The study, which is published in the journal Neurology, provides some support for a theory called the timing hypothesis. The timing hypothesis suggests that hormone replacement therapy (HRT) may be safer and perhaps even offer some longer-term benefits when it’s started within a few years of menopause.
It comes on the heels of early results from the Kronos Early Estrogen Prevention Study. That study found that hormones didn’t help or harm memory or thinking over four years of therapy.
“This new evidence adds a layer of reassurance for women if they were to consider taking hormones” for menopausal symptoms, says Victor W. Henderson, MD, professor of neurology at Stanford University in Stanford, Calif. Henderson wrote an editorial on the study, but was not involved in the research.
Estrogen and the Brain
Researchers have long believed that estrogen protects women’s brains as they age. That belief was based on animal studies and studies of women who were followed and compared after they made their own choices about whether or not to take hormones.
But in 2003, an arm of the large, government-funded women’s health initiative (WHI) trial unexpectedly showed that women taking estrogen in combination with progestin had nearly twice the risk of developing dementia as women who were assigned to take daily placebo pills.
Those findings are part of the reason experts now advise women against taking hormones after menopause to prevent diseases like osteoporosis and heart disease.
The findings of the WHI carry a lot of weight because unlike most other studies of HRT, WHI is a randomized, controlled trial. That means researchers were able to first balance and then randomly assign two groups of women to get hormones or daily placebo. Following those women revealed that women taking hormones were actually at greater risk of dementia than women who didn’t take hormones.
But the WHI wasn’t ideal. Most of the women in the study started taking hormones when they were well past menopause, which isn’t the way most women take them today. Experts have long wondered whether age might explain why the WHI found harm from hormones where other studies suggested benefits.
HRT and the Timing Hypothesis
For the new study, researchers followed nearly 1,800 women aged 65 and older.
After 11 years, 176 women were diagnosed with Alzheimer’s disease, including 87 of the 1,105 who took hormones and 89 of the 663 women who did not take them.
When researchers looked at when the women had started their HRT, they found that those who had started either estrogen alone or estrogen in combination with progestin within five years of menopause saw a significant reduction in their risk for Alzheimer’s disease of about 30%. The risk was reduced even more in women who stayed on their HRT for 10 years or longer.
Women who started taking a combination of estrogen and progesterone after age 65 tended to be at increased risk of Alzheimer’s, though the result wasn’t statistically reliable.
The study can’t prove that earlier use of hormones alone cut the risk of Alzheimer’s disease. Women who elected to take hormones may simply have been more health conscious than women who didn’t. They may have adopted overall healthier lifestyles that lowered their risk.
Study researchers acknowledge that such factors could be playing a role in the results, though they tried to take into account differences between women who did and did not take hormones.
“I do think this is important to stress that this is just one piece of evidence in the debate,” says researcher Peter P. Zandi, PhD, associate professor of mental health and epidemiology at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md. “I don’t think that based on the findings of this one study women should change their behavior just yet,” Zandi says.
Experts think hormones should only be used to treat menopausal symptoms like hot flashes, and vaginal dryness that are severe enough to disrupt daily functioning. The FDA advises women who need hormones to treat menopausal symptoms to use them at the lowest dose for the shortest amount of time.
Still, many women shy away from hormones for fear that using hormones during menopause may raise their risks for problems like dementia later in life.
“For the woman who’s thinking, ‘Should I go on hormone therapy? I don’t want to get Alzheimer’s disease.’ We now have, I think, a convincing body of evidence that suggests that it’s really important to distinguish between studies that are able to look at early use of hormone therapy versus later use,” says Pauline M. Maki, PhD, professor of psychiatry and psychology at the University of Illinois at Chicago.
Maki studies the effects of hormones on memory and thinking, but she was not involved in the research.
