The Hormone Dilemma
The latest flip-flop on hormone therapy gives new hope to younger women
After Janet Smith had a hysterectomy at the age of 48 in 2001, her doctor suggested she take hormones. "I'd already experienced some night sweats and hot flashes, and they're not a lot of fun," says Smith, who lives in Boulder, Colo. She did her own research but was baffled by the reams of conflicting studies. "The more I read, the more confused I got," says Smith, who decided to give hormone therapy a try. But just two years later, she quit. "There always seemed to be something scary in the news about it."
Smith had plenty of company in her hormone jitters. After the federal Women's Health Initiative halted one hormone study in 2002 and another in 2004 after concluding that the risks--including breast cancer and stroke--outweighed the possible heart benefits, women all over the country threw out their pills. Estrogen prescriptions dropped dramatically.
But now it seems some of those women may not have needed to give up their hormone regimens. Two new studies suggest that women like Smith who take hormones when they're relatively young and closer to menopause may actually be protected against heart disease--not at higher risk. "There's mounting evidence that age and time since menopause may make a difference," says JoAnn Manson, chief of preventive medicine at Harvard's Brigham and Women's Hospital and one of the authors of the two new papers as well as the original WHI studies. "These are important pieces of the puzzle."
Hormones started to look like a fountain of youth in the 1980s and 1990s, after several observational studies suggested a myriad of benefits, from preventing heart disease and osteoporosis to improving memory. "The perception that these hormones protect the heart was so strong that many doctors were prescribing it to prevent heart disease," says Manson. The assumption was that hormones were like vitamins, something you would take for the rest of your life.
Yet no large clinical trials supported the grand claims of hormone enthusiasts. So the WHI set out in 1992 to answer the question once and for all: Should hormones be prescribed for all older women to prevent heart disease?
The answer was--and remains--a resounding no.
The WHI studies looked at two types of hormone treatments. One trial randomly assigned 16,608 women to take estrogen plus progestin or a placebo. This combination is prescribed for women who have not had hysterectomies because estrogen alone increases the risk of cancer of the uterus. In the other trial, 10,739 women who had undergone hysterectomies were randomly assigned to take estrogen alone or a placebo.
Stunned. The results of the trials shocked the medical community. Not only did the studies find no benefit for heart disease, but the estrogen-plus-progestin trial also showed an increase in heart disease, as well as significant risks for breast cancer, stroke, and embolism. It also showed a decrease in colorectal cancer and hip fracture, but not enough to outweigh the risks. In 2002, the estrogen-plus-progestin trial was called off. Two years later, the WHI halted the other trial because of the increased risk for stroke with no benefits in stopping heart disease.
The studies changed medical practice for older women. Doctors stopped prescribing hormones for heart protection. But the pendulum may have swung too far the other way. "The response of the medical community was to say, 'No women should ever be on hormones,'which probably wasn't the most appropriate response," says Marcie Richardson, codirector of the Harvard Vanguard Menopause Consultation Service in Boston.
After the studies, doctors turned to shorter-term, lower doses of hormones, often administered by patch, not pills, for menopause symptoms. But the trials didn't look at hormones taken like this. And they didn't explain one very glaring contradiction: Why did some observational studies, including the renowned Nurses' Health Study of more than 120,000 women, show that hormones could reduce the risk of heart disease?
In February, WHI leaders put forth a possible answer in the Archives of Internal Medicine: Hormones may work differently depending on your age and how close you are to menopause. When the WHI authors looked at participants in the estrogen-alone trial by age, they found that women ages 50 to 59 saw a 34 percent reduction of heart attacks, heart bypass surgery, or angioplasty compared with the placebo group. But women 60 or older on estrogen alone didn't experience a heart benefit. As for women on estrogen plus progestin, although the researchers did not have enough data to issue a definitive analysis based on age, "we did see a suggestion of a similar trend with time since menopause, with increasing risk among women starting hormone therapy more than 10 years past menopause," says Manson.
Similarly, an article in the Journal of Women's Health in January took a closer look at the Nurses' Health Study findings. The study had suggested that hormone therapy could prevent heart disease and seemed to conflict with the WHI study--until researchers looked at the age and time since menopause. Those in the WHI trials were, on average, age 63, and many years past menopause, while the nurses were in their early 50s, the typical start of menopause in the United States. When researchers looked at the nurses who started estrogen within four years of menopause, they found these women were 34 percent less likely to suffer from heart disease; those who started estrogen plus progestin were 28 percent less likely. Women who started hormone therapy more than a decade after menopause did not have any heart benefit. "The takeaway is that if you start hormones around the time of menopause, if you take it when you start having hot flashes, it's probably good for your heart also," says Hugh Taylor, associate professor of reproductive endocrinology at Yale University and director of Yale's menopause program.
So what does all this mean for women nearing menopause? There's no cut-and-dried conclusion. But for women suffering serious symptoms of menopause, the risks and benefits of hormone therapy are well worth a closer look. "I see women suffering every day and afraid to take hormone therapy," says Taylor. "We've blown the risks out of proportion and forgotten a lot of the reason women started taking hormones."
Relief. The key benefit of hormones is the relief they bring to women going through menopause who suffer insomnia, vaginal dryness, or hot flashes, which typically last three to five years. "For those of us who haven't had a hot flash, it sounds like some nice, warm, fuzzy feeling," says Taylor. "But it can be much more devastating than it sounds." Most women going through menopause suffer from hot flashes, and about 10 percent suffer flashes severe enough to disrupt their lives.
There may also be side benefits of hormones. In addition to the possible heart protection, women taking hormones in the WHI studies suffered fewer hip fractures and less colorectal cancer. Meanwhile, another new study from the University of Illinois shows that hormones used for fewer than 10 years can improve your mental performance. However, hormones used for longer than 10 years can actually harm mental acumen. "With memory and cognitive issues, there may be a similar 'window of opportunity' related to age and time since menopause," says Manson, although she stresses that this theory remains unproved and requires further research.
And, of course, hormones help you look younger. While any woman who is taking hormones could attest to this, science now supports it, too. A 2005 article published in the journal Fertility and Sterility, coauthored by Taylor, showed that women on long-term hormone therapy had fewer wrinkles.
To say the least, whether or not to take hormones is a tough decision. The risk varies depending on how old you are, how close you are to menopause, and whether or not you're already at risk for cancer or heart disease. It also depends on the type of hormone and how you take it. "It's very important to go over the risks that we know about hormones with your doctor," says Margery Gass, professor of obstetrics and gynecology at the University of Cincinnati.
When assessing the risks, it's important to look behind the numbers. For example, in the WHI estrogen-alone trial, even though estrogen boosted the risk of stroke by 39 percent for all age groups, that translates into just 12 additional cases per year per 10,000 women. Younger women fared much better than older women. Women ages 50 to 59 taking hormones did not experience more strokes than those in the placebo group, while women ages 60 to 69 taking estrogen experienced 19 additional strokes a year per 10,000 women.
"Catch-22." The same trial also showed an overall 33 percent increase in venous thromboembolic disease (blood clots in the leg veins or heart), which translated into 7 additional cases a year per 10,000 women. But again, the risks were lower for younger women, as they experienced two extra blood clots per 10,000 women per year, compared with 12 extra cases among women in their 70s.
For women taking estrogen with progestin, the risks are a little different. The risk of breast cancer is 26 percent higher, or 8 additional cases per year per 10,000 women taking hormones. (The women on estrogen alone, however, did not show an increase in breast cancer.) The risk for stroke grew 41 percent (8 additional cases per 10,000 women), and the risk for embolism more than doubled (also 8 additional cases per 10,000).
Unfortunately, the new findings don't shed light on what is now the most common use of hormones--lower doses used for a few years around the time of menopause. "The Catch-22 of big studies like WHI is that you're always behind the eight ball," says Wulf Utian, executive director of the North American Menopause Society. "You set out to do the definitive study and use what is state of the art at that time. Then, several years later, you announce the results, but now everyone's using a different combination or dose."
The Kronos Longevity Research Institute in Phoenix is following 720 women to study the effects of lower-dose hormones administered by pill or by patch for shorter periods of time. But that study's results won't be available until 2010.
Despite the new information, some women, like Smith, still feel the risks just aren't worth it. Certainly, no one feels hormones should be used to prevent heart disease. For those women, specific heart medications, as well as diet and exercise, are far safer ways to prevent heart disease. For menopause symptoms, women may want to consider alternatives. A class of antidepressants, selective serotonin reuptake inhibitors, or SSRIs, can help some women with hot flashes and mood swings. Other women have found relief by turning to plant estrogens. "There's some data about increasing the plant estrogens in your diet by eating a lot of soy. It appears to work at least some of the time,"says Richardson. An American Indian herb called black cohosh also seems to ease menopause symptoms for some women. Of course, these alternatives may carry their own side effects, so women should be sure to consult their doctors.
In the end, hormone therapy still seems to be the most effective treatment for severe menopause symptoms. "For some women, I think hormones are worth the risk," says Richardson. "We just have to be honest with them about what we do know and don't know about those risks."For now, at least, it seems the more science knows about those risks, the more complicated the decision becomes.
This story appears in the March 6, 2006 print edition of U.S. News & World Report.