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New study finds adverse effects of estrogen replacement therapy are related to the dose
Date:4/7/2008

isting 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 17βestrodial (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 g/d); a low (L) dose (0.42 g/d); a moderate (M) dose (4.2 g/d); or a high (H) dose (28.3 g/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 cardiovas
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Contact: Donna Krupa
DKrupa@the-aps.org
619-525-6202
American Physiological Society
Source:Eurekalert

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