Estrogen
supresses inflamation
By
LOIS BAKER
Contributing Editor
Estrogen's
ability to reduce a woman's risk of heart disease during her reproductive
years may be based on a previously unexamined mechanism of the hormone:
its anti-inflammatory effects.
In
the first demonstration in humans of this capacity of estrogen, endocrine
researchers at UB have shown that estrogen may suppress production of
several pro-inflammatory components at the cellular, molecular and plasma
levels.
Results
of this preliminary study were presented at the annual meeting of The
Endocrine Society, held earlier this month in San Francisco.
"If
estrogen has a prominent anti-inflammatory effect, this action may help
to explain why women have a much lower risk of atherosclerosis (which
begins as an inflammation of the blood vessel walls) than men until
menopause," said Paresh Dandona, professor of medicine and head of the
Division of Endocrinology in the School of Medicine and Biomedical Sciences,
who is senior author on the study. "Once women hit menopause, their
heart-disease risk rises to that of men.
"This
is the first demonstration in vivo of estrogen's precise molecule
anti-inflammatory behavior," he said.
In
this preliminary study, Dandona and colleagues from the Diabetes-Endocrinology
Center of Western New York, located in Kaleida Health's Millard Fillmore
Hospital, used men as subjects to avoid the estrogen fluctuations that
take place during a woman's menstrual cycle, which would interfere with
results.
Nine
healthy men of normal weight with a mean age of 32 provided blood samples
before receiving a 5 mg. injection of estrogen in the form of Premarin,
the most commonly prescribed drug for estrogen-replacement therapy.
Dandona chose this amount of estrogen for a "single slug," which is
about four times the upper limit contained in daily doses of hormone-replacement
therapy, to determine if an anti-inflammatory effect would occur over
the short-term. Additional blood samples were drawn at two, four, six
and 24 hours after the injection.
Researchers
measured the generation of reactive oxygen species, or oxygen free radicalscomponents
known to damage cells in blood-vessel walls and induce inflammationin
specific cells (mononuclear cells), molecules (polymorphonuclear leukocytes)
and in plasma. They also assessed concentrations of three factors known
to be markers of the inflammatory process: intranuclear nuclear factor-kB
(NF-kB), C-reactive protein (CRP) and plasminogen activator inhibitor-1
(PAI-1).
Results
showed that estrogen significantly inhibited the generation of free
radicals by mononuclear cells and leukocytes, with peak inhibition39.9
percent and 47.3 percent respectivelyreached at four hours after
estrogen infusion.
NF-kB
activity fell to a low of 24 percent at six hours after infusion, and
C-reactive protein concentration dropped a maximum of 19.5 percent at
four hours, results showed. In addition, plasminogen activator inhibitor-1
fell nearly 50 percent at six hours.
"These
early results allow us to understand the mechanism and to say that estrogen
works in this fashion," said Dandona, who plans to conduct a similar
study in postmenopausal women.
"It
should be possible to separate estrogen's feminizing effects from its
anti-inflammatory effects," he said. "In the long run, estrogen may
prove helpful as an addition to current therapy in the treatment and
prevention of heart disease."
Additional
researchers on the study, all from the UB Department of Medicine, were
Priya Mohanty, Hasam Ghanim, Ahmad Aljada, Deborah Hofmeyer and Arindam
Bandyopadhyay.