The Role of Estrogen in Memory Loss

By Janna Gordon, R.Ph.
March 2005

(brought to you by Bellevue Pharmacy, a ProjectAWARE sponsor)

Memory loss is a growing problem in the elderly population. By the year 2050, it's estimated that 13 million Americans will be living with Alzheimer's disease.¹ There are a variety of prescriptions available to treat Alzheimer's, including Aricept, Namenda, Reminyl, etc.² Are there any other drugs that may be effective for treatment? It's common for most female patients to be on hormone replacement for treatment of menopause. Can estrogen be used to treat Alzheimer's disease or prevent memory loss in elderly patients? What is the role of estrogen in treating a decline in patient's memory and cognition?

There are a few studies available that oppose estrogen for treatment of Alzheimer's and other studies that propose a benefit in using estrogen. The theory behind estrogen's benefit in this patient population is based on the various locations of estrogen receptors throughout the body. Estrogen receptors are located in several areas of the brain and the limbic system, which are both important in memory involvement. Estrogen promotes growth of neuronal processes, neuronal differentiation, and formation of synaptic connections.³ With all of estrogen's involvement within the brain and limbic system it's easy to assume that it would have a benefit in memory loss or cognition.

However, the Women's Health Initiative Memory Study (WHIMS) opposed the use of estrogen for prevention of dementia or cognitive decline. It was reported that estrogen did not decrease the risk of developing dementia/cognitive impairment. In addition, this study reported an increase risk of developing dementia/cognitive impairment.

However, there were a few areas that weakened the study. The participants in the study were between the ages of 65 and 79 years old.¹ There's a possibility within this age range, irreversible neuronal degeneration may already be present. Therefore, late initiation of estrogen probably wouldn't be beneficial in this patient population. Also, a significant portion of the estrogen group in the study had comorbidities, hypertension and diabetes, that increased their risk for vascular damage (i.e. dementia).¹ These patients are already at a disadvantage of seeing benefits from estrogen because of the vascular damage. Lastly, the study used pooled data to show significant results against the use of estrogen for dementia.¹ Without pooled data, there wasn't any significant difference in the increase in patients with dementia in the estrogen group versus the patients not on estrogen.

There still isn't a definite answer for the use of estrogen in treating memory loss or cognitive impairment. There is inconsistency between the studies available and the role of estrogen in memory loss. Most practitioners will agree that estrogen is not monotherapy for treating Alzheimer's disease or dementia. However, if a patient is currently experiencing menopausal symptoms, estrogen may have the added benefit of preventing memory loss/cognitive impairment while treating menopausal symptoms.

References:

1. Shumaker SA, et al. Conjugated equine estrogens and incidence of probably dementia and mild cognitive impairment in postmenopausal women: women’s health initiative memory study. JAMA. 2004;291(24):2947-58.
2. Brief summary: Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. National Guideline Clearinghouse. Department of Health and Human Services. (Accessed 16 January 2006)
3. Sherwin BB. Can estrogen keep you smart? Evidence from clinical studies. J Psychiatry Neuroscience. 1999;24(4):315-321.

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