Globally, dementia affects more women than men. Now, a large Danish study has examined the association between the use of hormone replacement therapy (HRT), also called menopausal hormone therapy (MHT), and the development of dementia, according to the type of hormone treatment, duration of use, and age.
MHT relieves the common symptoms of menopause, such as hot flushes and night sweats. It also addresses long-term biological changes, such as bone density loss, that result from declining levels of the naturally occurring hormones estrogen and progesterone during and after menopause. MHT includes tablets containing only estrogen, a combination of estrogen and progestogen (a synthetic version of progesterone), and skin patches, gels and creams.
Using Danish national registries, researchers from Copenhagen University Hospital obtained information from 5,589 dementia cases and 55,890 age-matched dementia-free controls between 2000 and 2018. All women were aged between 50 and 60 at the commencement of the study. Education, income, and the presence of other conditions such as high blood pressure, diabetes and thyroid disease were also taken into account.
The primary MHT of interest to the researchers was combined estrogen and progestogen treatment. Previous studies have shown that estrogen affects the development and aging of brain regions crucial to cognitive functions such as memory that are implicated in diseases like Alzheimer’s. Progestogen’s effect on dementia risk is uncertain.
The average age at first diagnosis with dementia was 70. Prior to diagnosis, 32% of cases and 29% of controls had received estrogen-progestogen treatment from, on average, the age of 53. The average duration of use of MHT was 3.8 years for cases and 3.6 years for controls.
The researchers found that compared to women who’d never taken MHT, those who’d used estrogen-progestogen therapy had a 24% increased rate of developing dementia of all causes and Alzheimer’s disease. This included women who started taking combination MHT at age 55 or younger.
Dementia rates were higher with longer MHT use, ranging from 21% for one year or under to 74% for more than 12 years of use. The rate was similar between continuous (daily) and cyclic use (daily estrogen-progestogen taken 10 to 14 days per month). The use of progestogen alone and estrogen delivered vaginally were not associated with the development of dementia.
A limitation of the study was that it could not distinguish a particular type of dementia, vascular dementia, from other types. Vascular dementia is caused by brain damage from impaired blood flow to the brain, which can occur following a stroke. Further, the researchers couldn’t rule out whether the women using MHT were predisposed to both menopause symptoms and dementia.
The study has led some in the medical community to recommend caution when interpreting the results.
“This is an interesting addition to ongoing research around menopause and its treatment,” said Gino Pecoraro, Associate Professor of Obstetrics and Gynecology at the University of Queensland. “Unfortunately, it raises more questions than it answers, and caution needs to be applied in interpreting its results.”
Kaarin Anstey, Scientia Professor of Psychology at the University of New South Wales, said, “the sample included women who were aged 50-60 in the year 2000. Therefore the types of HRT that the study are based on were those prescribed in Denmark during this period and there may be factors associated with the patterns of prescribing at that time which do not apply currently.”
Some were more blunt in their appraisal of the study.
“As for all observational studies, despite statistical adjustments for variables such as weight or education etc., women who choose to take MHT are different from women who do not,” said Professor Susan Davis, Director of the Women’s Health Research Program at Monash University. “So, the real elephant in the room for this analysis is: is the observed risk of dementia in MHT users due to the use of oral synthetic MHT or due to the reasons why women ever took MHT? This has been overlooked.”
The researchers are keen to point out that this was an observational study; it doesn’t establish a causal relationship between MHT and dementia.
“Further studies are warranted to explore if the observed association in this study between menopausal hormone therapy use and increased risk of dementia illustrates a causal effect,” the researchers said.
The study was published in the BMJ.
Source: Copenhagen University Hospital via Scimex
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