There is a lot of talk about estrogen’s protective effects on the brain.
Estrogen is thought to prevent dementia in multiple ways: reducing inflammation of the nerves, preventing loss of estrogen receptors, reducing oxidative damage to the brain, helping the hippocampus and frontal cortex function better, and improving cholinergic and serotonin function.
But there was a large study (the Women’s Health Initiative Study in 2000) which said estrogen did not help. The original study’s findings have been challenged though, and it does appear there may be a window you need to start HRT, after which starting HRT may not be effective or may even be bad. This is called the
“window phase” theory of estrogen’s dementia prevention,
and the window is within the first five years of menopause.
We are always updating our information at Biohackr Health, as this is a rapidly evolving space. Menopausal women were neglected for decades, and it appears whether to do hormone replacement and its benefits and risks are being redefined. This was a 2023 comprehensive review in Cureus, “The Role of Estrogen Therapy as a Protective Factor for Alzheimer’s Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature.” We like comprehensive reviews like this, as they aggregate data, and bigger numbers means better more accurate insights.
What do they discuss? Estrogen seems to be related to dementia.
- There are many studies that postulate estrogen decline causes the increased risk of Alzheimers in women.
- There are studies that show faster cognitive loss in women who had early onset menopause (age 45).
- Women who had ovary removal before menopause have a higher lifelong risk of dementia and cognitive impairment
- The WHI study suggests an increased risk of Alzheimer’s disease in women over 65 who are given oral estrogen, with or without progesterone. (NOTE: please see the note above about the window phase theory- you need to start soon around menopause.)
Why do they think estrogen may help?
- Studies have shown estrogen helps maintain brain tissue integrity
- It promotes cholinergic activity. The cholinergic system plays an important role in memory and learning, and is prevalent in the hippocampus.
- Protects the brain from toxic insult. It lowers inflammation by reducing pro inflammatory cytokines.
- Stimulates neurons to be made
- Reduces deposition and helps clear Beta amyloid (Alzheimer plaques)
- With age, the gene expression of spliced ERα mRNAs and aromatase enzymes declines, especially in brain areas related to memory and learning. This correlates with what is seen in Alzheimers, which suggests estrogen plays a role.
- Brain mitochondria may be a target of estrogen’s effect. “Brain mitochondria are involved in brain energy production, oxidative stress regulation, and apoptosis. Oxidative stress accelerates with aging, accumulating reactive oxygen species that damage lipids, proteins, and mitochondrial DNA. Mitochondrial dysfunction from oxidative stress is the first pathology seen in the aging brain and dementia.
- Improves blood flow to areas of the brain, visible on functional MRI scans and PET scans, which correlated to better memory by estrogen via changes in the hippocampus and prefrontal cortex.
They conclude though that more studies need to be done. “Despite the promising positive cognitive effects estrogen therapy has displayed in laboratory studies, this has yet to be strongly and unequivocally replicated in human studies.”
How can Biohackr Health help?
We do believe in the many benefits of hormone replacement in menopausal women. There does appear to be growing support for a “window” in which you should start therapy, and that window seems to be within the five years immediately after menopause. The average age of menopause is 51-52, so that means you should start with HRT before age 57. The data for starting therapy in your 60s is more mixed. One idea that resonates is that HRT SLOWS decline, it cannot reverse it, which would explain the window theory.
As for how much? how long? Those are things to discuss with a doctor (yours or our telehealth visit with our clinicians). The answer will vary from person to person. What is your dementia risk? Dementia blogs
- TEST. See your hormone levels. There are also correlations between dementia and LDL, diabetes, and more. There is a test for the Alzheimer gene. All these tests are collected in our clinic and you may use FSA/HSA accounts to pay. BRAIN TESTING
- TREAT. We have bioidentical hormone pelleting, crafted to your individual lab results, and we have telehealth visits for those who want oral medications and patches.
- EVALAUTE YOUR OTHER RISK FACTORS FOR DEMENTIA. Strong genetics for dementia? Early menopause? Just really really want to prevent it? There are many other ways to lower your risk as well. Read the blogs (link above)
Estrogen and hormone replacement have a multitude of effects: brain, heart, blood sugar, libido, bone health, and more. The essence of biohacking is to TEST, figure out YOUR issues and goals, DO INTERVENTIONS from medications, supplements, exercise, weight loss, glucose monitors, building muscle and more, and the RETEST. There is no “one size” fits all here.
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MEDICAL REFERENCE: Comprehensive Review of Estrogen Protection for Dementia