MENOPAUSE AND DEMENTIA: CAN HORMONAL CHANGES CAN AFFECT THE BRAIN?

What pops into your mind when you think of menopause? Hot flashes? Night sweats? Mood swings? Dementia, though, might not have been on that list. 

Recently, researchers discovered an alarming link between early menopause and dementia. The authors of a study published in JAMA – in April 2023 – reported that women who entered menopause early (before turning 40) had a much higher risk of developing dementia than women who enter menopause at 50-51. They also linked the timing of hormone replacement therapy to the likelihood of developing dementia.

Previous studies have suggested that menopause can increase women’s risk of Alzheimer's Disease (one of the most common causes of dementia), but researchers were unsure how or why. Now, scientists believe that the sudden drop in estrogen levels that comes with menopause may be to blame.

Continue reading to learn more about the relationship between menopause and dementia and how hormonal changes may affect brain health.

Are Menopause And Dementia Linked?

The short answer is yes.

Menopause is a natural biological phase that marks the end of the reproductive stage in women, usually around the age of 50. And in the words of Tara Allmen, "Menopause is not a disease; it's a natural and normal transition that every woman goes through." 

On the other hand, dementia is a group of disorders that cause abnormal brain changes and may affect a person’s memory, thinking, language, and behavior.

Although every woman eventually enters menopause, not every woman goes on to develop dementia. While the two conditions may seem unrelated (one is a disorder while the other is natural), scientific evidence strongly suggests a link between menopause and dementia.

Earlier in 1996, researchers noticed that women receiving estrogen replacement therapy (ERT) responded better to Alzheimer’s Disease treatment than women who were not on ERT. That gave them the idea that estrogen may be involved in Alzheimer’s (a common cause of dementia).

Later in 2001, researchers published a review article that explains how sex steroids, like estrogen, have a role in age-related brain diseases, such as Alzheimer’s and dementia.

Fast forward to 2010, scientists gathered data from different studies and concluded that the decline in estrogen after menopause might be a risk factor for dementia due to Alzheimer’s disease. 

In 2014, researchers reported that women who had early surgical menopause – due to the necessity of surgery to remove their ovaries – were more prone to a decline in brain functions and dementia before turning 78 than women without early surgical menopause.  

Later in 2017, scientists compared the brain scans of three groups of adults of the same age: women around menopause (perimenopausal), women who entered menopause (menopausal), and men. They found that the brain images of perimenopausal and menopausal women had more markers for Alzheimer’s Disease than men of the same age, and the menopausal women had the most.  

Then in 2022, a study revealed that early menopause – before a woman turns 40 – increases the risk of dementia by 35% compared to menopause at 50-51 years old. Furthermore, the risk of developing dementia before the age of 65 is 1.3 times higher in women who experience menopause before the age of 45. 

A more recent article in 2023 further confirmed that early menopause puts women at a higher risk of dementia.

How Can Early Menopause Trigger Dementia?

Scientists are still not exactly sure what causes Alzheimer’s disease and dementia. They believe the cause might include a combination of variables, such as age-related brain changes, genetics, and environmental factors. 

It has been observed that people with Alzheimer’s have a noticeably abnormal buildup of the tau and beta-amyloid proteins in their brains. This buildup disrupts the connections between brain cells and affects a person’s ability to think straight, remember things, and (eventually) live independently.

One way beta-amyloid proteins can damage brain cells is by causing oxidative stress; the body produces too many harmful molecules (free radicals) and does not produce enough protective molecules (antioxidants) to get rid of them.     

Early in 1990, scientists found that estrogen helps protect the connections between cells in the hippocampus – a brain area important for learning and memory. Researchers also established that estrogen helps the body make more antioxidants, which protect the brain against oxidative stress and damage – they block the harmful effects of excess beta-amyloid proteins.

Both men and women produce the estrogen hormone, but women usually have more. When women enter menopause early, their estrogen levels drop sooner, i.e., they lose some protection against brain damage and dementia. 

And that is how scientists think early menopause might trigger dementia.

On the contrary, men continue to produce testosterone, which turns into estrogen in the brain – although testosterone levels gradually drop as men grow older. That could explain why women are more likely to develop dementia than men.    

Does Hormone Replacement Therapy (HRT) Help Against Dementia?

Many women undergo hormone replacement therapy (which includes estrogen) to help relieve unpleasant menopause symptoms, such as hot flashes, night sweats, and vaginal dryness.

Studies investigating whether hormone replacement therapy reduces the risk of dementia have been inconclusive.

Earlier, some studies showed that menopausal women treated with hormonal therapy had a lower risk of dementia, while others could not reach the same conclusion. Some even pointed out that HRT could even increase the risk of dementia in women.

In 2002, scientists examined the relationship between hormone replacement therapy (HRT) and the risk of Alzheimer’s disease followed by dementia. They found evidence that HRT may lower the risk of dementia if menopausal women start the therapy early on. Women did not have the same protection against dementia if they waited longer to start hormone replacement therapy after menopause.

In 2023, a group of researchers conducted a more comprehensive study and found that the longer women wait to start hormone replacement therapy after menopause (5 years or more), the more tau protein buildup they had in their brains compared to women who had early HRT. They also had a higher risk of developing dementia.

These findings suggest that the timing of hormone replacement therapy after menopause affects women’s chances of having dementia.

Final Thoughts

Despite the potential benefits of hormone replacement therapy in treating or preventing dementia in women, researchers still need to investigate whether the risks of HRT outweigh its benefits and exactly how and when women should start it. 

Regardless, these findings give scientists a new weapon in their fight against dementia while searching for other ways of using estrogen to prevent brain functions from worsening after menopause – or even possibly reverse the damage.  

They also give more insight into how this relatively mysterious disease happens and why women are more likely to develop dementia than men.

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Other related sources:

• Major Neurocognitive Disorder (Dementia) - StatPearls - NCBI Bookshelf
• Female Sex and Alzheimer’s Risk: The Menopause Connection - PMC
• Menopause and cognitive impairment: A narrative review of current knowledge - PMC 

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