Prescribing Hormone Replacement: What Now?

From OncoLog, April/May 2007, Vol. 52, No. 4/5

Prescribing Hormone Replacement: What Now?

by Dianne C. Witter

Rena Sellin, M.D., sums the issue up neatly, in five short words: “Nothing is good for everybody.”

With this statement, Dr. Sellin, a professor in the Department of Endocrine Neoplasia and Hormonal Disorders at M. D. Anderson, encapsulates the ever-changing lessons—and the subsequent questions—generated during several decades of research into the issue of hormone replacement therapy (HRT) for post-menopausal women. Are there cardiovascular benefits? Does it cause breast cancer? Can it improve cognitive function? How long should women take it—or should it be prescribed at all?

A recent study by M. D. Anderson spurred the ongoing debate into high gear, generating hundreds of articles in both lay and medical media and leaving both doctors and patients wondering—again—about the best course of action. The study highlighted a sharp decline in breast cancer incidence in 2003, suggesting the decline may be due to the fact that millions of older women stopped using HRT in 2002. Prescriptions for HRT nosedived that year, after an ongoing study by the Women’s Health Initiative found that the combination of estrogen and progestin significantly increased a woman’s risk of developing invasive breast cancer.

What happened next makes for even more compelling statistics: between 2002 and 2003, there was a 7% overall decline in breast cancer incidence—in marked contrast to the steady increase in incidence over the previous 20 years. More to the point, the steepest decline was seen in the diagnosis of estrogen receptor- positive breast cancer, which is dependent on hormones for growth, in women ages 50–69 years.

“To my knowledge, this represents the largest single drop in breast cancer incidence within a single year,” said Peter Ravdin, M.D., Ph.D., a professor in the Department of Biostatistics at M. D. Anderson and an investigator on the M. D. Anderson study. “Something went right in 2003, and it appears to be the decrease in the use of hormone therapy; but the analysis was based on population statistics. From these data, we can only indirectly infer that is the case.

“However, if the drop in incidence is due to the drop in HRT, it means that stopping the use of hormones had a dramatic effect on tumor growth over a short period of time—making the difference between whether a tumor was detected on a mammogram in one year’s time.”

A tricky intersection

This is one of the points at which drawing definitive conclusions becomes tricky, however. As Dr. Sellin points out, “It’s too soon to conclude that the incidence of breast cancer has been permanently affected—breast cancer develops over a long period of time. It’s possible that stopping the use of HRT slowed the growth of tumors (and therefore the number that could be detected in a year’s time) but didn’t change the number of breast cancers that will ultimately be diagnosed.”

Donald Berry, Ph.D., senior investigator on the M. D. Anderson study and professor and head of the Division of Quantitative Sciences, agrees that it’s important to be cautious when making inferences. “Here, we are primarily talking about existing cancers that are fueled by hormones and that slow or stop their growth when a source of fuel is cut,” he said. “These cancers are then more likely to make it under mammography’s radar.

“Epidemiology can never prove causation,” Dr. Berry noted. However, he and his colleagues looked at other factors that could be responsible for the decreased number of breast cancers diagnosed, such as decreased use of screening mammography or changes in the use of medications like antiinflammatory agents, selective estrogen receptor modulators, or statins. “Of these factors, only the potential impact of hormone replacement therapy was strong enough to explain the effect.”

Dr. Sellin notes that the current findings are part of a pendulum swing away from HRT that started about 5 years ago. For a number of years, women were automatically prescribed HRT during and after menopause, because studies had suggested it conferred a cardiovascular benefit as well. But in 2002, when the Women’s Health Initiative study found a substantial increase in breast cancer incidence in women taking HRT—and no decrease in heart disease—the pendulum began swinging back the other way. Many women decided to forego HRT and soldier through the side effects of menopause without it.

But other factors likely also influenced the statistics, and most researchers agree that the final answers are not in yet. Some feel the drop in incidence was too fast to fully explain causation for a disease that develops as slowly as breast cancer. In addition, said Dr. Sellin, “Incidence is dependent in part on detection practices. If fewer women are getting mammograms, fewer cancers will be detected.

“An important note from the Women’s Health Initiative that many overlooked was the fact that estrogen alone did not raise the incidence of breast cancer in the study—it was the combination of estrogen and progestin,” she said. “So we need to ask how many women stopped taking which kinds of estrogen before the incidence dipped.”

Finding middle ground

The real question, of course, is whether or not doctors should change the way they prescribe hormones for post-menopausal women based on this information—and what kind of counsel to give patients who are concerned about media reports they’ve heard.

In all likelihood, the answer is not to be found at either extreme, said Dr. Sellin. The answer, as it usually is in medicine, is that physicians should weigh the risks and benefits in each patient’s situation, taking into account the woman’s risk of breast cancer, the severity of her menopausal symptoms, and other factors. While the statistics are certainly of concern, Dr. Sellin notes that on an individual level, the risk of developing breast cancer is still quite small.

Current medical recommendations for HRT include prescribing a relatively low dose for a relatively short duration. “Hormone therapy should be now used specifically to address the symptoms of menopause rather than for any potential cardiovascular or cognitive benefits,” said Dr. Sellin.

Rather than putting a patient on HRT indefinitely, as was once the norm, physicians should now look at a more limited time frame, and then try to titrate the dose downward. How long is again dependent on the individual, but many physicians are finding that 6–12 months works well. “But some women will need to be on it for much longer,” Dr. Sellin cautioned.

Perhaps most important, physicians should develop a game plan in conjunction with their patients and explain the reasons for the recommendations. “There’s no point in writing a prescription that a patient’s going to carry around in her pocket for weeks, trying to decide whether or not to fill it,” said Dr. Sellin. “Ask about any doubts or concerns she has during her appointment, so you can be the one to address them rather than the media.”

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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