Issue 113 Item 19 Long-Term HRT Does Not Protect the Heart

Long-term follow-up of HERS II does not support the cardiovascular benefit once attributed to hormone replacement therapy (HRT). Long-term follow-up of the Heart and Estrogen/Progesterone Replacement Study (HERS II) reported in the July 3 issue of The Journal of the American Medical Association does not support the cardiovascular benefit once attributed to hormone replacement therapy (HRT). Furthermore, HRT was linked to increased risk of venous thromboembolism and biliary tract surgery.

"This follow-up study found no reduction in risk of heart attacks or death for women with heart disease during up to seven years of hormone therapy," lead author Deborah Grady, MD, MPH, from the University of California, San Francisco, says in a news release. "Not only was there no cardiovascular benefit, there were adverse affects, including blood clots and gallbladder disease."

HERS was a randomized, blinded, placebo-controlled trial of estrogen plus progestin in older postmenopausal women with heart disease. Contrary to expectation, risk of myocardial infarction (MI) increased during the first year of HRT, although risk seemed to decrease during the remainder of the study, which lasted 4.1 years. The HERS II follow-up open-label study, lasting 2.7 years, was therefore designed to evaluate the effects of longer-duration HRT.

In HERS, 2763 postmenopausal women with coronary heart disease, average age 67 years, received either 0.625 mg/d conjugated estrogen plus 2.5 mg medroxyprogesterone acetate, or placebo. During the HERS II follow-up, the women chose whether to take hormones based on advice from their personal physicians.

The initial trend from HERS suggesting a reduced risk of MI with longer duration of HRT did not persist with additional follow-up. Combining HERS and HERS II, there was no risk reduction from HRT during almost seven years.

In fact, HRT doubled the risk of thromboembolism in the legs and lungs, with most of the increased risk in the early years of treatment, and increased the risk of gallbladder disease requiring surgery by 48%. There was no benefit of HRT for any other major disease outcome including overall risk of death.

"These observations confirm the wisdom of ‘evidence-based medicine,’ basing treatment decisions on the balance of benefits and harms established in randomized clinical trials," says co-author Stephen Hulley, MD, MPH. "Our study indicates that for older women with heart disease, estrogen plus progestin therapy is not beneficial and does have some harmful effects."

Funding for these studies was provided by Wyeth-Ayerst Research.

In an accompanying editorial, Diana B. Petitti, MD, from Kaiser Permanente Southern California in Pasadena, agrees that pessimism for HRT is appropriate but should not cause pessimism for disease prevention in postmenopausal women. Although other observational studies touting benefits for HRT are unconfirmed, the focus should shift to other modalities of demonstrated benefit, such as angiotensin-converting enzyme inhibitors, aspirin, and blood pressure control to reduce cardiovascular risk.

"An appropriately pessimistic view of HRT as an omnibus agent to prevent disease in postmenopausal women should focus more attention on these preventive interventions, which have a strong evidence base," she writes. JAMA. 2002;288(1):49-57, 58-66, 99-101

Items For This Week. Issue 113

One Two Three Four Five Six Seven Eight Nine Ten Eleven Twelve Thirteen Fourteen Fifteen Sixteen Seventeen Eighteen Nineteen Twenty

Back To Issue 113 Main Page