An extended and detailed analysis of data from the landmark Women’s Health Initiative (WHI) clinical trials on menopausal hormone therapy is being published today in the Journal of the American Medical Association (JAMA).
The results support the WHI’s key earlier finding: Hormone therapy — whether estrogen alone or estrogen with progestin — should not be used long term by postmenopausal women, no matter what their age. The health risks, which for both types of hormone regimens include stroke, blood clots, gallstones and urinary incontinence, are too significant.
This latest analysis did find that the short-term use of hormone therapy by women just entering menopause to relieve severe symptoms of hot flashes and night sweats is probably safe. Just what constitutes short-term use is unclear, but the study’s lead author, Dr. JoAnn Manson, an endocrinologist at Brigham and Women’s Hospital in Boston, has told reporters that she considers such use to be less than five years.
Are these findings going to stop the relentless efforts by the pharmaceutical industry and others to portray menopause as an illness that needs treatment with hormone therapy?
Probably not. Too much money is at stake. Annual sales of prescription menopausal hormones reportedly totaled $1 billion before the initial findings of the WHI were published in 2002. A mere five months after that publication, sales for the drugs plummeted by 46 percent. And the downward trend in those sales has continued.
Two separate studies
The two original WHI clinical trials (which were stopped unexpectedly early in 2002 and 2004 because of the serious health risks they uncovered) involved more than 27,000 postmenopausal women aged 50 to 79. Women in the study who had an intact uterus were randomly assigned to take either a combination treatment of estrogen plus progestin or a placebo. Women who had undergone a hysterectomy were randomly assigned to take either estrogen alone or a placebo. (Progestin is given with estrogen to women who haven’t had a hysterectomy in order to protect them from endometrial cancer.)
The women were followed for five to seven years. The new data reported today in JAMA are from an additional six to eight years of follow-up after the original trials were halted and all the women were taken off the hormones.
The new data also offer the most detailed breakdown to date of how the risks vary by type of hormone therapy — and by age.
Estrogen plus progestin
The study found, for example, that women who took the estrogen/progestin combination therapy were at increased risk for heart disease, breast cancer, stroke, pulmonary embolisms (blood clots in an artery in the lungs), dementia (in women aged 65 and older), gallbladder disease and urinary incontinence.
These women also experienced two major health benefits: fewer hip fractures and a lower risk of diabetes.
Both the risks and the benefits tended dissipated after the women stopped taking the hormones — except for some elevation in the risk of breast cancer.
In addition, the risks tended to be lowest for the youngest women in the study (aged 50 to 59) and greatest for the oldest ones (aged 70 to 79).
For women who took only estrogen, the risks and benefits tended to be more balanced. They were at increased risk of stroke and other blood clots and at decreased risk of having a hip fracture. The data also revealed a nonsignificant reduction in breast cancer risk. After they stopped taking the estrogen, however, that breast cancer risk significantly decreased. And among those aged 50 to 59, the risk of having a heart attack also decreased.
“These findings demonstrate that menopausal hormone therapy has a complex profile of risks and benefits,” writes Dr. Elizabeth Nabel, a professor of medicine at Harvard who wrote an editorial accompanying the new study.
Both Nabel and the authors of the new analysis stress that these lastest findings do not support the use of hormone therapy for chronic disease prevention.
“There are clear risks,” says Manson in a video released with the study.
“However,” she adds, “it does still remain appropriate to use hormone therapy for treatment of menopausal symptoms in early menopause. And certainly younger women will have lower absolute risk. The distinction between use for chronic disease prevention and use for treatment of symptoms is a very important one.”
NOTE: In her editorial, Nabel includes comments about “the value of publicly funded, objective, prevention-oriented clinical studies,” such as the WHI — comments that seem particularly relevent this week, given the current government shutdown and the ongoing sequestration cuts, which are having a significant detrimental impact on research at the National Institutes of Health (NIH).
“The WHI underscores the decisive importance of taxperer-funded research conducted by the NIH,” she writes. “Further reductions in the NIH budget virtually ensure that vitally important studies like the WHI will not be conducted, and hence, US society will be poorly served. The fact that the public sector undertook this historic project (and that the researchers whos work is now reported have taken it to its next stage) has moved medical science forward by the most effective means of doing so — shattering prior dogma. For that, women and all patients whose health depends on sound science are grateful.”