The Biggest Questions About HRT Answered

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Almost no topic in modern medicine has been as controversial or confusing as hormone-replacement therapy. The issue got even more confusing last week thanks to a study published in The Journal of the American Medical Association and based on data collected for the ongoing federal Women's Health Initiative (WHI) that found that women taking estrogen and progesterin had an increased risk of breast cancer. As a result, most people have more questions than answers when it comes to HRT. "I've gotten more than 150 e-mails and calls from women as well as doctors" wanting more details, says coauthor JoAnn E. Manson, professor of women's health at Harvard Medical School and chief of preventive medicine at Brigham and Women's Hospital in Boston. Here, the answers to the questions Manson has gotten most often:

What about women who take estrogen only?

This particular study focused only on women who take a combination of estrogen and progestin or progesterone. It did not include any women who have had a hysterectomy and take estrogen alone (since they don't need progesterone to protect them from uterine cancer). Earlier findings from the WHI indicated that women who take estrogen alone saw their breast-cancer risk decrease over the first seven years of use, although they remained at higher risk of blood clots, stroke, and heart disease. (Women who take most types of combined HT are also at risk for those latter three conditions.)

Do these new results mean no menopausal woman should take combined HT?

Major health organizations' general advice about HT remains essentially the same: women who are experiencing moderate to severe hot flashes and night sweats that significantly disrupt their lives should consult with their doctor about how their medical history affects risks versus benefits in their case. For women with the most troublesome hot flashes, the benefits may still outweigh the risks, particularly if they have no family history of breast cancer. "I see women in my practice who haven't had a good night's sleep for months because of night sweats," says Manson. "There are definite adverse health effects to getting no sleep and being exhausted all the time, including an increased risk of accidents and injuries. Once patients understand the risks, they can make an informed decision as to whether they should be using these medications."

In this newest study, did all women taking combined HT experience the same doubling of risk?

The women who experienced the greatest increase in risk were those who had a previous history of taking hormone therapy and resumed taking it as part of the WHI study. "There was an 85 percent increase in breast cancer among the women who had used hormone therapy in the past," says Manson. This finding echoes results of other studies that a woman's risk of getting breast cancer increases the longer she takes combined HT. Manson says it is not yet clear whether risk increases even more for women who stop taking HT and then resume it, compared with those who never take a break.

Do we understand why the risks doubled?

The most plausible explanation for the increased risk is that combined HT leads to denser breasts, which make it harder to detect early signs of the disease, Manson says. "Estrogen taken alone [by women who have had hysterectomies] results in a very small increase in breast density," she says.

If I'm on combined HT now, should I quit immediately?

While the study found that women who took combined HT doubled their risk of dying of breast cancer, Manson says it's important to keep that percentage in perspective. "That means there were one to two extra deaths per 10,000 women per year among those using estrogen and a progestin," she says. "We don't want to minimize it, but it's also no reason to panic." For women who have severe symptoms that impair their quality of life and who are at low risk of breast cancer, hormone therapy may still have a favorable benefit-risk ratio, she says. But these results serve as a reminder that all women should regularly reevaluate the need to stay on hormones. To reduce the chance that your symptoms return when you stop taking hormones, work with your doctor to gradually dial down your dosage.

Long-term use is risky, but is it still considered safe to use HT only for a year or two, to get through the transition period?

Like earlier studies, this one shows that the first few years of combined hormone-therapy use do not increase the risk of breast cancer. "The risk does not increase until year four of treatment," Manson says. The problem is that once you start, it's sometimes difficult to get off these prescriptions. "We know that about half of the women who had previous hot flashes will have a recurrence when they try to come off hormones," she says. "But we don't know if they will be as severe or bothersome as they were when they began, or how much longer they will last. There's a strong need to answer those questions." And as this newest study makes clear, if you end up going back on HT, it's not as though your risk goes back to zero. "The cumulative risk of breast cancer that comes with HT use endures," Manson says. Once you stop for good, the risk of developing breast cancer will decline, she says, "but a small increased risk persists."

One more thing worth considering: since blood clot and stroke risks increase early with HT use, there has never really been a risk-free period to take the drugs, says Cindy Pearson of the National Women's Health Network. "You need to look at all the risks that HT increases when you're making decisions about short-term use," she says.

Are there safer alternatives to the Prempro prescription that was used in this study?

Researchers generally assume that the results of the WHI studies apply to all forms of combined HT in the absence of strong data proving otherwise. Prempro, which combines estrogen derived from horse urine with a synthetic progestin, remains popular with women who want a one-pill solution to hot flashes. However, many doctors now prescribe an FDA-approved micronized progesterone that more closely matches the natural hormone produced by women's bodies, based on early evidence that it "may not increase breast-cancer risk to the same extent as synthetic progestin," Manson says. More doctors are also combining micronized progesterone with non-oral forms of estrogen (patches, creams, gels, etc.) that allow the hormone to go straight into a woman's bloodstream, reducing the risk of blood clots. Research on the comparative safety of these alternatives is ongoing. There is no evidence that so-called natural, unregulated bioidentical hormones mixed in compound pharmacies are safer.

Will a lower dose of hormones further reduce risk?

Since the first WHI results came out in 2002, doctors have been prescribing smaller doses of hormones than those used in the original studies, with the hope that they will reduce the downsides. But Manson says there's no proof yet that dosage affects risk. "We don't know if any of these other forms or routes of delivery will be safer," she says. "We have to be cautious. We need more research about how risk is affected by lower doses and different delivery systems."

Are the risks lower for women who take HT in their 40s and 50s?

Age may make a difference, but there's no proof of it yet. The WHI was originally designed to determine whether HT could protect older women against heart disease (once a common practice), so the average age of participants enrolled in the study was 63. (The average age of menopause is 51.) Some researchers think that the overall risks of taking HT may be lower for women who start HT right after menopause, and studies are now underway to determine whether that is true.

Is there any good news here?

Yes, there is, says Pearson. Since the WHI started releasing results in the early 2000s linking HT with an increased risk of heart disease and breast cancer, a lot of women have quit taking hormones before they were put at higher risk. "There were some women who were destined to die who will live because they started heeding those results eight years ago," Pearson says. "Two thirds of the women who used to take HT are now off of it, and we should all feel good about that."