Women who enter the menopause early may be more likely to develop dementia, according to US researchers, who found that starting hormone replacement therapy around the time of diagnosis appeared to remove the risk.
The findings are tentative, and need to be confirmed by larger studies, but suggest that starting hormone therapy soon after the first symptoms occur may be better for brain health as well as reducing heart disease and other medical issues linked to the menopause.
“When it comes to hormone therapy, timing is everything,” said Dr JoAnn Manson, a senior author on the study at Brigham and Women’s hospital in Boston, Massachusetts.
Up to 10% of women experience premature menopause, defined as menopause that occurs spontaneously before the age of 40. The condition has been linked to a greater risk of Alzheimer’s disease, but whether changes in sex hormones drive dementia is not well understood.
Hormone replacement therapy can improve severe menopause symptoms from hot flushes to night sweats and mood swings, but its impact on brain health has been less clear.
Writing in Jama Neurology, the researchers describe how they used brain scans from 193 women and 99 men to map the presence of two proteins, beta-amyloid and tau, which are hallmarks of Alzheimer’s disease.
Women are more likely than men to develop Alzheimer’s, and as expected, the scans revealed more tau protein in women than men of the same age, particularly when they also had high levels of brain amyloid. But the scans also showed that the link between abnormal amyloid and tau was far stronger in women who entered the menopause prematurely.
When the scientists delved deeper, to see if hormone therapy was linked to the build-up of abnormal proteins, they found evidence that it was, but only when women started the therapy five years or more after entering the menopause.
“Hormone therapy can have negative effects on cognition, but only if initiated several years after age at menopause,” said Dr Gillian Coughlan, an author on the study at Massachusetts general hospital.
The authors say the findings are in line with clinical guidelines which state that HRT is safe when used close to the onset of menopause, but add that the therapy may increase the risk of dementia if started late.
Dr Sara Imarisio, head of research at Alzheimer’s Research UK, said that while the findings may seem concerning, the authors do not show that hormone therapy drives Alzheimer’s disease. “The researchers didn’t look at whether the participants went on to develop symptoms of dementia, and we can’t be sure of cause and effect in this kind of research,” she said.
“There’s a lot more to understand about how menopause and HRT influence dementia risk. We need to see larger studies and controlled clinical trials to better understand this complex area of research and make sense of conflicting findings that have emerged in recent years.
“Some past research has highlighted potential cognitive benefits of hormone therapy, while other studies point to an increased risk of memory and thinking problems. While this study contributes valuable new data to this topic, we still aren’t able to point to a definitive link between hormone therapy and Alzheimer’s or dementia,” she said.
