The latest data from a long-running study of hormone therapy suggests women who started taking hormone replacements within five years of menopause were 30 percent less likely to develop Alzheimer's disease than women who started years later.
The findings, reported on Wednesday in the journal Neurology, add to evidence suggesting that taking hormone treatments around the time of menopause may be doing more than just helping women cope with hot flashes and night sweats.
"Our results suggest that there may be a critical window near menopause where hormone therapy may possibly be beneficial," Peter Zandi of Johns Hopkins University in Baltimore, one of the study leaders, said in a statement.
The findings come as menopausal women and their doctors continue to parse out the risks and benefits of hormone replacement therapy.
Most researchers agree that hormone replacements do not protect women from diseases of aging, and taking these drugs for long periods of time are associated with significant risks, including breast cancer, heart disease and gall bladder disease.
Earlier this week, the U.S. Preventive Services Task Force reaffirmed its 2005 guidelines recommending against the treatment as a way to prevent chronic disease.
But the influential advisory panel did not weigh in on the use of hormones to treat symptoms of menopause, a practice many professional societies endorse as long as the drugs are prescribed at the lowest possible dose for the shortest period of time.
The most definitive study on hormone replacement therapy to date comes from the Women's Health Initiative study, a large, randomized trial that was stopped early in 2002 when it became clear that women who were taking a combination of estrogen and progestin for five years had higher rates of ovarian cancer, breast cancer, strokes and other health problems.
A related study known as the Women's Health Initiative Memory Study also showed an increased risk of Alzheimer's disease in women who took hormone therapy.
The findings came as a shock to many doctors and their patients, who thought the study would show a protective benefit. Prescriptions of hormone treatments plummeted, with sales of Wyeth's combination estrogen and progestin pill Prempro cut in half since 2001 to around $1 billion a year. Wyeth is now owned by Pfizer.
Because the average age of women in the Women's Health Initiative study was 63, several years past menopause, questions remain about whether the findings apply to younger women.
30 percent lower risk
Zandi and colleagues decided to investigate whether the timing of starting hormone replacement therapy had any effect.
Their findings come from the Cache County Study on Memory, Health, and Aging, a study backed by the National Institute on Aging that has been following nearly all of the residents of Cache County, Utah, over age 65 since the study began in 1995.
Earlier results of the Cache County study published in 2004 had suggested that hormone treatments might help reduce the risk of Alzheimer's disease.
So, the team turned back to this population, looking specifically at the timing of when women started taking hormone therapy and their risk of Alzheimer's disease.
Zandi's team followed 1,768 women ages 65 and older for 11 years. A total of 1,105 women had used hormone therapy, which consisted of estrogen alone or estrogen in combination with progestin. During the study, 176 women developed Alzheimer's disease, including 87 of the 1,105 women who had taken hormone therapy compared to 89 of the 663 others.
The study found that women who began hormone therapy within five years of menopause had a 30 percent lower risk of Alzheimer's dementia than those who had not used hormone therapy.
There was no change in the risk among other hormone users who had begun treatment more than five years after menopause, but they did find a higher risk of dementia among women who started combined estrogen and progestin at age 65 or older.
Zandi said the study findings support the so-called timing hypothesis - that earlier treatment with hormones may be beneficial while later treatment may be harmful.
"It doesn't prove the hypothesis, " Zandi said. "But it does suggest there might be something to that merits further investigation."
Given that there are no treatments that can alter the course of Alzheimer's disease, Zandi said a 30 percent reduction would be meaningful, if it proves to be real.
For now, however, the results should not be used to make treatment decisions, said Dr. Victor Henderson of Stanford University, who wrote an editorial on the study.
"The consideration of whether or not to use hormone therapy in midlife shouldn't be driven by concerns for Alzheimer's disease risk," Henderson said in a telephone interview.
But, he said, as women seeking treatment for menopausal symptoms weigh the other benefits and risks that go along with the decision, the Cache County study may offer evidence of another potential benefit, rather than an added risk.
Most professional societies advise against hormone therapy for chronic disease prevention, including the American Heart Association, the American Congress of Obstetricians and Gynecologists and the American Academy of Family Physicians.