Doubts Cast on Hormone Therapy

Chicago Tribune, July 10, 2002.

Doubts Cast on Hormone Therapy

The article cites that researchers have halted a large, nationwide study of hormone replacement therapy after discovering that the pills now happily being taken by millions of postmenopausal women cause breast cancer, heart attacks and other serious side effects.

The absolute risk is small: Only about 1 percent of the women who took estrogen plus progesterone during the five years of the study had a problem. Nevertheless, the study authors concluded, if you’re thinking of taking HRT in hopes of preventing heart disease–don’t.

HRT is usually prescribed to treat hot flashes and other symptoms of menopause and to prevent osteoporosis, and doctors said it’s still appropriate for those purposes. But the study shows it would not be justified for long-term use in a woman with mild or no symptoms whose rationale for taking it was to improve her overall health.

The chances of this study being contradicted in a few months by another piece of research are slim: This was a huge, well-designed, well-controlled clinical trial in which 16,000 healthy postmenopausal women from all over the country were randomly assigned to take HRT or a placebo.

The results were so clear that the directors of the Women’s Health Initiative of the National Institutes of Health halted their study because of the risk to participants.

“This is as close as we’re ever going to get to a definitive study,” said Dr. Linda Hughey Holt of the Northwestern University School of Medicine, a gynecological consultant to the Women’s Health Initiative.

The study, published in the July 17 issue of the Journal of the American Medical Association, was planned to run three more years. It was halted early when it became clear the risks of long-term combined HRT outweighed the benefits.

According to the study, if 10,000 women took the drugs for one year, the group would have a total of seven more heart attacks, eight more strokes, eight more blood clots and eight more cases of breast cancer than a comparable group who were not taking the pills.

The group of women would also have six fewer cases of colon cancer and five fewer hip fractures.

Risks increase

Although the numbers might seem small, the relative risk of getting ill increases significantly with the drugs.

A woman taking the drugs increases her risk of heart disease 29 percent; of stroke, 41 percent; and of breast cancer, 26 percent.

As word of the study got out Tuesday morning, doctors were besieged by calls from concerned patients. Dr. Lauren Streicher, a gynecologist at Northwestern Memorial Hospital, said her practice received about 100 calls.

Streicher said she prepared a written response, which she e-mailed or faxed to her patients, “because I couldn’t call 100 women back in one day.”

In principal, Streicher said, women who are taking hormones just for cardiac protection should stop. But she said they should see how they feel and then make a decision about long-term use.

“If you go off your medication and find you can’t have sex, you can’t sleep and you’re miserable–then, clearly, you’re better off on it,” she said.

Like many other Chicago-area women Tuesday, Maryann Clark said she was in “quite a dilemma.”

Clark, 63, a former nurse who now manages a downtown medical practice, has been on combination HRT for 13 years, since she began suffering the night sweats and mood changes of menopause.

“I had no family history of breast cancer,” said Clark, “so I was eager to go on it. And I’ve been extremely comfortable ever since.”

Clark said she plans to talk to her gynecologist as well as to the physicians she works with before deciding what to do. But right now she’s leaning toward going off her pills and seeing what happens.

“If all those symptoms come back,” she added, “I’m probably going to take the risk, because quality of life at my age is more important.”

Holt said she has treated “a string of desperate women who were taken off their hormones by well-meaning doctors and told it was dangerous to continue. They’re miserable. Their quality of life isn’t as good.”

She said she advises long-term users that they don’t have to quit cold turkey — “we could pull their dose down or taper them off.”

`Real progress’

As unpleasant as Tuesday’s news was for many women, Holt called it “an example of real progress in medical knowledge.”

“Initially, this drug came out for hot flashes,” she said. “Then it emerged, from observation, that the women who were taking it were having fewer bone fractures and fewer heart attacks. But we didn’t know if that was because of the drug or something else.”

Research in the 1970s and ’80s established that estrogen really does help prevent bone loss and osteoporosis. But it wasn’t until the 1990s that hormones were subjected to truly rigorous scientific review to find out whether they were heart-protective.

The Women’s Health Initiative started enrolling women in 1993 to answer that question, among others. On Tuesday, it announced it had the answer.

Not only do hormones not prevent heart disease, as the earlier observational studies had suggested; they actually increase the risk, albeit only slightly.

“This is the study we’ve been waiting for,” said Dr. Matthew Sorrentino, a cardiologist at the University of Chicago.

The study that was halted was testing Prempro, the most common combination hormone pill in the U.S., with 6 million women currently taking it. A separate study, still under way, is testing Premarin (estrogen alone) in women who have undergone hysterectomy, or surgical removal of their uterus.

Premarin has been helping women over the symptoms of menopause — and making many of them feel younger and happier — for 60 years. Some 20 years ago, it was shown to increase the risk of tumors in the endometrial lining of the uterus. Since then, women who still have an intact uterus are usually given Prempro, or some other combination of estrogen and progesterone, which neutralizes the excess risk of uterine cancer.

In the Premarin study, there is no evidence so far that the risks outweigh the benefits. There is also no indication that estrogen alone causes an increased risk of breast cancer, according to Dr. Leslie Ford of the National Cancer Institute, one of the collaborators in the study.

One limitation of the newly released Prempro study was that it evaluated only one form of progesterone. Some doctors said newer types of the hormone, at lower doses, may not be as harmful.

But Ford said: “The onus is on [the manufacturers of the newer drugs] to prove they’re safe. It’s likely these results will extend to other preparations. The hormones are basically the same.”

Sorrentino, the cardiologist, said there was some reason to believe the new drugs might be better, “but we shouldn’t just guess. A formal study should be put together to prove it.”

In an editorial accompanying the results of the Prempro study in JAMA, Dr. Suzanne Fletcher of Harvard noted that approximately 38 percent of postmenopausal women in the U.S. use hormone replacement therapy.

Calling the results of the study “unexpected and disquieting,” Fletcher said doctors should explain to their patients that the absolute risk posed to an individual patient by HRT is small. Nevertheless, “risks from the drug add up over time.”

“The whole purpose of healthy women taking long-term [combined HRT] is to preserve health and prevent disease,” she concluded. “The results of this study provide strong evidence that the opposite is happening for important aspects of women’s health, even if the absolute risk is low. Given these results, we recommend that clinicians stop prescribing this combination for long-term use.”

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