Update won’t stop Women’s Health Initiative

Women who are participating in the hormone replacement therapy (HRT) component of the Women’s Health Initiative (WHI) have been notified of a small increase in the number of heart attacks, strokes, and blood clots during the first two years of the national study in those taking active hormones.

"Over time, these differences seem to get smaller and may even disappear," states a patient update issued by the WHI.1 "In fact, overall, WHI women had fewer such events than would be expected in the general population."

While the WHI has alerted women of these findings, it also is emphasizing that its independent monitoring board recommends continuation of the study. Such reassurance is important given the reports of increased risks published in lay press, says Susan Wysocki, RNC, NP, president and chief executive officer of the Washington, DC-based National Association of Nurse Practitioners in Women’s Health.

"Apparently, the actual risk found in the treatment group, [which was] less than 1%, is still lower than the general population, but HRT makes big news," observes Wysocki. "I just hope this does not throw off the WHI, because we need that data."

HRT effects examined

The National Institutes of Health in Bethesda, MD, established the 15-year Women’s Health Initiative, one of the largest U.S. prevention studies of its kind, to address the most common causes of death, disability, and impaired quality of life in post-menopausal women. The HRT component of the study is examining the effects of HRT on heart disease, osteoporosis-related bone fractures, and breast and endometrial cancer.

More than 27,000 women ages 50 to 79 are participating in the HRT study. Women with uteruses have been randomized to receive estrogen plus progestin or a placebo, and women who have had hysterectomies have been randomly selected to receive estrogen alone or a placebo.

Women in the WHI trial are evaluated at least every six months by local clinic staff to make sure it is safe for them to stay on study pills. Local results are examined by a human subjects committee. An independent group of medical experts, the Data and Safety Monitoring Board (DSMB), reviews information from all participating clinics nationwide.

"Both your local clinic’s human subjects committee and the DSMB have the power to stop or change the study if they find important safety concerns," the WHI patient update reads. "They have not done so. In fact, the DSMB has recommended that the study continue."

Challenging the belief

The information issued by the WHI comes on the heels of two clinical trials that have challenged the belief that post-menopausal hormone therapy protects against coronary heart disease.2,3

The first study, the Heart and Estrogen/progestin Replacement Study (HERS), was a randomized, double-blind, placebo-controlled study of estrogen plus progestin therapy in post-menopausal women with established coronary heart disease. The clinical trial included 2,763 participants ages 44 to 79 who had atherosclerosis, experienced a heart attack, or undergone bypass surgery or angioplasty. Patients were randomized to receive Prempro [an HRT product containing conjugated estrogens and medroxyprogesterone acetate (MPA), manufactured by Wyeth-Ayerst Laboratories of Philadelphia] or placebo.

Researchers found that the estrogen/progestin combination did not decrease the overall risk of heart attack and coronary death among post-menopausal women with previous heart disease. The studied regimen appeared to increase the risk of heart attack in the first year of treatment and then to decrease it after two years of treatment. An observational follow-up study (HERS II) is planned to determine whether the benefi-cial trend seen in the last two years of the trial continues.

The second study, the Estrogen Replacement and Atherosclerosis (ERA) trial, was designed to determine the effect of unopposed estrogen or combined estrogen-progestin therapy on the progression of coronary artery disease in post-menopausal women with existing coronary disease. A total of 309 older women were randomly assigned to take estrogen, estrogen combined with a progestin, or a placebo. Researchers found that progression of atherosclerosis was not affected by 3.2 years of treatment with either unopposed estrogen or a combination of estrogen and MPA.

Statins, a class of drugs that lower cholesterol levels, have been shown to reduce the risk of coronary events by approximately 30% (greater in higher-risk individuals) in men and women.4,5 These drugs include atorvastatin (Lipitor from Parke-Davis in Morris Plains, NJ), lovastatin (Mevacor from Merck & Co. of West Point, PA), simvastatin (Zocor from Merck & Co.), pravastatin (Pravachol from Bristol-Myers Squibb Co. of Princeton, NJ), and fluvastatin (Lescol from Novartis Pharmaceuticals Corp. of East Hanover, NJ).

Be conservative in some cases

Leon Speroff, MD, professor of obstetrics and gynecology at Oregon Health Sciences University in Portland, says, "These trial results are reasons to be conservative regarding hormone therapy for older women with evidence of coronary heart disease; certainly, we should not promote estrogen as a first-line drug to prevent further clinical events in women with coronary artery disease, especially in women who have had a recent myocardial infarction."

Multiple clinical trials have established that treatment with statins is very effective in preventing clinical cardiac events, Speroff adds.

References

1. Women’s Health Initiative. What you should know about hormones and cardiovascular health. WHI HRT Update. Web: www.nhlbi.nih.gov/whi/hrt-en.htm.

2. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in post-menopausal women. JAMA 1998; 280:605-618.

3. Herrington D. The Estrogen Replacement and Atherosclerosis (ERA) trial. Presented at the American College of Cardiology Scientific Session 2000. Anaheim, CA; March 2000.

4. LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: A meta-analysis of randomized controlled trials. JAMA 1999; 282:2,340-2,346.

5. Vaughan CJ, Gotto AM Jr., Basson CT. The evolving role of statins in the management of atherosclerosis. J Am Coll Cardiol 2000; 35:1-10.