Study Finds a New Danger For Women on Hormones
By Scott Hensley
A troubling new finding deals a further blow to a once-common form of hormone replacement, eliminating nearly all remaining reasons for older women to keep using the therapy.
A new study shows that the most popular hormone combination, Wyeth's Prempro, doubled the risk of dementia in women over 65, instead of decreasing it. The finding comes less than a year after researchers halted a study of Prempro because early results showed that the drug conferred a higher risk of breast cancer, heart attacks and other cardiovascular problems.
The latest research may be the final blow in balancing the risks and benefits for anyone who isn't debilitated by the symptoms of menopause. Women were already frightened by last summer's findings, and Prempro prescriptions have plunged as a result.
"There's no reason for an older woman to take combination hormone therapy," concludes Sally Shumaker, a professor of public health at Wake Forest University School of Medicine, Winston-Salem, N.C., and the lead author of the dementia study.
Nevertheless, plenty of doctors are likely to continue to prescribe the therapy for short-term use by younger women -- those in their early 50s -- as they go through menopause. It remains one of the most effective remedies for intolerable cases of night sweats, hot flashes and vaginal dryness. The key, physicians believe, is to take the hormones in the lowest effective dose for the shortest period of time possible, usually less than two years. New low-dose versions of Prempro and the estrogen therapy Premarin, have been approved by the Food and Drug Administration and should be available to patients this summer.
"Nowadays we're really shifting to using hormone replacement only to treat symptoms," says Ann Honebrink, an assistant professor of obstetrics and gynecology at University of Pennsylvania School of Medicine.
Until recently, women who began taking hormone replacements at the onset of menopause often continued on the drugs for years, believing they could help stave off a variety of illnesses of old age, including Alzheimer's, heart disease and stroke. But the latest findings add to a growing body of research showing that the opposite seems to be the case.
Specifically, the new study found that women taking Prempro, which is a combination of estrogen and progestin, had twice the risk of dementia of those taking a sugar pill. That would lead to 23 additional cases of dementia per year among every 10,000 women taking Prempro, for a total of 45 cases, the study concluded.
The study appears in Wednesday's issue of the Journal of the American Medical Association. Another paper in the same edition showed that Prempro increases the risk of stroke by 31%, further confirming other recent analyses. And a third study in the medical journal showed no significant improvement in memory or thinking ability in women who took Prempro compared with those who took a placebo.
The new findings, as well as those of last summer, come from the Women's Health Initiative, the largest and most rigorous set of human studies to test hormone replacements in prevention of disease, rather than relief of symptoms of menopause. It was funded mostly by the federal government's National Institutes of Health, while Wyeth provided the drugs and placebos for the participants.
Precisely why Prempro would lead to declines rather than improvements in mental function is unclear, but one theory is that the medicine may increase the tendency of blood to clot, potentially leading to blockages in tiny vessels crucial for blood flow in the brain.
Researchers are continuing to study the effect of estrogen alone as a hormone-replacement therapy, but it remains unclear whether its benefits in disease prevention outweigh any risks. Estrogen is usually prescribed only for women who have undergone hysterectomies. For those who still have a uterus, it is rarely considered an option because it increases the risk of uterine cancer.
Weaning patients from hormone replacements can be difficult because many women experience bothersome symptoms even years after menopause. Some physicians, like Dr. Honebrink of the University of Pennsylvania, try to taper the dose over several months.
One limitation of the WHI study is that it looked only at women 65 years of age and older. Wyeth, which makes other hormone-replacement drugs besides Prempro, estimates that 86% of new prescriptions for the medicines are for women younger than 65.
About 20% of women experiencing symptoms of menopause find them severe enough to seek treatment. Those who do typically start hormone-replacement therapy between ages 51 and 55 and take the medicine for less than two years, according to Wyeth. "It's extremely important not to lose sight of HRT's proven benefits," says Victoria Kusiak, the company's vice president for global medical affairs.
Nevertheless, Wyeth doesn't contest the growing case against long-term use of its drug. It concurs with recommendations from clinicians and the FDA that the lowest effective dose of hormone be used for the shortest period of time. This summer, the company expects to begin selling low-dose versions of both Premarin and Prempro.
Prescriptions for hormone replacements plunged last year after the release of information documenting the risks from Prempro. Total U.S. prescriptions for Prempro stood at 553,000 in April, off 71% from 1.8 million a year ago, according to NDCHealth, a prescription tracker in Atlanta. Prescriptions for Premarin, which contains only estrogen, fell 37% to 2.44 million. Wyeth estimates about 1.2 million American women take Prempro compared with 3.4 million before the WHI studies were released last July. Some 2.7 million women currently use Premarin, compared with 5.6 million who took the drug before last July.
Doctors now say the only remaining reason to take hormone replacements for preventive purposes is to combat osteoporosis. But several drugs specifically developed to treat or prevent weak or brittle bones have become available in recent years, including Evista, from Eli Lilly & Co., and Fosamax from Merck & Co.