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Estrogen’ s BENEFICIAL effect on cognitive function

Estrogen’ s BENEFICIAL effect on cognitive function

Introduction: There are still many “myths” and “beliefs” about the negative effects of hormone replacement therapy, particularly estrogen. Many women (and providers) still believe that taking hormones increase their risk of breast cancer. *Most of this BELIEF (it is not FACT except as to certain forms of synthetic estrogens and progestins) is due to misunderstanding and misreading (in  most cases, never reading) the Women’s Health Initiative Study (WHI).

This study is popularly understood to mean that women should not take estrogen. *THE TRUTH IS that the study found that some women who took synthetic premarin WITH A PROGESTIN (the combination in the study was PREMPRO® (conjugated estrogens/medroxyprogesterone acetate tablets)  were at increased risk of breast cancer, stroke  and clotting.

WE AGREE WITH THIS FINDING and it is well documented. However, this does not seem to prevent  providers from prescribing PREMPRO® and other similar combinations (e.g. Birth Control Pills. In the case of PREMPRO®, they just advise women to take it for a “short time.”

*At NBH Lifetime Heath, we have stated for years, that the science clearly shows that PROGESTIN is not PROGESTERONE. This is why we recommend bioidentical progesterone and bioidentical estradiol to all women who are deficient in one or both (as has the Academy of Anti-Aging Medicine since 1999 and earlier).

Progesterone performs 195 different functions in the body and Estrogen has 400 functions. Bioidentical hormones have an unmatched safety record after approximately 100 years of use in Europe and at least 30 years of use in the United States. We have prescribed bioidentical hormones in our clinics (and personally used them) for more than 14 years.  The benefits have been both scientifically and clinically proven. They have been prescribed in California for at least 25 years.

Memory and Estrogen.

*So let’s look at ONE of the many benefits of Estrogen. It is the female’s primary MEMORY hormone. Brain lapses, memory loss, blank stares, confusion. Some women feel like they are losing their mind as they get older? What you may classify as old age and impaired brain function may truly be related to a decrease in estrogen.

Cognitive Decline as a Disease of Aging

*Cognitive decline is a common concern for an aging population, in which the growing rate of Alzheimer’s disease (AD) and dementia has led researchers to look for ways to prevent cognitive degeneration. By the year 2050, it is estimated that 13 million Americans will have Alzheimer’s disease.1 This number is likely understated as diabetes (a risk factor for AD) is increasing at an alarming rate.

*While hormone replacement therapy is not considered a treatment for cognitive degeneration, it has been considered a benefit for female patients to delay age-related cognitive decline and sustain healthy cognition.2 We know that studies have shown a greatly reduced risk of AD when women take estrogen and progesterone at least 10 years before the onset of AD. We also know that thyroid plays a role in memory and cognitive functions.

Estrogen and Cognition

A large concentration of estrogen receptors are found in the hippocampus – an area in the brain that regulates memory and learning.4,5 Estrogen’s role in cognitive function is to support communication between neurons, aid the development of neuronal processes, and sustain the synthesis of neurotransmitters.6,7

Overall, estrogen benefits cognition to:

• *Support regulation of the neurotransmitters, acteylcholine and glutamate8

• *Improve communication between neurons in the hippocampus2

• *Protect nerve cells from free radical and excitotoxin damage9,10

Summary of Estrogen Studies

Several studies have observed the effects of estrogen on cognitive function in older women. Researchers have found that among women who are over 65 years old, those that take estrogen replacement therapy (ERT) perform better on cognitive tests and show less cognitive deterioration over time.11,12,13,14 One study recruited 288 postmenopausal women that were either taking or not taking estrogen replacement therapy.15 Researchers found that women taking ERT had better visual memory when compared to those not taking the treatment. A similar study followed 788 older women for over two years to find that those taking ERT had better cognition than those who were not taking ERT.16 A series of studies found that women had higher scores on verbal and fine motor skills tests when estrogen levels were at their peak in their menstrual cycle. Additionally, these women performed better on speed and accuracy tests.17

The Impact of a Healthy Lifestyle

*Estrogen therapy may not be a main treatment for cognitive function, but it can help inhibit memory loss and cognitive impairment in women who already take HRT to treat their menopausal symptoms. It is important for the female patient to recognize that healthy cognitive function comes by living a healthy lifestyle. Along with balancing hormone levels, diet, nutrient supplementation, exercise, staying socially active, and a fascination to continue learning can help prevent age-related cognitive decline.18

*Exercise has also been showing as a significant factor in the prevention of cognitive decline including AD and Dementia.


  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. 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.
  3. 2 Sherwin BB. Estrogen and cognitive functioning in women. Endocrine Reviews. 2003;24(2):133-151.
  4. 3 Jaffe AB, Toron-Allerand CD, Greengard P, Gandy SE. Estrogen regulates metabolism of Alzheimer amyloid B-precursor protein. J Biol Chem. 1994;269:13065-13068.
  5. 4 Gazzaley AH, Weiland NG, McEwen BS, Morrison JH. Differential regulation of NMDAR1 mRNA and protein by estradiol in the rat hippocampus. J Neurosci. 1996;16:6830.
  6. 5 Luine VN. Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of femail rats. Exp Neurol. 1985;89:484.
  7. 6 Sherwin BB. Can estrogen keep you smart? Evidence from clinical studies. J Psychiatry Neuroscience. 1999;24(4):315-321.
  8. 7 Morley BJ, Rodriguez-Sierra JF, Clough RW. Increase in hypothalamic nicotinic acetylcholine receptors in prepubertal female rats administered estrogen. Brain Res. 1983;278:262.
  9. 8 Luine VN, Khylchevskaya RI, McEwen BS. Effect of gonadal steroids on activities of monoamine oxidase and choline acetylase in rat brain. Brain Res. 1975;86:293–306.

10.  9 McEwen BS. Clinical review 108: The molecular and neuroanatomical basis for estrogen effects in the central nervous system. J Clin Endocrinol Metab. 1999;84:1790.

11.  10 McEwen BS. Estrogen action throughout the brain. Recent Prog Horm Res. 2002;57:357–384.

12.  11 Yaffe K, Lui L, Grady D, Cauley J, et al. Cognitive decline in women in relation to non-protein-bound oestradiol concentrations. Lancet. 2000;356:708-712.

13.  12 Matthews K, Cauley J, Yaffe K, Zmuda JM. Estrogen replacement therapy and cognitive decline in older community women. J Am Geriatr Soc. 1999;47:518-523.

14.  13 Grodstein F, Chen J, Pollen DA, Albert MS, et al. Postmenopausal hormone therapy and cognitive function in healthy older women. J Am Geriatr Soc. 2000;49:746-752.

15.  14 Rice MM, Graves AB, McCurry SM, Gibbons LE, et al. Postmenopausal estrogen and estrogen-progestin use and 2-year rate of cognitive change in a cohort of older Japanese American women: the Kame project. Arch Intern Med. 2000;160:1641-1649.

16.  15 Resnick SM, Metter EJ, Zonderman AB. Estrogen replacement therapy and longitudinal decline in visual memory. A possible protective effect? Neurology. 1997 Dec;49(6):1491-1497.

17.  16 Jacobs DM, Tang MX, Stern Y, Sano M, et al. Cognitive function in nondemented older women who took estrogen after menopause. Neurology. 1008 Feb;50(2):368-373.

18.  17 Hampson E, Kimura D. Cognitive pattern in men and women is influenced by fluctuations in sex hormones. Curr Dir in Psychol Sci. 1994;3:57-61.

19.  18 Fillit HM, Butler RN, OConnell AW, et al. Achieving and maintaining cognitive vitality with aging. Mayo Clin Proc. 2002;77:681-696.

Credit goes to Medquest Pharmacy for the studies cited herein and the content regarding the studies. September 9, 2012.

*The information on this site is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. All content, including text, graphics, images and information, contained on or available through this web site is for general information purposes only.

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