HRT fails to stall atherosclerosis in postmenopausal women with pre-existing coronary artery lesions

August 06, 2003

LOS ANGELES (Aug. 7) - A daily dose of estrogen, whether given alone or with progestin, failed to keep arteries with pre-existing lesions from narrowing further, according to results of a randomized, controlled trial in postmenopausal women led by investigators at the Keck School of Medicine of the University of Southern California.

Results of the Women's Estrogen-Progestin Lipid-Lowering Hormone Atherosclerosis Regression Trial, or WELL-HART, were published in the Aug. 7 issue of the New England Journal of Medicine. The findings add further evidence that hormone replacement therapy is ineffective against established coronary artery disease in older women many years past menopause.

"WELL-HART and similar trials clearly tell us that estrogen and progestin should not be used to treat atherosclerosis in women who already have cardiovascular disease," said Howard N. Hodis, M.D., professor of medicine and preventive medicine at the Keck School, director of the USC Atherosclerosis Research Unit and the study's lead investigator.

"However, we need to be reserved in generalizing results from trials in women with established cardiovascular disease or women who were started on hormones long after menopause, to women without pre-existing cardiovascular disease who are currently undergoing the change of life."

Hormone therapy has traditionally been prescribed to reduce the discomforts of menopause, such as hot flashes.

Atherosclerosis, the build-up of fatty material along inner artery walls, can eventually result in life-threatening heart attacks and stroke. It causes one of every two deaths in the United States and is the number-one killer of women.

For WELL-HART, researchers at five medical centers recruited 226 postmenopausal women who had at least one area of narrowing, found through angiograms, in arteries supplying blood to the heart. They divided them randomly into three groups: those who received only estrogen, those who took estrogen and progestin and those who received the usual medical care without hormones. The women, whose average age was nearly 64 and who were about 18 years past menopause, did not know which group they were in.

As part of care, participants changed their diets and took lipid-lowering medications to reduce their levels of LDL , the so-called "bad" cholesterol.

After an average of more than three years of follow-up, researchers found no significant difference in coronary artery narrowing among the groups.

The findings are consistent with those of other trials of hormone replacement therapy for atherosclerosis in women decades beyond menopause who have pre-existing cardiovascular disease. But they are surprisingly different from those of the Estrogen in the Prevention of Atherosclerosis Trial, or EPAT, a sister study to WELL-HART conducted by the same researchers.

EPAT found that estrogen without progestin slowed atherosclerosis progression in postmenopausal women. These women, however, had no pre-existing cardiovascular disease and were younger than the WELL-HART women.

"When carefully reviewed, observational studies, experimental data and EPAT results-in contrast to WELL-HART and similar trials-indicate that the timing of initiation of hormones may be important in determining whether estrogen reduces atherosclerosis progression," says Hodis. "In other words, when estrogen is initiated in atherosclerosis' early stages, it can slow progression. But when initiated after lesions have developed beyond a certain stage, estrogen seems to have no effect."

For the WELL-HART study, physicians used 17beta-estradiol, the form of estrogen identical to human estrogen. This estrogen, available generically but also known as Estrace, was paired with a progestin called Provera (given for 12 days each month). Most prior studies have studied another form of estrogen known as Premarin, or Prempro when paired with progestin every day.

Hodis notes that use of unopposed estrogen should generally be restricted to postmenopausal women who have had a hysterectomy. Women considering using hormones should discuss risks and benefits with their doctors.

Investigators in WELL-HART included those at USC and the following centers: Kaiser Permanente Medical Center, Good Samaritan Hospital in Los Angeles, Harbor-UCLA Medical Center in Torrance, Calif., and Huntington Memorial Hospital in Pasadena, Calif. The National Heart, Lung and Blood Institute and the Office of Research on Minority Health supported the study.
Howard N. Hodis, Wendy J. Mack, et al, "Hormone Therapy and the Progression of Coronary-Artery Atherosclerosis in Postmenopausal Women," New England Journal of Medicine. Vol. 349, No. 6, pp. 535-545.

University of Southern California

Related Cardiovascular Disease Articles from Brightsurf:

Changes by income level in cardiovascular disease in US
Researchers examined changes in how common cardiovascular disease was in the highest-income earners compared with the rest of the population in the United States between 1999 and 2016.

Fighting cardiovascular disease with acne drug
Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg and Stanford University have found the cause of dilated cardiomyopathy - a leading cause of heart failure - and identified a potential treatment for it: a drug already used to treat acne.

A talk with your GP may prevent cardiovascular disease
Having a general practitioner (GP) who is trained in motivational interviewing may reduce your risk of getting cardiovascular disease.

Dilemma of COVID-19, aging and cardiovascular disease
Whether individuals should continue to take angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the context of coronavirus disease 2019 (COVID-19) is discussed in this article.

Air pollution linked to dementia and cardiovascular disease
People continuously exposed to air pollution are at increased risk of dementia, especially if they also suffer from cardiovascular diseases, according to a study at Karolinska Institutet in Sweden published in the journal JAMA Neurology.

New insights into the effect of aging on cardiovascular disease
Aging adults are more likely to have - and die from - cardiovascular disease than their younger counterparts.

Premature death from cardiovascular disease
National data were used to examine changes from 2000 to 2015 in premature death (ages 25 to 64) from cardiovascular disease in the United States.

Ultrasound: The potential power for cardiovascular disease therapy
In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp.

Despite the ACA, millions of Americans with cardiovascular disease still can't get care
Cardiovascular disease (CVD) is the leading cause of death for Americans, yet millions with CVD or cardiovascular risk factors (CVRF) still can't access the care they need, even years after the implementation of the Affordable Care Act (ACA).

Excess weight and body fat cause cardiovascular disease
In the first Mendelian randomization study to look at this, researchers have found evidence that excess weight and body fat cause a range of heart and blood vessel diseases (rather than just being associated with it).

Read More: Cardiovascular Disease News and Cardiovascular Disease Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to