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Estrogen & Memory

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Memory Loss, 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.
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Q: Does estrogen have an impact on functions of the mind?

A: Yes. Estrogen influences language skills, mood, attention, and a number of other functions in addition to memory.
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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.
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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.
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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 outside panel.
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Q: I am on hormone replacement and my symptoms persist. What next?

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.
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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 help delineate 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.
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Q: Ideally, what areas should be covered in neurocognitive testing?

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.
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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 your physician.
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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.
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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. 
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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.
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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.
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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.
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Q: What is the difference between a patch and an oral preparation?

A: Skin patches are often used when oral estrogen is not tolerated. Skin absorption bypasses the liver circulation and is more easily titrated.
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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 menopause. 
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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.
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Women need to be well informed about all options available to them as they undergo menopause.  These and many other questions are answered in the book Estrogen, 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.
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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.


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