In the Journals

Long-term oral contraceptive use linked to increased risk for surgery in Crohn's disease

An increased risk for surgery was found to be associated with long-term use of combination oral contraceptives among women with established Crohn’s disease in a Swedish nationwide analysis.

“Exogenous hormone use in the form of oral contraceptives has previously been linked to risk of Crohn’s disease,” the researchers wrote. “Although the exact mechanism underlying this association is unclear, the effect is plausibly mediated by alterations in intestinal permeability, immune function, and potentially the gut microbiome. Nonetheless, a specific role of oral contraceptives on progression, rather than the etiology of Crohn’s disease, is unclear.”

The research team therefore aimed to evaluate the association between oral contraceptives and risk for Crohn’s disease complications, including need for surgery and steroid use. They identified 4,036 women with Crohn’s disease (aged 16 to 51 years) who did not have prior surgery, using Swedish National Patient Register data from January 2002 to December 2013. They ascertained oral contraceptive use using Prescribed Drug Register data from July 2005 to December 2013.

Overall, 482 incident surgeries occurred (median follow-up, 58 months). Multivariate analysis revealed an increased risk for surgery among both past users of oral contraceptives (adjusted HR = 1.14; 95% CI, 0.8-1.63) and current users (aHR = 1.3; 95% CI, 0.89-1.92). This risk increased with longer duration of oral contraceptive use (P trend = .036; >3 years, aHR = 1.68; 95% CI, 1.06-2.67) and higher daily dose (P trend = .016).

Steroid use did not appear to increase with past or current use of oral contraceptives.

“We explored the possibility that the effect of oral contraceptive use on risk of surgery may vary by types of hormones and evaluated the risk according to the progestin-only or combination of estrogen and progestin oral contraceptives,” the researchers wrote. They found the increased risk for surgery was only associated with combination oral contraceptives.

Risk for surgery increased by almost 30% with every 1 year of combination oral contraceptive use (aHR = 1.29; 95% CI, 1.05-1.57) and by almost 24% with every 300 defined daily dose increase (aHR = 1.24, 95% CI 1.01-1.52). For every 83 patients with Crohn’s disease receiving combination oral contraceptives for at least 1 year, one extra surgery is required, the researchers estimated.

“In conclusion, we show that consistent and long-term use of oral contraceptives, particularly the combination type, is associated with increased risk of surgery among women with established Crohn’s disease,” the researchers wrote. “Future studies should focus on mechanisms by which oral contraceptive use alters the risk and progression of Crohn’s disease. Finally, our data suggests the importance of carefully evaluating contraceptive options among women with established Crohn’s disease.” – by Adam Leitenberger

Disclosure: Khalili reports he has received consulting fees from AbbVie. Please see the full study for a list of all other researchers’ relevant financial disclosures.

An increased risk for surgery was found to be associated with long-term use of combination oral contraceptives among women with established Crohn’s disease in a Swedish nationwide analysis.

“Exogenous hormone use in the form of oral contraceptives has previously been linked to risk of Crohn’s disease,” the researchers wrote. “Although the exact mechanism underlying this association is unclear, the effect is plausibly mediated by alterations in intestinal permeability, immune function, and potentially the gut microbiome. Nonetheless, a specific role of oral contraceptives on progression, rather than the etiology of Crohn’s disease, is unclear.”

The research team therefore aimed to evaluate the association between oral contraceptives and risk for Crohn’s disease complications, including need for surgery and steroid use. They identified 4,036 women with Crohn’s disease (aged 16 to 51 years) who did not have prior surgery, using Swedish National Patient Register data from January 2002 to December 2013. They ascertained oral contraceptive use using Prescribed Drug Register data from July 2005 to December 2013.

Overall, 482 incident surgeries occurred (median follow-up, 58 months). Multivariate analysis revealed an increased risk for surgery among both past users of oral contraceptives (adjusted HR = 1.14; 95% CI, 0.8-1.63) and current users (aHR = 1.3; 95% CI, 0.89-1.92). This risk increased with longer duration of oral contraceptive use (P trend = .036; >3 years, aHR = 1.68; 95% CI, 1.06-2.67) and higher daily dose (P trend = .016).

Steroid use did not appear to increase with past or current use of oral contraceptives.

“We explored the possibility that the effect of oral contraceptive use on risk of surgery may vary by types of hormones and evaluated the risk according to the progestin-only or combination of estrogen and progestin oral contraceptives,” the researchers wrote. They found the increased risk for surgery was only associated with combination oral contraceptives.

Risk for surgery increased by almost 30% with every 1 year of combination oral contraceptive use (aHR = 1.29; 95% CI, 1.05-1.57) and by almost 24% with every 300 defined daily dose increase (aHR = 1.24, 95% CI 1.01-1.52). For every 83 patients with Crohn’s disease receiving combination oral contraceptives for at least 1 year, one extra surgery is required, the researchers estimated.

“In conclusion, we show that consistent and long-term use of oral contraceptives, particularly the combination type, is associated with increased risk of surgery among women with established Crohn’s disease,” the researchers wrote. “Future studies should focus on mechanisms by which oral contraceptive use alters the risk and progression of Crohn’s disease. Finally, our data suggests the importance of carefully evaluating contraceptive options among women with established Crohn’s disease.” – by Adam Leitenberger

Disclosure: Khalili reports he has received consulting fees from AbbVie. Please see the full study for a list of all other researchers’ relevant financial disclosures.