MARGARET WARNER: Federal researchers already knew that hormone replacement therapy relieves postmenopausal symptoms like hot flashes and night sweats. But they wanted to know if there were added health benefits to taking these hormones, as 6 million American women do. So about nine years ago they began enrolling volunteers in an NIH study called the Women's Health Initiative.
Ultimately, more than 16,000 postmenopausal women took part. Roughly half were given a combination of the hormones estrogen and progestin. Half were given placebos.
Today NIH halted the study, saying researchers found significant adverse effects, even in areas they didn't expect. Specifically, the women who had been on hormone therapy had a 22 percent higher incidence of heart disease, a 26 percent higher incidence of breast cancer, a 29 percent higher incidence of heart attacks, and a 41 percent higher incidence of strokes. To explain these findings we're joined by Dr. Marcia Stefanick, who led the study and is an associate professor of medicine at Stanford University.
Welcome, Dr. Stefanick.
DR. MARCIA STEFANICK: Thank you.
MARGARET WARNER: First of all, the human story here, you've had 16,000 women who've been doing this for years and years. Suddenly, what, today they all get letters saying stop, stop taking these drugs?
DR. MARCIA STEFANICK: They got their letters yesterday and today. Some of them may still be getting the letters. And what we're hearing is that they're generally very excited to be part of a historic finding like this. Certainly there will be some women who will be upset, but in general, these women have entered the study with the idea that they are getting answers for future generations, and they will all say, I'm doing this for my daughters, for my granddaughters. It's an amazing spirit these participants have.
MARGARET WARNER: But it is unusual, is it not, to stop a study in mid stream?
DR. MARCIA STEFANICK: It's very unusual. In fact, it was a surprise to the investigators primarily because of why it was stopped. We did not expect to see breast cancer increase at 5.2 years into the study. And then, in addition, we set out with the idea that we would be seeing a prevention of heart disease, when, in fact, we have higher heart attack rates, higher strokes, higher blood clots in the legs, in the lungs. So it was a surprise for everybody.
MARGARET WARNER: Now, if you're one of the 6 million women who are taking these and you see these risk percentages, that looks really scary. I mean, should every woman conclude that they're taking a dangerous drug or combination of drugs?
DR. MARCIA STEFANICK: No, actually, these are called relative risks. When you actually look at the absolute risk, which is, how many women does it really affect? To give you an example, for breast cancer, three women out of every 1,000 of the placebo group got breast cancer per year, and 3.8 women out of every 1,000 in the active estrogen plus progestin group, so 3.8 to 3 is the 26 percent, but it's actually very few women getting breast cancer and a fair number of them were in the placebo group.
MARGARET WARNER: But is the reason it's considered now so risky just when you extrapolate that out, if you think of the whole 6 million women?
DR. MARCIA STEFANICK: Yes. I think on a public health basis this is a very important finding from a population perspective. And even with respect to an individual, these risks are small but the reason that many women are on hormones is for prevention, and what we are very clear now is estrogen plus progestin is not an effective approach to prevent heart disease or other chronic diseases. There were benefits in the study.
MARGARET WARNER: Yes.
DR. MARCIA STEFANICK: In particular, this was the first trial to demonstrate that estrogen plus progestin actually reduces hip fractures and vertebral factures and other bone fractures. Up to this time we've relied pretty much on information from bone mineral density, which is intermediate marker. So this is a finding, but when I use those numbers of the 1,000, we're talking about a very - a much smaller percent of women were actually getting those benefits than were those getting the risk. And the other benefit we saw was colorectal cancer, that that was also significantly decreased. But, again, many fewer women got the benefits relative to the number that got these risks.
MARGARET WARNER: Now, how do you explain particularly the surprising finding about heart disease and stroke when other kinds of studies that we've been reading about over the years - many women thought, well, I might be slightly increasing my risk of breast cancer but I'm really protecting myself against heart attack, how could they be so wrong?
DR. MARCIA STEFANICK: Well, it was a very consistent observation and observational studies that women who are using estrogen, most of the data comes from estrogen only - I do want to make that distinction before we finish - women who were taking estrogen had less heart disease. However, we know that the estrogen users were by and large a healthier group of women, and so we have what we call the healthy user bias effect, and there are a number of other kinds of biases that have led to this, now we know, incorrect belief that estrogen would prevent heart disease or estrogen plus progestin.
MARGARET WARNER: So just so I understand, you mean in general the kinds of women who were taking this hormone therapy were also the kind of women who probably took better care of themselves, saw their doctor more often, exercised more, et cetera, et cetera.
DR. MARCIA STEFANICK: Kept their weight down. They were doing a number of other things, which we now would like to encourage women to recognize as a better approach to preventing heart disease. But I did want to make the distinction that the previous research was primarily based on estrogen alone. And estrogen plus progestin is quite different, and this study reveals it even more so. In fact, in the Women's Health Initiative we have an "estrogen only" study, which is continuing, because it may still be that the benefits outweigh the risks.
MARGARET WARNER: But isn't the estrogen only - aren't really only women who've had hysterectomies now taking that?
DR. MARCIA STEFANICK: Yes. In fact, medical - the medical community is quite clear that it's not a safe approach for a woman with a uterus to take estrogen alone. This increases your risk of cancer of the uterus.
MARGARET WARNER: All right. So let's talk about these women - the 6 million who are taking this, especially the ones who have menopausal symptoms. What are they supposed to do?
DR. MARCIA STEFANICK: Well, I think the important thing to recognize is that menopause, the menopausal symptoms are occurring in relatively young women in the sense that they're 45 to 55. Their absolute risk for these conditions - heart attacks, breast cancer - is low, and low enough that when you start to weigh the benefits of relieving serious menopausal symptoms against these clear risks, you can come to a point where you might think my menopausal symptoms are worth relieving with this hormone. However, what our research shows is that even in the first year these risks are apparent, and so…
MARGARET WARNER: For all of these different risks?
DR. MARCIA STEFANICK: Well, actually specifically heart attacks and blood clots were appearing in the very first year. Stroke didn't really appear until nearly two years. The breast cancer - there was really no difference or no increased risk until about four years it started to emerge, but it became very clear by five years, so it increased dramatically in the past year. And that was the main reason the study was stopped.
MARGARET WARNER: So you were saying what these women should do?
DR. MARCIA STEFANICK: I think they should have a serious discussion with their health care provider, and fortunately, we do have the information now available to the medical community, and discuss why they're taking the hormones, how severe are these symptoms that they have, and then take into account the risk and benefit. And every drug, every medication we take comes with some risk, and then it is a thoughtful decision that needs to be made. I think where we have such a different orientation out of the hormones is that the medical community was quite convinced that this was a good thing to do to prevent these diseases, and now what we can clearly say is that the risks outweigh the benefits, and that even for the benefits, we should consider alternative approaches.
MARGARET WARNER: Like?
DR. MARCIA STEFANICK: Well, for the hip fractures and for the colorectal cancer, at least we might consider calcium and vitamin D supplementation, which we are also studying in the Women's Health Initiative. And there are many medications as well, but we didn't study them, so we'll have to wait and look in other studies.
MARGARET WARNER: All right, Dr. Stefanick, thank you so much.
DR. MARCIA STEFANICK: Thank you.