Hormone replacement therapy, a controversial treatment used by millions of women, increases the risk of stroke, according to a new analysis of nearly 40,000 patients, the most in-depth study of its kind.
The study confirms and expands the results of the Women’s Health Initiative, which halted a study of more than 16,000 women in 2002 after doctors decided the risks of hormone replacement therapy — including greater incidence of heart attacks, strokes and breast cancer outweighed the benefits.
Some observers had criticized that study for being limited to a single hormone therapy regime (Prempro estrogen-progestin pills) and a single class of women those aged 50 to 79 who had never had a heart attack.
The new research took data from 28 previous studies of menopausal and post-menopausal women, including the Women’s Health Initiative. It analyzed a greater number of patients who had more varied medical histories and took both estrogen-progestin pills and estrogen-only drugs.
”It doesn’t matter that these studies were different, that they involved different sorts of women, different ages, sometimes with a previous stroke or heart attack,” said Dr. Philip Bath, a stroke researcher who co-authored the study. “The results are the same.”
Dr. Rachel Eidelman, a Mount Sinai Medical Center cardiologist who has studied HRT, said the new research provides a useful big-picture analysis of stroke risk.
”You can’t take one study, isolated, and get the end-all, be-all,” she said. “This sums it up and gives you a large body of evidence.”
In the new study, published today in the British Medical Journal, the risk of stroke for all patients was relatively low 2.7 percent for women taking hormones, versus 2 percent for women not taking the pills.
Of about 19,700 women who took hormones, 534 had strokes, the study found. That compares with 406 who had strokes among the just over 20,000 women who did not take the drugs.
”These are small risks,” said Dr. Andrew Kaunitz, a University of Florida/Jacksonville gynecologist who worked on the Women’s Health Initiative. ”If [a patient] has bothersome hot flashes and is requesting treatment, it’s perfectly appropriate and good clinical medicine to make hormone use available to her,” he said.
Before menopause, women have much lower rates of heart disease and stroke than men. After menopause, when estrogen levels decline, the rates increase dramatically. That led doctors to believe that estrogen therapy could lower the risk of heart attack and stroke. The recent studies including the halting of WHI clearly contradicted that hypothesis.
Bath said there may be some types of hormone therapy not examined in any of the studies that could show a lower risk of stroke. One example, cited in the study, is phytoestrogen, a form of estrogen that occurs in plants and hasn’t been widely studied.
Dr. Judith Turgeon, an endocrinologist at the University of California at Davis, said scientists could still develop a form of HRT that would lower risk of heart attack and stroke.
”The trick is finding the right formulation,” she said, noting that new forms of synthetic estrogen or delivering HRT through a patch could increase benefits and decrease risks.
After the Women’s Health Initiative was halted in 2002, women went off HRT in droves. Sales of Prempro, which at the time was the most popular treatment, fell by 60 percent. More than six million women had taken it.
More recently, doctors have reported women coming back to HRT for the relief it gives them from menopausal symptoms like hot flashes and insomnia.
Bath said the results of his study don’t mean HRT is always inappropriate. Instead, he said, women and their doctors need to decide what to do on a case-by-case basis.
”These are generalities,” he said of his results. “They don’t tell us about an individual.”