What you can’t say is whether, given this clash of benefits and risks, hormone replacement is right for any individual woman. Nor will scientists and physicians be able to make that call even after the proverbial “more research” comes in: ongoing studies will tell us more about the risks and benefits of hormone replacement in postmenopausal women in general, but even the best study cannot answer whether any particular woman will be more helped or harmed by it. The decision to try HRT will, in the end, turn on each woman’s personal risk factors, her tolerance for the changes that menopause brings–and her fears. “People are looking for the simple answer, the one-size-fits-all solution,” says Wulf Utian, executive director of the North American Menopause Society. “I’ve got bad news: it doesn’t exist.”
By the year 2000, there will be about 50 million women in America over 50,many of them candidates for hormone-replacement therapy. In the United States, about 46 percent of menopausal women try HRT; in Japan, 6 percent do. What does exist is a growing body of knowledge about the effects of estrogen on cells from the brain to the bones to the skin. “Estrogen” should actually be “estrogens”: more than 200 members of this family of hormones have been found in humans, animals and even plants. There are three common human estrogens, called estradiol, estrone and estriol. Estradiol, the most potent, is created mostly in the ovaries and circulates in the bloodstream. For years it was believed to work primarily in sexual and reproductive tasks, but recent studies have shown that cells throughout the body have estrogen “receptors,” which act like biochemical locks for which estrogen is a key. These receptors have been found in the brain, in the bones and throughout the cardiovascular system. By docking with these receptors, the estrogen that a woman produces “unlocks” cell growth that had been dormant. No wonder that the plunge in estrogen after menopause–levels in the blood can fall 90 percent from their lifetime high–may produce a suite of symptoms, including brittle bones, thinning skin, diminished circulation and vaginal dryness.
Enter estrogen replacement. (Or, more accurately, hormone replacement. Many prescription estrogen replacements include progesterone, which eliminates the risk of estrogen-related uterine cancer.) Estrogen’s chief undisputed benefit is that it prevents osteoporosis. Bones are in a constant state of flux. Older parts are nibbled away so that newer, stronger bone can be built up. Without estrogen the bones forget how to rebuild. Doctors don’t know for sure how the mechanism works, but they think that estrogen signals where older bone has been purged and is ready to form new bone. Women who do not replace their estrogen can lose 3 to 4 percent of their bone mass every year for the first five years after menopause. But numerous studies have shown that when a woman goes on estrogen replacement, the bone will actually increase its mass by 3 percent in the first year or so, then practically maintain that heft indefinitely as long as she keeps taking hormones. Postmenopausal women who take estrogen have approximately 50 percent fewer hip fractures and 75 percent fewer spinal fractures. The rebuilding process can begin within weeks. The only downside may be waiting to start: estrogen can work only with what bone exists. Bone that has already lost 15 percent of its mass can never be completely restored.
Estrogen also seems to curb cardiovascular disease, by far the leading killer of American women (30 percent will eventually die from it, as compared with 3 percent from breast cancer). Estrogen appears to handcuff cholesterol, the gunky substance that blocks arteries and is a chief cause of heart attacks. A 1995 study of 875 healthy women ages 45 to 64 found that estrogen both raises the level of HDL (“good” cholesterol) and lowers LDL (“bad” cholesterol). Incidence of heart disease decreases approximately 50 percent for women who take estrogen. One caveat: in women who have heart disease, HRT is associated with a 50 percent increase in the number of heart attacks and heart-related deaths in the first year of taking the hormones, though after four years the risk disappears.
Estrogen might even combat age-related memory loss. Several studies have found that postmenopausal women taking estrogen performed better on some memory tests than women who were not. The differences in memory were small, less than 10 percent, but consistent. Others have also reported that estrogen therapy may help prevent or slow the progress of Alzheimer’s. Larger Alzheimer’s studies are now underway. The completed studies aren’t definitive, but almost every report has found some relationship between estrogen therapy and memory. At the same time, biologists have identified estrogen receptors in brain cells that are important for memory. And estrogen may halt the brain’s production of the toxic beta amyloid protein associated with Alzheimer’s.
Balanced against these benefits of estrogen replacement is an 800-pound gorilla: breast cancer. Scientists don’t know for sure if the hormone causes breast cancer or not. The most compelling evidence that it does comes from a 1997 study of 40,000 registered nurses. In those postmenopausal women who had taken estrogen for five years, the prevalence of breast cancer was 40 percent higher than in nonusers. Most doctors don’t think that means estrogen actually causes breast cancer, but it may accelerate the growth of existing cancers. But the take-home message of that study isn’t clear. A 1996 study by the American Cancer Society found that women who had taken estrogen even for more than a decade were 15 percent less likely to die of breast cancer than women who took no hormones at all. One of the researchers’ hypotheses is that while estrogen may stimulate breast cancers, the type of cancer it promotes is actually less aggressive than breast cancers in women who never used estrogen. In other words, you might get breast cancer on HRT, but you’re less likely to die of it.
If a woman opts for hormone-replacement therapy, she faces more choices: what kind? The widely prescribed Premarin, which is derived from the urine of pregnant mares, contains dozens of estrogens; it’s the form used in the studies showing both benefits and risks from HRT. The most common human estrogen, called 17-beta estradiol, is the only one that has been synthesized in a form potent enough for estrogen-replacement therapy. It’s available as Estratab, Estraderm or Estring skin patches, vaginal creams and a ring inserted like a diaphragm. All the patches and creams seem to be effective against osteoporosis. But pills like Premarin and Estratab appear to be the most effective against heart disease because, like everything we swallow, they are processed by the liver, where cholesterol levels are adjusted. With skin patches and creams, estrogen is absorbed directly into the bloodstream, bypassing the liver and the potential heart benefits. We know the least about plant estrogens, or phytoestrogens. Estrace and Ogen are prescription pills containing estrogens from yams, and they seem to be as effective against hot flashes as Premarin or any other prescription form of estrogen. But over-the-counter sources of phytoestrogens, such as soy powders or herbs like red clover or black cohosh, are largely unregulated, so no one knows how much estrogen (if any) they contain.
There are also high hopes for drugs called SERMs: selective estrogen receptor modulators. SERMs turn on the estrogen receptors in the bones, and probably the heart and brain as well. Most important, in the breast and uterus they work like fake keys that jam the locks and prevent cells from reproducing–and overreproducing, a key source of cancer. One SERM, raloxifene, is already approved for osteoporosis (though it does not ease menopause symptoms like hot flashes). Still, “the most common reason women will not take hormone-replacement therapy is fear of breast cancer,” says Dr. Steven Goldstein, coauthor of “The Estrogen Alternative.” “For them, SERMs are a whole new ball game.”
But until the perfect SERM comes along, women must weigh the pros and cons of estrogen. Although women have many options for reducing their risk of heart disease (don’t smoke, do exercise, eat right), we know little about preventing breast cancer. In other words, women can take steps to stay heart-healthy without HRT, but not to stay breast-healthy with HRT.
Doctors have long said that, as a general rule, women with a high incidence of breast cancer in their families have more reason to be concerned about taking estrogen, while for women whose parents died of heart disease the benefits might outweigh the risks. But what about women whose family history is riddled with both? To help sort out the pros and cons, Dr. Nananda Col of New England Medical Center has developed a questionnaire that asks a woman her health status and history and assigns weights to each answer. Software tallies the responses, and predicts how HRT will affect her life expectancy.
Some doctors are suggesting a now-and-later approach. Try hormone replacement just as you go through menopause if you are made miserable by hot flashes, insomnia, moodiness or forgetfulness. Then, especially if you have low risk factors for osteoporosis and heart disease, stop for a decade or so. When you’re 60, reconsider HRT for its bone, heart and anti-Alzheimer’s benefits. At that age, any nascent breast cancer will likely take so long to grow into anything dangerous that it’s not a big risk. Even Dr. Susan Love, a breast-cancer surgeon and one of the most outspoken critics of estrogen therapy, says that she’s not entirely opposed. “If you’ve seen your mother die of a heart attack at 55, that fear may drive you [to take HRT],” she says. “And that’s maybe not so bad.” Even better will be the day when estrogen is no longer such a frightening word.
To HRT or Not to HRT?Here is a sample from a computer program that weights answers to 39 questions and determines whether a woman is more likely to be helped or harmed by HRT. Many yeses suggest you’ll derive more benefit; nos suggest thinking twice.
Have you and close blood relatives been free of breast cancer?
Have you had children, and were you younger than 30 when you had your first child?
Have you or close relatives suffered bone fractures, height loss or heart disease?
Are you physically inactive, a smoker or a less-than-healthy eater?
Are you often bothered by menopausal symptoms?
YES NO SOURCE: BASED ON “A WOMAN DOCTOR’S GUIDE TO HORMONE THERAPY,” BY DR. NANANDA COL
