May 20th, 2007 by Dr. Val Jones in Expert Interviews
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These are the references for the post about HRT and “chemo brain:”
References
1. Gross J. Lingering fog of chemotherapy is no longer
ignored as illusion. New York Times April 29, 2007 p1.
2. Paganini-Hill A, Henderson VW. Estrogen replacement
therapy and risk of Alzheimer’s disease. Arch Intern Med 1996;156:2213-7.
3. Tang MX, Jacobs D, Stern Y, Marder K, Schofield P,
Gurland B, Andrews H, Mayeux R. Effect of oestrogen during menopause on risk
and age at onset of Alzheimer’s disease. Lancet 1996;348:429-32.
4. Manly JJ, Merchant CA, Jacobs DM, Small SA, Bell K, Ferin
M, Mayeux R. Endogenous estrogen levels and Alzheimer’s disease among
postmenopausal women. Neurology 2000;54:833-7.
5. Chung SK, Pfaff DW, Cohen RS. Estrogen-induced
alterations in synaptic morphology in the midbrain central gray. Exp Brain Res
1988;69(3):522-30.
6. Jones KJ. Steroid hormones and neurotrophsim:
relationship to nerve injury. Metab Brain Dis 1988;3:1-16.
7. Nilsen J, Diaz Brinton R. Mechanism of estrogen-medicated
neuroprotection: regulation of mitochondrial calcium and Bcl-2 expression. Proc
Natl Acad Sci USA 2003;100(5):2842-7.
8. Nilsen J, Brinton RD. Mitochondria as therapeutic targets
of estrogen action in the central nervous system. Curr Drug Targets CNS Neurol
Disord 2004;3(4):297-313.
9. Alvarez-de-la-Rosa M, silva I, Nilsen J, Perez MM,
Garcia-Segura LM, Avila J, Naftolin F. Estradiol prevents neural tau
hyperphosphorylation characteristic of Alzheimer’s disease. Ann NY Acad Sci
2005;1052:210-24.
10. Singh M, Meyer EM, Millard WJ, Simpkin JW. Ovarian
steroid deprivation results in a reversal learning impairment and compromised
cholinergic function in female Sprague Dawley rats. Brain Res. 1994;644:305-12.
11. McEwen B, Alves S. Estrogen actions in the central
nervous system. Endocrin Rev 1999;20:279-307.
12. Kampen DL, Sherwin BB. Estrogen use and verbal memory in
healthy postmenopausal women. Obstet Gynecol 1994;83(6):979-83.
13.
Shaywitz SE, Shaywitz BA, Pugh KR, Fulbright RK, Skudlarski P, Mencl WE,
Constable RT, Naftolin F, Palter SF, Marchione KE, Katz L, Shankweiler DP,
Fletcher JM, Lacadie C, Keltz M, Gore JC. Effect of estrogen on brain
activation patterns in postmenopausal women during working memory tasks. JAMA
1999;281(13):1197-202.
14. Duff SJ Hampson E. A beneficial effect of estrogen on
working memory in postmenopausal women taking hormone replacement therapy. Horm
Behav 2000;38(4):262-76.
15.
LeBlanc ES, Janowsky J, Chan BKS, Nelson HD. Hormone replacement therapy and
cognition. Systemic review and meta-analysis. JAMA 2001;285(11):1489-99.
16.
Zandi PP, Carlson MC, Plassman BL, Welsh-Bohmer KA, Mayer LS, Steffens DC,
Breitner JC. Hormone replacement therapy and incidence of Alzheimer’s disease
in older women. The Cache County
Study. JAMA 2002
288(17):2123-9.
17.
MacLennan AH, Henderson VW, Paine BJ, Mathias J,
Ramsay EN, Ryan P, Stocks NP, Taylor
AW. Hormone therapy, timing of initiation, and cognition in women aged older
than 60 years: the REMEMBER pilot study. (Research into Memory, Brain function
and Estrogen Replacement). Menopuase: The Journal of the North American
Menopause Society 2006;13(1):28-36.
18.
Shumaker SA, Legault C, Rapp SR, and the WHIMS investigators. Estrogen plus
progestin and the incidence of dementia and mild cognitive impairment in
postmenopausal women: The Women’s Health Initiative Memory Study: A randomized
controlled trial. JAMA 2003;289(20):2651-62.
19.
Shumaker SA, Legault C, Kuller L, 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.
This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.
May 20th, 2007 by Dr. Val Jones in Expert Interviews
2 Comments »
Every now and then I have the pleasure of featuring a guest blogger – someone whose medical opinions are particularly intriguing or controversial. Dr. Avrum Bluming submitted a really interesting post last month about cancer – and whether or not we scientists really do understand it fully. In this post, Dr. Bluming reviews the scientific literature on Hormone Replacement Therapy, and finds some interesting evidence that estrogen might actually be good for the brain – to reduce the risk of dementia. He also suggests that “chemo brain” – the mental fog associated with cancer therapy (especially breast cancer), may be caused by a rapid decrease in estrogen. Read his comments carefully and let me know if you find his analysis convincing… And watch out for the passionate “zinger” at the end!
————
The April 29th 2007 issue of the Sunday New York
Times carried a front-page article about the mental fog following treatment of
cancer with chemotherapy.(1) This fog, referred to as chemo brain, usually
clears, but, in approximately 15% of treated patients, may persist for years,
according to the article. All the patients presented
in the article were women, most or all were breast cancer survivors, and the
article does state that a possible cause of chemo brain in these women may be
the lowered estrogen in their bodies, due to their being catapulted into
premature menopause by treatment. The article further states that abrupt
menopause leaves many women fuzzy headed in a more extreme way than natural
menopause, which usually develops gradually. The article goes on to say that
studies of chemo brain have been conducted, overwhelmingly among breast cancer
patients because they represent the largest group of cancer survivors and
because they tend to be sophisticated advocates, challenging doctors and
volunteering for research.
In 1996 a
14-year study concluded that estrogen replacement therapy may be useful for
preventing or delaying the onset of Alzheimer’s disease.(2)
In 1997 a Columbia University study reported a significant
reduction in the risk of Alzheimer’s disease among postmenopausal women taking
estrogen.(3)
In 2000 that same group reported lower levels
of circulating estradiol, the most common form of circulating estrogen, among
women who developed Alzheimer’s disease compared to those who did not.(4)
Estrogen
has been reported to stimulate nerve growth and synapse formation.(5) (Synapses
are nerve to nerve connections), and to play a beneficial role in nerve response to injury.(6)
In 2003 researchers at the University
of Southern California
identified a mechanism for estrogen-mediated nerve cell protection, which
involved preventing the accumulation of calcium within the mitochondria of the
nerve cells.(7,8)
Estrogen
has also been shown to prevent the buildup of the abnormal chemical called
hyperphosphorylated tau protein, characteristic of Alzheimer’s disease.(9)
Estrogen
administered to female rats who have had their ovaries removed enhanced the
rats’ learning ability.(10,11)
Estrogen
administration to postmenopausal women has been associated with improved verbal
memory.(12-14)
A 2001 analysis of 29 published studies concluded that hormone replacement therapy was
associated with a 34% decreased risk of dementia.(15)
A 2002 study from Johns Hopkins reported a 67% decreased incidence of Alzheimer’s
disease associated with hormone replacement therapy.(16)
A 2006 study from Stanford and the University
of Adelaide in Australia
concluded that early initiation of hormone replacement therapy, from around the
time of menopause may contribute to improved cognition with aging and may delay
dementia.(17)
One can
often selectively quote the medical literature to support a particular point of
view. However, in the face of all these previously quoted studies, one should
at least look skeptically upon the 2003 report from the Women’s Health
Initiative, which found that combination estrogen plus progestin hormone
replacement therapy increased the risk for dementia when started in women over
age 65. The study reported increased dementia as early as 12 months after
starting HRT, but no increased incidence of mild cognitive impairment
associated with HRT use.(18) If HRT
were really harmful to the brain, a finding that goes against most of what we
think we understand about the beneficial effects of estrogen on brain function,
one would expect early cognitive impairment to become apparent before
full-blown dementia was encountered.
A June, 2004 update of that same study concluded that even estrogen alone increased the
risk for dementia. This update reported an increase in mild cognitive
impairment as well, but the results for mild cognitive impairment were not
statistically significant after women who had this impairment at the start of
the study were excluded from analysis.(19)
The report
on chemo-brain from the New York Times should force us to look again at the
role of estrogen in maintaining normal brain function. Throughout history, male
dominated societies have adopted practices harmful to women. These include foot
binding, genital mutilation, and withholding privileges such as the right to
vote, hold office, and participate in government and education activities. We
should not add premature elimination of HRT, based on facile conclusions and
conflicting data to this list.
Avrum Bluming,
MD, MACP
Clinical Professor of Medicine
University
of Southern California
(References on next post)
This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.
