Toronto Globe and Mail
By PAUL TAYLOR
Saturday, April 24, 2004
Researchers found signs of trouble decades ago, writes PAUL TAYLOR. So why did doctors continue recommending hormone-replacement therapy for menopausal women?
When Sandy Bohl began to experience the hot flashes of menopause 10 years ago, she was advised to undergo hormone-replacement therapy.
“My doctor said to me, ‘You absolutely have to go on it or your skin is going to dry up, your vagina will dry up . . . you’ll get osteoporosis and heart disease,’ ” recalled Ms. Bohl, a Toronto actress and model.
Ms. Bohl had heard that HRT — a medication consisting of either estrogen or a combination of estrogen and progestin, a synthetic form of progesterone — could relieve common menopause symptoms and possibly ward off a number of other health problems as well. But she was concerned that it could also increase her chances of getting breast cancer.
Her doctor assured her that the risk was extremely small because she had no family history of the disease. So, like millions of other women, she embraced the therapy, which seemed almost an elixir of youth. It turned out to be extremely effective at cooling her hot flashes as well.
Since then, of course medical researchers have raised a series of troubling questions about HRT. In March, a major U.S. study of 11,000 women taking the hormone estrogen was halted after it was discovered that it increases the risk of suffering a stroke.
The study was part of an investigation known as the Women’s Health Initiative, which two years ago delivered an even bigger blow to HRT. An examination of women taking the most common therapy — the estrogen/progestin combination — found that it increased the chances of invasive breast cancer, heart disease, strokes and blood clots.
Women like Ms. Bohl now feel deceived: “I felt I had not been given enough information — I had been cheated of information.”
The Society of Obstetricians and Gynecologists of Canada, once a leading proponent of HRT, supported the treatment based on “the best evidence that we had at that date in time,” associate executive vice-president Vyta Senikas says.
But critics say evidence of the negative effects of HRT was there all along — for those who chose to look for it. How could the medical community have been so wrong?
“I think you have to go to a basic fundamental societal concept — this [therapy] fit with the idea that woman were deficient, not quite good enough and needed some fixing,” said Jerilynn Prior, professor of endocrinology at the University of British Columbia in Vancouver.
What’s more, pharmaceutical companies stood to profit by marketing hormones as a treatment for female deficiencies.
Both these factors came together with a publication in the late 1960s of the best-selling Feminine Forever in which U.S. physician Robert Wilson argued that menopause is both “unnecessary and harmful” and that many of the health problems that accompany this change of life could be prevented if women took supplements of the female sex hormone estrogen to augment their own dwindling production.
The New York Times revealed that a pharmaceutical company had paid Dr. Wilson’s expenses for writing the book. Even so, his ideas resonated with a lot of doctors and patients.
After all, women tended to develop heart disease a decade later than men. But once they reached menopause — when ovulation stops and the production of some hormones declines — their risks for heart attacks, osteoporosis and Alzheimer’s disease started to climb.
Initial research seemed to bolster the notion that taking hormones had protective effects, and the practice spread. However, there were early signs of trouble. In 1975, two studies published in the New England Journal of Medicine found that women taking estrogen were at increased risk of endometrial cancer — a cancer of the uterus lining.
The pharmaceutical companies found a way around this problem by giving estrogen in combination with progestin, which provokes monthly menstruation, preventing a build-up of tissue that might be harbouring cancerous cells.
HRT was back on track, propelled by new studies suggesting it could help prevent various diseases.
Persuasive evidence seemed to come from the Nurses’ Health Study, a major initiative launched in 1976 involving more than 120,000 U.S. nurses who were free to make their own health choices — researchers simply observed what happened to them. Initial results indicated that the women who took HRT had a 40 per cent lower chance of developing heart disease. They also had more breast cancers, but this risk seemed small, and by the early 1990s, Wyeth, a leading manufacturer, had asked the U.S. Food and Drug Administration for permission to bill hormone therapy as a prevention for heart disease.
The FDA wanted more substantial proof, so Wyeth launched HERS (the Heart and Estrogen/Progestin Replacement Study), which compared the health of women given hormone therapy with that of women given a placebo. The results came as a surprise: In the first year of the study, women on the therapy were found to be at 50 per cent greater risk of suffering from a heart attack.
HRT proponents played down the negative aspects of HERS, emphasizing that the results appeared to improve with time. Others, however, began to re-examine the older, positive studies.
Many were found to be flawed, said Donna Stewart, a professor and chairwoman of women’s health at the University Health Network and the University of Toronto.
Dr. Stewart noted that in the Nurses’ Health Study the women who chose to take hormone therapy also tended to exercise regularly, take better care of themselves and refrain from smoking — all factors that could reduce the chances of getting heart disease. “But their better outcomes [in terms of heart health] were all attributed to the hormones,” she noted.
Other trials that cast doubts on the merits of HRT had been overlooked or simply ignored. For example, a study conducted in the early 1970s had shown that taking estrogen didn’t reduce the chance of heart disease for men, said Ruth Wilson, a professor of family medicine at Queen’s University in Kingston, Ont. A follow-up with women should have been done right away, she said, but instead didn’t happen for many years. Dr. Prior, director of the centre for menstrual cycle and ovulation research at UBC, said she has been trying to raise a warning flag about HRT for years, sometimes writing letters to medical journals to point out what she considered to be the failing of various HRT studies. Her actions were often met with disapproval from medical colleagues.
Then, in July, 2002, the Women’s Health Initiative findings were released. They showed that women on HRT had more cases of heart disease, strokes, invasive breast cancer and blood clots. They also had fewer cases of colorectal cancer and hip fractures, but researchers concluded the risks far outweighed the benefits. For example, there would be an additional seven cases of coronary heart disease each year (37 versus 30 for the placebo) for every 10,000 women on HRT.
The numbers may appear low, but Heath Canada called them “highly significant,” adding: “Given that millions of women are taking combined HRT, the number affected over many years is an important public health issue.”
In the wake of the bombshell study financed by the U.S. National Institutes of Health, women have abandoned HRT in droves. According to Statistics Canada, more than 1.2 million Canadian women were taking HRT before the release of the study. IMS Health Canada, which tracks sales of prescription drugs, found that the value of HRT prescriptions in Canada dipped to $175-million last year from $238-million in 2001.
Because their menopausal symptoms came back with a vengeance, some women have resumed the therapy . Elaine Chin, a Mississauga family physician, said that stopping it cold turkey often produces a rebound effect and a worsening of symptoms. She uses a variety of remedies such as red clover extract to help ease the side effects of weaning off HRT. “You don’t have to go off it suffering from symptoms — there are choices.”
Yet even critics agree that hormone therapy is the most effective means of treating severe menopausal symptoms. It also remains an appropriate treatment for some women who experience early menopause or undergo a hysterectomy before they reach menopause, usually around the age of 50. In these cases, the therapy simply supplies the hormones their bodies would have normally produced.
But the new caveat is that hormone therapy for menopausal symptoms should be taken at the lowest possible dose for the shortest period of time.
“Even short-term use is associated with an increased risk of blood clots, stroke and coronary heart disease,” Health Canada’s website warns about combined estrogen-progestin therapy. “HRT should only be used if your symptoms are severe and if you have been fully informed of the risks. HRT requires regular medical evaluation.”
What does “short-term” mean? The Society of Obstetricians and Gynecologists of Canada says five years, Health Canada three to four, and some doctors say two.
“What I say to patients is, ‘Start tapering off once a year and you will know whether you are able to come off it,’ ” said Dr. Prior, who keeps a memento of the medical profession’s long struggle with HRT on a desk in her Vancouver office. It’s a needlepoint of a rose, done by a patient who’d been on hormones for 20 years and had bad heart disease.
Dr. Prior said she tried to get the woman to stop, but lost out to another doctor arguing the opposite.
“She passed away at least 10 years ago. She was a real person who was harmed by a therapy that everyone enthusiastically believed would help — without having the data to prove it.”
Paul Taylor is a Globe and Mail assistant national editor, responsible for health and science coverage.
Playing the numbers
A review of the Women’s Health Initiative study of hormone-replacement therapy established the following health risks and benefits, based on the changes in incidence of disease per 10,000 women on combination HRT in one year:
Seven more cases of heart disease (37 on combined HRT versus 30 on placebo);
Eight more cases of strokes (29 versus 21);
Eighteen more cases (34 versus 16) and a twofold greater rate of total blood clots in the lungs and legs;
Eight more cases of invasive breast cancer (38 versus 30);
Six fewer cases of colorectal cancer (10 versus 16);
Five fewer cases of hip fractures (10 versus 15).
— Source: Health Canada