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Epidemiological data suggest that there is a small increase in the risk of Crohn’s disease in women who use the combined oral contraceptive pill,1-3 the relative risk being about twofold. On this basis, many physicians advise women with Crohn’s disease not to use this form of contraception. Is there really sufficient evidence to justify this advice? Unlike smoking,1 there is no clear evidence of an association between oral contraceptive use and the prevalence of Crohn’s disease. The available data are confounded by problems with study design and also the influence of smoking, as some studies have shown that smokers are more likely to use oral contraception. There is little information on whether the type of oral contraception may explain some of the differences observed, in particular the oestrogen dose and the length of use.
Patients with active inflammatory bowel disease are at increased risk of developing thromboembolic disease and there are also theoretical reasons to suppose that the pill might precipitate or exacerbate Crohn’s disease. High dose oral contraceptives, containing more than 50 μg ethyloestradiol, may induce prothrombotic changes in both coagulation and fibrinolytic enzyme systems, thereby predisposing to the formation of microthrombi. This would fit with the microvascular hypothesis of the pathogenesis of Crohn’s disease.4 Early reports that the withdrawal of oral contraception was associated with long term remission in patients with Crohn’s colitis could be used to support this hypothesis.5 For many years, however, low dose oral contraceptive preparations containing 30 μg ethinyloestradiol or less have usually been prescribed, and although these do activate coagulation and fibrinolysis, the effects are less pronounced. The influence of the type and dose of progestogen and the length of time for which the pill has been taken as well as other factors such as combination with smoking and the increasing recognition of inherited causes of thrombophilia, may also be of relevance.6
Smoking has been associated with increased severity in terms of disease activity in patients with Crohn’s disease. A number of small studies have also looked at whether oral contraceptive use is associated with increased disease severity and activity. In this issue, Cosneset al (see page 218) report the results of a carefully performed, prospective observational study examining the effect of oral contraceptive use on the clinical course of Crohn’s disease in a cohort of 331 women aged 16–50 who were followed for up to 18 months. Of the women, 134 (40.5%) used oral contraceptives, defined as taking the pill during the month before inclusion into the study. The oral contraceptive users were younger, with a median age of 28 years compared with a median of 32 for the non-users; the non-users had a longer duration of disease: 78 compared with 52 months. There were no differences in smoking habits, disease activity in the previous year, current disease activity, or other medication. Most of those using oral contraceptives were taking a 30 μg ethinyloestradiol preparation but there is no information about the duration of oral contraceptive use or whether non-users had taken oral contraceptives in the past. It is possible that they had as they were older than the current users. The relapse rate during the study period was similar: 46% in users compared with 43% in the non-users. No thrombotic events were observed during the study period.
These results differ from another recently published prospective study from Canada.8 Timmer et alreported the influence of smoking, oral contraceptive use and other factors influencing Crohn’s disease relapse. Their results in a small cohort of 88 women who were randomised to placebo in a controlled trial of mesalamine in the prevention of Crohn’s disease relapse, suggest that women who had ever used oral contraceptives had a threefold increase in relapse rate. It is difficult to explain how past use of the pill could affect current relapse rates, although it is possible to postulate that these women had taken high dose pills in the past and this could have been an aetiological factor in their disease in the first place. There are methodological problems with using these placebo treated women and in Timmer et al’s study current pill users did not in fact have different relapse rates from non-users, unless the current users were combined with women who had ever used the pill, making this difficult to attribute to an effect of oral contraception on relapse.
Cosnes et al’s study shows that despite the weak association between oral contraceptive use and the development of Crohn’s disease, in women with Crohn’s disease the use of low dose oral contraceptive is not associated with increased disease activity compared with non-users. The power of this study was adequate to detect the effect of smoking and so this would concur with evidence from other investigators that the use of the low dose pill is not associated with increased Crohn’s disease recurrence.8
So, how should we advise our patients on the basis of this new evidence? Strong advice not to smoke is obviously essential and the pill does not seem to be an appropriate form of contraception for smokers. Women with quiescent or mildly active Crohn’s disease who do not smoke or have any other risk factors for thromboembolic disease may, however, make an informed decision after discussion with their physician whether to start or continue taking the pill.
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