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Hormone Therapy: Does Timing Matter?

Apr. 21, 2008 — Women who began hormone therapy soon after menopause did not show reduced blood vessel function raising the question of whether the negative effects of hormone therapy in recent trials might be avoided in younger patients.


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Results of ongoing rigorous, randomized and controlled studies of younger menopausal women on hormone therapy are needed before considering changes to current guidelines.

The results of this small, observational study do not suggest that women entering menopause should start hormone therapy.

Hormone therapy may have different effects on blood vessels if it is started early in menopause as opposed to later, researchers suggested at the American Heart Association's Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2008.

"Abnormal endothelial function is a marker of early heart disease. We have found that endothelial function is just as good, if not slightly better, among women who have risk factors for heart disease and have taken hormone therapy around menopause onset as it is among women who are about the same ages but have no risk factors for heart disease and are not taking hormone therapy," said James Arrowood, M.D., lead author of the study and associate professor of internal medicine and cardiology at Virginia Commonwealth University Medical Center in Richmond, Va.

"Previous findings in randomized controlled trials suggesting that hormone therapy could be deleterious to cardiovascular health were conducted in women who started taking hormones years after menopause onset versus observational studies of women initiating hormone treatment around the time that menopause began suggesting cardiovascular benefit."

Conducting an observational trial, Arrowood and colleagues analyzed four groups of postmenopausal women (127 total), average ages 52 to 54 years:

One group was not on hormone therapy, had no heart disease risk factors and was an average 8.1 years postmenopausal.

Another group had risk factors for coronary disease (such as smoking, high blood pressure, high cholesterol or diabetes), was not on hormone therapy and was an average 9.3 years postmenopausal.

Two groups had heart disease risk factors and were on hormone therapy: one was on estrogen alone and was an average of 11.7 years postmenopausal and the other was on estrogen plus progestin therapy and was an average 7.6 years postmenopausal. The estrogen group was an average 10.1 years on hormone therapy and the estrogen plus progestin group was an average 6.6 years on hormone therapy.

"The years that they were postmenopausal and years on hormone replacement indicate that the hormone therapy was started around the time of menopause onset," Arrowood said.

The researchers measured flow mediated dilation (FMD), which is a measure of how well the endothelium (the layer of cells that form the inner lining of blood vessels) functions. Keeping in mind that the higher the percentage the better the endothelial function:

  • The no-risk, no hormone group measured an average 7.4 percent FMD.
  • The no hormone group with risk factors measured an average 5 percent FMD.
  • The estrogen group with risk factors measured an average 7.7 percent FMD.
  • The estrogen-progestin group with risk factors measured an average 8.1 percent FMD.

"Essentially, the hormone therapy groups with risk factors for heart disease had similar endothelial function as the no-risk, no-hormone group of women," Arrowood said. "And they had better endothelial function than women with cardiovascular risk factors who were not on hormone therapy. We also found that it doesn't seem to matter for this measure of blood vessel function whether women are taking estrogen or estrogen and progestin." Women who have had a hysterectomy do not need to take a progestin with their estrogen, but those with an intact uterus do.

"The results of this study do not suggest that women starting menopause should start hormone therapy. Current guidelines say that women should not take hormone therapy to improve their cardiovascular risk and that hormone therapy is only recommended for symptoms of menopause and should be taken at the lowest dose and for the shortest time possible. Other ongoing rigorous, randomized and controlled studies looking at younger menopausal women on hormone therapy may help to clarify our results."

The American Heart Association does not advise women take postmenopausal hormone therapy (PHT, formerly called hormone replacement therapy or HRT) or selective estrogen receptor modulators (SERMs) to reduce the risk of coronary heart disease or stroke.

The study was funded by American Heart Association - Virginia Affiliate (now Mid-Atlantic Affiliate) and in part by National Center and was supported by the General Clinical Research Center at Virginia Commonwealth University.

Co-authors are: Jonathan Potfay, M.D.; Cheryl Stacklin, B.S.N.; Rhonda P. Poole, R.D.C.S.; and Frances P. Fua, M.D.

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The above story is reprinted from materials provided by American Heart Association, via EurekAlert!, a service of AAAS.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


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