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Hormone Replacement Therapy: It Might Be Good For Your Brain?

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.

Crosses to bear

Although these 3 stories are incredibly sad, they serve to
illustrate the realities of this imperfect world – and how heavy some “crosses”
are for people.  We should count our
blessings when things go right for us, and reach out to those who are suffering
in unimaginable ways…

From Hallway Four:  A
40 year old woman was seen for difficulty breathing and eventually diagnosed
with pneumonia and fluid-overload secondary to need for dialysis.  This
lovely lady had been diagnosed recently with kidney cancer of her right kidney
and had undergone nephrectomy (removal of the diseased kidney).
Ordinarily, this would still have left her with one good kidney, which is all
you need.  But, as luck would have it, this lady had donated her left
kidney to her ailing sister three years prior.

From Charity Doc: A father of a 7 y/o little boy brings him
into the ED last night reporting that his mother’s boyfriend had beaten him
black and blue with a belt, an assertion that the mother did not deny. The couple had
been divorced for a little over a year. On physical exam, the little boy had
indeed not been spared the rod at all. His buttocks and back were ecchymotic,
black and blue with scattered scabbed marks from numerous whippings and
beatings. It was unbelievable.  [Child
protective services ruled that the child should go home with the mother
because] the mother has legal custody of the kid and we can’t send him home
with his father.

From a story relayed at a Rehabilitation Medicine
conference
: A set of conjoined twins were born fused at the hip.  They were sickly, sharing a circulatory
system that was insufficient to serve both of their needs.  The doctors had to make an educated guess as
to how to dissect the two apart from one another – there was only one set of
male genitals, and three legs.  They
carefully studied the anatomy and decided to part the twins, giving the
healthier appearing one two legs and the genitalia, leaving the other with only
one leg and no genitals.  Several weeks
after the surgery the first twin (with the 2 legs) died.  The second twin is still alive, is in his 20’s,
and has been in and out of jail for drug trafficking.

Makes our own problems seem pretty trivial, doesn’t it?

This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.

Best of the Blog, Part 2

The best way to cheer
yourself up is to try to cheer somebody else up.
Mark Twain

In this post we focus on cheerful, positive stories – my favorite
blog theme.

The cookie series

Girl Scout cookies – the story of a little girl who went
beyond the call of duty

9/11 cookies – what some of us did on that fateful day

Baking cookies part 2 – how one man made it back from near
death

Good can come from
evil…

The strength of weakness – Dr. Rob shows how we can turn
suffering into a force for good

Back Pain 911 – my own back injury teaches me compassion for
others

More than skin deep – a burn victim finds a way to “pay it forward”

Unexpected heroes

Two teen girls take on Glaxo Smith Kline – the ultimate
David & Goliath story

Spider saves man from cancer – a spider bite called
attention to a suspicious nearby lesion

Make a wish – An 8 year old “President” shows great bravery in
his final months

Your mom will always be your mom – and mine has impulse
control problems

My medical heroes – some doctors who are making a difference

Slice of life

Easter exercises – how creative parents get their kids to
exercise

An elderly woman assesses her healthcare problems

Understanding introverts – they’re worth getting to know

What the heck is a rehab doc? – my specialty is the least
understood in all of medicine!

Well, there you have it.
My thoughts in a nutshell from the past 6 months.  Stay tuned for more random thoughts… or make
a suggestion and I may blog about it!

This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.

Pet food scandal has scary implications for humans

The recent death of hundreds of beloved pets was traced back to a wheat gluten factory near Shanghai, China. The wheat gluten, a thickener used in pet food, was contaminated with melamine (a chemical used in plastics, fertilizers, and flame retardants). It is believed that the melamine may have been processed or stored in the same containers used for the gluten.

How did the contaminated gluten make it into over 100 brands of US pet food? Chinese ingredients are less expensive than American ones, and so large companies purchase many plant and animal products from China to save on costs. The fact that over 100 brands were recalled speaks to the pervasiveness of Chinese agricultural products contained within American food products.

A very alarming article was published by Forbes Magazine, describing the serious quality control problems that China has been having, and America’s limited ability to screen incoming goods:

Over the past 25 years, Chinese agricultural exports to the U.S. surged nearly 20-fold to $2.26 billion last year, led by poultry products, sausage casings, shellfish, spices and apple juice.

Inspectors from the U.S. Food and Drug Administration are able to inspect only a tiny percentage of the millions of shipments that enter the U.S. each year.

Even so, shipments from China were rejected at the rate of about 200 per month this year, the largest from any country, compared to about 18 for Thailand, and 35 for Italy, also big exporters to the U.S., according to data posted on the FDA’s Web site.

Chinese products are bounced for containing pesticides, antibiotics and other potentially harmful chemicals, and false or incomplete labeling that sometimes omits the producer’s name.

The problems the [Chinese] government faces are legion. Pesticides and chemical fertilizers are used in excess to boost yields while harmful antibiotics are widely administered to control disease in seafood and livestock. Rampant industrial pollution risks introducing heavy metals into the food chain.

Farmers have used cancer-causing industrial dye Sudan Red to boost the value of their eggs and fed an asthma medication to pigs to produce leaner meat. In a case that galvanized the public’s and government’s attention, shoddy infant formula with little or no nutritional value has been blamed for causing severe malnutrition in hundreds of babies and killing at least 12.

Assuming that Forbes has not overstated the case, Americans have good cause for concern about the safety of food that includes ingredients from China – is it only a matter of time before the pet food debacle is played out in humans? I don’t know, but I’m worried. Do you know of any other credible reports about this problem? Please share!

This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.

Cancer: do we really understand it? Part 2

-Continued from previous post

In contradistinction to these patients exposed to tumor cells who did not develop malignancies, other studies have shown that normal cells can become malignant in an environment where a malignancy had developed. One study, for example, followed two leukemia patients whose bone marrows were eradicated with radiotherapy and who subsequently received bone marrow transplants from normal donors. Two to four months following the procedure, the transplanted bone marrow donor cells were found to have become leukemic.(11)

Clearly, cellular environment plays a critical role in cancer development. Malignant cells infused into a normal environment may not produce a tumor while normal cells placed into an environment that had previously harbored a tumor can become malignant. We are no longer even sure from what cell type a particular cancer develops. Stomach cancer in mice has been shown to originate not from the lining cells of the stomach, as we had thought, but from bone marrow cells responding to experimentally-induced stomach inflammation.(12) The problem may be the environment not the “malignant” cell.(13)

Are we at least able to recognize clinically significant cancer? Can we confidently say, as one judge did when defining pornography, “I know it when I see it.?” Apparently not.

Autopsies on people who died of non-malignant causes have caused us to re-examine our definition of cancer. Patients with previously treated Hodgkins disease—showing no clinical evidence of tumor and thought to have been cured, who died of unrelated causes—were found on autopsy to have residual foci of the disease.(14) Although thyroid cancer is diagnosed in only 1 in 1000 adults between the ages of 50 and 70, on autopsy it has been found in 1 of 3 adults.(15) The prevalence of clinically apparent prostate cancer in men 60 to 70 years of age is about 1%; nevertheless, over 40% of men in their 60s with normal rectal examinations have been found to have histologic evidence of the disease,(16) and autopsy studies have found evidence of prostate cancer in 1 out of 3 men by age 50(17), a finding which rises to 7 out of 10 men by age 80.(18) Similarly, clinical breast cancer is diagnosed in 1 out of 100 women between the ages of 40 and 50;(19) on autopsy it was found in a startling 1 out of 2.5 women in this age group. Moreover, over 45% of the autopsied women had more than one focus of breast cancer and 40% had bilateral breast cancer.(20)

What, then, is cancer? What is responsible for the clinical behavior of cancer, sometimes lying dormant and undiagnosed because it causes no symptoms, sometimes progressing inexorably to death?

For the present, we don’t know the answers to these questions. We have developed treatment programs that offer the best current options for cure, but we should, and do, remain unsatisfied with these approaches. First, because they don’t always work and, second, because with rare exception, they are based on trial and error, not on an understanding of the disease process we are treating.

Once we identify the processes responsible for the accumulation of cells into tumors, we can treat these conditions more effectively, reduce or eliminate the side effects associated with many of our current “best practice” treatments, and remove the terror currently shadowing cancer the way terror used to shadow diseases like syphilis, tuberculosis, and pernicious anemia before we learned how they were caused and developed treatments directed at those causes. We are making progress. Stay tuned.

REFERENCES

1. Bennington JL. Cancer of the kidney – etiology, epidemiology and pathology. Cancer 1973;32:1017-29

2. Salvador AH, Harrison EG Jr, Kyle RA. Lymphadenopathy due to infectious mononucleosis: its confusion with malignant lymphoma. Cancer 1971;27:1029-40

3. Lukes RJ, Tindle BH, Parker JW. Reed-Sternberg-like cells in infectious mononucleosis. Lancet 1969;2:1003-4

4. Agliozzo CM, Reingold IM. Infectious mononucleosis simulating Hodgkin’s disease: a patient with Reed-Sternberg cells. Am J Clin Pathol 1971;56:730-5

5. Mirra JM, Kendrick RA, Kendrick RE. Pseudomalignant osteoblastoma versus arrested osteosarcoma. A case report. Cancer 1976;37:2005-14

6. Taubert HD, Wissner SE, Haskins AL. Leiomyomatosis peritonealis disseminata. Obstet Gynecol 1965;25:561-74

7. Croslend DB. Leiomyomatosis peritonealis disseminata: a case report. Am J Obstet Gynecol 1973;117:179-81

8. Mintz B, Illmensee K. Normal genetically mosaic mice produced from malignant teratocarcinoma cells. Proc Natl Acad Sci 1975;72(9):3585-9

9. Lanman JT, Bierman HR, Byron RL Jr. Transfusion of leukemic leukocytes in man. Hematologic and physiologic changes. Blood 1950;5:1099-1113

10. Greenwald P, Woodard E, Nasca PC, Hempelmann P, Dayton P, Maksymowicz G, Blando P, Hanrahan R jr, Burnett WS. Morbidity and mortality among recipients of blood from preleukemic and prelymphomatous donors. Cancer 1976;38:324-8

11. Thomas ED, Bryant JI, Bruckner CD, Clift RA, Fefer A, Neiman P, Ramberg RE, Storb R. Leukemic transformation of engrafted human marrow. Transpl Proc 1972;4:567-70

12. Houghton J, Stoicov C, Nomura S, Rogers AB, Carlson J, Li H, Cai X, Fox JG, Goldenring JR, Wang TC. Gastric cancer originating from bone marrow-derived cells. Science 2004;306:1568-71

13. Bluming AZ. Cancer: The eighth plague – A suggestion of pathogeneisis. Isr J Med Sci 1978;14:192-200

14. Dorfman RF. Biology of malignant neoplasia of the lymphoreticular tissues. J Reticuloendothelial Soc 1972;12:239-56

15. Harach HR, Franssila KO, Wasenius VM. Occult papillary carcinoma of the thyroid. A “normal” finding in Finland. A systematic autopsy study. Cancer 1985; 56 (3): 531-8

16. Montie JE, Wood DP Jr, Pontes E, Boyett JM, Levin HS. Adenocarcinoma of the prostate in cytoprostatectomy specimens removed for bladder cancer. Cancer 1989;63:381-5

17. Oottamasathien S, Crawford D. Should routine screening for prostate-specific antigen be recommended? Arch Intern Med 2003;163:661-2

18. Pienta KJ, Esper PS. Risk factors for prostate cancer. Ann Intern Med 1993;118:793-803

19. Feldman AR, Kessler L, Myers MH, Naughton MD. The prevalence of cancer, estimates based on the Connecticut Tumor Registry. N Engl J Med 1986; 315:1394-7

20. Nielsen M, Thomsen JL, Primdahl S, Dyreborg U, Andersen JA. Breast cancer and atypia among young and middle-aged women: a study of 110 medicolegal autopsies. (Br J Cancer 1987; 56:814-9

This post originally appeared on Dr. Val’s blog at RevolutionHealth.com.

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