author and copyright: Mihailo Alic (alic@rocketmail.com)
March 1999

In the Clinical Alert from March 1999 issue of journal Gut, commenting on a recent study of risk factors for relapse in Crohn's disease (1) the author concluded that, unlike the established association with smoking, association with oral contraceptives (OC) use remains controversial. To contribute to this discussion, we have investigated temporal trends in age and sex specific disease incidence and correlated them to the chronology of OC use.

Birth control pill was introduced in 1960 and soon became widely accepted with number of American women using it rising to 10 million by 1973 (2). Concerns about side effects prompted further research, and by the mid-1970s most women who used OC were taking pills that contained 50 mcg or less of estrogen -- a considerable decrease over the 100 to 150 mcg of the 1960s.

Majority of Crohn's epidemiological studies (especially those from the U.S.) has observed rapid rise in incidence between the early 1960s and early 1970s, followed by a plateau phase in the 1980s (3). Although some studies reported incidence rates and age and sex distribution, very few provided combined age and sex specific details necessary for our analysis. We were glad to find two such studies for the U.S. (4, 5), expecting it to be the most appropriate fit for U.S. data on OC use (2).

The fact that the introduction and adoption of the Pill matched Crohn's overall incidence trends would not be sufficient to establish OC use as a risk factor without investigating incidence trends for 20-29 year old female group as most likely users of OC. From 1964 there was a striking increase of incidence among the age group 20-29 and increased female to male incidence ratio in both studies. Unpublished data from the Olmsted County study (5) showed crude incidence of 26.8 cases per 100,000 person-years for this female age group in 1964-73 period. This is the highest incidence among all age and sex groups in the entire study period (1940-93), and the highest incidence rise between consecutive time periods. Male incidence rise for the same period was much less dramatic and the crude rate for the same age group was 17.2. Data for Baltimore (4) showed 9.46 fold incidence increase for female 20-29 group between 1960-63 and 1973 survey, and only 2.33 increase for the same age male group. Again, this jump in female incidence was the most abrupt and the highest incidence among all age and sex groups in all periods. Consistent with introduction of OC with lower estrogen content, Crohn's incidence studies reported lessening of predominance of 20-29 female group from the mid-1970s. Figure shows changing female to male (F/M) incidence ratio for the age group 20-29 corresponding to data of OC use.

Although detailed incidence and OC use data were not available, two European studies (6, 7) were investigated as controls, and both showed the highest F/M incidence ratio in the period 1960-65 corresponding to the rise in the U.S.

Above epidemiological findings are concordant with commented study (1) in their explanation of a finding that previous use of OC was more strongly associated with relapse than current use (their former users group was older and more likely to have taken higher-dose pills). Historical change in estrogen content of OC may be one of the sources of contradictory findings in studies of association between OC use and Crohn's disease published in past 15 years, contributing to the controversy.

Acknowledgement - The author would like to thank Edward V. Loftus, Jr. for contributing unpublished data for the Olmsted County study.
 

References:

1. Timmer A, Sutherland LR, Martin F. Oral contraceptive use and smoking are risk factors for
relapse in Crohn's disease. Gastroenterology 1998; 114: 1143-50.

2. Snider S. The Pill: 30 Years of Safety Concerns. FDA Consumer Magazine 1990; 24: 8-11.

3. Logan RF. Inflammatory bowel disease incidence: up, down or unchanged? Gut 1998; 42: 309-11.

4. Calkins BM, Lilienfeld AM, Garland CF, et al. Trends in incidence rates of ulcerative colitis and
Crohn's disease. Dig Dis Sci 1984; 29: 913-920.

5. Loftus EV Jr, Silverstein MD, Sandborn WJ, et al.  Crohn’s disease in Olmsted County, Minnesota, 1940-1993: incidence, prevalence, and survival. Gastroenterology 1998; 114: 1161-8.

6. Kyle J. Crohn’s disease in the northeastern and northern isles of Scotland: an epidemiological
review. Gastroenterology 1992; 103: 392-9.

7. Fellows IW, Freeman JG, Holmes GK. Crohn’s disease in the city of Derby, 1951-85. Gut, 1990; 31: 1262-5.