Many women have questions and concerns about hormone replacement therapy (HRT). For example, Premarin, the commercial name for a mixture of the main female sex hormone estradiol and other compounds derived from the urine of pregnant mares, has been linked to an increased risk of heart disease, breast cancer, and dementia.

Now, however, there may be some good news. A recent study suggests that if women start HRT early in menopause, synthetic estradiol may slow the rate of cognitive decline in those at risk for dementia rather than accelerate it as Premarin seems to do.

Some data suggest that the time to begin HRT is just as a woman’s estradiol level starts to decline.

The study is unique in that the investigators did not give women hormone replacement therapy, but modified their existing regimen by randomized design, Heather Kenna, an author on the study, told TheDoctor.

Sixty-four women between 50 and 65 years old were recruited for the study. They all were in good health, but were at risk for dementia because of a history of major depression; a first-degree relative (parent or sibling) with Alzheimer’s disease; or a positive test for the Apo4 allele, a part of a gene that increases a woman’s risk for Alzheimer’s disease. All of the women had started taking HRT within a year of their last menstrual period.

The women had brain scans at the start of the study and then were assigned to either continue or discontinue their HRT regimen. After two years, 45 of the women — 28 who continued taking HRT and 17 who stopped it — had a second brain scan.

The scans revealed that in those women who continued HRT, the rate of metabolic activity did not decline in the region of the brain associated with decision-making, the medial prefrontal cortex. But changes were seen in several other brain regions that tend to predict the risk of dementia, and the changes in metabolic activity varied according to the type of HRT a woman used.

In particular, metabolic activity declined significantly in a brain region often associated with visible signs of dementia among women who discontinued estradiol, but activity stayed the same among women who continued to take the sex hormone.

Metabolic activity in the region did keep on declining in those women who continued taking Premarin. And adding progestin, a synthetic version of the hormone progesterone, to either Premarin or estradiol only hastened the decline in metabolic activity.

What Should Women Do?
“I am not a physician, but personally, I feel that the take home message should be that Premarin should be used with caution,” says Kenna, a research manager at Stanford University. “If you are a woman who uses hormone therapy, you should try and use estradiol, rather than Premarin,” said Kenna.

Ultimately, HRT should only be used if absolutely needed. “We are not proposing that women go on estradiol, if their doctors don’t feel that they need it, or if they are not having severe hot flashes or vaginal dryness, or other symptoms.”

The second take home message is that if estrogen is prescribed, it has to be started during a certain window of opportunity — within about one year of menopause.

Lead author Natalie Rasgon, MD, PhD, professor of psychiatry and behavioral sciences and director of the Stanford Center for Neuroscience in Women's Health, said the findings indicate that hormone therapy's neurological effect on women at risk for dementia depends on when they begin therapy and on whether they use estradiol or Premarin.

Some data suggest that the time to begin HRT is when a woman’s estradiol level starts to decline. According to Kenna, it is not a good idea to start hormone therapy without a lot of estrogen in your system.

The study is published online in PLOS ONE.