Estrogen a Culprit in Inflammatory Bowel Disease
Positive relationship discovered between hormone replacement therapy, ulcerative colitis, and Crohn's disease.
By Nancy Walsh, MedPage Today
Medically Reviewed by Robert Jasmer, MD
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SAN DIEGO — SUNDAY, May 20, 2012 (MedPage Today) —Postmenopausal women who take hormone replacement therapy (HRT) are at increased risk for developing ulcerative colitis, whereas younger women using oral contraceptives are more likely to develop Crohn's disease, a researcher said here during a session on inflammatory bowel disease.
Among current users of HRT, there was a 74 percent increase in risk of ulcerative colitis, compared with women who had never taken hormone replacements, according to Hamed Khalili, MD, of Massachusetts General Hospital in Boston, and colleagues.
Estrogen is thought to have various effects on the intestinal barrier, modifying colonic permeability and mediating inflammation through effects on estrogen receptors, which could lead to changes in gut immunity.
However, previous research has been limited to retrospective analyses and small numbers, so Khalili and colleagues examined rates of ulcerative colitis and Crohn's disease in the Nurses' Health Study, which began enrolling women in 1976.
For the postmenopausal HRT analysis, they included 108,589 women whose median age was 54 and who had no history of either ulcerative colitis or Crohn's disease.
During 1,891,153 person-years of follow-up, there were 138 new cases each of Crohn's disease and ulcerative colitis.
Risk of ulcerative colitis was increased not only among current users of HRT, but also among former users.
The risk of ulcerative colitis was higher with longer use of HRT, but that risk dropped based on the length of time the woman had stopped HRT.
The type of hormone therapy used did not appear to influence ulcerative colitis risk.
Among these older women, there was no association between HRT and Crohn's disease, Khalili said.
In the oral contraceptive analysis, Khalili and colleagues followed 232,730 women for a total of more than 5 million person-years.
During that time, there were 309 cases of Crohn's disease and 362 cases of ulcerative colitis.
For Crohn's disease, the risk remained elevated even among past users of oral contraceptives.
In contrast to the HRT study, this analysis found no link between oral contraceptives and risk for ulcerative colitis.
Together, these two analyses suggest that estrogen influences the biological pathways that lead to inflammatory bowel disease, Khalili said.
As to why the effects would be different for estrogen levels associated with oral contraceptives compared with those with hormone replacement therapy, he observed that "estrogen has pleiotropic effects," and there may be different risk factors at different ages, but said he had no specific mechanism to offer.
One implication of the study was that clinicians might advise women who have a strong family history of Crohn's disease to use other forms of birth control to minimize their chance of developing the condition.
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