Widespread discontinuance of hormone replacement therapy in the past decade possibly contributed to the deaths of nearly 50,000 U.S. women who had had a hysterectomy, a new analysis contends.
The findings refer only to women who've had a hysterectomy and then experience menopausal symptoms, the researchers emphasized.
"In women who have had a hysterectomy who have symptoms of hormone deficiency [such as hot flashes], it can be lifesaving for them to take estrogen," said review author Dr. Philip Sarrel, of Yale University School of Medicine.
For women between the ages of 50 and 59, estrogen-only therapy after a hysterectomy reduces the risk of heart attack and death, Sarrel said.
"The main reduction [in deaths] is the reduction in heart attacks, but there is also a clear reduction in the incidence of breast cancer and deaths from breast cancer," Sarrel said.
The use of hormone therapy -- both estrogen-only and the combination of estrogen plus progestin -- declined greatly after the U.S. Women's Health Initiative Study found in 2002 that combination therapy had ill effects, including an increase in breast cancer, heart disease, stroke and blood clots. Prescriptions for both regimens plummeted even though the research didn't apply to women without a uterus or to women on estrogen-only therapy, said Sarrel, who is a consultant for Noven Therapeutics, which makes an estrogen patch.
Subsequent trials found health benefits for women who took estrogen-only therapy after a hysterectomy, compared to those who took a placebo. According to a 2011 report, estrogen-only therapy could reduce 13 deaths per 10,000 women a year among this population.
Despite those findings, prescriptions for estrogen-only therapy after hysterectomy remain low.
The new analysis, published online July 18 in the American Journal of Public Health, was funded by the U.S. Centers for Disease Control and Prevention. For the study, Sarrel and his colleagues analyzed U.S. census data, the hysterectomy rate and the decline in estrogen use in this group of women, and calculated which deaths could be attributed to estrogen avoidance.
They found that use of estrogen-only therapy in U.S. women aged 50 to 59 declined nearly 79 percent between 2001 and 2011.
During that time, at least 18,000 excess deaths occurred because of estrogen avoidance and possibly more than 91,000, depending on the calculations used, Sarrel's team said. For this reason, their best estimate -- of about 50,000 deaths -- may be conservative, said Sarrel.
While the study found an association between a decline in hormone therapy and deaths among women who have had a hysterectomy, it did not prove the existence of a cause-and-effect relationship.
As experts have analyzed and re-analyzed WHI trial data and other studies, they have found support for a "timing hypothesis" -- that estrogen's heart protection occurs when it is started close to the time of menopause. By age 60, research suggests, changes in blood vessel cells compromise estrogen's ability to inhibit hardening of the arteries (a heart disease risk) and to promote good blood flow.
This new study finding should reassure women who had a hysterectomy and began estrogen at the time of menopause, said Dr. Jennifer Leighdon Wu, an obstetrician-gynecologist at Lenox Hill Hospital in New York City, who was not involved in the analysis.
"I think we always knew from the WHI study that the estrogen-progestin combination was more dangerous than estrogen alone," she said. However, women tended to lump the findings of adverse effects together for both types of treatment, even though the risks and benefits were different, she said.
Even with the new results, Wu said it's crucial to individualize treatment with hormone therapy. "You wouldn't just put every patient who had a hysterectomy on estrogen," she said.