Women With Heart Disease Warned of Hormone Risk

Women contemplating hormone replacement therapy may need to reconsider if they already have heart disease, according to new research that rattles the received wisdom on protecting women from the nation’s No. 1 killer.

In a study of 2,763 post-menopausal women with diagnosed heart disease, 4.3% of those undergoing combined estrogen and progestin therapy had a heart attack within a year, compared to 2.8% of women who did not take the drugs.

However, after four years, the medical researchers found some benefits of hormone replacement therapy, with fewer heart attacks and less chest pain among the women who received hormone therapy than among those who did not. Overall, those longer-term benefits of therapy were offset by the shorter-term risks.

Sifting through the unexpected and complex findings, published today in the Journal of the American Medical Assn., the researchers said they do not recommend that post-menopausal women with heart disease start estrogen treatment if they have not done so already.

The results have no bearing on the 95% of women who take estrogen replacement therapy for reasons such as reducing the risk of osteoporosis and easing symptoms of menopause.

But for those women who have heart disease and who are considering hormone therapy in order to reduce their risk of heart attacks, “there doesn’t seem to be at this point good reason for starting estrogen plus progestin therapy because the overall effect was neutral,” said Dr. Stephen Hulley, chairman of epidemiology and biostatistics at UC San Francisco and the study’s lead author.

“But if a woman has been on the therapy for at least two years,” he said, “our study would suggest that she’s gotten to the phase where the hormones may be having some benefit.”

Women with heart disease who have been on the therapy less than two years should discuss the risks with their physicians, Hulley and other medical experts said.

The women studied averaged 67 years old at the outset and were sicker than most women on hormone replacement therapy. Because of that, the results “should not be generalized to women who are healthy,” the American Heart Assn. said in a statement.

The study, the first scientifically controlled clinical trial of the therapy in women with preexisting heart disease, was conducted at 20 medical centers nationwide.

“I was stunned by the findings,” said Dr. Steven Kahn, a cardiologist at Cedars-Sinai Medical Center in Los Angeles, who participated in the study. “We were all very much surprised. You could hear a pin drop in the room when the data were first presented.”

Until now, the published evidence has consistently suggested that hormone replacement therapy benefited women with preexisting heart disease. At least five “observational” studies--comparing women in the community who happened to be taking the therapy to women who were not--have shown that it cut heart attack risk 35% to 80%.

Researchers say that estrogen helps prevent heart disease in post-menopausal women by improving blood cholesterol levels and maintaining the healthy elasticity of coronary arteries, among other things. The hormone progestin is sometimes added to the formulation to counter side effects of estrogen supplementation, including uterine bleeding.

Although those studies formed the basis of conventional wisdom in cardiology, they could not rule out the possibility that women who sought out hormone therapy did better because they were healthier and more conscientious than those women who chose not to be treated.

The new research “trumps” the earlier work because it is more scientifically rigorous, said Dr. Diana Petitti, a medical researcher at Kaiser Permanente Southern California in Pasadena. Among other things, the new research avoids the problem of skewed results because researchers randomly assigned the women to the treatment and control groups before they began the hormone therapy.

In the study, half of the women received estrogen and progestin combination therapy in the form of a drug called Prempro, and half received an inactive placebo pill. After four years, there were 172 heart attacks in the treatment group and 176 in the placebo group.

“To give the impression that there is terrible harm going on here would be inappropriate,” said Dr. Phillip de Vane, vice president of clinical affairs for Wyeth-Ayerst Laboratories, the drug company that makes Prempro and funded the study. Still, he agreed that women with preexisting heart disease should perhaps reconsider starting hormone replacement therapy if their goal is heart disease reduction.

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The Hormone Therapy Decision

Estrogen replacement therapy, with or without progestin, may benefit many post-menopausal women--but not all. The decision to undergo the therapy depends on a woman’s medical history. Research suggests that in addition to easing menopausal symptoms, the therapy can benefit healthy women by reducing the risks of:

* Osteoporosis and hip fracture

* Cardiovascular disease

* Alzheimer’s disease

* Colon cancer

* Osteoarthritis

* Cataracts

* Vaginal atrophy

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But it also can increase the risk of:

* Uterine cancer (if used without progestin)

* Breast cancer

* Gallbladder disease

* Thromboembolic disease (such as blood clots)

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Among the disorders that may preclude taking hormone therapy:

* Estrogen-dependent cancer

* Undiagnosed, abnormal genital bleeding

* Current or past history of thrombophlebitis or thromboembolic disorders

* Known or suspected breast cancer

* Coronary heart disease

Sources: Physicians’ Desk Reference, Dr. Susan Love’s Hormone Book, Los Angeles Times files.

Compiled by Times Staff Writer Shari Roan.