ESTROGEN - A CULPRIT IN INFLAMMATORY BOWEL DISEASE

By*Nancy Walsh, Staff Writer, MedPage Today

Published: May 20, 2012 Reviewed*by*Robert Jasmer, MD; Associate
Clinical Professor of Medicine, University of California, San Francisco
and Dorothy Caputo, MA, BSN, RN,

Note that these studies were published as abstracts and presented at a
conference.

These data and conclusions should be considered to be preliminary until
published in a peer-reviewed journal.

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.

Note that it is unknown why the effects on inflammatory bowel disease
would be different for estrogen levels associated with oral
contraceptives compared with those with hormone replacement therapy. SAN
DIEGO --

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% increase in risk of
ulcerative colitis (HR 1.74, 95% CI 1.09 to 2.77), compared with women
who had never taken hormone replacements, according to Hamed Khalili,
MD, of Massachusetts General Hospital in Boston, and colleagues.

But among premenopausal women, the aged-adjusted hazard ratio for
Crohn's disease was 2.65 (95% CI 1.53 to 4.60) among those currently on
oral contraceptives compared with those who had never used these agents,
Khalili reported here during the annual Digestive Disease Week.

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 (HR 1.68, 95% CI 1.05 to 2.71).

The risk of ulcerative colitis was higher with longer use of HRT (P=0.02
for trend), but that risk dropped based on the length of time the woman
had stopped HRT.

The adjusted risk was 2.11 (95% CI 1.16 to 3.84) among those who had not
been taking the hormones for 5 years or less.

The adjusted risk was 1.27 (95% CI 0.72 to ?2.24) for those who had
stopped more than 5 years previously.

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 (HR 1.19, 95% CI 0.78 to 1.81), 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 (HR 1.50, 95% CI 1.13 to 1.98).

After adjustment for multiple reproductive factors including age at
menarche, parity, and menopause status, the multivariate hazard ratios
for Crohn's disease remained at 2.66 (95% CI 1.52 to 4.64) for those
currently taking oral contraceptives and 1.40 (95% CI 1.06 to 1.86) for
those who had done so in the past.
In contrast to the HRT study, this analysis found no link between oral
contraceptives and risk for ulcerative colitis, with a multivariate
adjusted hazard ratio of 1.22 (95% CI 0.71 to 2.09).

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.
Khalili had no financial disclosures.

One co-author is a consultant to Policy Analysis, and a second is a
consultant for Bayer AG, Millennium Pharmaceuticals, and Pfizer.

Primary source: Digestive Disease Week
Source reference:

Khalili H, et al "Hormonal replacement therapy and risk of ulcerative
colitis and Crohn's disease among postmenopausal women: results from a
large prospective cohort of U.S. women" DDW 2012; Abstract 401.

Additional source: Digestive Disease Week
Source reference:

Khalili H, et al "Reproductive factos and risk of ulcerative colitis and
Crohn's disease: results from two large prospective cohorts of U.S.
women" DDW 2012; Abstract 402.
Staff Writer

Nancy Walsh has written for various medical publications in the United
States and England, including Patient Care, The Practitioner, and the
Journal of Respiratory Diseases. She also has contributed numerous
essays to several books on history and culture, most recently to The
Book of Firsts (Anchor Books, 2010).
F

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Donna G.
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