Subject: Re: EFA'a
From: Raymond Peat <[email-masked]>
To: "Earl Conroy" <[email-masked]>
Date: Tue, 19 Jan 1999 20:38:59 -0800

I don't know whether you have my newsletter on prostate, from a year or two
ago, but its discussion suggests why low testosterone, high growth hormone,
and high estrogen (GH and estrogen are directly associated with increased
free fatty acids) are associated with poor outcome in prostate cancer.
In 1968 I was just starting graduate school in biology, and at that time
there was a real mania for "cell membrane" studies.  We had special
seminars on it, and it all seemed so phony that I started seriously looking
into the history of the idea.  Around that time, D.O. Rudin was co-author
of a couple of papers in Nature which, seen historically, even at that time
looked as if Nature had lost its mind; earlier in the century, people had
done similar things with all sorts of physical and chemical systems,
imitating cell electrical behavior, and now they were doing it with, in
effect, soap bubbles.  I wouldn't be surprised if that were the same person
who is now on the orthomolecular medicine circuit.

				Prostate Cancer

	It was noticed several decades ago that estrogen causes the prostate gland
to enlarge in experimental animals, but by then an oversimplified view of
the sex hormones was already well established, that led people to say that
"estrogen causes the female organs to grow, and testosterone causes the
male organs to grow."  Logically extending this mistaken idea led many of
the same people to suppose that the "hormones of one sex would inhibit the
growth of the reproductive organs of the other sex."
	When a friend of mine was told he had prostate cancer, though he had had
no symptoms, and should receive large doses of estrogen, I reviewed the
literature, to see whether his doctor might have seen something I had
neglected.  Since that time, I have found it necessary to use quotation
marks around the phrases "medical research" and "medical science," because
there is a certain kind of "research" performed within the medical
profession which is peculiar to that profession.
	When I read through the studies cited by the current articles as the basis
for using estrogen to treat prostate cancer, I saw that the decisive
"research" had consisted of mailing a questionnaire to physicians asking
them if they thought it was reasonable to administer estrogen to these
patients on the basis of its opposition to testosterone, which was
considered to be responsible for the growth of the prostate gland.  Many
physicians answered the questionnaire affirmatively.
	If the questioner's purpose was to determine his legal status in using a
treatment, his research method was appropriate, to see whether the
treatment seemed reasonable to others in the profession.  Legally, a
physician is safe if he can count on others to testify that his practice is
standard.  Unfortunately, for generations his study of the opinions of his
peers became the "evidence" of the value of the estrogen treatment.
Phrases such as "it is indicated," "treatment of choice," and "standard
practice" are used in medicine, as part of the pseudo-scientific mystique
of the profession.  Physicans who attempt to base their practice on methods
that have a sound scientific basis are likely to find that they are
violating the norms of their profession.
	More than 25 years ago, when I started pointing out that deliberate
misrepresentation had been involved in the continued designation of
estrogen as "the female hormone," used as a basis for "hormone replacement
therapies," I saw that it was hard for people to sustain a critical
attitude toward language.  Language is prior to judgment, law, science,
reason.  Those who define the terms set the rules.
By the mid-1980s, some studies had shown that estrogen treatment didn't
prolong the survival of prostate cancer patients at all, but it was argued
that the patients who received estrogen were happier than those who didn't.
	Apparently, many physicians who were experts in conventional cancer
treatment hadn't been impressed by the happiness of their patients who were
receiving estrogen, because a survey at a conference of physicians found
that many of them would choose to have no treatment if they learned they
had prostate cancer.  And more recently, there have been recommendations
that older patients shouldn't be treated aggressively, because their
cancers are usually so slow growing that they are likely to die of
something else related to old age.
	In spite of the articles I showed my friend, and my warning that estrogen
can cause strokes and heart attacks, he decided to take the estrogen
treatment.  Within a few days he began suffering from asthma and disturbed
sleep.  Then he had a series of strokes and died.  
	Since it was known that estrogen treatment was dangerous for men, and that
it increases blood clotting and vascular spasms, there had to be some
overriding belief that led to its general use in treating prostate cancer.
That belief seems to be that "estrogen, the female hormone, opposes
testosterone, the male hormone, which is responsible for the growth--and
therefore for the cancerization--of the prostate gland."  Everything is
wrong with that sentence, but you can find every part of the belief present
and functioning in the medical literature.  Just to give some context to
the association of growth and cancerization, I should mention that Otto
Warburg observed that all of the carcinogenic factors he studied caused
tissue atrophy before cancer appeared.  Another important contextual point
is that every hormone does many things, and every endocrine gland produces
multiple hormones.
	Since the time of Brown-Sequard and Eugen Steinach, it has been accepted
that declining testicular function is a common feature of aging, and
testosterone was probably the first hormone that was clearly found to
decrease consistently with aging.  (Vermeulen, et al., 1972, 1979.)  
	It has seemed odd to many people that enlargement of the prostate should
occur mainly in older men, if testosterone is the hormone that causes its
growth, and estrogen is antagonistic to its growth.  The nature of the
growth of the old man's prostate is very different from its natural growth
in youth.
	It was also recognized decades ago that estrogen rises in men during old
age (Pirke and Doerr, 1975), as it rises in stress, disease, malnutrition,
and hypothyroidism (which are also associated with old age).  Estrogen is
produced in fat (Siiteri, and MacDonald, 1973, Vermeulen, 1976) which tends
to increase with age, when thyroid and progesterone are deficient.  The
conversion of testosterone to estrogen occurs in the testicle itself, but
this conversion is also inhibited by the favorable hormonal environment of
youth.  The active thyroid hormone, T3, declines with aging, and this
necessarily lowers production of pregnenolone and progesterone.
Increasingly, in both sexes, it appears that DHEA may rise during stress as
a result of a deficiency of thyroid, progesterone, and pregnenolone.
	In 1786, John Hunter reported that castration causes a decrease in the
size of the prostate gland, and by the end of the 19th century castration
was being advocated for treating enlargement of the prostate.  In aging
men, the prostate gland (both central and peripheral zones) atrophies, and
it is within the atrophic gland that cancer cells can be found.  Nodular,
noncancerous enlargement may occur, with or without cancer.  In 1935, an
autopsy study showed carcinoma in the prostates of 30% of men by the age of
50.  Proliferation of ductal and epithelial tissue is closely associated
with prostate cancer, a situation similar to that of the cancerous or
precancerous breast.  (Simpson, et al., 1982; Wellings, et al., 1975;
Jensen, et al., 1976.)  The high probability of "epitheliosis" in
association with cancer was seen in women in their early 40s, and in women
over 60. (Simpson, et al.)  (Epitheliosis just refers to an exaggerated
proliferation of epithelial cells, the cells covering all surfaces,
including the lining of glands, and things as simple as irritation and
vitamin A deficiency can cause these cells to proliferate.)  In the breast,
the proliferative epitheliosis is clearly caused by estrogenic stimulation.
 The antagonism between estrogen and vitamin A in controlling epithelial
proliferation (and possibly other cell types: Boettger-Tong and Stancel,
1995) is clear wherever it has been tested; vitamin A restrains epithelial
proliferation.  (Wherever estrogen is a factor in the development of
abnormal tissue, vitamin A supplementation would seem beneficial.)
	 In aging women and men, as the breasts and prostate atrophy, their
estrogen/antiestrogen ratio increases.
	In men with prostate cancer, the fluid secreted by the prostate contains
significantly more estradiol than the fluid from men without cancer (Rose,
et al., 1984).  This is analogous to observations made in women with breast
cancer.
The pituitary hormones have diverse functons, including effects on
epithelial tissues, other than their "classical" functions.  Growth
hormone, ACTH (Lostroh and Li, 1957), and ACTH with prolactin (Tullner,
1963) stimulate prostate growth.  Prolactin--which is increased by
estrogen--stimulates growth of the rat's lateral prostate (Holland and Lee,
1980), and stimulates the growth of human prostate epithelial cells in
vitro (Syms, et al., 1985).  LH (luteinizing hormone) increases when
progesterone or testosterone is deficient, and growth hormone and prolactin
(which are closely associated in evolution) both increase under a variety
of stressful situations, and with estrogenic stimulation.  Prostate cancer
patients who had higher levels of LH and lower testosterone died most
quickly.  (Harper, et al., 1984.)  Also, a high ratio of testosterone to
estradiol or of testosterone to prolactin corresponded to better survival
(Rannikko, et al., 1981.)  Considered separately, patients with higher
testosterone levels had a better prognosis than those with lower levels,
and patients with lower growth hormone levels did better than those with
higher growth hormone levels. (Wilson, et al., 1985.)  Has anyone ever
tried testosterone therapy for prostate cancer?  Or, more practically, a
generalized antiestrogenic therapy, using thyroid, progesterone, and
pregnenolone?  Other drugs (naloxone, bromocriptine, gonadotropin-releasing
hormone agonists, and anti-growth hormone druges, e.g.) are available to
regulate the pituitary hormones, and might be useful therapeutically or
preventively.  (See Blaakaer, et al., 1995.)  Biskind and Biskind's work
(1944) with ovarian tumors might be relevant to both testicular and
prostate cancer.
	Abnormal patterns of pituitary hormones reflect stress and hormonal
imbalance, but they are also directly involved in widespread changes in
tissue content of glycoproteins.  The prostate is specialized to secrete
large amounts of mucin.  The endocrine physiology of prostate mucin
secretion is poorly understood, but it is likely that there are
interactions between growth-regulatory and secretion-regulatory systems.
	In recent years, prostate cancer has been one of the fastest increasing
kinds of cancer, and it isn't apparent that increased treatment has had an
effect in lowering the death rate.  The postwar baby-boom (following the
baby-bust of the great depression) created an abnormal age-structure of the
population, that has been used to argue that the war against cancer is
being won.  Increasing environmental estrogens are known to cause many
reproductive abnormalities, and their contribution to prostate cancer would
get more attention if estrogen's role in prostate disease were better
known.  Environmental estrogens are clearly responsible for genital
deformities and sterility in many species of wild animals, but when the
causal link is made between estrogens and human abnormalities, the estrogen
industry sends its shills in to create controversy and confusion.  Even the
effects of estrogens in sewage, known for decades, are treated as State
Secrets:  "There had been reports of hermaphroditic fishes in one or two
rivers, and government investigators had been studying them since the late
1970s.  But no one had been aware of the work because it was classified."
(Lutz, 1996.)
Testicular cancer is easy to diagnose, and its incidence has clearly
increased (100% in white men, 200% in black men) since 1950.  Undescended
testicles, urethral abnormalities, etc., similar to those seen in DES sons
and in wild animals, have also increased.  So the tremendous increase in
the death rate from prostate cancer during the same time has a meaningful
context.
	Although the animal studies showed that estrogen treatment promotes
enlargement of the prostate, it was possible to suppose that the human
prostate's growth might be stimulated only by testosterone, until tests
were done in vitro to determine the effects of hormones on cell division.
	In human prostate slices, several hormones (including insulin, and
probably prolactin) stimulated cell division; testosterone did not, under
these experimental conditions. (McKeehan, et al., 1984.) Contrary to the
stereotyped ideas, there are suggestions that supplementary androgens could
control prostate cancer (Umekita, et al., 1996), and that antagonists to
prolactin and estrogen might be appropriately used in hormonal therapy (for
example, Wennbo, et al., 1997; Lane, et al., 1997).
By the age of 50, men often show an excess of both prolactin and estrogen,
and a deficiency of thyroid and testosterone.  This is the age at which
enlargement of the prostate often becomes noticeable.
	Estrogen's role in prostate growth and cancerization is clear:
"...simultaneous treatment of intact...rats with testosterone and
estradiol-17beta for 16 weeks consistenly induced a putative precancerous
lesion, termed dysplasia, in the dorsolateral prostate of all animals.
Since treatment of rats with androgen alone did not elicit the same
response, we concluded that estrogen played a critical role in the genesis
of this proliferative lesion."  (Ho and Yu.)
	Progesterone and pregnenolone also decline in aging men.  Several studies
using synthetic progestins have shown that they effectively shrink the
hypertrophic prostate, and the saw palmetto remedy for prostate enlargement
has been reported to contain pregnenolone, or something similar to it.
These materials might be expected to reduce conversion of testosterone or
other androgens to estrogen.
	The prostaglandins were discovered in prostatic fluid, where they occur in
significant concentrations.  They are so deeply involved with the
development of cancers of all sorts that aspirin and other prostaglandin
inhibitors should be considered as a basic part of cancer therapy.  The
prostaglandins have local and systemic effects that promote cancer growth.
("The prostaglandins and related eicosanoids synthesized from
polyunsaturated fatty acid precursors have been implicated as modulators of
tumor metastasis, host immunoregulation, tumor promotion, and cell
proliferation."  Hubbard, et al., 1988.)
	Estrogens cause elevation of free fatty acids, and  there are many
interactions between the unsaturated fatty acids and estrogen, including
their metabolism to prostaglandins, and their peroxidation.  Estrogen's
roles as free-radical promoter, DNA toxin, carcinogen, tumor promotor,
modifier of tissue growth factors, anti-thymic hormone, etc., as well as
its local effects on the prostate gland, have to be kept in mind.  Most of
the interest in studying estrogen's contributions to prostate cancer
relates to the existence of estrogen receptors in various parts of the
prostate.  While that is interesting, it tends to distract attention from
the fact that many of estrogen's most important actions don't involve the
"receptors."  A direct excitatory action on prostate cells, and indirect
actions by way of the pituitary, pancreas, thyroid, adrenal, fatty acids,
prostaglandins, histamine and circulation are probably essential parts of
the cancerization process.
	The unsaturated fatty acids, but not the saturated fatty acids, free
estrogen from the serum proteins that bind it, and increase its
availability and activity in tissue cells.

	Thyroid supplementation, adequate animal protein, trace minerals, and
vitamin A are the first things to consider in the prevention of prostate
hypertrophy and cancer.  Nutritional and endocrine support can be combined
with rational anticancer treatments, since there is really no sharp line
between different approaches that are aimed at achieving endocrine and
immunological balance, without harming anything.
Avoiding tissue atrophy is very closely related to promoting healthy
regeneration.  	These processes require efficient energy production, and an
appropriate balance between stimulation and resources.  Growth hormone is
sometimes recommend to correct tissue atrophy, but the evidence seems
reasonably clear that it is a factor in the promotion of tumefaction of the
prostate.  The only study I have seen suggesting that it might be
beneficial in prostatic cancer was a 14 day experiment done in female rats.
 	Numerous publications suggest that blocking growth hormone is beneficial
in treating prostate cancer; in future newsletters I will be discussing the
evidence that growth hormone, like estrogen, cortisol, and unsaturated
fats, tends to promote degenerative changes of aging.

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PRL was not primarily mediated through elevated plasma IGF-I levels. "The
present study suggests that PRL is an important factor in the development
of prostate hyperplasia acting directly on the prostate gland or via
increased plasma levels of testosterone."