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MONDAY, APRIL 7, 2008
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dkrupa@the-aps.org
New Study Finds Adverse
Effects Of Estrogen Replacement Therapy (ERT)
Are Related To The Dose
Moderate and high doses linked to kidney and heart problems; no kidney
damage found with low amounts
SAN DIEGO, CA – Recent clinical trials
indicate that estrogen replacement therapy (ERT) may increase the risk of
cardiovascular diseases. A new study in mice has examined whether adverse
effects of ERT are related to the doses used. The study found that moderate
and high doses of ERT increased problems in the kidney and heart. These
results suggest that ERT dosage may be an important determinant in a woman’s
overall health.
The study, Dose-Response Effect of Estrogen on the
Kidney and Heart, was conducted by Xiaomei Meng, Martin Antonio
D’Ambrosio, Tang-Dong Liao and Xiao-Ping Yang. The researchers are members
of the Hypertension and Vascular Research Division of Henry Ford Hospital,
Detroit, MI. Dr. Yang is presenting her team’s findings during the 121st
Annual Meeting of the American Physiological Society (APS;
www.the-APS.org/press/), part of the Experimental Biology 2008
scientific conference
Background
The frequency of
cardiovascular disease (CVD) and the deaths that are associated with it are
much lower in premenopausal women than in men of similar age. This female
gender advantage becomes far less or disappears with increased age and
reduced estrogen levels after menopause, suggesting that ovarian hormones,
most likely estrogen, protect women against CVD.
Studies have show that
postmenopausal women who receive hormonal replacement therapy (HRT) have a
lower incidence of CVD and die less frequently than those not receiving HRT.
As a result, HRT has commonly been used for prevention of CVD in
postmenopausal women. However, recently published data by the Heart and
Estrogen/Progestin Replacement Study (HERS) and the Women’s Health
Initiative (WHI) showed an unfavorable effect of HRT on the risk and events
of CVD in women. But while the data were convincing, there are other
considerations such as composition of the drugs, dosage, time when HRT was
initiated, age, and pre-existing risk factors for CVD, which may have
affected the outcome of HERS and WHI.
The dosage of estrogen
may also be a contributing factor in the unfavorable outcome of HRT since it
has been shown that certain types of estrogen can decrease heart attacks and
stroke in women who have no history of CVD. Conversely, certain levels of
estrogen, in combination with progestin, increase the risk of stroke.
The Study
In an effort to isolate the factors involved in the
estrogen-CVD connection, and more specifically, to understand what role the
dose of the drug might play, the researchers examined whether the adverse
effects of ERT were related to the doses being used. For a 60 day period
ovariectomized (OVX) mice received the estrogen hormone 17β—estrodial (E2),
a drug very similar to that used in treating the symptoms of menopause. The
mice received one of four dosing levels every day throughout the study
period: a very low (VL) dose (0.001 µg/d); a low (L) dose (0.42 µg/d); a
moderate (M) dose (4.2 µg/d); or a high (H) dose (28.3 µg/d).
The researchers found that:
-
Moderate and high doses of ERT increased the
plasma estrogen levels in the mice more than four fold (4.5). This was
associated with fluid retention in the uterus, amounts of protein in the
urine, and dilated kidneys.
-
By contrast, low doses of E2 restored plasma
estrogen to levels similar to the control rats and neither fluid
retention nor renal damage was found in this group of mice.
-
Moderate and high doses of E2 also increased
atrial natriuretic peptide (ANP), a cardiac hormone that is increased as
a marker of severity of heart failure.
At low level dosing this did not occur.
-
Overall blood pressure and cardiac function were
not changed by ERT at any given dose.
Conclusions
“This shows that the size of the estrogen dose may be
critical in determining whether ERT leads to cardiovascular or kidney
disease,” said Dr. Yang, the study’s lead researcher. Other factors such as
the ratio of estrogen to progestin, the age when the therapy begins and the
cardiovascular health of the patient when treatment starts may also be
important factors to investigate.”
*****
Physiology
is the study of how molecules, cells, tissues and organs function to create
health or disease. The American Physiological Society (APS;
www.The-APS.org/press) has been an integral part of this discovery
process since it was established in 1887.
# # #
NOTE TO EDITORS: The APS annual meeting is part
of the Experimental Biology 2008 (EB ’08) gathering and will be held April
5-9, 2008 at the San Diego, CA Convention Center. To schedule an interview
with Dr. Yang please contact Donna Krupa at 301.634.7209 (office),
703.967.2751 (cell) or
DKrupa@the-APS.org.
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