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Menopausal hormone therapy may have an impact on dementia risk. Anna Berkut/Stocksy
  • About 45% of all women use menopausal hormone therapy to help alleviate symptoms of menopause.
  • Previous research shows certain types of hormone replacement therapy (HRT) may increase a woman’s risk of severe diseases.
  • Researchers from Copenhagen University Hospital – Rigshospitalet say menopausal hormone therapy is associated with an increased risk of dementia and Alzheimer’s disease.
  • These findings contradict previous studies stating HRT may help lower a woman’s risk of developing dementia.

About 45% of all women globally use menopausal hormone therapy — also known as hormone replacement therapy (HRT) — to help alleviate the symptoms of menopause.

HRT has some known side effects, like migraine and nausea. Previous research also shows women who use certain types of HRT may increase their risk for stroke, gallbladder issues, and certain cancers, including breast and endometrial cancers.

Now, researchers from Copenhagen University Hospital – Rigshospitalet have found that menopausal hormone therapy is associated with an increased risk of dementia and Alzheimer’s disease.

These findings contradict previous studies stating HRT may help lower a woman’s risk of developing dementia.

This study was recently published in the journal The BMJ.

Every woman goes through menopause — a time when their ovaries cease producing and releasing eggs, and their menstrual cycle ends.

A person typically enters menopause between the ages of 45 and 55. The menopausal transition, known as perimenopause, may last between seven to 14 years.

Common symptoms that a woman starting menopause may have include:

Although menopause is a natural aging process, it includes changes a person may want to alleviate as much as possible. Possible treatments for menopause-related symptoms include:

Additionally, certain lifestyle changes can help provide relief from some symptoms:

HRT is a medication that aims to increase and balance the amount of the hormones estrogen and progesterone in a woman’s body.

Although both of these hormones are naturally made by the body’s ovaries, during menopause, this decreases, causing menopausal symptoms.

Depending on a woman’s situation and needs, there are two main types of menopausal hormone therapy a doctor may prescribe:

HRT is available in various applications, including pills, nasal sprays, skin patches, and vaginal creams or suppositories.

Potential side effects of HRT include:

According to Dr. Nelsan Pourhadi, a researcher in the Danish Cancer Society and the Danish Dementia Research Centre in the Department of Neurology at Copenhagen University Hospital – Rigshospitalet in Copenhagen, Denmark, and lead author of this study, the aim of the study was two-sided and based on understudied aspects of the research area.

“Firstly, we wanted to investigate the association between the use of menopausal hormone therapy as recommended in guidelines and the risk of dementia. Second, we wanted to investigate continuous versus cyclic treatment regimens,” he explained to Medical News Today.

For this study, Dr. Pourhadi and his team analyzed data from a national registry database, including about 5,600 women with dementia and almost 56,000 age-matched women who had no dementia diagnosis as the study’s controls. The data spanned from 2000 to 2018 and included Danish women ages 50 to 60 years in 2000 with no history of dementia or that didn’t have any contraindication for the use of HRT.

The average age of dementia diagnosis for the participants was 70 years. Before receiving a diagnosis, 32% of women with dementia and 29% of controls had received estrogen-progestin (a synthetic form of progesterone) therapy from an average age of 53. The average duration of therapy was 3.8 years for women with dementia and 3.6 years for the control group.

Upon analysis, the researchers found women who received estrogen-progestin therapy had a 24% increased risk of developing all-cause dementia and Alzheimer’s disease. This was even in women who received the treatment at the age of 55 or younger.

“The findings align with those of the largest clinical trial in the area, the Women’s Health Initiative Memory Study (WHIMS),” Dr. Pourhadi said.

“While WHIMS reported an increased rate of dementia in women using menopausal hormone therapy from age 65 years, we additionally observed this increase in women using menopausal hormone therapy close to the age of menopause.”
— Dr. Nelsan Pourhadi

Additionally, researchers reported the risk rates increased with longer HRT use, ranging from 21% for one year or less of use to 74% for more than 12 years of use.

This is not the first time researchers have looked for an association between HRT and dementia risk.

Previous studies have reported menopausal hormone therapy may help decrease a woman’s risk of developing dementia. One study published in May 2021 linked menopausal hormone therapy use to a reduced risk of developing all neurodegenerative diseases, including Alzheimer’s disease and dementia.

And a study in June 2022 found HRT used after menopause was associated with a decreased risk for Alzheimer’s disease and vascular dementia in women with depression.

And other studies have also outlined an association between HRT and an increased risk of developing dementia. Research published in September 2022 found HRT was associated with an increased risk of dementia.

And a study just published in April 2023 says women who started menopause early or who began HRT more than five years after menopause began had higher levels of tau protein in their brain, which is considered to be one of the driving factors of Alzheimer’s disease.

“It is important to note that our findings are in line with those of the largest clinical trial on the topic, WHIMS,” Dr. Pourhadi said when asked why previous and current research may have contradictory findings. “Most other clinical trials were hampered by limitations such as small selection, sample sizes, short follow-up time, and outcomes solely based on cognitive testing, not a clinical assessment of dementia.”

“Further, previous observational studies were unable to assess the use of menopausal hormone therapy close to menopause, especially short-term use,” he added. “These differences may explain the differences between the findings of those studies and our study.”

When asked about the next steps in this research, Dr. Pourhadi said as this is an observational study, it is unable to determine causality between menopause hormone therapy and dementia.

“Therefore, further research is needed to clarify if the observed association can be expected to be causal. Furthermore, it is of interest to differentiate between various modes of administration of menopausal hormone therapy, (e.g. tablets, patches, gels),” he added.

Dr. Mindy Pelz, a holistic health expert focused on women’s health and hormonal health, who was not involved in this study, agreed.

“This new study is observational, and it’s important not to overstate its findings. Correlation is not causation, and previous studies have found that menopausal hormone therapy actually reduces dementia risk, so it’s possible there’s a missing variable here that we haven’t considered yet,” she said.

“For example, a lot of women experience cognitive deficits during menopause — a possible indicator of future dementia — and they may be more likely to pursue hormone replacement therapy to help relieve their symptoms,” ,” she explained to Medical News Today.

After reviewing this study, Dr. Jewel Kling, assistant director of Women’s Health Internal Medicine at Mayo Clinic in Arizona, who was not involved in this study, also told Medical News Today that as this is an observational study using national registry data, we cannot infer a causal relationship between menopausal hormone therapy and dementia risk.

“(We) can only say there was a relationship found between the two in their results — the only way to infer causation is through a randomized control design, which this wasn’t. That relationship could be potentially explained by multiple other factors that cannot be better accounted for based on the design of the study,” she continued.

“Randomized control studies evaluating these outcomes, and/or studies looking at brain imaging biomarkers would be better positioned to evaluate the effects of hormone therapy on dementia to inform clinical care,” she added.

As for the next steps in this research, Dr. Melanie Marin, director of the Menopause Program in the Raquel and Jaime Gilinski Department of Obstetrics, Gynecology, and Reproductive Science at the Icahn School of Medicine at Mount Sinai, also not involved in the study, said she would like to see the U.S. have a nationwide database of HRT users to follow all these factors.

“Menopausal symptoms, other medical problems, type of hormone use, and length of hormone use. The best studies are long-term randomized, controlled studies. These require dedication, and most importantly funding. I would like to see our government dedicate more funding to these important questions of health for our populace,” she told MNT.