It’s world IBD day and I’ve decided to write on an important subject – the relationship between the use of oral contraceptives and the development or possible worsenings of IBD. In 2020 we are in a new era in understanding and witnessing the prolific rise of IBD around the world, and I hope this blog post will shine a small spotlight on one particular environmental factor that we need to pay attention to.
– What Causes IBD? –
To this date, no one has a firm understanding of what causes or worsens Inflammatory Bowel Disease, however, it is understood that a combination of genetic and environmental factors likely contribute in notable ways. IBD is probably not purely an environmental or genetic disorder. Even in genetically identical twin studies for example, if one twin has IBD then there is a relatively low risk that the other twin will also develop IBD. Although that risk is higher than when comparing two unrelated or less related individuals, indicating genetic susceptibility, there is clearly a complex interplay of BOTH environmental and genetic factors contributing to the disease.
I refer to this interplay as a “perfect storm” as there are many variables that influence IBD including those that are immunoregulatory, micro-bacterial, psychological, and even mitochondrial in nature among many other factors.
One possible risk factor that seems seldom discussed in the context of IBD is the use of oral contraceptives.
– The Evidence Linking Oral Contraceptives and IBD –
So we can ask the question: does the use of oral contraceptives cause or worsen IBD?
Well as always the answer is not clear cut, however, Inflammatory Bowel Disease expert Dr. Hamed Khalili, MD, MPH of Havard Medical School in a 2016 review article stated: “Beyond Smoking, perhaps the most consistent environmental risk factor for Crohn’s Disease is the use of oral contraceptives.” (Note that tobacco use and smoking are well-accepted risk factors for developing Crohn’s Disease, and it also appears that smoking and in parallel with oral contraceptive use magnifies this in a commensurate manner [3,4])
A meta-analysis from 2008 of 14 studies indicated nearly a 50% increase in the risk of developing Crohn’s Disease, and for Ulcerative Colitis the data was less clear cut but may also have indicated a higher risk. Then in large prospective studies with over 200,000 women, the results also demonstrated increased risk in CD but not UC.[6,7] Most recently in 2017, a meta-analysis of 20 studies confirmed the results and found that among users of oral contraceptives there was a 24% increase risk for CD and a 30% increase risk for UC.
There have been older studies and meta-analyses demonstrating mixed results in both UC and CD,  however, a 2016 study in Sweden examining 4036 female CD patients demonstrated an increased probability of surgery among women taking oral contraceptives – especially those who are on combination types.
– Summaries, Mechanisms, and Takeaways –
In summary, the evidence seems to be stronger in drawing correlations between the development of Crohn’s Disease, and less so with Ulcerative Colitis in regards to the use of oral contraceptives. Most experts also agree that the evidence is potentially less strong for demonstrating worsening of disease course or severity, however, just because there is a lack of evidence does not mean that the evidence does not exist. Many experts found both strengths and weaknesses to the large Swedish study for instance, however, the results should not be taken lightly.
At this time I have not been able to find any study examining other hormonal birth control methods including IUDs, rings, and implants, and the relationship with IBD. It might make theoretical sense that oral contraceptives may pose a greater risk given their direct interaction with the gut lining, however, this seems unknown especially since there is an overlap in hormones used.
Of all the hormones discussed in the context of contraceptives and IBD, it seems that the relationship between estrogen-containing contraceptives and IBD (primarily in Crohn’s Disease) is strongest in regards to either disease development or unfavorable outcomes (like surgery). Interestingly, progesterone containing contraceptives, may not show this risk and may even contribute to ameliorations in symptoms in women with CD. [8,9]
From a mechanistic standpoint, there may be several reasons for why oral contraceptives magnify risk or worsen CD. It’s possible that estrogen could modulate the mucosal immune system’s response, membrane permeability, and even the human microbiome’s composition among other mechanisms, many hormonal in nature. 
I hope that this short post will inspire you to do your own research. I hope it will help you make empowered decisions with your sexual partner and your gastroenterologist and medical team about the risks and benefits of hormonal birth control in the context of IBD. This disease is complex. I believe those willing to go deep, step in the ring, get their hands dirty with the science, and understand the nuances like this one will be more likely to achieve their intended health goals and remission too.
Lastly, I want to acknowledge that although I have Crohn’s Disease, I also have a Y chromosome. I want to acknowledge my male privilege. I do not understand and will never understand the complex decisions of women’s health and specifically women’s issues on a personal level, however, I hope to support you in any way I can and empower you to change your life for the better. Knowledge = Power.
– Literature Cited –
- Gordon H, Moller FT, Andersen V, Harbord M. Heritability in Inflammatory Bowel Disease: From the First Twin Study to Genome-Wide Association Studies. Inflamm Bowel Dis. 2015;21: 1428.
- Khalili H. Risk of Inflammatory Bowel Disease with Oral Contraceptives and Menopausal Hormone Therapy: Current Evidence and Future Directions. Drug Saf. 2016;39: 193–197.
- Timmer A, Sutherland LR, Martin F. Oral contraceptive use and smoking are risk factors for relapse in Crohn’s disease. The Canadian Mesalamine for Remission of Crohn’s Disease Study Group. Gastroenterology. 1998;114: 1143–1150.
- Logan RF. Smoking, use of oral contraceptives, and medical induction of remission were risk factors for relapse in Crohn’s disease. Gut. 1999;44: 311–312.
- Cornish JA, Tan E, Simillis C, Clark SK, Teare J, Tekkis PP. The risk of oral contraceptives in the etiology of inflammatory bowel disease: a meta-analysis. Am J Gastroenterol. 2008;103: 2394–2400.
- Ortizo R, Lee SY, Nguyen ET, Jamal MM, Bechtold MM, Nguyen DL. Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: a meta-analysis of case-controlled and cohort studies. Eur J Gastroenterol Hepatol. 2017;29: 1064–1070.
- Khalili H, Higuchi LM, Ananthakrishnan AN, Richter JM, Feskanich D, Fuchs CS, et al. Oral contraceptives, reproductive factors and risk of inflammatory bowel disease. Gut. 2013;62: 1153–1159.
- Khalili H, Granath F, Smedby KE, Ekbom A, Neovius M, Chan AT, et al. Association Between Long-term Oral Contraceptive Use and Risk of Crohn’s Disease Complications in a Nationwide Study. Gastroenterology. 2016. pp. 1561–1567.e1. doi:10.1053/j.gastro.2016.02.041
- Long MD, Hutfless S. Shifting Away From Estrogen-Containing Oral Contraceptives in Crohn’s Disease. Gastroenterology. 2016. pp. 1518–1520. doi:10.1053/j.gastro.2016.04.032
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