- Estrogen is a key hormone that may help protect the brain and blood vessels.
- Experts want to understand how hormonal components affect brain health in the long term.
- One study among older women suggests that greater estrogen exposure across the life span, such as through menopausal hormone therapy, may benefit cerebrovascular health.
A recent study published in Neurology, the medical journal of the American Academy of Neurology, examined how estrogen affected neurovascular health in a group of older women
The findings suggest that greater long-term exposure to estrogen may benefit women’s brain health, as women make up two-thirds of the dementia population and have a higher risk for Alzheimer’s disease
The researchers observed that the use of menopausal hormone therapy, for example, was associated with greater white matter integrity
These results point to the need for more research into estrogen’s protective effects and how this may relate to preventing dementia
Assessing reproductive life span, contraceptives, and menopause therapy
Research has found that estrogen supports cerebrovascular health and that problems with estrogen may contribute to certain brain problems. This study focused on key aspects of estrogen exposure among Swedish women
For the study, researchers selected participants from a longitudinal study called the Gothenburg H70-1944 Birth Cohort
There were three main components to the research: participants’ reproductive lifespans, oral contraceptive use, and menopausal hormone therapy. Reproductive lifespan is the period from the first period to menopause
This research included 352 women, with an average age of 70. All women had undergone brain MRIs and did not have neurological conditions like dementia. Researchers also analyzed data from 205 participants who underwent MRIs five years later
The participants provided data on reproduction and hormone use, such as the ages at which they experienced menopause, as well as their use of oral contraceptives and menopausal hormone therapy. The average reproductive span for participants was just over 37 years
Researchers looked at a number of markers of cerebral small vessel disease
, which are certain findings in the brain that can increase dementia risk. They also examined other components of brain health, such as white matter integrity
Overall, researchers found that a longer reproductive span was associated with lower levels of cerebral small vessel disease. More specifically, being older at the time of menopause was linked to lower cerebral small vessel disease burden, but the age of participants’ first period didn’t have a significant association
Researchers also found that oral contraceptive and menopausal hormone therapy use were both linked to greater white matter integrity. However, after correction, the association for oral contraceptives did not remain
Menopausal hormone therapy was further linked to lower cerebral small vessel disease burden
Further analysis of the individual markers of cerebral small vessel disease found only marginal associations between most factors and menopausal hormone therapy. Experiencing menopause at a later age was linked to a lower chance of having one cerebral small vessel disease marker: lacunes
When looking at combined effects, women who used menopausal hormone therapy and oral contraceptives had lower chances of cerebral small vessel disease and greater global integrity of white matter, compared to women who didn’t use either
How the Alzheimer’s gene affects the study results
Researchers also sought to see how APOE-ε4 played a role in everything. People who are carriers of this specific form of the APOE gene are at a higher risk
for Alzheimer’s disease
The greatest key finding in this area was that among participants who were APOE-ε4 carriers, menopausal hormone therapy was linked to greater thickness in key areas of the brain that are related to Alzheimer’s disease. However, these findings didn’t remain after correction
When looking at the five-year MRI follow-ups, researchers found that menopausal hormone therapy use trended toward a slower accumulation of white matter hyperintensity volume, another marker of cerebral small vessel disease
Study authors Giulia Lorenzon, MSc, PhD, Postdoctoral Associate, and Anna Marseglia, PhD, Assistant Professor, summarized the main findings of the study to Medical News Today:
“We found that women with a longer reproductive life span—the time between their first period and menopause—had fewer signs of damage to the brain’s small blood vessels at age 70. Women who had used menopausal hormone therapy also showed less small-vessel disease.”
“Additionally, use of hormonal birth control and menopausal hormone therapy was associated with better-preserved white matter, the tissue connecting different brain regions, with the most favorable profile among women who had used both. Menopausal hormone therapy was also associated with better-preserved gray matter in Alzheimer’s-vulnerable regions, but only among women carrying the APOE-ε4 genetic risk factor,” Lorenzon and Marseglia added.
What the study may be missing
This research does have a number of limitations. First, it doesn’t establish any causal relationships. Second, researchers lacked data in certain areas, such as how long participants were using menopausal hormone therapy, so delving into more specifics may be warranted with future research
They also had limited information in areas like gender identity and adverse experiences regarding hormone use. Third, researchers had to rely on participants’ self-reports, which are not always accurate
How researchers chose to define surgical menopause may also be different from how it is defined in other studies, since it focused on removal of both ovaries rather than hysterectomies
Researchers were also limited by their reliance on a cohort from a longitudinal study. While the sample was useful, it may limit generalizability. Researchers only had limited data from the five-year follow-up. Additionally, the follow-up period was relatively short and limited to participants who didn’t have cognitive impairment. There’s a possibility of selection bias in the follow-up as well.
It’s also worth noting that only certain findings remained statistically significant after correction. Researchers were limited in certain analyses, such as having only a small subsample when examining cerebrospinal fluid
While the results suggest a benefit of long-term estrogen exposure, additional research is still required to confirm the findings, and looking at more diverse populations may be useful
What these findings mean for dementia risk
This research does point to possible brain benefits of long-term estrogen exposure in women. This could be helpful in addressing dementia risk, a critical health issue
Dung Trinh, MD, internist, of MemorialCare Medical Group and Chief Medical Officer of Healthy Brain Clinic in Irvine, CA, who was not involved in the study, noted the following:
“It is very important for researchers to continue to find new ways to potentially lower dementia risk in postmenopausal women because women account for a large proportion of people living with Alzheimer’s disease and dementia, and menopause represents a major biological transition that may influence brain metabolism and long-term neurologic health.”
“We still do not have a way to completely prevent Alzheimer’s disease, so identifying modifiable risk factors during midlife could have a major public-health impact. Even a modest reduction in dementia risk, if applied across millions of women, could translate into a meaningful reduction in future cases,” Trinh told us
However, it is important to note the need for more research and that these findings don’t change current clinical recommendations when it comes to external exposure to estrogen, such as from menopausal hormone therapy. Lorenzon and Marseglia explained:
“Our findings are not intended to change current clinical recommendations for oral contraceptives or menopausal hormone therapy. The study is observational, so we cannot establish cause and effect or determine whether hormonal exposure protects against cognitive decline or dementia.”
“In particular, there is currently insufficient evidence to recommend menopausal hormone therapy solely for long-term brain protection. Treatment decisions should remain individualized, considering symptoms, age, time since menopause, medical history, and individual risk factors,” Lorenzon and Marseglia said
