who are considering the COC but are concerned about weight gain.
The section about women on the COC who require antibiotics was helpful. The difference between being on the COC already and starting antibiotics versus being on antibiotics and starting the COC was particularly interesting.
Similarly the clarification between migraine with and without aura was useful, although it won't change my current practice.
It was also interesting to learn about Qlaira and the possibility of a 365-day pill in the future and it will be interested to see what role both these developments, as well as innovations such as the NuvaRing, have on practice.
The link between progestogenic side-effects and PMS and oestrogenic side-effects and pregnancy isn't one I'd considered before.

Dr Mandy Fry is a GP in Cirencester, Gloucestershire, and senior primary care lecturer at Oxford Brookes University

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