Evidence continues to support use of hormone replacement


My menstrual periods have stopped over the past few months. My doctor has urged me to start hormone replacement, but I am reluctant to follow her advice. Is my doctor right?

Absolutely! Every year the evidence grows stronger for the benefits of hormone replacement in postmenopausal women.

It has been clear for a number of years that estrogen replacement is the most effective way to prevent osteoporosis, the loss of bone mineral that predisposes to fractures of the hip, spine and wrists.

More than 30 epidemiological studies have shown that replacement with estrogen alone greatly reduces the risk of heart attacks and other complications of coronary artery disease (CAD) in postmenopausal women, especially if they have a prior history of CAD. Estrogen raises the level of the protective HDL cholesterol and lowers the level of the dangerous LDL cholesterol.

Although estrogen taken alone increases the risk of uterine cancer, this risk is eliminated by adding a progestin to the replacement regimen in postmenopausal women whose uterus has not been removed by surgery.

Since progestins "oppose" the helpful effects of estrogen on HDL and LDL cholesterol values, it has not been clear whether the combination of estrogen and a progestin will still protect against CAD. But recent news is hopeful.

In the PEPI trial, published in January 1995, 875 postmenopausal women, ages 45-64, were treated for three years with a placebo, estrogen alone (Premarin), or estrogen plus a progestin (Provera). Estrogen alone increased the "good" HDL cholesterol by 9 percent. When Provera was taken along with Premarin, the HDL cholesterol rose by only 2 percent, as expected; but alone or in combination with Provera, Premarin lowered "bad" LDL cholesterol by about 12 percent. In addition, none of the treatments was associated with weight gain or an increase in blood pressure. Many women on estrogen alone, but not those taking both estrogen and progestin, developed tissue changes in the uterus that can lead to cancer.

Particularly exciting is the Aug. 15 publication in the New England Journal of Medicine of the 16-year follow-up of more than 59,000 women enrolled in the Nurse's Health Study. Major coronary disease (defined as fatal or nonfatal heart attacks or the need for bypass surgery or angioplasty) was reduced by 40 percent in women currently taking estrogen and by 60 percent in those taking both estrogen and progestin.

These findings indicate that the beneficial effects of estrogen remain when a progestin is also taken. The protective effects of hormone replacement persisted for at least five years after the hormones were stopped, but no beneficial effects were found in women who had not taken the hormones for more than 10 years.

Many women are concerned that hormone replacement may increase the danger of breast cancer. Many studies have examined this issue, and it appears that long years of estrogen replacement do increase the risk of breast cancer, but only by a small amount. Because CAD is responsible for many, many more deaths than breast cancer in postmenopausal women, the small increase in the incidence of breast cancer is far outweighed by the protection provided against CAD and osteoporosis.

Dr. Margolis is professor of medicine and biological chemistry at the Johns Hopkins School of Medicine.

Pub Date: 9/03/96

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