Estrogen supplements may protect against dementia

Globally, one new person is affected by dementia every four seconds. In 2010, 36 million people were estimated to have dementia.

Now, findings in a doctoral thesis from the Norwegian University of Science and Technology (NTNU) show that estrogen supplements can reduce the risk of dementia in women.

"estrogen supplements can have a positive effect against dementia if women start early enough with treatment," says Carl Pintzka, a medical doctor and PhD candidate at NTNU.

The finding has been just published in the journal Neurobiology of Aging.

A sample of 80 women who had used estrogen supplements through menopause was compared with 80 women who had never used estrogen supplements. All had participated in the Nord-Trøndelag Health Study (HUNT), a general population-based study in mid-Norway.

The brain shrinks with less estrogen

Following menopause, womens' estrogen levels drop significantly compared to levels before menopause.

MRIs of the brains of the women in the study showed that those who had taken estrogen supplements throughout menopause had a larger hippocampus. The hippocampus is one of the most important structures for memory and sense of place, and is one of the structures that is affected early in the progression of Alzheimer's disease.

"We also examined the shape of the hippocampus and found that areas where hormone therapy had the greatest effect are the same areas that are affected by Alzheimer's disease in its early stages," says Pintzka.

Other studies have shown that women who start estrogen supplements several years after menopause do not benefit from the same positive effect on the hippocampus.

Must start estrogen from the late 40s

Pintzka's findings show that boosting estrogen levels increases the volume of the hippocampus. As of yet there are no drugs that stop or prevent the course of Alzheimer's disease, and the focus has shifted towards strategies to prevent or delay the onset of dementia.

Successful strategies are thought to be those that increase brain volume, and that in particular preserve the hippocampus. The risk of dementia may therefore be reduced for women taking estrogen supplements around the time of menopause, according to Asta Håberg, a Professor of Neuroscience at NTNU and Pintzka's supervisor.

Until 2002, many women in Norway and internationally took estrogen supplements during and after menopause. The reasons for boosting estrogen levels are to reduce hot flashes and osteoporosis and to prevent cardiovascular disease. Then the number of women taking supplements fell dramatically.

The studies that scared women

Pintzka points to two specific studies as the reason for the steep decline in the use of estrogen supplements. In the summer of 2002, a large study of menopausal women conducted by the "Womens Health Initiative" was published.

This study landed like a bombshell in professional circles and the media. The conclusion was that the disadvantages of long-term treatment with estrogen far outweighed the benefits.

The study included 16,000 women and showed that the combination of estrogen and progestin increased the risk of both heart disease and breast cancer. Furthermore, the study showed that those who took estrogen supplements had poorer memory and greater risk for dementia than the control group.

Soon after, The Journal of the American Medical Association published another study, which had followed 44,000 women for 20 years. This study showed that estrogen therapy increased the risk of ovarian cancer if treatment persisted for over 10 years.

Some risks increase, others drop

"It's true that the risk of some cancers increases with estrogen supplements, but we also know, for example, that the risk of hip fractures and colorectal cancer drops with their use," says Pintzka.

According to Håberg, it's a big question whether the findings of the American studies can be transferred to Norwegian women, because women [in the American studies] started using estrogen at a later age. "estrogen supplements used in the United States are also different from the ones used in Europe," she says.

More recent studies suggest that boosting estrogen levels has protective effects on the brain if started around menopause, but that the same treatment could be harmful for women if they start supplements later than a few years after menopause.

"The women who participated in the Women's Health Initiative study started with estrogen supplementation 15-30 years after menopause. This was probably too late to expect a positive effect," Pintzka says.

More and more people will be affected by dementia

According to Norway's 2014 Public Health Report, Norway has approximately 70,000 people with dementia, and that number is anticipated to increase greatly in the coming years due to a growing population and higher average age.

Norway is not alone in facing this development, which is associated with the increasing average age of the population.

The World Health Organization has identified the fight against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, as some of the biggest health challenges society faces in the coming years.

Women should start early with estrogen if they decide to use it

Håberg believes that positive effects on the brain from using estrogen supplements are highly probable, but whether supplements eventually protect against dementia remains unclear.

"Women who want to take estrogen supplements should start early to benefit from the positive effect on the brain," says Håberg.

Pintzka points out that none of the participants in his doctoral thesis had dementia at the start of the study, nor have any developed the disease since the MRIs were taken. He adds that neither he nor his supervisor know how many participants may develop dementia as they continue to age. An NTNU research group plans to follow up on this question in the next HUNT study.

Pintzka is now employed by St. Olav's University Hospital in Trondheim as a researcher for the National Competence Service for Functional MRI.