Hard Looks at Hormones

By John Langone

Besides being emotionally stressful for some, menopause can bring physical discomfort and may lead the way to serious health risks in older women. When their reproductive years end and the production of sex hormones drops, women face not only the prospect of hot flashes and insomnia but also a greater chance of worse conditions, such as heart disease and a weakening of the bones called osteoporosis. Over the years, pharmaceutical companies have developed pills designed to replace the hormones the women have lost, and these drugs have come into wide use. Now, however, new questions are being raised about their safety. Although the evidence is far from conclusive, a major study published last week in the New England Journal of Medicine suggests that at least some of the post-menopause medication may increase the risk of breast cancer.

The study, conducted in Sweden, involved 23,244 women who were taking various types of estrogen, one of the main female sex hormones, after menopause; a third of them were also on progestin, an artificial form of the hormone progesterone. The researchers compared these women with others who had not taken hormones. The results: after nine years the women who took a kind of estrogen called estradiol had about twice the breast-cancer rate of those who were not on replacement therapy. The women on estrogen and progestin had a higher rate -- about four times as many cases of breast cancer after they used the combination for six or more years. Medical experts point out that parts of this report contradict some earlier evidence and that data on many more women must be collected before the Swedish results are either confirmed or refuted. Nonetheless, the study injects new doubts into the already difficult choices that women must make concerning which hormones, if any, to take.

Estrogen came into favor many years ago because it helped prevent osteoporosis and appeared to guard against heart disease. But it was discovered that estrogen increased the risk of uterine cancer. To lower the odds of contracting uterine cancer, many doctors added progestin to the treatment, and it was hoped that the drug would also help reduce any risk of breast cancer associated with estrogen alone. The drawback to progestin seemed to be that it reduces some of the benefits of estrogen, in particular the apparent protection against heart disease. Now the possibility of a breast- cancer risk has further muddled an already confused situation.

So what is a woman to do? In an editorial published along with the Swedish study in the New England Journal, Dr. Elizabeth Barrett-Connor of the University of California, San Diego, argues that the "benefits of estrogen seem strongly established. In my opinion, the data are not conclusive enough to warrant any immediate change in the way we approach hormone replacement." Dr. I. Craig Henderson of the Dana-Farber Cancer Institute in Boston notes that estradiol, the estrogen implicated in the Swedish report, is not the same as the estrogens most commonly used in the U.S. "While women should not conclude yet that they are totally without risk," he says, "it is highly likely that the estrogen American women use may be safer for a longer period of time than the estrogen used in Sweden."

There is more uncertainty, however, about adding progestin to estrogen, since the study raised the possibility that this combination produces a greater risk of breast cancer than does estrogen alone. Dr. Charles Hammond, chairman of the department of obstetrics and gynecology at Duke University Medical Center, is not convinced that he should change his prescribing habits. "We shouldn't frighten women into not taking progestin," he says. "We could find an increase in uterine cancer." But that disease is less common and less lethal than breast cancer. Some experts, including Malcolm Pike, a professor of preventive medicine at the University of Southern California, suggest that the benefits of progestin may not be worth the potential dangers.

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With reporting by Janice M. Horowitz/New York