Is estrogen-only hormone replacement therapy (HRT) the key to avoiding dementia? Or is using any kind of HRT protective against dementia?

According to two new studies published in Neurology and Alzheimer’s & Dementia, there may be a connection between HRT use in menopause and lower dementia risk, but researchers still haven’t found conclusive evidence that can inform treatment decisions.

Menopause isn’t just a hormone shift — it can also signal that other age-related conditions may be on the horizon, including dementia. Alzheimer’s disease and age-related dementia affect more than 7.4 million Americans, and two-thirds of them are women, according to the Alzheimer’s Association.

Because of dementia’s prevalence, new research in this area is exciting. However, physicians caution that while new research is good, we are far from finding a definitive reason why women are disproportionately impacted by cognitive issues after menopause.

The Dementia and Menopause Link

Dr. Sarah Doran, a neurologist with Northwestern Memorial Hospital, said that when it comes to dementia risk, lots of factors play a role, and menopause is just one of them.

“I think it’s one piece of a much bigger puzzle. If you take menopause out of it, women are just at higher risk of having dementia in general,” Dr. Doran said. “I think people want to say, ‘What’s the difference between men and women?’ and they immediately think of estrogen, and they blame hormones.”

Dr. Doran said that while this might seem logical, little hard data backs up the assumption. Although there is some evidence that women may be more prone to dementia after early surgical menopause, even that needs further research.

“I don’t think estrogen alone can protect you against Alzheimer’s disease. I don’t think we know that there is a causal relationship between estrogen and Alzheimer’s disease,” Dr. Doran said. “If you have a hysterectomy at 40, you are not guaranteed to have dementia.”

Study Design Impacts Results

Dr. Doran noted much of our confusion stems from the types of studies researchers are able to produce.

“It’s really hard to figure out what is, unless we do a trial where we take people who are entering menopause and then introduce exogenous estrogen and follow them long term and really see the benefit there,” she explained. “But a lot of [studies] are retrospective, and for the most part, they don’t take into account a lot of other factors.”

Looking back at disease progression can be useful, but only when you account for all the variables. Unfortunately, many moving parts are unaccounted for in most studies, including:

Even the researchers involved with the recent study in Alzheimer’s & Dementia acknowledged they didn’t have data on the type of HRT each participant was taking. While researchers can acknowledge their studies’ limitations, these important caveats often get left out of the headlines.

Until researchers can complete interventional studies, women should work with their healthcare providers to determine the best treatment options, including if and when to take HRT. There is still much we don’t know about menopause, hormones, and dementia risk.