Oral Contraceptives May Triple Risk of Crohn's Disease

Women may be three times more likely to develop Crohn's disease if they have used oral contraceptive pills for five years or more, according to data from a Harvard University study.

The increased risk of Crohn's was especially pronounced in women who already had genetic predispositions to chronic gastrointestinal disease.

"The pill" is the most widely used form of contraception in the United States, and while it is highly effective in preventing unwanted pregnancies, it is not without adverse effects. This is important to consider given the wide public demand for access to oral contraception and wider coverage for it under the Affordable Care Act.

Harvard University gastroenterologist Dr. Hamed Khalili and colleagues analyzed data from 232,452 American women with no prior history of ulcerative colitis (UC) or Crohn's disease (CD) and who were enrolled in the US Nurses Health Studies I and II from 1976 to 2008.

They compared the gastrointestinal health of women who had used the pill for long periods of time with that of women who never used oral contraception. The researchers found 315 cases of CD and 392 cases of UC (confirmed by review of medical records).

Major Risk Increase

Compared with women who had never used oral contraceptives, current users had a 2.82 multivariate-adjusted hazard ratio for CD (95% CI 1.65 to 4.82). For past users of oral contraceptives the hazard ratio was 1.39 (95% CI 1.05 to 1.85).

Reflecting on the strong association between use of oral contraceptives and CD, the authors note that, "After adjusting for known or potential risk factors for CD, including BMI, smoking, hormone use, age at menarche, menopause type and parity, these risk estimates did not materially change."

Further, the association could not be explained by the presence of endometriosis—a condition which is sometimes associated with CD, and which is sometimes treated with oral contraceptives (Khalili H, et al. Gut. 2013 Aug; 62(8): 1153–1159. )

The association between oral contraceptives and UC was weaker than the one observed with CD, and it differed according to smoking history, with smokers at higher risk. The authors stressed that age at menarche, age at first birth and parity were not associated with risk of UC or CD.

Khalili's group at Harvard is not the first to report an association between oral contraceptive use and digestive disorders.

The possibility was first suggested by British investigators in the mid-1980s. In 1994, Veterans Affairs researchers reported a twofold increase in relative risk of UC, and a 2.6-fold increased risk of CD in women who had used oral contraceptives versus never-users. Those who had been on the pill for 6 years or more had a 5-fold relative risk for Crohn's (Boyko EJ, et al. Am J Epidemiol. 1994; 140 (3): 268-78).

Confirming Earlier Findings

More recently, an analysis of data from the UK General Practitioner Research Database showed a similar pattern: long-term oral contraceptive users showed a 2.4-fold increased lifetime risk of developing UC, and a 3.15-fold increased risk for CD. In this study, both disorders were also found to be strongly associated with use of hormone replacement therapy later in life (Garcia Rodriguez LA, et al. Aliment Pharmacol Ther. 2005 Aug 15;22(4):309-15).

A 2008 metanalysis, including data from 14 different studies and nearly 76,000 women, concluded that after adjusting for smoking, current oral contraceptive use confers a 1.5-fold relative risk for both Crohn's and UC (Cornish JA, et al. Am J Gastroenterol. 2008 Sep;103(9):2394-400).

So, what's going on?

Khalili and colleagues suggest that estrogen—the key hormone in oral contraceptives—"enhances cellular proliferation and the humoural immune system, modifies colonic barrier function, and contributes to thrombosis, which may lead to multifocal gastrointestinal infarction."

Though the precise pathophysiology of UC and CD is still somewhat unclear, these estrogenic effects could certainly play a role. Dr. Khalili suggested that the link between UC, oral contraceptives and smoking, "may provide additional support for the role of subacute thrombosis in mediating risk of UC since a synergistic effect of smoking and oral contraceptives on hypercoagulability has been well described."

There may be a microbiome effect as well. Estrogen can affect healthy bacteria residing in the gut, increasing the colon's permeability and thereby affecting gut immunity leading to leaky gut syndrome. This allows yeast and other pathogenic organisms to thrive, further worsening inflammation.

Dysbiosis—the disruption of the healthy gut flora and presence of pernicious species-- also interferes with one's ability to digest food and absorb nutrients and minerals like folic acid, zinc, selenium, magnesium, vitamins C and B and amino acids. These deficiencies result in mental and other health impairments, along with birth defects. It is important to recognize that impaired bacterial flora can be passed down to children via the vaginal canal and may result in dysbiosis and inflammation in the very young.

An imbalanced gut flora also predisposes one to allergies, asthma and eczema. In more severe cases, learning disabilities manifest such as ADHD, depression, anxiety, autism, dyslexia and dyspraxia, as well as autoimmune diseases like inflammatory bowel disease.

Weigh the Pros & Cons

Oral contraceptives are a highly effective and extremely convenient method of birth control. While they may be safe for many women, they may also be contributing to the large and growing burden of chronic digestive disorders.

Clinicians should ask about oral contraceptive use in any female patient who shows symptoms of Crohn's, UC or other chronic digestive complaints.

Instead of blindly submitting patients to the gut-damaging effects of the pill, we need to be honest with our patients and carefully weigh the benefits and risks of oral contraception, especially for women at high risk, or already experiencing digestive problems.

There are more natural and safer options to estrogen-based oral contraceptives, such as the barrier and fertility-awareness methods, as well as technology that can help such as personal fertility monitors. For some women, especially those with predispositions to autoimmune digestive disorders, these may be the better options.

Clinicians should ask about oral contraceptive use in any female patient who shows symptoms of Crohn's, UC or other chronic digestive complaints. Given the many potential contributing factors, this one is easy to overlook. Yet multiple studies suggest it can be a significant driver.

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