Hormone Replacement Therapy: What Now?

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Feb. 9, 2000 -- Sixteen years ago, Kathryn Shea's body suddenly went haywire. At night, the San Francisco schoolteacher found herself tossing and turning. Once she finally fell asleep, she'd wake often, clammy with sweat. Her fitful nights left her foggy-headed and headachy in the morning. Worst of all were the moments when she'd be standing talking with someone and, in an instant, her face would turn unbearably hot and she'd break out in a sweat.

Though Shea was only 40, it turned out that she was going through menopause, suffering the vexing symptoms that befall many women as their bodies' production of female hormones slows and finally stops. Once she and her doctor realized what was happening, they tried several therapies, with mixed success. "I experimented with everything I could experiment with," Shea says.

Finally, Shea's doctor put her on a mix of the hormones estrogen and progestin (a form of progesterone). At last, Shea slept soundly at night and sailed through her days undisturbed by hot flashes. Though she started the regimen to quell her menopausal symptoms, she's still taking it today because of its bone-strengthening and heart-protecting effects.

Shea is among an estimated 16 million women taking hormone replacement therapy (HRT), according to the North America Menopause Society. The estrogen/progestin mix that brought relief to Shea has grown increasingly popular; taking estrogen alone raises a woman's risk of uterine cancer, but adding progestin greatly reduces this untoward effect.


A Precarious Position

Unfortunately, a new study published last week in the January 26 issue of the Journal of the American Medical Association has found that estrogen/progestin therapy comes with a price of its own: It increases the risk of breast cancer. Following more than 46,000 women over 15 years, National Cancer Institute researchers found that women who took the hormone combination were 20% more likely to develop breast cancer than women on estrogen therapy alone, and 40% more likely than women taking no hormones at all. The longer a woman took hormones, the greater the chance of breast cancer. While this study is not the first to find that the combination therapy increases breast cancer risk, it's by far the largest. And experts are taking the results very seriously.

So what's a woman to do? Is it time to toss progestin altogether?

That would be unreasonable, said Meir Stampfer, MD, professor of epidemiology and nutrition at the Harvard School of Public Health, and co-author of an editorial accompanying the study. He points out that progestin was added to the mix for very good reasons; without it, breast cancer risk would lessen, but the risk of uterine cancer would rise.

A Very Personal Decision

Instead, experts say, the new finding makes it more crucial than ever for women to look closely at their own family history, lifestyle, risk of particular diseases -- and deepest fears -- when making the hormone decision. Depending on how those factors stack up, women might come to very different decisions about hormone therapy -- all of them acceptable.

If a woman's primary goal is to relieve menopausal symptoms, for instance, researchers say she shouldn't feel concerned about taking the combo for a few years. "I feel very comfortable saying that fear of breast cancer should not discourage women from using drugs in the short term if they have severe menopausal symptoms," said Catherine Schairer, PhD, an epidemiologist at the National Cancer Institute and lead author of the study. "Any increase in risk would be slight."

Long-term use, though, is more problematic. If a woman's main concern is to stave off heart disease or osteoporosis, she may be able to get most of the benefits while minimizing risk by delaying the start of HRT until close to age 60, when the likelihood of those ailments climbs more steeply, says Laura Esserman, MD, director of the University of California, San Francisco/Mount Zion Breast Care Center.


Medical factors alone, though, often aren't enough to clinch a woman's decision. It's frequently emotional issues that will determine whether she takes hormone therapy, and in what form.

"A woman has to decide what she's most scared of and how she feels," said John Robbins, MD, of the University of California, Davis, and a principal investigator of the Women's Health Initiative, a 15-year study of women's health.

That's a process that Joanne Watson, 58, understands only too well. Watson, a counselor in San Francisco, has been taking estrogen ever since she had a hysterectomy at the age of 35. One of her biggest fears is developing Alzheimer's, particularly since her mother, grandmother, and aunt died from the disease. The evidence that estrogen can protect against Alzheimer's is still inconclusive, but because of her personal experience with the debilitating illness, Watson continues to take estrogen. "I'd stay on Premarin (estrogen) until I drop dead if it can keep me from getting Alzheimer's," she said.

Modifying the Dose

Physicians recognize that a woman's decision to take or forgo HRT is extremely personal. What is needed, they say, are more studies on how to make hormones safer for women who choose to take them.

One likely outcome of last week's study, experts say, is that it will spur researchers to examine whether prescribing lower doses of progestin can whittle down the likelihood of breast cancer. Already, some physicians are experimenting with giving the hormone only every few months, hoping that the dosage will preserve benefits while reducing risk. Others, including Malcolm Pike, MD, chair of preventive medicine at the University of Southern California School of Medicine, suggest that since the aim of including progestin is to protect the uterus, placing a dose in the vagina might eventually be shown to be more effective, while generating fewer side effects, than taking a pill.

The results from this latest study provide evidence that is "plenty strong enough for us to make changes," said Laura Esserman, MD, director of the University of California, San Francisco/Mount Zion Breast Care Center. "The trend is so strong; it keeps coming up in study after study, so we have to take this seriously."


Making the Effort

The downside of pill taking should encourage women to try making lifestyle changes that can bring similar results without the risks, Esserman and other researchers say. Eating a low-fat diet that includes plenty of calcium and fruits and vegetables, and getting regular exercise, can reduce the risk of heart disease and improve bone health.

"Right now there's no pill that's better than making real lifestyle changes," said Susan Love, MD, during a live WebMD audiocast on January 25. Love is the medical director of the Santa Barbara Breast Cancer Institute and the author of two books on breast cancer and hormones. "But doctors don't push lifestyle changes as much as they push pills."

As for Shea, she's not planning to stop the therapy that has served her so well. She and her doctor have thoroughly explored her family history and other risk factors, and she's confident that the decision they reached several years ago is still the right one for her.

"I rely 100% on the advice and intelligence of my doctor," Shea says. "It's working for me."

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