A large study has found an unexpected link between estrogen-only hormone therapy used later in life and a lower likelihood of dementia.
Women who had used the treatment were less likely to receive a dementia diagnosis and were also less likely to show several signs of Alzheimer’s disease in their brains after death.
The researchers stress, however, that the findings do not prove hormone therapy prevents dementia.
Hormone therapy is most commonly used to ease symptoms related to menopause, including hot flashes, night sweats, and vaginal symptoms.
Estrogen levels fall during menopause, and replacing some of that estrogen can provide relief for certain women. Decisions about hormone therapy are individualized because benefits and risks vary with age, medical history, the type of therapy, and when treatment begins.
Estrogen-only therapy is generally used in women who have had their uterus removed in a hysterectomy.
For women who still have a uterus, taking estrogen alone can increase the risk of cancer of the uterine lining, so a progestogen is usually added to protect the uterus. The new study focused only on estrogen-only treatment.
Researchers have debated for years whether menopausal hormone therapy affects the aging brain. Earlier studies have produced mixed results, and timing may be important. Some research has raised concerns about dementia risk when certain hormone treatments are started at older ages, while other work has suggested possible benefits under different circumstances.
The new research was led by Jennifer Bruno, Ph.D., of Stanford Medicine. Researchers examined information from two large datasets containing a combined 21,462 women who had undergone clinical assessments while alive. Participants were about 71 years old on average when follow-up began and were tracked for approximately three to five years.
Among all participants, 1,953 had used estrogen-only hormone therapy and 19,509 had not. The women who used hormone therapy had started it at an average age above 70. That detail is unusual because modern hormone therapy is generally started much earlier, often around the time of menopause rather than decades later.
The researchers examined several different measures of brain health instead of relying only on dementia diagnoses. One group of 728 women had brain imaging or biological marker testing while they were alive. Another 2,959 participants underwent brain autopsies after death, at an average age of 82.
The autopsy analysis looked for three major signs associated with Alzheimer’s disease. These included amyloid-beta plaques, abnormal tau tangles inside nerve cells, and neuritic plaques, which are amyloid deposits surrounded by damaged nerve fibers. Researchers combined these findings to estimate the amount of Alzheimer’s-related disease in the brain.
Women who had used estrogen-only hormone therapy showed fewer signs of Alzheimer’s disease at autopsy. About 18% of hormone therapy users had none of the three Alzheimer’s features, compared with 10% of women who had not used the treatment. At the other end of the scale, 40% of hormone users had all three features compared with 51% of nonusers.
After accounting for factors including age, education, genetic risk, race, and high blood pressure, hormone therapy users had 35% lower odds of showing Alzheimer’s disease signs at autopsy. This association remained even after the researchers tried to account for several important differences between the groups. Still, other unmeasured differences could have influenced the results.
Biomarker testing offered additional evidence. Women who used hormone therapy had patterns of amyloid-related proteins in blood and cerebrospinal fluid that were consistent with less amyloid being deposited in the brain. Amyloid is one of the proteins that can begin accumulating years before Alzheimer’s symptoms appear.
The clinical findings pointed in the same general direction. Estrogen-only hormone therapy use was associated with 39% lower odds of being diagnosed with dementia. Users were also less likely to show memory difficulties or declines in their ability to carry out everyday activities.
The study was published in Neurology. Its strength is that the researchers were able to examine several kinds of evidence, including clinical diagnoses, memory and function, biological markers, and actual brain tissue after death. Seeing similar patterns across these different measures makes the association worth further investigation.
However, this was an observational study rather than a clinical trial. Women were not randomly assigned to receive estrogen or no treatment, so the two groups may have differed in ways that affected dementia risk. Health, healthcare access, reasons for receiving hormone therapy, and other lifestyle or medical factors could partly explain the findings.
Another major limitation is that the treatment pattern in the study is very different from current medical practice. Participants who used estrogen began at around age 70 on average, while hormone therapy today is usually considered near the menopausal transition, often in a woman’s late 40s or 50s. Results from women treated decades ago therefore cannot simply be used to guide treatment decisions today.
The findings also should not be interpreted as a reason to begin estrogen at an older age to protect the brain. Hormone therapy can carry important risks and benefits that depend on the individual, and this study was not designed to establish whether starting treatment later in life is safe or beneficial. Randomized studies and further modern research would be needed before hormone therapy could be recommended for dementia prevention.
Overall, the study provides an intriguing clue about the relationship between estrogen and the aging brain. The consistent association with fewer Alzheimer’s changes, better biomarker patterns, and lower dementia odds deserves attention, but it does not establish cause and effect.
For now, hormone therapy decisions should continue to be based on established medical uses and an individual discussion of benefits and risks rather than on dementia prevention.
If you care about brain health, please read studies about Vitamin B9 deficiency linked to higher dementia risk, and flavonoid-rich foods could help prevent dementia.
For more health information, please see recent studies that cranberries could help boost memory, and how alcohol, coffee and tea intake influence cognitive decline.
Source: Stanford Medicine.
