Birth control pills pose inflammatory bowel disease risk

The use of combined oral contraceptive pills (COCPs) appears to confer some risk of inflammatory bowel disease (IBD), which increases accordingly with duration of COCP exposure, as shown in a study.

In a cohort of 4,932 IBD patients and 29,340 controls, COCP users had a 30–60-percent higher likelihood of developing Crohn's disease (odds ratio [OR], 1.60, 95 percent CI, 1.41–1.82) and ulcerative colitis (OR, 1.30, 95 percent CI, 1.15–1.45). [Aliment Pharmacol Ther 2021;doi:10.1111/apt.16647]

Moreover, each additional month of COCP exposure per year of follow-up translated to an increase of 6.4 percent in the risk of Crohn's disease and 3.3 percent in the risk of ulcerative colitis.

When it came to other birth control pill preparations, progestogen-only pills had a null effect on Crohn's disease risk (OR, 1.09, 95 percent CI, 0.84–1.40) and contributed to only a modest increase in ulcerative colitis risk (OR, 1.35, 95 percent CI, 1.12–1.64). Parenteral contraception, on the other hand, was not associated with either IBD subtypes.

“No previous studies have looked at IBD risk specifically in relation to progestogen-only contraceptive methods and our finding that increased Crohn’s disease risk was [limited] to oestrogen-containing contraception is novel. Of note, a study exploring associations between contraceptive pills and disease outcomes in Crohn’s disease found that there was an increased risk of surgery in those taking COCPs but not progestogen-only methods,” according to the investigators. [Gastroenterology 2016;150:1561-1567.e1561]

“Although we found no difference in IBD risk between users of low strength and standard strength oestrogen-containing COCPs, it should be noted that differences in oestrogen content amongst most COCPs are small (usually containing 20-35 µg ethinyloestradiol or equivalent),” they added.

The source cohort of the study population comprised 3,202,575 women aged 15-49 years (median 28.2 years) who contributed to over 16,000,000 person-years of follow-up. Crohn’s disease had an overall incidence of 14.7 per 100,000 person-years, while ulcerative colitis had 17.8 per 100,000 person-years. The median lookback period in the IBD and matched control cohorts was 5.4 and 5.2 years, respectively.

A driver of IBD pathogenesis

The mechanism linking birth control pills to IBD is unclear, but oestrogen has been reported to modulate intestinal wall barrier function, and an episode of bacterial gastroenteritis is fourfold more likely to trigger IBD in the following year. The investigators pointed out that if the barrier function of the intestinal wall is compromised by exogenous oestrogen, the risk of subsequent IBD is high in a genetically susceptible individual. [J Physiol 2009;587:3317-3328; Am J Physiol Gastrointest Liver Physiol 2011;300:G621-626; Gastroenterology 2006;130:1588-1594]

“Additionally, some enteric infections can be sexually acquired, and one could hypothesize that women taking contraception may be at greater risk of exposure,” they said. [F1000Research 2016;5:2510]

The present data are said to be broadly consistent with the hypothesis that the oestrogen component of contraception may drive IBD pathogenesis. Nevertheless, the investigators believe that the benefits of contraceptives greatly outweigh the risk of developing IBD in the vast majority of individuals.

“Our findings may be useful to women seeking contraception who have a strong family history of IBD,” the investigators pointed out.

“Importantly, our research does begin to shed some light on the potential biological mechanisms involved in the pathogenesis of [IBD], highlighting the importance of future studies focusing on specific exogenous sex hormones,” they added.