Estrogen, Menopause & Alzheimer's Disease
Gayatri Devi, M.D.
Menopause symptoms due to estrogen deficits, include memory problems,
trouble finding words, inability to pay attention, mood swings and irritability, in
addition to the more well known symptoms. These symptoms are often overlooked or left
untreated but should be addressed. Treatment will not only result in symptom remission but
may also, in my opinion, have preventive value. Some common questions I have
encountered in my practice about estrogen and memory loss include the following:
Q: Do I have Alzheimer's disease?
A: This unspoken fear is often the reason why women suffer in silence when they
experience cognitive symptoms during menopause. Scared about what they may
discover, many women opt not
to seek treatment. However, menopause related memory and cognitive disturbances are being
increasingly described in scientific literature and are generally responsive to treatment.
They can and should be addressed and treated.
Q: Does estrogen have an impact on functions of
A: Yes. Estrogen influences language skills, mood, attention, and a number of other
functions in addition to memory.
Q: How does estrogen affect the mind?
A: Estrogen docking sites are present in several regions of the brain, including those
involved in memory (such as the hippocampus). When activated by estrogen, these
sites, in turn, activate processes that are beneficial to the brain. In addition, estrogen may,
in effect, raise levels of certain brain chemicals (neurotransmitters). These
include the neurotransmitters acetylcholine (implicated in memory), serotonin (implicated
in mood), noradrenaline (implicated in mood and other autonomic functions), and dopamine
(implicated in motor coordination). Thus, estrogen facilitates networking between nerve
cells, promoting their ability to "talk to" one another.
Q: Does this mean that my recent irritability, apathy,
'foggy' state of mind, trouble finding words, constantly losing my keys, inability to
function at my job, etc. may be related to estrogen deficit?
A: Given estrogen's myriad role in brain processes, it should come as no surprise that it
can influence many of the mind's functions. However, a careful history and a thorough
examination are needed to sort through symptoms and rule out other
conditions. You should plan to spend about an hour with your physician to discuss the issues related to menopause,
symptoms and treatment options.
Q: What do the recent Women's
Health Initiative data mean to the average menopausal women?
A: This large, multi-center study found that replacement with an equine
estrogen and progestogen combination caused a higher incidence
of dementia, breast cancer, heart disease and blood clotting than in those
women on a placebo ("sugar pill"). In interpreting the
results, there are important caveats that need to be remembered:
1) Women were started on hormone
replacement in their sixties and some experts feel that starting
treatment earlier may have resulted in more benefits.
2) The data was derived from using equine estrogen
derived from pregnant mares. Whether the use of a
soy-based, biologically identical estrogen would
have changed the results is unclear.
3) The decision to discontinue the study was
not without dissenters. Significantly, researchers conducting a
similar trial called WISDOM in the United Kingdom, reviewed the
data from the WHI trial and unanimously voted to continue
on with their trial, given the lack of statistical significance
of difference in risks in the WHI trial. This decision was
reversed in several weeks following the recommendations of an
Q: I am on hormone replacement and my symptoms persist.
A: If your symptoms do not resolve with hormone replacement, you may need to discuss the
dosage and type of hormone replacement you are on with your doctor. Sometimes, changing to
another preparation is helpful. If problems still persist, you might want to seek further
help from a physician who specializes in this area.
Q: What are other treatment options for my problems?
Estrogen related cognitive deficits may be differentiated from those associated with other
conditions through a careful history, examination and testing. During this time in a
woman's life, many problems coexist, including treatable causes (e.g.: depression,
hypothyroidism). Neuropsychological testing is useful in this regard to
the nature of the problem. Testing will also establish a cognitive baseline for future
comparison. Treatment options will depend on the cause(s) of the memory loss.
Q: Ideally, what areas should be covered in
A: As estrogen affects various cognitive functions, comprehensive testing should assess
all aspects of language (reading, naming, understanding, word fluency), memory (both short
and long term memory, visual and verbal memory), and other cognitive functions (problem
solving skills, visuospatial skills, etc). Simple screening tools, such as the mini mental
status examination, will most often remain normal in peri- and post-menopausal cognitive
loss. A good neurocognitive battery of tests should establish a cognitive baseline for
future comparison and allow monitoring of treatment response.
Q: Will my depression get better if I go on estrogen?
A: If the mood changes are related to estrogen deficiency, they usually will respond to
hormone or estrogen treatment. If the mood changes persist, you need to discuss this with
Q: I have heard that estrogen prevents Alzheimer's
disease. Is this true?
A: Several naturalistic studies suggested that estrogen may reduce risk
for Alzheimer's by up to 50% although other studies did not find
this benefit. However, the definitive Women's Health Initiative
Memory Study (WHIMS), which followed several thousand woman for
several years found that treatment with horse-derived estrogen
was associated with an increase in the risk for
developing Alzheimer's. However, there is
controversy surrounding this study.
Q: My friend's mother has Alzheimer's disease. Will
estrogen or hormone replacement help in this case?
A: Data in this area is conflicting. An multi-center trial found that
conjugated equine estrogens was not helpful in treating
Alzheimer's. A smaller study, using an estradiol patch found a
beneficial effect. In my opinion, further work still needs to be done in this area.
Q: Is there a beneficial
effect from consuming naturally occurring estrogens
found in substances like soy milk: the so-called phytoestrogens?
A: There is not enough data on the use of these naturally occurring
substances for treatment
of cognitive symptoms of menopause.
Q: Why do I need hormone replacement? Isn't it the
natural order of life that women go into menopause?
A: The average age of menopause is 52.3 years and has not changed much over the
years. However, a century ago, life expectancy was much less for a woman than it is today.
Today, the average woman will spend from a fourth to up to half of her life without the
protective and beneficial effects of estrogen.
Q: What is the difference between hormone replacement
and estrogen replacement therapy (HRT vs. ERT)?
A: Hormone replacement therapy is a combination of estrogen and progestogen and is
generally given to women who have not undergone hysterectomies.
Q: What is the difference between a patch and an
A: Skin patches are often used when oral estrogen is not tolerated. Skin absorption
bypasses the liver circulation and is more easily titrated.
Q: If my blood hormone levels are normal on testing, but
my periods are becoming irregular, am I going through menopause?
A: Hormone levels fluctuate monthly during the menstrual cycle and
during the course of a woman's reproductive life. The current
guidelines for a diagnosis of peri-menopause and menopause are
based on a woman's history and examination. Blood hormone
levels may be normal during peri-menopause and early in
Q: Is hormone replacement a
possible treatment for me?
A: This is a question that every peri-menopausal and menopausal woman needs to discuss with
her physician. Pros and cons of estrogen use in an individual woman vary.
Women need to be well informed about all options available to them as they undergo
These and many other questions are answered in the book
Memory and Menopause. Please note that due to the volume of mail, I
am unable to answer individual questions. You may find answers
to some questions on our discussion board.
Please note that all material contained herein is provided for informational purposes
only and should not be considered as medical advice or instruction. Consult your health
care professional for advice relating to a medical problem or condition. Please also read
the disclaimer section.