Horse ranchers who produce pregnant mare’s urine under contract for the pharmaceutical giant Wyeth remember the lasting implications of the first round of the Women’s Health Initiative study that crippled their industry.
The U.S. study, which began in 1999 and involved more than 16,000 women between the ages of 50 to 79, was halted three years early in 2002 because researchers felt the risks outweighed the potential benefits of using hormone replacement therapy, or HRT.
The results shocked the PMU industry because Wyeth uses PMU to make an HRT drug called Premarin. Demand for Premarin plunged, which led to production cutbacks and buyouts in the PMU ranching industry.
But now, secondary analyses of WHI findings published in the April 4 issue of the Journal of the American Medical Association suggest women who begin hormone therapy within 10 years of menopause have less risk of coronary heart disease due to hormone therapy than women farther away from menopause.
The study’s authors also reported a statistically significant reduction, of around 30 percent, in total mortality among women aged 50 to 59 in the group that received hormone therapy compared with those in the placebo group, with a nonsignificant trend for increasing risk across other age groups.
Researchers also found that for older women, the farther from the onset of menopause that they begin hormone therapy, the greater their risk of coronary heart disease due to hormone therapy.
“There is no benefit for (heart disease) overall, and it doesn’t change the recommendation that HRT should not be used for prevention of (heart disease),” said Dr. Jacques Rossouw, chief of the Women’s Health Initiative Branch at the National Heart, Lung, and Blood Institute and lead author of the study.
“We are now analyzing it with more complete data to get a better idea of whether there is a period in which women can use hormones without increasing their risk of heart disease.”
Rossouw said the implications may be reassuring to younger women considering the therapy for short-term relief of symptoms.
The researchers found that women who used HRT for an average of four to five years within 10 years of the onset of menopause showed a small increased risk of stroke and breast cancer but no increase in heart attacks. Women considering hormone therapy should measure and manage risk factors such as blood pressure and blood cholesterol, he added, as well as have regular mammograms.
“If you look at everything altogether, total deaths are still in a favourable direction. So it appears to be a reasonable option for women within that window. What we do know is that if you start it at older ages, it’s harmful. That was really clear,” he said.
“But what was really interesting was that the increased risk in older women was confined to those who had hot flashes or night sweats. Somehow, those hot flashes and night sweats are a signal that there is something not right. They have more risk factors for heart disease. So, if you give them hormones, their risk increases.
“There is a flip-flop in the potential benefits and potential harm. It’s OK to use it for symptoms over the short term within the first 10 years of menopause, but it’s not OK to use it after that for symptoms.”
A British study of a million women, released last week, found HRT use led to a 20 percent increase in ovarian cancers. Like the U.S. study, it recommended hormone use only for a short time.
WHI is a 15-year U.S. research program designed to address the most frequent causes of death, disability and poor quality of life in postmenopausal women: cardiovascular disease; cancer and osteoporosis.
The WHI’s estrogen plus progestin and estrogen-alone trials were stopped early because of increased health risks and failure to prevent heart disease.
The estrogen plus progestin trial was stopped after 5.6 years because of an increased risk of breast cancer and because overall risks, including increased risks for heart attack, stroke and blood clots, outnumbered benefits. The estrogen-alone study was stopped after 6.8 years because of an increased risk of stroke and no reduction in risk of coronary heart disease. The estrogen-alone study also found an increased risk of blood clots.
The new findings are consistent with the first round of WHI trials of estrogen plus progestin and estrogen-alone, which involved 27,347 participants, in showing no overall benefit for coronary heart disease and in suggesting that risk due to hormones may differ depending on age or years since menopause.
In the latest WHI analysis, the authors combined the data from the two trials to explore in more detail the previously observed trends in hormone effects by distance from menopause.
In the age 50 to 59 group, they looked at the data collected from more than 9,000 women.
“The secondary question would not have been a question at all if our primary question had been positive,” said Rossouw, adding that the first WHI round expected to find that giving HRT to menopausal women of all ages would be beneficial.
“Since the primary answer was that it is harmful, the secondary question was, ‘well, yes, but is it still harmful for this different group of women,’ ” he said.