In July, 2002, scientists abruptly halted one arm of the Women’s Health Initiative, a massive U.S. study of hormone-replacement therapy (HRT), after data suggested the treatment significantly increased women’s risk of breast cancer, strokes and heart attacks.
The news landed like a bomb for millions of women taking HRT to treat the symptoms of perimenopause and menopause. Few medical studies have ever had such a dramatic impact on medical practice. In the U.S., HRT prescriptions plummeted – from 112 million in 2001 to 32 million in 2008.
To this day, many women are still reluctant to take HRT because of the lingering belief that doing so increases their risk of heart disease and cancer.
But, more than two decades after that earth-shaking study, hormone replacement therapy is being rehabilitated.
In fact, the same researchers who published the WHI results in 2002 are now saying, in an article published in the Journal of the American Medical Association, that HRT is not only safe, but it’s the most effective treatment for women under 60 suffering symptoms like hot flashes and night sweats.
So, what happened?
In a word, nuance.
Researchers jumped to some conclusions about the safety of HRT based on flawed analysis. Then it took some time and effort to figure out what the data were really saying.
The use of hormone replacement therapy became popular in the 1960s. One byproduct of the feminist revolution was that many women stopped accepting they had to suffer through menopause in silence. (Menopause is diagnosed after a woman has gone 12 months without a menstrual period; the transition phase, perimenopause, can last four to eight years.)
HRT promised not only to relieve symptoms but to prevent chronic conditions like cardiovascular disease and dementia. The WHI was designed to test those theories.
The average age of 160,000 women enrolled in the WHI was 63. Most were postmenopausal. (The average age of menopause is 51.) And they were in a demographic group wherein the risk of heart disease and breast cancer increases, regardless of HRT.
When age stratification studies were done, belatedly, a different story emerged.
In short, what the research shows is that for women under the age of 60 whose last period was less than five years earlier, the benefits of HRT clearly outweigh the risks.
In fact, the 2024 JAMA paper shows that for women under 60:
· There is no increase in mortality;
· There is no difference in heart-attack risk (the 2002 study said it was 29 per cent higher);
· Stroke risk is low: Less than one case per 1,000 for those taking an estrogen-progestin combo, and no difference for estrogen-only;
· Longer term use of estrogen-progestin HRT increases the risk of breast cancer slightly – the equivalent of consuming one to two alcoholic drinks daily;
· The risk of bone fracture decreases 33 per cent.
“The WHI findings should never be used as a reason to deny hormone therapy to women in early menopause with bothersome menopausal symptoms,” said lead researcher Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital in Boston.
Yet, at the same time, many of the cautions from the 2002 study still hold true for older, postmenopausal women, as well as younger women considered high-risk – those who have had estrogen-sensitive cancer, or who have a history of heart disease or blood clots.
Combination estrogen-progestin HRT can increase risks, especially if used long-term and taken orally, in pill form. But there are alternatives, such as vaginal estrogen-only treatments, and patches and gels. There are also non-hormonal treatments, such as fezolinetant (brand name Veozah), and antidepressants.
To be fair, the evidence has been building for years that the safety of hormonal therapy was not a black-and-white issue.
There was pushback immediately after the dire warnings about HRT from the WHI, and then a recognition that when HRT may have been overprescribed, the pendulum swung back too far and women were being denied effective treatment.
In Canada, the guidelines recommend a pragmatic approach to the management of menopause, including judicious prescription of hormone replacement therapy.
Women should not be suffering unduly from symptoms of perimenopause and menopause where there are safe, effective treatments available. They also need an accurate assessment of the risks and benefits of treatments like HRT.
For too long, we have been unduly fearful, and hopefully the new data and analysis will alleviate those fears.
But, as we know all too well, it’s a lot easier to scare people than to un-scare them.
André Picard