Hormones and dementia

Dementia affects more women than men and it is thought that hormones may play a role in this. Some research suggests that hormone replacement therapy, used to help with symptoms of menopause, may reduce dementia risk in women – though other studies say opposite.

Are women more at risk of dementia?

Women make up an estimated 65% of  people who currently have dementia. Whilst age is the main risk factor for dementia, and women tend to live longer than men, this does not completely explain the difference.

It is not fully understood why women are more likely to develop Alzheimer's disease , the most common cause of dementia. One idea is that it may be to do with the hormone oestrogen.

Whilst both men and women produce oestrogen, it’s the main female sex hormone and so women usually have more of it. When women go through menopause, their bodies stop producing as much oestrogen.

On the other hand, men continue to produce testosterone, the male sex hormone, throughout their lives. Testosterone is converted into oestrogen inside brain cells. This means that women who have been through menopause have lower levels of oestrogen in their brains than men of the same age.

What can increase a person's risk of dementia?

There are different types of risk factors for dementia, including medical, lifestyle and environmental factors.

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Does hormone replacement therapy reduce dementia risk?

It is not clear whether hormone replacement therapy (HRT) reduces dementia risk or not.

Some women choose to have HRT when they go through menopause. It can help relieve some of the more unpleasant symptoms, such as hot flushes and mood swings. HRT is usually a combination of oestrogen and another hormone called progesterone, although there are different types.

The research into whether taking oestrogen (as part of HRT) can reduce women's risk of dementia has been mixed. Some studies suggest that oestrogen may reduce dementia risk whilst others say it increases it.

Research on HRT and dementia risk

Studies into hormone replacement therapy and dementia are conflicting. With some suggesting a benefit on memory and thinking abilities, or dementia risk, and others finding the opposite.

In 2021 a study of nearly 400,000 women, found both new and old HRT drugs reduced the risk of diseases that cause dementia. The study found that the effects differed based on many things: dose, type of medication, length of treatment, age, and time from menopause. Another study in Denmark, following dementia rates of over 55,000 women showed the opposite, that HRT increases dementia risk.

Part of the reason that the uncertainty, is that many studies only show a connection between dementia and HRT, but they can’t tell us if HRT leads to dementia. Brain fog is a common symptom of menopause, but may also be an early symptom of dementia. If early dementia symptoms are confused for menopause symptoms and HRT is prescribed, it may also skew the numbers.

Other complications are around the  type of HRT used. Older types of HRT were known to have higher risks related to them than the newer types. Also the timing of the HRT and the age it is taken may be important.

Researchers are currently working to understand the link better, to clarify whether HRT really does reduce dementia risk. 

Risk factors for dementia

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Oestrogen in the brain and dementia risk

Alzheimer's disease is more common in women after menopause. So it is possible that oestrogen plays a role in protecting the brain from the damage caused by Alzheimer’s disease. This protective effect may be lost when oestrogen levels are decreased.

Research in rats has shown that oestrogen helps to increase the number of connections in the memory centre of the brain. The reduction of oestrogen in post-menopausal women may make the more prone to learning and memory problems that are related to Alzheimer's disease.

Oestrogen can also affect the way chemical messengers such as serotonin, acetylcholine and dopamine are used to send signals throughout the brain. Some Alzheimer's disease symptoms are linked to these chemical messengers which are thought to contribute to symptoms.

Research has shown that oestrogen may help to protect the brain from Alzheimer's by blocking some of the harmful effects of the amyloid-β protein, which builds up in the disease and causes brain cells to become damaged or die. 

One way that amyloid-β harms cells is by increasing the production of molecules inside the cells, called free radicals. Free radicals are a normal by-product of energy production, but too many of them can be harmful. The damage these excess free radicals cause to brain cells has been linked to Alzheimer's disease.

Molecules called antioxidants act as an antidote to free radicals by neutralising them, so they are no longer harmful. Studies in rats have shown that higher oestrogen levels can reduce the number of free radicals produced by cells. Researchers think oestrogen does this by helping make more antioxidants. This could explain why the sudden drop in women's oestrogen levels following menopause seems to make them more vulnerable to Alzheimer's disease.