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The Timing of Hormone Replacement Therapy Could be Key to Success, Says Wake Forest Researcher

WINSTON-SALEM, N.C. – The timing of treatment may be a key factor in whether hormone replacement therapy (HRT) can slow heart vessel disease, report researchers from Wake Forest University Baptist Medical Center and Tufts-New England Medical Center in the winter issue of Menopausal Medicine.

“Mounting evidence points to the conclusion that HRT can help prevent heart vessel disease – if the therapy begins around the time that the body stops making its own estrogen,” said Thomas B. Clarkson, D.V.M., of Wake Forest. “The question may not be if estrogen helps, but when is the optimum time to begin therapy.”

Clarkson, a professor of comparative medicine, and Richard H. Karas, M.D., Ph.D., director of the preventive cardiology center at Tufts, reviewed numerous studies of postmenopausal women and monkeys that evaluated the cardiovascular effects of HRT.

Their evaluation included the Women’s Health Initiative (WHI), which showed an increased risk of heart attacks in women taking HRT and led to recommendations that women not begin hormone replacement therapy for the purpose of preventing heart disease. They also reviewed trials of postmenopausal monkeys conducted at Wake Forest over the past 12 years.

“The literature demonstrates that HRT has beneficial effects in inhibiting the early stages of heart vessel disease, but can have deleterious effects if initiated at older ages when some women have already developed disease,” said Clarkson.

For years, doctors had prescribed hormone replacement therapy to prevent heart disease in postmenopausal women. These treatment decisions were based on observational studies showing that women who took estrogen had fewer heart attacks. But, these assumptions were called into question with studies such as WHI.

Clarkson and Karas said there are several possible explanations for the discordant findings between observational studies and WHI. “One of the most striking differences is the age of the patients being studied,” they wrote. “In the observation studies, women began HRT at a relatively young age. WHI women, however, averaged 63 years old when therapy was begun.”

Clarkson and Karas believe that the timing of HRT initiation significantly influences its potential for cardiovascular benefits or harm.

“When estrogen replacement was administered to monkeys at the onset of estrogen deficiency – which compares to the postmenopausal transition in women – there was a 70 percent inhibition of fatty build-up in the heart’s arteries. In contrast, when estrogen replacement was delayed for a period comparable to six years in women, there was no benefit on the heart’s arteries,” they wrote.

Clarkson and Karas said the data they reviewed support their theory that HRT may be able to maintain vessel health when it is initiated in younger women without an advanced buildup of fatty deposits in their heart vessels. But, the treatment may be either ineffective or potentially harmful when it is given to older women with more advanced vessel disease.

“It is noteworthy that 70 percent of the women in the WHI were in the age groups that would be expected to experience deleterious effects of HRT, while only 10 percent were in the age groups that are likely benefited by HRT,” they wrote.

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Media Contacts: Karen Richardson, (336) 716-4453, krchrdsn@wfubmc.edu; Barbara Hahn, (336) 716-6877, bhahn@wfubmc.edu

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