Hormone Replacement Therapy Controversy
It was a flashpoint in the long, hot debate about how to treat menopause symptoms. Last week, the U.S. National Institutes of Health revealed that a panel of physician monitors had called a halt to a major clinical trial of hormone replacement therapy, because the specific treatment being used was causing "more harm than good." The discontinued study was just one component of the Women's Health Initiative, an ambitious eight-year investigation of the effects of diet, exercise and other lifestyle factors on the well-being of 161,800 menopausal women. It weighed the usefulness of a combination of estrogen and progestin in preventing heart disease. The results: far from offering protection, the treatment may even cause a slight increase in heart attacks, strokes and blood clots. The 8,000 women in the HRT trial also showed a slightly higher incidence of breast cancer compared to the control group. But there was the positive side, as well: the women taking part had slightly fewer hip fractures and colorectal cancer.
The news shocked and confused millions of North American women now taking HRT. The drug in question, Prempro, is the most commonly used form of HRT in the United States. In Canada, the product is available in a different form, as two pills, packaged as Premplus, but most women use other hormone formulations (there are about 20) or take estrogen or progestin from patches, gels, creams and injections. Practitioners quickly responded that the U.S. announcement underplayed the benefits of the hormones that at least 25 per cent of menopausal Canadian women use to relieve their hot flashes, mood swings, sleeplessness and other often debilitating symptoms.
What should women do? Senior Writer Sharon Doyle Driedger talked with four medical experts about the implications of the study: University of British Columbia endocrinologist Dr. Jerilynn Prior; gynecologists Dr. Jennifer Blake of Toronto, Dr. Donna Fedorkow of Hamilton and Dr. Elaine Jolly, head of the menopause clinic at the Ottawa Hospital.
So now what do you say to women who might take HRT?
Jolly: This study tells a patient she's got to know why she's on hormones. She has to look at her own personal risk/benefit ratio with her physician and see what her personal ideals are. No woman should stop hormones because of this without seeking attention from her physician. If women stop hormones abruptly we'll have a nation full of women having horrible hot flashes, night sweats, insomnia, irritability and mood swings.
Fedorkow: Certainly, people at high risk or with a history of cardiac disease may want to discuss hormone replacement therapy more fully with their physicians. But there's got to be a lot more interpretation of the data before we can make adequate recommendations.
Prior: Women should not stop therapy if they're on it for a good reason. If they're on it for an unjustifiable reason, then - and this is a very important point - they should come off their estrogen therapy extremely slowly. The brain gets used to high estrogen levels and it reacts just like an addict's brain reacts when their drug of choice is withdrawn. You need to sort of de-condition the brain.
Who should take HRT?
Blake: It's the most effective thing we have for menopausal symptoms and there's no evidence of harm in the short term for that indication. Some women really need to take it. It's the kind of risk you can choose to take.
Prior: There are justifiable, legitimate reasons for therapy with estrogen and progestin. One is, if menopause is too early, which is classically before the age of 40. The second is if a woman is having night sweats that are chronically disturbing her sleep. And thirdly - and this is what the Women's Health Initiative showed - it's a good therapy for a woman who already has low bone density at the time of menopause. But prevention of heart disease or Alzheimer's - or to keep women young and sexy - are not good reasons.
Jolly: If women are taking hormones for quality of life, they need to try to take them for the shortest period of time. I'm not talking two months, but until now we've considered therapy of up to five years to be short-term, longer than five years long-term. We may have to bring it down to three or four years. I'm also going to suggest that all my patients have annual mammograms instead of every two years.
Would you take HRT yourself?
Jolly: I do.
Fedorkow: Absolutely. Would I recommend to my mother that she stop? Not at all.
How do you allay women's fears?
Fedorkow: The treatment group did not have a higher mortality rate, so whatever's going on is not a sufficiently adverse outcome to cause somebody to die. I am not dismissive of their fears; certainly this study raises some important points. But unless someone has ongoing or active heart disease, do we have compelling evidence to change things immediately? No, we don't.
What does this study tell us?
Blake: The message is don't use Premplus to help prevent heart disease. The study was asking a very specific question: Does hormone replacement therapy prevent heart disease? The answer, which is no, confirms what we'd already suspected, and if that's the only reason to be taking hormone replacement then there isn't any evidence to support doing that.
Jolly: They only looked at one specific drug regimen - what they call Prempro in the United States and Premplus in Canada. It's one pill there and it's two pills in Canada but it is the same medication, made by the same pharmaceutical company. Are the risks the same with the many different formulations? Does this apply to lower doses of other formulations and the same formulations? To all the estrogens, progestins and their various combinations?
Why did the panel pull the plug?
Blake: They stopped it because they had enough data to answer their question: Is it going to prevent heart disease in healthy women? The answer was no and, in fact, they were seeing some evidence of early harm. They were not saying, Stop hormone replacement therapy. The parts of the study that are looking at plain estrogen are carrying on.
See also WOMEN AND HEALTH.
Maclean's July 22, 2002