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516 lines
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<head><title></title></head>
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<body>
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<h1></h1>
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<p></p>
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<hr />
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<p>
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<span>"...simultaneous treatment of intact...rats with testosterone and estradiol-17beta for 16 weeks
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consistenly induced a putative precancerous lesion, termed dysplasia, in the dorsolateral prostate of
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all animals. Since treatment of rats with androgen alone did not elicit the same response, we
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concluded that estrogen played a critical role in the genesis of this proliferative
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lesion." <span>Shuk-mei Ho and M. Yu, in "Selective increase in
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type II estrogen-binding sites in the dysplastic dorsolateral prostates of Noble rats," Cancer
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Research 53, 528-532, 1993.</span></span>
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</p>
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<p><span><hr /></span></p>
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<h1>Prostate Cancer</h1>
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<p>
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It was noticed several decades ago that estrogen causes the prostate gland to enlarge in experimental
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animals, but by then an oversimplified view of the sex hormones was already well established, that led
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people to say that "estrogen causes the female organs to grow, and testosterone causes the male organs to
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grow." Logically extending this mistaken idea led many of the same people to suppose that the
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"hormones of one sex would inhibit the growth of the reproductive organs of the other sex."
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</p>
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<p>
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When a friend of mine was told he had prostate cancer, though he had had no symptoms, and should receive
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large doses of estrogen, I reviewed the literature, to see whether his doctor might have seen something I
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had neglected. Since that time, I have found it necessary to use quotation marks around the phrases
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"medical research" and "medical science," because there is a certain kind of "research" performed within the
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medical profession which is peculiar to that profession.
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</p>
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<p>
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When I read through the studies cited by the current articles as the basis for using estrogen to treat
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prostate cancer, I saw that the decisive "research" had consisted of mailing a questionnaire to physicians
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asking them if they thought it was reasonable to administer estrogen to these patients on the basis of its
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opposition to testosterone, which was considered to be responsible for the growth of the prostate
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gland. Many physicians answered the questionnaire affirmatively.
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</p>
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<p>
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If the questioner's purpose was to determine his legal status in using a treatment, his research method was
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appropriate, to see whether the treatment seemed reasonable to others in the profession. Legally, a
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physician is safe if he can count on others to testify that his practice is standard. Unfortunately,
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for generations his study of the opinions of his peers became the "evidence" of the value of the estrogen
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treatment. Phrases such as "it is indicated," "treatment of choice," and "standard practice" are used
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in medicine, as part of the pseudo-scientific mystique of the profession. Physicans who attempt to
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base their practice on methods that have a sound scientific basis are likely to find that they are violating
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the norms of their profession.
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</p>
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<p>
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More than 25 years ago, when I started pointing out that deliberate misrepresentation had been involved in
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the continued designation of estrogen as "the female hormone," used as a basis for "hormone replacement
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therapies," I saw that it was hard for people to sustain a critical attitude toward language. Language
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is prior to judgment, law, science, reason. Those who define the terms set the rules.
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</p>
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<p>
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By the mid-1980s, some studies had shown that estrogen treatment didn't prolong the survival of prostate
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cancer patients at all, but it was argued that the patients who received estrogen were happier than those
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who didn't.
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</p>
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<p>
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Apparently, many physicians who were experts in conventional cancer treatment hadn't been impressed by the
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happiness of their patients who were receiving estrogen, because a survey at a conference of physicians
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found that many of them would choose to have no treatment if they learned they had prostate cancer.
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And more recently, there have been recommendations that older patients shouldn't be treated aggressively,
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because their cancers are usually so slow growing that they are likely to die of something else related to
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old age.
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</p>
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<p>
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In spite of the articles I showed my friend, and my warning that estrogen can cause strokes and heart
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attacks, he decided to take the estrogen treatment. Within a few days he began suffering from asthma
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and disturbed sleep. Then he had a series of strokes and died.
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</p>
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<p>
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Since it was known that estrogen treatment was dangerous for men, and that it increases blood clotting and
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vascular spasms, there had to be some overriding belief that led to its general use in treating prostate
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cancer. That belief seems to be that "estrogen, the female hormone, opposes testosterone, the male
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hormone, which is responsible for the growth--and therefore for the cancerization--of the prostate
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gland." Everything is wrong with that sentence, but you can find every part of the belief present and
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functioning in the medical literature. Just to give some context to the association of growth and
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cancerization, I should mention that Otto Warburg observed that all of the carcinogenic factors he studied
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caused <span>tissue atrophy before cancer</span> appeared. Another important contextual
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point is that every hormone does <span>many </span>things, and every endocrine gland produces
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multiple hormones.
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</p>
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<p>
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Since the time of Brown-Sequard and Eugen Steinach, it has been accepted that declining testicular function
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is a common feature of aging, and testosterone was probably the first hormone that was clearly found to
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decrease consistently with aging. (Vermeulen, et al., 1972, 1979.)
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</p>
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<p>
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It has seemed odd to many people that enlargement of the prostate should occur mainly in older men, if
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testosterone is the hormone that causes its growth, and estrogen is antagonistic to its growth. The
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nature of the growth of the old man's prostate is very different from its natural growth in youth.
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</p>
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<p>
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It was also recognized decades ago that estrogen rises in men during old age (Pirke and Doerr, 1975), as it
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rises in stress, disease, malnutrition, and hypothyroidism (which are also associated with old age).
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Estrogen is produced in fat (Siiteri, and MacDonald, 1973, Vermeulen, 1976) which tends to increase with
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age, when thyroid and progesterone are deficient. The conversion of testosterone to estrogen occurs in
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the testicle itself, but this conversion is also inhibited by the favorable hormonal environment of
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youth.<span> </span>The active thyroid hormone, T<sub>3</sub>
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<span><sub>, </sub></span>declines with aging, and this necessarily lowers production of pregnenolone
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and progesterone. Increasingly, in both sexes, it appears that DHEA may rise during stress as a result
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of a deficiency of thyroid, progesterone, and pregnenolone.
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</p>
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<p>
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In 1786, John Hunter reported that castration causes a decrease in the size of the prostate gland, and by
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the end of the 19th century castration was being advocated for treating enlargement of the prostate.
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In aging men, the prostate gland (both central and peripheral zones) atrophies, and it is within the
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atrophic gland that cancer cells can be found. Nodular, noncancerous enlargement may occur, with or
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without cancer. In 1935, an autopsy study showed carcinoma in the prostates of 30% of men by the age
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of 50. Proliferation of ductal and epithelial tissue is closely associated with prostate cancer, a
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situation similar to that of the cancerous or precancerous breast. (Simpson, et al., 1982; Wellings,
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et al., 1975; Jensen, et al., 1976.) The high probability of "epitheliosis" in association with cancer
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was seen in women in their early 40s, and in women over 60. (Simpson, et al.) (Epitheliosis just
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refers to an exaggerated proliferation of epithelial cells, the cells covering all surfaces, including the
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lining of glands, and things as simple as irritation and vitamin A deficiency can cause these cells to
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proliferate.) In the breast, the proliferative epitheliosis is clearly caused by estrogenic
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stimulation. The antagonism between estrogen and vitamin A in controlling epithelial proliferation
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(and possibly other cell types<span>:</span> Boettger-Tong and Stancel, 1995) is clear wherever it has
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been tested<span>;</span> vitamin A restrains epithelial proliferation. (Wherever estrogen is a
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factor in the development of abnormal tissue, vitamin A supplementation would seem beneficial.)
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</p>
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<p>
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<span> </span>In aging women and men, as the breasts and prostate atrophy, their estrogen/antiestrogen
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ratio increases.
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</p>
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<p>
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In men with prostate cancer, the fluid secreted by the prostate contains significantly more estradiol than
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the fluid from men without cancer (Rose, et al., 1984). This is analogous to observations made in
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women with breast cancer.
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</p>
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<p>
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The pituitary hormones have diverse functons, including effects on epithelial tissues, other than their
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"classical" functions. Growth hormone, ACTH (Lostroh and Li, 1957), and ACTH with prolactin (Tullner,
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1963) stimulate prostate growth. Prolactin--which is increased by estrogen--stimulates growth of the
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rat's lateral prostate (Holland and Lee, 1980), and stimulates the growth of human prostate epithelial
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cells <span>in vitro</span> (Syms, et al., 1985). LH (luteinizing hormone) increases when
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progesterone or testosterone is deficient, and growth hormone and prolactin (which are closely associated in
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evolution) both increase under a variety of stressful situations, and with estrogenic
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stimulation. <span>Prostate cancer patients who had higher levels of LH and </span>
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<span>lower testosterone</span>
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<span> died most quickly. (Harper, et al., 1984.) Also, a </span>
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<span>high ratio of testosterone to estradiol or of testosterone to prolactin</span>
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<span> corresponded to better survival (Rannikko, et al., 1981.) Considered separately, patients
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with </span>
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<span>higher testosterone levels had a better prognosis</span>
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<span> than those with lower levels, and patients with lower growth hormone </span>levels did
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better than those with higher growth hormone levels. (Wilson, et al., 1985.) Has anyone ever tried
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testosterone therapy for prostate cancer? Or, more practically, a generalized antiestrogenic therapy,
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using thyroid, progesterone, and pregnenolone? Other drugs (naloxone, bromocriptine,
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gonadotropin-releasing hormone agonists, and anti-growth hormone druges, e.g.) are available to regulate the
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pituitary hormones, and might be useful therapeutically or preventively. (See Blaakaer, et al.,
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1995.) Biskind and Biskind's work (1944) with ovarian tumors might be relevant to both testicular and
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prostate cancer.
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</p>
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<p>
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Abnormal patterns of pituitary hormones reflect stress and hormonal imbalance, but they are also directly
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involved in widespread changes in tissue content of glycoproteins. The prostate is specialized to
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secrete large amounts of mucin. The endocrine physiology of prostate mucin secretion is poorly
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understood, but it is likely that there are interactions between growth-regulatory and secretion-regulatory
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systems.
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</p>
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<p>
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In recent years, prostate cancer has been one of the fastest increasing kinds of cancer, and it isn't
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apparent that increased treatment has had an effect in lowering the death rate. The postwar baby-boom
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(following the baby-bust of the great depression) created an abnormal age-structure of the population, that
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has been used to argue that the war against cancer is being won. Increasing environmental estrogens
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are known to cause many reproductive abnormalities, and their contribution to prostate cancer would get more
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attention if estrogen's role in prostate disease were better known. Environmental estrogens are
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clearly responsible for genital deformities and sterility in many species of wild animals, but when the
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causal link is made between estrogens and human abnormalities, the estrogen industry sends its shills in to
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create controversy and confusion. Even the effects of estrogens in sewage, known for decades, are
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treated as State Secrets: "There had been reports of hermaphroditic fishes in one or two rivers, and
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government investigators had been studying them since the late 1970s. <span>But no one had been
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aware of the work because it was classified."</span> (Lutz, 1996.)
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</p>
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<p>
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Testicular cancer is easy to diagnose, and its incidence has clearly increased (100% in white men, 200% in
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black men) since 1950. Undescended testicles, urethral abnormalities, etc., similar to those seen in
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DES sons and in wild animals, have also increased. So the tremendous increase in the death rate from
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prostate cancer during the same time has a meaningful context.
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</p>
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<p>
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Although the animal studies showed that estrogen treatment promotes enlargement of the prostate, it was
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possible to suppose that the human prostate's growth might be stimulated only by testosterone, until tests
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were done <span>in vitro</span> to determine the effects of hormones on cell division.
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</p>
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<p>
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In human prostate slices, several hormones (including insulin, and probably prolactin) stimulated cell
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division<span>;</span> <span>testosterone did not,</span> under these experimental conditions.
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(McKeehan, et al., 1984.) Contrary to the stereotyped ideas, there are suggestions that supplementary
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androgens could control prostate cancer (Umekita, et al., 1996), and that antagonists to prolactin and
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estrogen might be appropriately used in hormonal therapy (for example, Wennbo, et al., 1997; Lane, et al.,
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1997).
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</p>
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<p>
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By the age of 50, men often show an excess of both prolactin and estrogen, and a deficiency of thyroid and
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testosterone. This is the age at which enlargement of the prostate often becomes noticeable.
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</p>
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<p>
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Estrogen's role in prostate growth and cancerization is clear<span>:</span> "<span>...</span
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>simultaneous treatment of intact...rats with testosterone and estradiol-17beta for 16 weeks consistenly
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induced a putative precancerous lesion, termed dysplasia, in the dorsolateral prostate of all animals.
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Since treatment of rats with androgen alone did not elicit the same response, we concluded that estrogen
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played a critical role in the genesis of this proliferative lesion." (Ho and Yu.)
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</p>
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<p>
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Progesterone and pregnenolone also decline in aging men. Several studies using synthetic progestins
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have shown that they effectively shrink the hypertrophic prostate, and the saw palmetto remedy for prostate
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enlargement has been reported to contain pregnenolone, or something similar to it. These materials
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might be expected to reduce conversion of testosterone or other androgens to estrogen.
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</p>
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<p>
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The prostaglandins were discovered in prostatic fluid, where they occur in significant concentrations.
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They are so deeply involved with the development of cancers of all sorts that aspirin and other
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prostaglandin inhibitors should be considered as a basic part of cancer therapy. The prostaglandins
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have local and systemic effects that promote cancer growth. ("The prostaglandins and related
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eicosanoids synthesized from polyunsaturated fatty acid precursors have been implicated as modulators
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of <span>tumor metastasis, host immunoregulation, tumor promotion, and cell proliferation."</span
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> Hubbard, et al., 1988.)
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</p>
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<p>
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Estrogens cause elevation of free fatty acids, and there are many interactions between the unsaturated
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fatty acids and estrogen, including their metabolism to prostaglandins, and their peroxidation.
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Estrogen's roles as free-radical promoter, DNA toxin, carcinogen, tumor promotor, modifier of tissue growth
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factors, anti-thymic hormone, etc., as well as its local effects on the prostate gland, have to be kept in
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mind. Most of the interest in studying estrogen's contributions to prostate cancer relates to the
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existence of estrogen receptors in various parts of the prostate. While that is interesting, it tends
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to distract attention from the fact that many of estrogen's most important actions don't involve the
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"receptors." A <span>direct excitatory</span> action on prostate cells, and <span
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>indirect</span> actions by way of the pituitary, pancreas, thyroid, adrenal, fatty acids,
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prostaglandins, histamine and circulation are probably essential parts of the cancerization process.
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</p>
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<p>
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The unsaturated fatty acids, but not the saturated fatty acids, free estrogen from the serum proteins that
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bind it, and increase its availability and activity in tissue cells.
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</p>
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<p>
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Thyroid supplementation, adequate animal protein, trace minerals, and vitamin A are the first things to
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consider in the prevention of prostate hypertrophy and cancer. Nutritional and endocrine support can
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be combined with rational anticancer treatments, since there is really no sharp line between different
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approaches that are aimed at achieving endocrine and immunological balance, without harming anything.
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</p>
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<p>
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Avoiding tissue atrophy is very closely related to promoting healthy regeneration. These processes
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require efficient energy production, and an appropriate balance between stimulation and resources.
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Growth hormone is sometimes recommend to correct tissue atrophy, but the evidence seems reasonably clear
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that it is a factor in the promotion of tumefaction of the prostate. The only study I have seen
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suggesting that it might be beneficial in prostatic cancer was a 14 day experiment done in female
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rats. Numerous publications suggest that blocking growth hormone is beneficial in treating prostate
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cancer<span>; </span>in future newsletters I will be discussing the evidence that growth hormone, like
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estrogen, cortisol, and unsaturated fats, tends to promote degenerative changes of aging - <a
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href="http://raypeat.com/articles/articles/growth-hormone.shtml"
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>Growth hormone: Hormone of Stress, Aging, and Death?</a>
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</p>
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<p> </p>
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<p> <span><h3>REFERENCES</h3></span></p>
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<p> </p>
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<p>
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<span>M.C. Audy, et al., "17beta-Estradiol stimulates a rapid Ca2+ influx in LNCaP human prostate cancer
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cells," Eur. J. Endocrionol.135, 367-373, 1996.</span>
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</p>
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<p>
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<span>M. S. Biskind and G. S. Biskind, "Development of tumors in the rat ovary after transplantation into
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the spleen," Proc. Soc. Exp. Biol. Med. 55, 176-179, 1944.</span>
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</p>
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<p>
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<span>J. Blaakaer, et al., "Gonadotropin-releasing hormone agonist suppression of ovarian tumorigenesis in
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mice of the W<sup>x</sup>/W<sup>v</sup> genotype," Biol. of Reprod. 53, 775-779, 1995.</span>
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</p>
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<p>
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<span>Clinton, SK Mulloy AL, Li SP, Mangian HJ, Visek WJ, J Nutr 1997 Feb;127(2):225-237 "Dietary fat and
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protein intake differ in modulation of prostate tumor growth, prolactin secretion and metabolism, and
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prostate gland prolactin binding capacity in rats." </span>
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</p>
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<p>
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<span>J. R. Drago, "The induction of Nb rat prostatic carcinomas," Anticancer Res. 4, 255-256, 1984.</span>
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</p>
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<p>
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<span>J. Geller, et al., "The effect of cyproterone acetate on adenocarcinoma of the prostate," Surg. Gynec.
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Obst. 127, 748-758, 1968.</span>
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</p>
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<p>
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<span>J. Geller, J. Fishman, and T. L. Cantor, "Effect of cyproterone acetate on clinical, endocrine and
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pathological features of benign prostatic hypertrophy," J. Steroid Biochemistry 6, 837-843, 1975.</span>
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</p>
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<p>
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<span>Ho, Shuk-mei, and M. Yu, "Selective increase in type II estrogen-binding sites in the dysplastic
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dorsolateral prostates of Noble rats," Cancer Research 53, 528-532, 1993. "...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
|
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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."</span>
|
|
</p>
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<p>
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<span>M. E. Harper, et al., "Carcinoma of the prostate: relationship of pretreatment hormone levels to
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survival," Eur. J. Cancer Clin. Oncol. 20, 477-482, 1984.</span>
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</p>
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<p>
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<span>J. M. Holland and C. Lee, "Effects of pituitary grafts on testosterone stimulated growth of rat
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prostate," Biol. Reprod. 22, 351-355, 1980.</span>
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</p>
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<p>
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<span>W. C. Hubbard, et al., "Profiles of prostaglandin biosynthesis in sixteen established cell lines
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derived from human lung, colon, prostate, and ovarian tumors," Cancer Research 48, 4770-4775,
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1988. "The prostaglandins and related eicosanoids synthesized from polyunsaturated fatty acid
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precursors have been implicated as modulators of tumor metastasis, host immunoregulation, tumor
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promotion, and cell proliferation."</span>
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</p>
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<p>
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<span>Izes JK, Zinman LN, Larsen CR, Urology 1996 May;47(5):756-759 "Regression of large pelvic desmoid
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tumor by tamoxifen and sulindac," "A 54-year-old man was evaluated for symptoms of bladder outlet
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obstruction. Evaluation revealed a 10 by 9.8-cm tumor composed of bland, fibroblastic, poorly cellular
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material adjacent to the prostate. Administration of a course of <span>antiestrogen (tamoxifen) and
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a nonsteroidal anti-inflammatory agent (sulindac) resulted in prompt relief of symptoms and a slow
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decrease in the size of the tumor</span><span> as measured by computed tomography. After 54
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months of therapy, the tumor was undetectable clinically and dramatically reduced in size as seen on
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computed tomography. Data on the natural history of desmoid tumors and the efficacy of various
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therapeutic strategies are reviewed.</span></span>
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</p>
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<p>
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<span>Jungwirth A, Schally AV, Pinski J, Halmos G, Groot K, Armatis P, Vadillo-Buenfil M., Br J Cancer
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1997;75(11):1585-1592, "Inhibition of in vivo proliferation of androgen-independent prostate cancers by
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an antagonist of growth hormone-releasing hormone."</span>
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</p>
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<p>
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<span>Kroes R; Teppema JS Development and restitution of squamous metaplasia in the calf prostate after a
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single estrogen treatment. An electron microscopic study. Mol Pathol, 1972 Jun, 16:3,
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286-301.</span>
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</p>
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<p>
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<span>Lane KE, Leav I, Ziar J, Bridges RS, Rand WM, Ho SM, Carcinogenesis 1997 Aug;18(8):1505-1510
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"Suppression of testosterone and estradiol-17beta-induced dysplasia in the dorsolateral prostate of
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Noble rats by bromocriptine." "We, and others, have previously described the histological changes that
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occur in the prostate gland of intact Noble (NBL) rats following prolonged hormonal treatment.
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Dysplasia, a pre-neoplastic lesion, develops specifically in the dorsolateral prostates (DLPs) of NBL
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rats treated for 16 weeks with a combined regimen of testosterone (T) and estradiol-17beta (E2) (T +
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E2-treated rats). </span>
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<span>Concurrent with DLP dysplasia induction, the dual hormone regimen also elicits hyperprolactinemia, in
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addition to an elevation of nuclear type II estrogen binding sites (type II EBS), no alteration in
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estrogen receptors (ER), and marked epithelial cell proliferation in the dysplastic foci.</span>
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<span> The aim of this study was to investigate whether the dual hormone action is mediated via
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E2-induced hyperprolactinemia. Bromocriptine (Br), at a dose of 4 mg/kg body wt per day, was used to
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suppress pituitary prolactin (PRL) release. Serum PRL levels were lowered from values of 341 +/- 50
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ng/ml in T + E2-treated rats to 32 +/- 10 ng/ml in Br co-treated animals. The latter values were
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comparable to those in untreated control rats. In addition, Br co-treatment effectively inhibited the
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evolution of dysplasia (six out of eight rats) </span>
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<span>and the often associated inflammation</span>
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<span> (five out of eight rats) in most animals. In contrast, Br co-treatment did not suppress the T +
|
|
E2-induced type II EBS elevation nor alter ER levels in the DLPs of these rats, when compared with T +
|
|
E2-treated rats. These data extend the many previous studies that have detailed marked influences
|
|
of </span>
|
|
<span>PRL on rat prostatic functions. However, the current study is the first to implicate PRL in prostatic
|
|
dysplasia induction in vivo.</span>
|
|
<span>"</span>
|
|
</p>
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<p>
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<span>I. Leav, et al., "Biopotentiality of response to sex hormones by the prostate of castrated or
|
|
hypophysectomized dogs: Direct effects of estrogen," Am. J. Pathol., 93, 69-92, 1978.</span>
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</p>
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<p>
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<span>H. C. Levine, et al., "Effects of the addition of estrogen to medical castration on prostatic size,
|
|
symptoms, histology and serum prostate specific antigen in 4 men with benign prostatic hypertrophy<span
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|
>," J. Urol. 146, 790-93, 1991.</span></span>
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</p>
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<p><span>Diana Lutz, The Sciences, January/February 1996.</span></p>
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<p>
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<span>W. L. McKeehan, et al., "Direct mitogenic effects of insulin, epidermal growth factor, glucocorticoid,
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cholera toxin, unknown pituitary factors and possibly prolactin,<span>but not androgen,</span><span
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> on normal rat prostate epithelial cells in serum-free, primary cell culture," Cancer Res. 44(5),
|
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1998-2010, 1984.</span></span>
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</p>
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<p>
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<span>Nevalainen MT, Valve EM, Ingleton PM, Nurmi M, Martikainen PM, Harkonen PL, J Clin Invest 1997 Feb
|
|
15;99(4):618-627 "Prolactin and prolactin receptors are expressed and functioning in human prostate."
|
|
"The highest density of prolactin receptors was detected in the secretory epithelial cells by
|
|
immunohistochemistry. Finally, we report that prolactin is locally produced in human prostate
|
|
epithelium, as evidenced by marked prolactin immunoreactivity in a significant portion of prostate
|
|
epithelial cells, with parallel expression of prolactin mRNA in human prostate. Collectively, these data
|
|
provide significant support for the existence of an autocrine/paracrine loop of prolactin in the human
|
|
prostate and may shed new light on the involvement of prolactin in the etiology and progression of
|
|
neoplastic growth of the prostate."</span>
|
|
</p>
|
|
<p>
|
|
<span>A. J. Lostroh and C. H. Li, "Stimulation of the sex accessories of hypophysectomised male rat by
|
|
non-gonadotrophin hormones of the pituitary gland," Acta endocr. Copenh. 25, 1-16, 1957.</span>
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</p>
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|
<p>
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|
<span>F. B. Merk, et al., "Multiple phenotypes of prostatic glandular cells in castrated dogs after
|
|
individual or combined treatment with androgen<span> </span><span>and estrogen,"</span><span
|
|
> Lab. Invest. 54, 42-46, 1986.</span></span>
|
|
</p>
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|
<p>
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|
<span>Pirke, K.M. and P. Doerr, "Age related changes in free plasma testosterone, dihydrotesterone, and
|
|
oestradiol," Acta endocr. Copenh. 89, 171-178, 1975</span>
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|
</p>
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<p>
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|
<span>S. Rannikko, et al., "Hormonal patterns in prostatic cancer 1. Correlation with local extent of
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|
tumour, presence of metastases and grade of differentiation," Acta endocr. Copenh. 98, 625-633,
|
|
1981.</span>
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</p>
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<p>
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<span>P. H. Rolland, et al., "Prostaglandins in human breast cancer: Evidence suggesting that an
|
|
elevated prostaglandin production is a marker of metastatic potential for neoplastic cells," J. Natl.
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|
Cancer Inst. 64, 1061-1070, 1980.</span>
|
|
</p>
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|
<p>
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|
<span>D. P. Rose, et al., "Hormone levels in prostatic fluid from healthy Finns and prostate cancer
|
|
patients," Eur. J. Cancer clin. Oncol. 20, 1317-1319, 1984.</span>
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</p>
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<p>
|
|
<span>L. M. Schuman, et al., "Epidemiologic study of prostatic cancer: Preliminary report," Cancer
|
|
Treat. Rep. 61, 181-186, 1977.</span>
|
|
</p>
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|
<p>
|
|
<span>Siiteri, P.K. and P. C. MacDonald, "Role of extraglandular estrogen in human endocrinology," In
|
|
Handbook of Physiology, section 7, Endocrinology Vol II (Eds. S. R. Geiger, et al.,) pp. 615-629,
|
|
Williams & Wilkins, Baltimore.</span>
|
|
</p>
|
|
<p>
|
|
<span>H. W. Simpson, et al., "Bimodal age-frequency distribution of epitheliosis in cancer mastectomies,
|
|
Cancer 50, 2417-2422, 1982; S. R. Wellings, et al., "Atlas of subgross pathology of the human breast
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|
with special reference to possible precancerous lesions," J. Nat. Cancer Inst. 55, 231-273, 1975; H. M.
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|
Jensen, et al., "Preneoplastic lesions in the human breast," Science, N.Y. 191, 295-297,1976.</span>
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|
</p>
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|
<p>
|
|
<span>Sugimura Y, Sakurai M, Hayashi N, Yamashita A, Kawamura J., Prostate 1994;24(1):24-32
|
|
"Age-related changes of the prostate gland in the senescence-accelerated mouse." "Wet weight and numbers
|
|
of ductal tips in ventral and dorsolateral prostate glands in senescence accelerated-prone (SA-P) mice
|
|
were significantly smaller than those of senescence accelerated-resistant (SA-R) mice, although the
|
|
changes of patterns of gross ductal morphology were virtually identical in these groups. <span>High
|
|
incidence of stromal hyperplasia with fibrosis and inflammation</span><span> was observed...."
|
|
"These data suggest that the aging process occurs heterogeneously within the prostate gland, and
|
|
that SA-P mice may be an important model for the study of age-related changes in the prostate
|
|
gland."</span></span>
|
|
</p>
|
|
<p>
|
|
<span>W. W. Tullner, "Hormonal factors in the adrenal-dependent growth of the rat ventral prostate," Nat.
|
|
Cancer Inst. Monograph 12, 211-223, 1963.</span>
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|
</p>
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|
<p>
|
|
<span>Umekita Y, Hiipakka RA, Kokontis JM, Liao S, Proc Natl Acad Sci U S A 1996 Oct
|
|
15;93(21):11802-11807 "Human prostate tumor growth in athymic mice: inhibition by androgens and
|
|
stimulation by finasteride," "When the human prostate cancer cell line, LNCaP 104-S, the growth of which
|
|
is stimulated by physiological levels of androgen, is cultured in androgen-depleted medium for > 100
|
|
passages, the cells, now called LNCaP 104-R2, are proliferatively repressed by low concentrations of
|
|
androgens. LNCaP 104-R2 cells formed tumors in castrated male athymic nude mice. <span>Testosterone
|
|
propionate (TP) treatment prevented LNCaP 104-R2 tumor growth and caused regression of established
|
|
tumors in these mice.</span><span> Such a tumor-suppressive effect was not observed with tumors
|
|
derived from LNCaP 104-S cells or androgen receptor-negative human prostate cancer PC-3 cells. 5
|
|
alpha-Dihydrotestosterone, </span><span>but not 5 beta-dihydrotesto- sterone, 17
|
|
beta-estradiol,</span><span> or medroxyprogesterone acetate, also inhibited LNCaP 104-R2 tumor
|
|
growth. Removal of TP or implantation of finasteride, a 5 alpha-reductase inhibitor, in nude mice
|
|
bearing TP implants resulted in the regrowth of LNCaP 104-R2 tumors. Within 1 week after TP
|
|
implantation, LNCaP 104-R2 tumors exhibited massive necrosis with severe hemorrhage. Three weeks
|
|
later, these tumors showed fibrosis with infiltration of chronic inflammatory cells and scattered
|
|
carcinoma cells exhibiting degeneration. TP treatment of mice with LNCaP 104-R2 tumors reduced tumor
|
|
androgen receptor and c-myc mRNA levels but increased prostate-specific antigen in serum- and
|
|
prostate-specific antigen mRNA in tumors.</span><span> Although androgen ablation has been the
|
|
standard treatment for metastatic prostate cancer for > 50 years, our study shows that androgen
|
|
supplementation therapy may be beneficial for treatment of certain types of human prostate cancer
|
|
and that the use of 5 alpha-reductase inhibitors, such as finasteride or anti-androgens, in the
|
|
general treatment of metastatic prostate cancer may require careful assessment."</span></span>
|
|
</p>
|
|
<p>
|
|
<span>A. Vermeulen, "Testicular hormonal secretion and aging in males," in Benign prostatic hyperplasia (J.
|
|
T. Grayhack, et al., eds), pp. 177-182, DHEW Publ. No. (NIH) 76-1113, 1976.</span>
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</p>
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|
<p>
|
|
<span>A. Vermeulen, et al., "Testosterone secretion and metabolism in male senescence," J. Clin. Endocr.
|
|
Metab. 34, 730-735, 1972.</span>
|
|
</p>
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|
<p>
|
|
<span>A. Vermeulen, et al., "Hormonal factors related to abnormal growth of the prostate," in Prostate
|
|
Cancer (D. S. Coffey and J. T. Issacs, eds). UICC Technical Workshop Series, Vol 48, 81-92, UICC,
|
|
Geneva.</span>
|
|
</p>
|
|
<p>
|
|
<span>S. Zuckerman and J. R. Groome, "The aetiology of benign enlargement of the prostate in the dog," J.
|
|
Pathol. Bact. 44, 113-124, 1937.</span>
|
|
</p>
|
|
<p>
|
|
<span>B. Zumoff, et al., "Abnormal levels of plasma hormones in men with prostate cancer: Evidence
|
|
toward a 'time-defense' theory," The Prostate 3, 579-588, 1982.</span>
|
|
</p>
|
|
<p>
|
|
<span>M. Wehling, "Non-genomic steroid action--take a closer look, it's not rare!" Eur. J. of Endorinol.
|
|
135, 287-288, 1996.</span>
|
|
</p>
|
|
<p>
|
|
<span>Wennbo H, Kindblom J, Isaksson OG, Tornell J., Endocrinology 1997 Oct;138(10):4410-4415. "Transgenic
|
|
mice overexpressing the prolactin gene develop dramatic enlargement of the prostate gland," "An
|
|
altered endocrine status of elderly men has been hypothesized to be important for development of
|
|
prostate hyperplasia. The present study addresses the question whether increased PRL expression is of
|
|
importance for development of prostate hyperplasia in mice. Three lines of PRL transgenic mice were
|
|
generated having serum levels of PRL of approximately 15 ng/ml, 100 ng/ml, and 250 ng/ml, respectively.
|
|
These mice developed dramatic enlargement of the prostate gland, approximately 20 times the normal
|
|
prostate weight and they had a 4- to 5-fold increased DNA content. Histologically, the prostate glands
|
|
in the transgenic mice were distended from secretion, and the amount of interstitial tissue was
|
|
increased. The levels oftestosterone and IGF-I were increased in the PRL transgenic animals. In mice
|
|
overexpressing the bovine GH gene, displaying elevated IGF-I levels, the prostate gland was slightly
|
|
larger compared with normal mice, indicating that the effect of PRL was not primarily mediated through
|
|
elevated plasma IGF-I levels. "<span>The present study suggests that PRL is an important factor in the
|
|
development of prostate hyperplasia</span><span> acting directly on the prostate gland or via
|
|
increased plasma levels of testosterone."</span></span>
|
|
</p>
|
|
<p> </p>
|
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© Ray Peat Ph.D. 2013. All Rights Reserved. www.RayPeat.com
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