The hormone replacement therapy (HRT) could be related to a decrease in the risk of dementia, especially in certain profiles of women, according to research developed by the University of East Anglia and the University of Exeter (United Kingdom).
The work followed more than 180,000 British postmenopausal women, making it the largest analysis of its kind to date. The data reveal that those who resorted to HRT had a 16 percent lower likelihood of developing Alzheimer’s, the most common form of dementia, compared to those who had never used this treatment.
The most pronounced reduction in risk was observed in women with surgically induced menopause, who showed a 26 percent lower risk of suffering from any type of dementia compared to those who did not take HRT.
The study, published in "Alzheimer's & Dementia," also found that women with lower natural exposure to estrogens throughout their lives, whether due to late menarche or early menopause, seemed to gain an additional benefit from HRT, with a 16 percent lower risk of suffering from any form of dementia.
The research was led by Professor Anne-Marie Minihane, from the Norwich Medical School at the University of East Anglia and director of the Norwich Institute for Healthy Ageing.
"Dementia affects millions of people worldwide, and women represent almost two-thirds of Alzheimer's disease cases, the main form of dementia. As populations age, understanding how sex-specific factors influence the risk of dementia is increasingly important," Minihane explained.
According to the expert, in addition to the greater female life expectancy, this difference is thought to be due to the impact of menopause on brain metabolism and the more pronounced effect in women of the main genetic risk factor, APOE4. "We wanted to better understand how HRT could prevent dementia and determine if certain groups of women might respond differently," she added.
HOW THE RESEARCH WAS CONDUCTED
To carry out the analysis, the team used health data from the UK Biobank and followed 183,450 postmenopausal women for an average of 13.3 years.
In that interval, nearly 4,000 diagnoses of dementia were recorded. The authors evaluated whether the use of hormone replacement therapy for at least one year was associated with the risk of developing dementia and whether this relationship changed according to different biological and genetic factors.
Likewise, the results were adjusted for variables that could influence both the probability of dementia and the prescription of HRT, such as age, socioeconomic status, the presence of other pathologies, and the use of medications.
"We found that women who had used HRT had about a 10 percent lower chance of developing dementia and a 16 percent lower chance of developing Alzheimer’s, compared to those who had never used this treatment. However, the protective association between HRT and dementia was not the same for all women," it was detailed.
GREATER BENEFITS IN CERTAIN GROUPS
"We found that HRT is especially beneficial for women who have undergone surgical menopause, for example, after the removal of the ovaries. In this group, women who used HRT had about a 26 percent lower chance of developing dementia than those who did not resort to this treatment," the researcher emphasized.
They also observed that women whose bodies had naturally produced fewer estrogens throughout their lives, due to starting menstruation later or reaching menopause early, seemed to gain greater benefit from HRT. Likewise, their risk of developing dementia was about 16 percent lower when they used HRT.
Genetics also proved to be relevant. The associations between the use of HRT and dementia were more intense in women carrying the APOE4 variant, a known risk factor for Alzheimer’s.
"This is really important because carriers of APOE4 are often considered women at higher risk and have fewer demonstrated prevention options," Minihane added.
THE TIMING OF STARTING TREATMENT MAY BE KEY
The age at which hormone replacement therapy was started also seemed to condition the results. Women who began HRT between the ages of 46 and 56 showed the greatest reduction in the risk of dementia.
This finding supports the so-called critical window hypothesis, which posits that hormone therapy offers more protection when started around the transition to menopause, and not many years later.
When HT was started outside that age range, the study did not observe the same level of benefit, reinforcing the importance of the timing of treatment initiation.
IMPLICATIONS FOR PERSONALIZED CARE
"Our results add to the growing evidence that the effects of hormone therapy on brain health are complex and influenced by individual biological factors," noted Professor Minihane.
"Although HT has traditionally been prescribed mainly to relieve menopause symptoms, such as hot flashes and night sweats, this work suggests that it could also play a role in the long-term cognitive health of some women," she emphasized.
This work expands on a previous study from the University of East Anglia, which had observed that HT was associated with better memory, superior cognitive performance, and greater brain volume in older ages in women carrying the APOE4 variant, linked to dementia risk.
The authors point out that this new data opens the door to more individualized strategies in the prescription of HT, considering the type of menopause, genetic burden, accumulated hormonal exposure, and the age of treatment initiation.
"These results represent a significant advance. Instead of simply asking whether HT affects the risk of dementia, we have been able to identify which women are more likely to benefit and at what time. This is the basis on which truly personalized approaches can be developed to protect women's brain health," concluded Professor David Llewellyn from the Faculty of Medicine at the University of Exeter.