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| Making a Decision About Hormone Replacement Therapy |
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By Camille Mojica Rey, PhD
Reviewed by Miriam Komaromy, M
Last updated March 21, 2001
Doctors once believed that keeping aging women healthy was as easy as replacing the hormones they stopped producing after menopause. But new data are challenging that old assumption. What's confusing for both women and their doctors are the seemingly conflicting reports about which diseases hormone replacement therapy (HRT) increase or decrease a woman's risk of developing. Many researchers say that women would be wise to put off deciding whether or not to take hormones until the results from a clinical trial that's underway become available in a few short years.
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Presumed Benefits
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| Hormone replacement therapy (HRT) was thought to reduce a woman's risk of cardiovascular disease, osteoporosis, and symptoms of menopause. |
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The most dramatic biochemical changes a woman experiences at menopause is the drop in estrogen being produced by the ovaries. In the 1960s, doctors reasoned that by replacing estrogen they could reduce a woman's risk of post-menopausal diseases such as cardiovascular disease and osteoporosis (thinning of the bones). Once it became widely used, estrogen replacement therapy was also found to reduce symptoms of menopause, including vaginal dryness, hot flashes, and night sweats.
Since then, the hormone progestin was combined with estrogen and given to women to prevent uterine cancer. The combination of estrogen and progestin is what is called HRT today. More recently, however, doctors have also prescribed testosterone to increase sex drive and vaginal sensation in post-menopausal women.
Since HRT became widely used, observational studies in which researchers simply compare the health status of women who do versus those who do not take HRT have confirmed the idea that the drugs prevent osteoporosis and heart disease. Other studies have suggested that estrogen replacement may protect against the onset of Alzheimer's disease, urinary incontinence and infections, colon cancer, and diabetes.
Until recently, doctors believed that the relief of menopausal symptoms and prevention against other conditions such as heart disease and osteoporosis came with few risks to a woman's health. They viewed the few side effects — including bloating, nausea, breast tenderness, and vaginal bleeding — as acceptable given the presumed benefits. Slight increases in the risks of breast cancer and blood clots were deemed acceptable in light of the fact that heart disease accounts for 45 percent of deaths in post-menopausal women, while breast cancer causes only 4 percent of those deaths.
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Unexpected Results
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| The HERS trial challenged the idea that HRT protects the heart. |
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More recently, however, these expected benefits have been challenged by preliminary results from clinical trials. In 1998, the Heart & Estrogen-progestin Replacement Study (HERS) reported that after an average of 4.1 years, HRT actually increased the risk of death from heart disease in the first year, but that risk later declined. "When the study ended, there was no difference between the two groups," said Dr. Joel A. Simon, M.D., a researcher at the University of California, San Francisco. Research Simon published this year also showed that HRT did not significantly increase or decrease the risk of stroke in women receiving it.
To many doctors, these results were an unexpected and disturbing surprise. "The new evidence confuses rather than illuminates," said Dr. Andrea LaCroix of the Fred Hutchinson Cancer Research Center in Seattle. "The results meant physicians could no longer assume that HRT was safe for all women." We have to step back and acknowledge that we may have been wrong," LaCroix said.
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Sorting out Scientific Uncertainty
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In order to sort out the scientific uncertainty, LaCroix said, scientists must conduct controlled clinical trials such as those required by the U.S. Food and Drug Administration. In these types of trials, researchers take two similar groups of women and give one group HRT and the other group a placebo. Then they can compare the two groups of women after several years. However, until now most studies have looked back in time at women who chose whether or not to to take HRT. In these types of studies, it's difficult to interpret differences between groups of women at the end of the trial because researchers don't know if the women initially had the same disease risk. Even the HERS trial involved women who had preexisting heart disease — not a random sample — so it can't be used to determine how HRT affects healthy women. Because of these drawbacks, previous studies have reported conflicting evidence about how HRT affects a woman's risk of breast cancer or heart disease, which has added to the confusion about the risks and benefits of HRT. (For recent news from HRT studies, see Related News below.)
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| "It's really going to take the Women's Health Initiative to understand the risks,"
— Andrea LaCroix
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LaCroix and others say that a study that began in 1991 — called the Women's Health Initiative (WHI) — will give them the answers they desperately need. In this study, 27,000 women between the ages of 50 and 79 are either prescribed HRT or given a placebo. The 15-year, multi-million dollar study is being conducted by the National Institutes of Health and involves more than 40 research institutes around the country. The first results are expected by 2005. "It's really going to take the Women's Health Initiative to understand the risks," LaCroix said. Until then, she added, "We are on hold."
In the mean time, results from the HERS trial and other studies continue to be reported. These studies may not give the definitive answers LaCroix and others are waiting for, but they do point to the likely future assessment of HRT: good for some but not for others. For example, a recent study found that the risk of death from heart disease was not reduced for heavy women on HRT, but was reduced by 50 percent in thinner women. The authors of this study pointed out that the majority women in the HERS trial were overweight, which could be one reason why HRT did not protect those women's hearts. LaCroix and others expect that the WHI may reveal additional groups of women who respond differently to HRT. With this information in hand, doctors will be able to predict which women will respond well to HRT and which should avoid the drugs.
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Managing Menopause and Preventing Disease
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| Many doctors recommend that women try alternatives to HRT until results from the Women's Health Initiative are available. |
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Many doctors agree that studies being reported now should be re-evaluated in light of the WHI results expected in a few years. Until then, some doctors say women and their health care providers should consider alternatives to HRT for both treating menopause and preventing disease, particularly if these women are only considering HRT to reduce their risk of heart disease or osteoporosis.
First and foremost, doctors said, women should consider:
- Reducing their risk of cardiovascular disease by quitting smoking, losing weight if obese, and changing diet and exercise habits as recommended by their doctor.
- Treat high blood pressure and high cholesterol levels.
- Slow bone loss through activities such as walking and other weight-bearing exercise and by getting at least 1.2 grams of calcium per day.
These options don't address symptoms of menopause, which is why many women take the drugs. For these women there are additional options. "We have many more options to deal with the specific organs rather than treating the whole the body," said Dr. Susan Hendrix, D.O., a researcher and gynecologist at Wayne State University in Detroit, Michigan.
According to Hendrix and other experts, the drug alternatives to HRT include:
- Drugs such as Prozac and Zoloft — known as selective serotonin reuptake inhibitors, or SSRIs — can be used to treat night sweats and hot flashes.
- Topical estrogen delivered by vaginal suppositories or rings can relieve vaginal dryness, atrophy and incontinence without introducing large amounts of estrogen into the bloodstream.
- Vaginal lubricants, especially those containing Vitamin E, can relieve less severe dryness and make intercourse less painful.
- Selective estrogen receptor modulators (SERMS) like raloxifene and tamoxifen, have been shown to reduce a woman's risk of breast cancer and prevent osteoporosis. These compounds have the ability to act like estrogen in some tissues, but not in others.
- A class of drugs called aminobisphosphonates have also been shown to reduce the rate of bone loss.
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Making a Decision
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Hendrix said she encourages her patients to consider the alternatives to HRT. "It's a confusing time, but a woman's bones are not going to fall apart in a couple of years," she said. Women who come to their doctor already familiar with alternatives to HRT can help the decision process go more smoothly, she said.
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Before making decisions about HRT, women and their doctors should consider:
- Family history of disease
- Other risk factors for disease
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Hendrix and other experts worry that women unaware of the controversy may ask for the treatment and easily get it, said Dr. Elizabeth Barrett-Connor, M.D., a WHI researcher at the University of California, San Diego. A woman who requests HRT should not automatically be prescribed the regimen, Barrett-Connor said. "The doctor should ask them why they want to take it," she suggested. Physicians should consider alternatives to address the patient's concerns and consider family history, current health condition and other risk factors before prescribing hormones, she explained.
But even the most thorough and individualized consultation done today will not have the benefit of the kind of answers clinical trials can provide. For that reason, women considering HRT should consider holding off on that decision, Barrett-Connor said.
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Resources
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References
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Hully, S. et al. (1998). Randomized Trial of Estrogen Plus Progestin for Secondary Prevention of Coronary Heart Disease in Postmenopausal Women. JAMA, 280, 605-613.
Dr. Elizabeth Barrett-Connor, M.D. (personal communication). Director, Women's Health Initiative and Professor of Family and Preventative Medicine, University of California, San Diego.
Dr. Susan Hendrix, D.O. (personal communication). Director, Women's Health Initiative and Associate Professor of Gynecology, Wayne State University, Detroit, Michigan.
Dr. Andrea Z. LaCroix, Ph.D. (personal communication), Researcher, Women's Health Initiative and Professor of Epidemiology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Dr. Sander Shapiro, M.D. "Addressing Postmenopausal Estrogen Deficiency: A Position Paper of the American Council on Science and Health," (2001).
Dr. Joel Simon, M.D. (published statement from the American Heart Association). University of California, San Francisco and Veterans Affairs Medical Center.
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