Taking hormone therapy within the first few months or years of menopause offers women no protection against heart disease, a clinical trial conducted by researchers at Brigham and Women’s Hospital and elsewhere has found.
The 727 menopausal women in the study were randomly assigned to get a daily estrogen pill, an estrogen skin patch, or a placebo, and after four years, all had the same minimal amount of plaque progression in their arteries — considered an early sign of heart disease.
About half of the women recruited for the study had hot flashes, night sweats, mood swings, or depression related to low hormone levels, and those who took either form of estrogen experienced an 80 to 90 percent reduction in these symptoms. They were also no more likely to experience serious adverse effects such as breast cancer, strokes, or heart attacks than those taking the placebo.
All estrogen users took a synthetic form of progesterone to reduce the risk of uterine cancer associated with taking estrogen alone.
Results were published Monday in the Annals of Internal Medicine.
“For women with moderate to severe symptoms of early menopause, our study found that the benefits of hormone therapy for symptom reduction were likely to outweigh the risks,” said study coauthor Dr. JoAnn Manson, chief of the division of preventive medicine at Brigham and Women’s. “But we’re not going to recommend the initiation of hormone therapy for the express purpose of trying to prevent chronic disease in younger women.”
Hormone replacement therapy was once routinely given to postmenopausal women to prevent cardiovascular disease, osteoporosis, and other aging ills, but prescriptions plunged more than a decade ago when the large government-funded Women’s Health Initiative trial, led by Manson, found that women who took hormones had a higher likelihood of developing breast cancer, heart disease, stroke, and deadly blood clots compared with those who took placebos.
Most of the women in the Women’s Health Initiative, however, started treatment years after starting menopause. A few smaller studies since then have indicated that women who began taking hormones during the menopause transition have a slower accumulation of plaque on their arteries, which could delay the onset of heart disease, but this new finding — which used more sensitive tests — contradicts those results.
“I think it calls into question the theory that the timing of hormone therapy initiation makes a difference” for preventing heart disease, “but the good news is we don’t see great harm in younger women and that’s reassuring,” said Dr. Margery Gass, executive director for the North American Menopause Society, a nonprofit education organization that is partially funded by pharmaceutical companies.
The study included only healthy women with little evidence of atherosclerosis, based on an imaging test to measure calcium deposits in their arteries.
“Our hypothesis was that we didn’t believe estrogen would treat significant artery disease, so we screened out women who had a high calcium score,” said study lead author Dr. S. Mitchell Harman, interim chief of the internal medicine service at the Phoenix VA Hospital. “In retrospect, that was probably a tactical error” because artery plaque may have accumulated faster in women at higher heart disease risk, making it potentially more likely for any beneficial effect from the estrogen to be seen.
There were mild differences between the pill and the patch: The pill, which contained 0.45 milligrams of estrogen, improved levels of “bad” LDL cholesterol and “good” HDL cholesterol but also led to a small increase in triglycerides. The patch improves blood sugar levels and may be more appropriate for women with type 2 diabetes.
Those findings have been seen in previous studies, and doctors have already been recommending the patch to women with increased diabetes risks, according to Dr. Isaac Schiff, chief of obstetrics and gynecology at Massachusetts General Hospital. “I think this study confirms what’s happening in practices today,” he said.