Hormones and dementia

Women are more at risk of dementia than men with women making up 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. Below we describe other reasons women may be more likely to develop dementia.

Most of the following research has focused specifically on Alzheimer's disease, which is the most common cause of dementia.

Why are women more likely to develop dementia?

We don't fully understand why women are more likely to develop Alzheimer's disease than men, but one of the main theories is 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 actually converted into oestrogen inside brain cells. This means that women who have been through menopause have lower levels of oestrogen in their brain than men of the same age. 

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

Oestrogen and the brain

Oestrogen affects the brain in several different ways, some of which researchers think could help explain how it could protect against Alzheimer's. For example, one study on rats has found that oestrogen helps to increase the number of connections in a particular area of the brain. This brain area, called the hippocampus, is important for memory and certain types of learning, which are both affected by Alzheimer's disease. 

Oestrogen can also affect the way chemicals such as serotoninacetylcholine and dopamine are used to send signals throughout the brain. Some of the symptoms of Alzheimer's disease are linked to problems with the acetylcholine signalling system, which could be connected to decreased oestrogen levels. Read ‘HRT and its effect on normal ageing of the brain and dementia’ for more information on this.

Oestrogen's protective effects

Alzheimer's is characterised by a build-up of amyloid-β and tau proteins in the brain. 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.

We still don't know exactly how these two proteins cause Alzheimer's, but we think it is by causing brain cells to become damaged or die.

One way that amyloid-β may do this 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.

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

Hormone replacement therapy

Some women choose to have hormone replacement therapy (HRT) when they go through menopause to 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.

Studies looking at whether replenishing oestrogen levels using HRT can reduce women's risk of dementia have been inconclusive and contradictory. For example, some studies of women who were already using HRT during menopause found that their risk of dementia was lower than those not on HRT. However, other studies found no strong evidence for this. There is some evidence that HRT may even increase dementia risk. Clinical trials looking at the use of HRT to treat Alzheimer's disease in women, rather than prevent it, did not show any beneficial effects on cognition.

Until there is better evidence, the potential benefits of HRT as a way to reduce the risk of Alzheimer's disease do not outweigh the potential risks of HRT, which includes an increased risk of certain types of cancer, heart disease and stroke.

Hormones may still provide a way to treat or prevent dementia though. Researchers continue to look for other hormones, and other ways of using oestrogen, which could be safer and more effective. More research into why women are more likely to get dementia than men is also important to help us understand exactly what causes it.

Understand more about risk factors for dementia with our interactive tool.