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Estrogen Hormone Replacement Therapy and Alzheimers Disease


Written by Dr. Welsh, Published on 13 September 2013

Estrogen Hormone Replacement Therapy and Alzheimer's Disease

Hormone Replacement Therapy can do a lot of amazing things. In the early twenty-first century, scientists are just exploring the tip of the iceberg when it comes to the benefits of various hormone treatments, including Estrogen, Testosterone, and Human Growth Hormone.

Although research has shown no evidence that Estrogen Replacement Treatments can alleviate the symptoms of Alzheimer's disease, there is promising evidence that Estrogen Therapy can reduce the risk of Alzheimer's disease in women, even women that are otherwise healthy.

Menopause Problems

As we all know, Menopause is a period of great Hormone Imbalance. From puberty to menopause, women experience a fairly predictable pattern of hormone levels, and their body ultimately benefits from this stability. Upon Menopause, however, hormone levels start to change significantly. Primarily, Estrogen Levels drop like a rock as the Ovaries greatly reduce their production.

There are multiple symptoms associated with Menopause, and they all have a negative impact on both life and health. Among these symptoms are:

Cold Sweats

Hot Flashes

Memory Loss

Emotional Instability

Loss of Sexual Desire and Ability

These are the symptoms that women experience explicitly during the period of Menopause. For the most part (with the exception of sexual issues), these symptoms of Menopause dissipate slowly over time.

Long Term Symptoms of Hormone Deficiency

In recent years, however, researchers are discovering that there are many issues related to Hormone Deficiency that put women at risk for the rest of their lives. One risk that seems highly correlated with Estrogen Deficiency after Menopause is Alzheimer's disease.

Alzheimer's is a disease which is much more common among women than men. The risk for a woman to develop Alzheimer's is almost double that of a man. Of course, part of that increased risk is due to the fact that women, on average, have a longer lifespan than their male counterparts, but that only explains away a small portion of the difference.

Why do Women Get Alzheimer's More than Men?

In recent years, there have been a limited amount of studies conducted regarding the connection between Estrogen Deficiency and Cognitive Decline, but the research has been illuminating, to say the least. This research suggests that the administration of Estrogen Hormone Replacement Therapy can have a stimulative effect upon mental health in women, both assuaging Age-Related Cognitive Decline and even postponing or reducing the risk of Alzheimer's Disease.

For many patients, especially those that are experiencing Estrogen Deficiency before Menopause, Estrogen Replacement Therapy can be combined with Progestin in order to maximize the effectiveness and safety profile of the treatment.

How Many People Struggle with Alzheimer's in America?

Alzheimer's is one of the worst medical issues plaguing modern American society. It is estimated that four million men and women are afflicted with Alzheimer's today. Considering that twice as many women as men will experience Alzheimer's in their lifetime, this is a significant portion of aging women.

Nearly every person in America intimately knows someone that has struggled with Alzheimer's, whether they had to take care of an immediate family member, or were simply an acquaintance. A few years ago, several research teams sought to answer once and for all, if Estrogen Replacement Therapy could be a legitimate treatment option for women that are at risk of Alzheimer's.

Can Estrogen Treat Alzheimer's?

As a result of their research, they found that Estrogen was ultimately not effective as a means to directly treat Alzheimer's Disease. Although they were unable to establish Estrogen as a potential Alzheimer's treatment, their research still strongly suggested that Estrogen Therapy could reduce the risk of developing Alzheimer's for women across the world.

Can Estrogen Prevent Alzheimer's?

There is potential that Estrogen Replacement could significantly delay the onset of Alzheimer's Disease, or, at a minimum, postpone the onset of the disease. Even if Estrogen only postpones Alzheimer's, it could still be an amazingly useful tool in combination with other treatments that would all but eliminate the risk of Alzheimer's Disease someday in the future.

The Benefits and Risks of Estrogen Replacement Therapy

There are countless women across America that have turned to Estrogen Treatments as a means to relieve the symptoms of Menopause. Every woman experiences Menopause in a different way, and some women are either more sensitive to the changes that take place, or produce lower baseline levels of Estrogen after Menopause.

Decades of research have proven the effectiveness of Estrogen at reducing the potential tempest associated with Menopause, and medical researchers have discovered powerful links between Estrogen Replacement Therapy and a reduced risk of Osteoporosis.

Cautious links have also been made between Estrogen Replacement Therapy and reduced risk of heart disease, although this link has not been confidently established. For some women, however, Estrogen Replacement Therapy can increase the risk of breast cancer, although the exact level of risk is not fully discerned. Although there are certain risks involved with Estrogen HRT, for a huge number of women, it seems likely and clear that the benefits far outweigh the costs.

Before new research regarding memory and cognition, this was essentially the state of play in regard to the potential benefits and risks of Estrogen Deficiency and Estrogen Replacement. Today, researchers are becoming keenly aware of the way that Estrogen and Estrogen Deficiency affect the brain and mental health.

Estrogen and Acetylcholine

In research utilizing both laboratory animals and cultivated brain matter, there is evidence that supports the notion that Estrogen has the ability to protect and support the health of neurons in the brain. One means by which it accomplishes this is by boosting resting levels of Acetylcholine in the brain.

Acetylcholine acts as a protective force in the brain, which safeguards against the breakdown of brain tissue associated with Alzheimer's disease. One of the physiological symptoms of Alzheimer's is that Acetylcholine Levels drop significantly among patients that suffer from the disease. In addition to this, Estrogen Replacement Therapy also seems to be able reduce the rate at which Beta-Amyloids form in the brain.

What are Beta-Amyloids?

Beta-Amyloid is the primary actor which leads to the physiological deterioration associated with Alzheimer's Disease. Although you have probably never heard of Beta-Amyloid, you probably know what it is whether you realize it or not. Beta-Amyloids are proteins which, when produced in the brain, lead to the clumps of tangled Amino Acids which are referred to as Plaques.

Estrogen Research in the 1990s

Before the turn of the century, there were only a small set of studies regarding the connection between Estrogen Supplementation and Alzheimer's. These studies suggested that Estrogen Replacement Therapy could restore some memory and cognitive ability in women suffering from Alzheimer's.

The problem with these studies is that they were for the most part small studies, and they also only evaluated patients over a short period of time. Although the studies showed some promise, they were not powerful enough to establish a significant link between Estrogen and the improvement of Alzheimer's.

In the years following these initial studies, however, three new studies were conducted which intended to explore these potential benefits in a way that could more firmly establish the potential effects of Estrogen Treatment on Memory and Alzheimer's. The biggest and longest of these studies was released in the Journal of the American Medical Association.

Testing the Hypothesis: Estrogen and Alzheimer's

This study was conducted by Ruth Mulnard of Cal-Irvine, a representative of the Institute for Brain Aging and Dementia. This study had a participant pool of 120 patients, half of whom had been discovered to have Alzheimer's disease. Half of the women in both groups were treated with Estrogen Replacement Therapy, the other half of both groups was treated with a placebo.

All patients received treatment for twelve months, and were regularly tested for alterations in language ability, mood, memory, and other cognitive abilities, in order to monitor any symptoms of cognitive decline. If Estrogen Replacement Therapy were able to improve the function of patients with Alzheimer's disease, then the treatment would cause women taking Estrogen to decline more slowly than the patients that did not receive the treatment.

Estrogen Ineffective at Treating Alzheimer's

Sadly, results showed that Estrogen has no effect upon patients that were already experiencing symptoms of Alzheimer's. Among the ninety-seven women that finished the study, the women with Alzheimer's taking Estrogen did not experience any improvement greater than placebo.

Two other studies displayed similar results, no conclusive evidence that Estrogen could relieve Alzheimer's. Dr. Henderson, a medical researcher from USC Los Angeles, said that he felt the studies were fairly conclusive, and that Estrogen Therapy alone probably doesn't have any significant benefits in regard to patients currently experiencing Alzheimer's Disease.

Estrogen May Benefit Alzheimer's Patients in Combination with other Treatments

Although these studies appear to put that aspect of the Estrogen-Alzheimer's Care debate to rest, that does not mean that Estrogen Replacement Therapy does not have other beneficial effects. Even Dr. Henderson feels that there may be a place for Estrogen Treatments when combined with other forms of therapy.

There are researchers that feel that Estrogen HRT may have beneficial effects when combined with a common Alzheimer's treatment known as Aricept (scientific name: Donepezil). Estrogen shares an important aspect in common with these common Alzheimer's medications: They all have the effect of increasing Acetylcholine in the brain, and there is strong reason to believe that Alzheimer's may have the ability to increase the effectiveness of these other forms of treatment.

Today, there is a limited amount of data supporting this hypothesis, but the data is promising. There have been two studies thus far conducted with regard to Estrogen's ability to supplement existing Alzheimer's treatments. Data-analysis after the studies were completed showed that a small segment of participants were taking Estrogen Treatments in combination with other forms of Alzheimer's medication. Although there were not enough women to lend significance to the results, it does show a certain level of potential, although we should be cautiously optimistic, perhaps.

Using Estrogen to Prevent Alzheimer's Disease

Although no studies today are able to confirm Estrogen Replacement as a means to alleviate the effects of Alzheimer's, there are a number of studies which provide evidence that Estrogen may be able to postpone Alzheimer's in women that do not suffer from the disease. There is even some hope that it may be a tool in Alzheimer's prevention.

In one of the most recent studies, 472 women were monitored over the course of sixteen years of their lives in the Baltimore Longitudinal Study of Aging. Although this study was not intimately concerned with Hormone Replacement Therapy as an Anti-Aging Treatment, the study was performed in a way which allowed a broad scope of analysis to be conducted.

Among the 472 subjects, there were a number which chose Estrogen Hormone Replacement Therapy, while many others went without such treatment. Looking back at the data, researchers found that women that chose to utilize Estrogen during and after menopause experienced Alzheimer's disease at half the rate of women that did not.

Small Pool of Participants Still Provides Promise

Although this research shows an immense amount of promise, more work needs to be done in order to more accurately assess the viability of Estrogen to Prevent Alzheimer's. At this point, the findings of the BLSA study amount simply to an exciting observation: Estrogen may be one of the most powerful tools that women have against both Alzheimer's and general Cognitive Decline.

Although we should be excited at such a prospect, we must also realize that there are other factors which may be at play. Women that choose Estrogen Replacement Therapy may experience these benefits for other reasons not fully associated with treatment, including genetics or nutrition. In addition to this, the reduced risk of Alzheimer's could also be the result of other factors which help them live a healthier life.

In general, women that choose Estrogen Replacement tend to be more conscientious about their health. Women that take Estrogen also tend to have stronger health care plans which allow them access to better treatments and health and wellness programs.

More Estrogen-Alzheimer's Studies Underway

Today, there are three more studies being conducted in order to more clearly show the benefits of Estrogen Replacement Therapy in regard to Alzheimer's. Of these three studies, two are being conducted by scientists in the United States, and a third by researchers in Great Britain.

Because these studies were designed specifically to uncover the potential benefit of Estrogen Replacement for Alzheimer's, they will be able to declare, once and for all, the Effect of Estrogen on Alzheimer's Patients.

All three of these studies will be placebo-controlled and double-blind in order to maximize the predictive value of the data. At random intervals, the patients will be tested and analyzed for cognitive ability. Researchers hypothesize that the combination of Estrogen and modern Alzheimer's care will slow down the rate at which the disease progresses.

As we all well know, Alzheimer's is a dreadful disease for which there is no known cure. If it indeed does have the ability to benefit women with regard to Alzheimer's risk or treatment, then it will completely change the way that we think about Estrogen Replacement Therapy in the future.

The Potential of Hormone Replacement

Even if Estrogen simply delays Alzheimer's or slows down the rate of decline associated with the disease, it will likely become a recommended treatment, especially for women that have a high risk for the disease as a result of genetics or other factors. Even if the link between Estrogen and Alzheimer's Prevention is weak, it will still significantly broaden our knowledge of the disease and how it should be most effectively treated.

Who Should Consider Estrogen Replacement Today?

Until the benefits of Estrogen for Alzheimer's can be fully proven, women should consider Estrogen Replacement Therapy in regard to other benefits that are more concrete, including cardiovascular health, Osteoporosis prevention, and to relieve the harshness of Menopause.

Although conclusive evidence regarding Alzheimer's and Estrogen Treatment are still years away, there are numerous reasons to consider Estrogen for Your Health.


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Estrogen Hormone Replacement Therapy May Diminish Alzheimer's Disease Risk

What is Alzheimer's?

Alzheimer's disease is the most diagnosed form of dementia in the world. As of yet there is no cure for the disease, but researchers worldwide are spending their entire careers attempting to discover ways to alleviate or even cure the syndrome. Our knowledge of the disease grows more quickly by the year and there is significant hope that within the coming generation our world's greatest minds will discover a means to defeat this dreaded degenerative condition. Alzheimer's develops in a different pattern and at a different speed for every patient, but the common symptoms are:

  • Increased aggression and irritability

  • High levels of confusion and disorientation

  • Rapid changes in mood

  • Atrophy of language ability

  • Long term, and eventually short term memory loss

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  • In later stages, a loss of physiological control, in which over time, the patient is eventually completely dependent upon a caregiver

There are three primary hypotheses regarding the cause of Alzheimer's:

Cholinergenic Hypothesis:

This was the original hypothesis regarding Alzheimer's disease, and treatment approaches using this theory as a starting point produce only minimal beneficial effects. This hypothesis predicts that Alzheimer's disease is largely the result of a reduced ability for the brain to synthesize acetylcholine.

Tau Hypothesis:

This hypothesis centers around the idea that abnormalities in a certain type of protein known as Tau Protein can cause the effects of Alzheimer's disease. It is hypothesized that hyperphosphorylated tau interacts with other forms of tau protein, creating clumps of protein known as neurofibrillary tangles inside of nerve cells. These tangles disrupt the function of nerve cells, clogging up the active transport system and preventing neuronal messages from reaching target destinations. At first, this leads to misdirected neuron firing but can eventually lead to the death of the neurons themselves.

The Amyloid hypothesis

The Amyloid Hypothesis is the most widely researched and studied hypothesis, and is the hypothesis for which the research discussed in this article is related to. According to this hypothesis, Alzheimer's is primarily caused by the formation of Beta-Amyloid deposits in the brain which clog up neuronal pathways, leading to the detrimental effects of the disease. One of the primary reasons why this hypothesis carries so much weight is because individuals who display an increased proclivity for the formation of these proteins display a greatly increased risk of the disease. Individuals with Down syndrome have three copies of this genetic abnormality, and as a result, these patients display symptoms of Alzheimer's at an age as early as 40.

New Study: APoE4 Precursor for Alzheimer's and Advanced Aging

Endocrinologists have made a number of discoveries regarding the effect of Estrogen Replacement Therapy on Alzheimer's, and New clinical research provides evidence that Estrogen Hormone Treatments may be able to slow down the process of aging in middle-aged females who are at increased risk of Alzheimer's disease. In this clinical study, otherwise healthy female patients who were going through menopause while also harboring a genetic increased risk of Alzheimer's did not succumb to the disease when treated with Hormone Replacement Therapy.

The genetic abnormality APoE4 has been linked to processes which speed up the natural aging process in women. Hormone Replacement Therapy featuring Estrogen may counteract the detrimental effects of this genetic condition and help older women avoid the ravages of Alzheimer's disease.

What is APoE4?

AP0e4 is the strongest causal genetic link for developing Alzheimer's disease. This gene is responsible for the production of an enzyme known as Apolipoprotein E Type 4. Apolipoprotein E is primarily released by macrophages and the liver in order to break down triglycerides. Ap0E4 performs this function, but is also correlated with creating devastating protein abnormalities in the brain which lead to Alzheimer's. Those who carry 2 copies of the Ap0E4 gene have a ten to thirty times increased likelihood of developing Alzheimer's disease.

Ap0E4 is so strongly correlated with Alzheimer's disease that James Watson, one member of the duo of scientists who first discovered the existence of DNA, refuses to be tested for the genetic abnormality. Individuals who have an active Ap0E4 gene have a 90% chance of developing Alzheimer's by the age of eighty without treatment. Although Alzheimer's research is incredibly active, there are still more questions than answers in regard to this devastating disease.

APoE4 Slowly Degrades the Body

According to Dr. Natalie Rasgon, ApoE4 affects women at the cellular level long before these changes affect the body to a noticeable extent, increasing the physiological age of the cells long before this aging process becomes apparent and symptomatic. Dr. Rasgon is a professor of behavioral science and psychiatry at the Stanford School of Medicine in California.

This new study provides further evidence that Estrogen Replacement Therapy may be able to shield many older women from the effects of Alzheimer's diseaseespecially those who harbor this critical gene.

One of a Number of Studies Linking APoE4 to Alzheimer's

There have been a number of previously conducted studies which have shown that ApoE4 likely plays a role in Alzheimer's disease and general cognitive decline as a result of the aging process.

In another similar study, not directly related to ApoE4, 472 female patients were followed for 16 years. Some of the participants utilized Hormone Replacement Therapy while others did not utilize the treatment. Researchers found that patients who used Estrogen in addition to other forms of Hormone Replacement Therapy had an incidence of Alzheimer's which was fifty percent lower than those patients which did not use the therapy.

This gene is incredibly common among Alzheimer's patients, and is active in around forty percent of patients that are afflicted with the disease.

Dr. Rasgon's laboratory group focused primarily on telomeres, which are caps which close off the ends of chromosomes and are responsible for genetic stability. These telomeres function like genetic fuses over time. Each time that a cell reproduces, the telomeres become slightly shorter in length.

What are Telomeres?

Telomeres are areas of DNA which are at the ends of chromosome strands which consist of repeating lines of genetic data which are inert. These lines form a sort of cap on the ends of the chromosomes in order to prevent them from breaking down. During the process of cell replication, the enzymes which encourage the reproduction of chromosomes are unable to perform their function all the way to the very ends of cells, leaving a very brief portion of the chromosome un-copied.

If chromosomes did not have telomeres which featured this inert genetic data, then every time the cells divided, our chromosomes would lose vital genetic code and our bodies would deteriorate. These telomeres are partially consumed by the enzymes which encourage cell replication, but there are other cellular enzymes which are responsible for rebuilding telomeres. These cells are known as Telomerase Reverse Transcriptase. Under normal circumstances, telomeres set a soft limit on the natural life spans of animals, including humans. Telomeres play a major role in the aging process.

Studies such as those performed by Dr. Ragson help us understand more about telomeres and how we can extend our lifespans by manipulating the rate at which telomeres break down. There is also ongoing research regarding ways that telomeres can be adequately preserved or even lengthened in order to extend the lifespan. In many ways Hormone Replacement Therapy and Telomere Maintenance appear to be related.

Alzheimer's Correlated to Quicker Aging

The current body of scientific knowledge suggests that Alzheimer's and the biological aging process are likely correlated in a large subset of female patients.

If the telomeres reach a certain abridged size, the cells can begin to die off, or in other cases, the cells may lose their ability to continue to divide.

When the cells start to function abnormally as a result of the aging process, the signs of aging begin to become physiologically apparent on a holistic level. Symptoms of aging such as loss of muscle tone and cognitive sharpness, as well as wrinkled skin start to manifest, in addition to other negative side-effects which affect every system of the human body.

The rate at which the telomeres shorten is highly variable among individuals, and this can be used in order to accurately measure biological age, which is systematically different from chronological age, affecting each individual at a unique rate not entirely dependent upon simply time.

The researchers studied telomeres sampled from white blood cells drawn from seventy completely healthy women, generally aged between forty five and sixty five. All seventy were taking Estrogen Hormone Replacement Therapy.

How Might Estrogen Prevent Alzheimer's?

When menopause begins, estrogen levels decline at a rapid pace. There are a number of symptoms that almost all women are aware of, including cold sweats, hot flashes, mood instability, and lapses in memory. What most women probably do not realize is that menopause can increase the risks of a number of other medical issues as well, including Alzheimer's disease. In the past, there have been a few small scale studies that suggested that Estrogen Replacement Therapy may be a treatment option for those who suffer from Alzheimer's disease.

Although the benefits in regard to reversing the effects of Alzheimer's with Estrogen Replacement Therapy seem to be slim, there is growing evidence that Estrogen may be able to prevent the disease or slow its progression, especially when utilized during the period of Menopause. These benefits may persist later in life as well, when Estrogen HRT is utilized in smaller doses.

New studies have also shown that Estrogen provides a number of benefits to the brain in addition to safeguarding it against the threat of Alzheimer's. There has been a significant amount of animal research performed in regard to the Effects of Estrogen on Brain Cells, and it is apparent that the hormone plays a major role in protecting and supporting the function of brain cells.

Estrogen Associated with Healthy Acetylcholine Levels

Healthy Estrogen levels are associated with optimal levels of acetylcholine in the brain, which is important to the maintenance of cognition and memory. Estrogen also apparently has the ability to shut down the formation of plaques known as Beta Amyloids, which cause the symptoms of Alzheimer's disease. Beta Amyloid plaques are the result of an enzyme abnormality which causes the enzymes to produce malfunctioning proteins which breakdown the function of the brain, eventually leading to total cognitive breakdown and death.

Although Estrogen alone may not be a proper treatment for active Alzheimer's, there is still promise that Estrogen HRT when utilized in combination with other forms of Alzheimer's medical treatment such as Aricept (donepezil) may be able to improve health outcomes for patients with Alzheimer's disease.

APoE4 Study Parameters

The seventy women on Estrogen HRT were split into two variable groups. The first group of women stayed on Hormone Replacement Treatments, while the second group stopped all hormone therapy.

After two years, the participants had their white blood cells drawn a second time, and the scientists measured the rate by which the length of the telomeres shortened.

Among the healthy patients who halted Hormone Replacement Therapy, those with the active Alzheimer's gene were found to be 6 times as likely to have telomeres which shortened at an abnormally rapid pace than participants who did not have an active Alzheimer's gene.

For these women who did have the active ApoE4 gene, the telomeres reduced in length at a rate which would normally be expected over the course of a decade, rather than simply two years. Physiologically, these women were aging at a rate which was five times as fast as those with the deactivated gene.

Estrogen Slows Down Biological Aging Associated with APoE4

Hormone Replacement Therapy featuring Estrogen was shown to alleviate this issue, however. In patients who were at enhanced risk of Alzheimer's yet remained on Estrogen HRT, telomere length shortened at a normal rate which correlated with their cohorts with the deactivated gene.

This is powerful evidence that Hormone Replacement Treatments with Estrogen may have the ability to delay or prevent Alzheimer's disease, although much more study is needed in order to prove the hypothesis.

Professor Rasgon says that this study increases our knowledge of the benefits of Estrogen Replacement Therapy and in the future will help us pinpoint exactly which patients are likely to receive the maximum benefit from the hormone treatment.


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Written by Dr. Welsh, Published on 02 May 2013

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