Dementia risk rises with menopausal hormone therapy

A nationwide study explores the link between menopausal hormone therapy and dementia.


A study from Denmark suggests that menopausal hormone therapy might be linked to a higher risk of dementia and Alzheimer’s disease. This was true for both those who used it for a long time and those who used it for a short time around the age of menopause (around 55 years). This matches what the most significant clinical trial on this topic found. While these findings are necessary, we can’t say for sure that hormone therapy directly causes dementia.

The researchers want more studies to see if there’s a real connection. Another group of researchers also says that while this study is good, we can’t automatically say that hormone therapy causes dementia based only on these results.

Menopausal hormone therapy (known as HRT) is used to help with menopausal symptoms like hot flashes. It comes as pills with only estrogen or a mix of estrogen and progestogen. There are also patches, gels, and creams. Studies show that using HRT for a long time might lead to dementia. This agrees with the most prominent research on this topic. But it’s not sure about short-term use around menopause age like recommended.

Researchers also don’t know how different HRT types affect dementia risk. Researchers in Denmark wanted to learn more, so they looked at how using a mix of estrogen and progestin affected dementia risk based on the kind of treatment, how long it was used, and the age when it was used.

Using information from a national database, the researchers found 5,589 cases of dementia and 55,890 women without dementia (matched by age) between 2000 and 2018. They focused on Danish women aged 50 to 60 in 2000 who had no history of dementia or conditions stopping them from using menopausal hormone therapy. They also considered other important factors like education, income, hypertension, diabetes, and thyroid disease.

The average age when dementia was diagnosed was 70 years. Before being diagnosed, 1,782 cases (about 32%) and 16,154 controls (about 29%) had used estrogen-progestin therapy. They started using it around age 53, on average. Both cases and controls used it for about 3.8 years on average.

The results show that compared to those who never used this treatment, those who used estrogen-progestin therapy had a 24% higher chance of developing any kind of dementia, including Alzheimer’s. This higher risk was seen even in women who started the treatment at age 55 or younger.

The longer women used the treatment, the higher the rates of dementia, ranging from 21% for one year or less to 74% for over 12 years. Whether they used the treatment every day (continuous) or just some days of the month (cyclic), the dementia rate increase was similar. Using progestin-only therapy or vaginal estrogen only didn’t show a link to dementia risk.

This study can’t prove a cause-and-effect relationship. It couldn’t separate one type of dementia from others or compare tablets to other hormone therapy methods, like patches.

Additionally, it’s possible that women who used hormone therapy were more likely to have both menopausal symptoms and a risk for dementia.

Despite being an extensive and well-done study with a long follow-up time, it’s important to remember that it can’t prove whether hormone therapy causes dementia. The researchers were able to look at different types of hormone therapy when women started and how long they used it. This helped them explore an essential question about short-term use around the age of menopause, which is recommended. The researchers suggest that more studies are needed to figure out if hormone therapy affects dementia risk or if there’s something else going on with the women who need this treatment.

American researchers also agree with this idea in a linked article. They say other health issues might make it look like hormone therapy is linked to higher dementia risk, especially in younger women. They also mention that the best evidence comes from randomized clinical trials, where people randomly assign treatments. Additionally, they think that using brain imaging tests could help understand hormone therapy’s effect on dementia in the early stages.

Journal Reference:

  1. Nelsan Pourhadi, physician et al., Menopausal hormone therapy linked to increased rate of dementia. The BMJ. DOI: 10.1136/bmj-2022-072770.
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