Effects of estrogen on cognitive function

This information should not be construed as medical advice. If you have a medical concern, consult your doctor.

  • Estrogen may be very specific in its effect on memory. Postmenopausal women may be experiencing a change in thinking rather than a decline.
  • In older men a higher level of testosterone is associated with better cognitive performance. The level of estrogen had no apparent effect.
  • Estrogen-only Hormone replacement therapy appears to have a positive effect on mental functioning for women 65 years and older, and especially for women over 85.
  • Combined Hormone Therapy (estrogen and progestin) doubles the risk of dementia (including Alzheimer's).
  • Older women taking estrogen only (but not estrogen and progesterone) performed better and more consistently on memory tests.
  • The estrogen drug raloxifene may help prevent decline among women older than 70 and women whose cognitive performance is declining regardless of age.

News reports

September 2007

Combined hormone therapy doesn't boost memory

A study of 180 recently menopausal women found no effect of hormone therapy (a combination of estrogen and progesterone) on cognitive function. Previous research has indicated a positive benefit of estrogen on cognition, so it is speculated that progestin may counteract these positive effects.
The study appeared in the September 25 issue of Neurology.    Full reference 
http://www.eurekalert.org/pub_releases/2007-09/aaon-hti091807.php

August 2007

Removing ovaries before menopause increases risk of cognitive impairment

A very long-running study of some 1,500 women who underwent the removal of one or both ovaries for non-cancer-related reasons, has found that women who had one or both ovaries removed before menopause were nearly two times more likely to develop cognitive problems or dementia compared to women who did not have the surgery. In addition, those women who were younger when their ovaries were removed were more likely to develop dementia than women who were older when their ovaries were removed. This finding adds to other research suggesting that there may be a critical age window for the protective effect of estrogen on the brain in women.
The study was published online August 29 in Neurology.     Full reference
http://www.eurekalert.org/pub_releases/2007-08/aaon-rob082107.php

Fitness counteracts cognitive decline from hormone-replacement therapy

A study of 54 postmenopausal women (aged 58 to 80) suggests that being physically fit offsets cognitive declines attributed to long-term hormone-replacement therapy. It was found that gray matter in four regions (left and right prefrontal cortex, left parahippocampal gyrus and left subgenual cortex) was progressively reduced with longer hormone treatment, with the decline beginning after more than 10 years of treatment. Therapy shorter than 10 years was associated with increased tissue volume. Higher fitness scores were also associated with greater tissue volume. Those undergoing long-term hormone therapy had more modest declines in tissue loss if their fitness level was high. Higher fitness levels were also associated with greater prefrontal white matter regions and in the genu of the corpus callosum. The findings need to be replicated with a larger sample, but are in line with animal studies finding that estrogen and exercise have similar effects: both stimulate brain-derived neurotrophic factor.
The study appeared online January 6 in advance of regular publication in Neurobiology of Aging. Full reference
http://www.eurekalert.org/pub_releases/2006-01/uoia-fcc012406.htm

October 2004

Cognitive benefit of estrogen minimal for the highly educated?

A mouse study sheds light on the mixed results coming from investigations into the cognitive effects of hormone replacement therapy. The study found no beneficial effect of estrogen in female mice who were raised in a stimulating environment. On the other hand, mice raised in standard conditions showed significant spatial and object memory improvement when treated with a high dose of estrogen (following removal of their ovaries). Among mice not treated with estrogen, an enriched environment alone significantly improved spatial memory. These results might help to explain why studies of hormone replacement therapy do not show beneficial effects for all women. Most studies of HRT use very well-educated women.
The report appeared in the October issue of Neuroscience. Full reference
http://www.eurekalert.org/pub_releases/2004-10/yu-eos102204.htm

New insights into hormone therapy highlight when estrogen best aids brain

Several studies have been exploring some of the many variables that may be important in determining the effect of hormone replacement therapy.
A mouse study compared the effects of receiving daily estrogen injections (“continuous treatment”) with the effects of receiving it every four days (“cyclical treatment”). The treatment lasted three months. Ovariectomized mice receiving the continuous treatment performed better on memory tasks than those receiving cyclical treatment.
Another mouse study compared the brains of ovariectomized mice treated with continuous estrogen for 47 days with those not so treated, and found that, after five days on estrogen, estrogen-treated mice produced more of the proteins important for neuron repair and neuronal function. However, with prolonged, continuous estrogen treatment, this effect diminished, and by day 47 the estrogen-treated mice were similar to the non-estrogen-treated mice in levels of the repair proteins. Mice that did not receive estrogen showed an elevation of a brain protein associated with the negative aspects of brain aging, while estrogen-treated mice did not.
A rat study examined the effects of progesterone (a component of many hormone therapies), and found that ovariectomized rats receiving progesterone exhibited deficiencies in learning and memory, supporting the hypothesis that progesterone negatively affects memory during aging. It’s suggested that the negative outcome of several studies evaluating combined estrogen/progesterone HT may be due, in part, to unfavorable effects of progesterone.
Other rat studies have found that two established protective actions of estrogen with relevance to Alzheimer's are negatively affected by the presence of progesterone.
Another study using neurons in culture demonstrated the importance of timing. Neurons exposed to estrogen prior to exposure to beta-amyloid (the protein implicated in Alzheimers) had a significantly greater rate of survival than those exposed to estrogen after being exposed to beta-amyloid. The results are consistent with clinical studies in which women who received estrogen hormone therapy at the time of menopause, before cognitive degeneration becomes apparent, have a lower risk of developing Alzheimer's disease than women who never receive any sort of HT, while for women in their 60s and 70s, hormone therapy may make things worse.
http://www.eurekalert.org/pub_releases/2004-10/sfn-nii102604.htm

Testosterone deprivation makes men forget

A study of men undergoing testosterone deprivation therapy for prostate cancer has found that verbal memory is significantly affected. While initial learning of words is unaffected, such testosterone-deprived men show marked forgetting after two minutes. This rapid drop in memory suggests the lack of testosterone affects the function of the hippocampus. Healthy older men, on average, have about a 40% loss in their normal levels of testosterone as they age, from the ages of 20 or 30, to 70.
http://www.eurekalert.org/pub_releases/2004-10/ohs-ost102504.htm

May 2003

Much to the researchers’ surprise and disappointment, a four-year experiment involving 4,532 women at 39 medical centers, has found that combined hormone therapy (involving both estrogen and progestin) doubles the risk of Alzheimer's disease and other types of dementia in women who began the treatment at age 65 or older, although the risk is still small : for every 10,000 women 65 and older who take hormones, 23 of the predicted 45 cases of dementia a year, will be attributable to the hormones. The study also found that the combined hormone therapy produced no improvement in general cognitive function, and in fact had adverse effects on cognition among some women.
http://www.eurekalert.org/pub_releases/2003-05/wfub-chr052203.htm

March 2003

Estrogen has been implicated as having a role in memory in a number of studies, although findings have been mixed as to the value of HRT for improving memory in post-menopausal women. A new study helps us understand why estrogen might be helpful. The study details how nerve cells in the hippocampus "grow in complexity" when exposed to estrogen, increasing connections among the nerve cells. It may be that, without estrogen, the connections that are there might not work as efficiently in storing and recalling certain types of memories. Previous studies have shown that the ability of women to remember word lists varies during their normal monthly cycle.
The study was published in the March 15 issue of The Journal of Neuroscience. Full reference 2
http://www.eurekalert.org/pub_releases/2003-03/ru-rwc031403.htm

May 2002

Several studies have suggested estrogen may be beneficial for cognitive functioning in women. New research using rats suggests estrogen may be very specific in what types of learning it helps - and what types it may impair. In rats, it appeared to enhance place-learning, at the expense of response learning. It is suggested that postmenopausal women may experience a shift into a problem-solving mode more common to men. "Women may actually get better at performing a task from a different approach, but they are not used to doing it that way, so they view the change as an impairment."
The findings were published in the June issue of Behavioral Neuroscience. Full reference http://www.eurekalert.org/pub_releases/2002-05/uoia-emd051502.htm

April 2002

A study of the levels of estrogen and testosterone in 300 older men enrolled in a larger study of risk factors for osteoporosis in men found that a higher level of testosterone was associated with better performance on various cognitive tests. The level of estrogen had no apparent effect. The study looked only at natural levels of hormones, and it is too soon to say whether testosterone supplements would help prevent cognitive decline. Although some previous studies have suggested that testosterone might benefit the brain, most of these studies have been of younger men.
The study was published in the April issue of the Journal of the American Geriatrics Society. Reference
http://www.eurekalert.org/pub_releases/2002-04/uoc--tao041502.htm

January 2002

A study of more than 2,000 women 65 or older, found that those who underwent hormone replacement therapy after menopause appeared to enjoy better mental functioning. Women 85 and older did especially well. The improvements were seen only in women free from dementia. However, the sample does not reflect the general population - most of the participants were Mormon, and the prohibition of alcohol and tobacco might be a significant factor.
The report appeared in Neurology. Full reference
http://www.nytimes.com/2002/01/01/health/womenshealth/01THER.html?rd=hcmcp?p=041sRk041sTt436WO012000mo9$ho9mk

November 2001

Postmenopausal women who take estrogen and young college-aged women performed more consistently on memory tests compared with postmenopausal women not taking the hormone. Consistency differs from overall memory ability and is a relatively new area in research about the neuropsychology of aging. Consistency measures memory capability on multiple administrations of the same test or on several related tests in a short period of time.
The study involved 48 postmenopausal women (aged 60 - 80), and 16 younger women (18 - 30). The older women were divided into three groups: 16 non-hormone users, 16 estrogen-users and 16 estrogen and progesterone-users. Younger women and older women taking estrogen performed more consistently than the older women not taking the hormone, as well as having higher overall memory scores. Women taking a combination of estrogen and progesterone did not perform as consistently as the estrogen-only users. This finding suggests progesterone may block some of the beneficial effects of taking estrogen alone.
The study results were presented by Dr Wegesin on Sunday, Nov. 11 at the Society for Neuroscience meeting in San Diego. Reference
http://www.eurekalert.org/pub_releases/2001-11/cuco-ssp111501.htm

June 2001

A number of studies in recent years have provided evidence that estrogen is critical to a woman's mental functioning, in particular, her memory and her ability to process words. Estrogen also may reduce a woman's chance of developing Alzheimer's disease, suggesting that hormone replacement therapy might help protect against Alzheimer's. More will hopefully be known in 2005, when results are expected from the Women's Health Initiative, a 15-year nationwide study into the effects of hormone therapy, diet and supplementary calcium and vitamin D on osteoporosis, heart disease and cancer in older women.

April 2001

The designer estrogen drug raloxifene has been prescribed to millions of postmenopausal women for osteoporosis, but its effects on the aging brain are unclear. A new study shows that although raloxifene does not affect the cognitive performance of most women, it may help prevent decline among women older than 70 and women whose cognitive performance is declining regardless of age.
The study was published in the April 19 issue of the New England Journal of Medicine.
http://www.eurekalert.org/pub_releases/2001-04/UNKN-Derm-1704101.htm

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