Library:Prostate Cancer

A Ray Peat newsletter, 2013-07-11.

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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. Physicians 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.

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, as it rises in stress, disease, malnutrition, and hypothyroidism (which are also associated with old age). Estrogen is produced in fat 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. The high probability of “epitheliosis” in association with cancer was seen in women in their early 40s, and in women over 60. (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) 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. 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, and ACTH with prolactin stimulate prostate growth. Prolactin—which is increased by estrogen—stimulates growth of the rat's lateral prostate, and stimulates the growth of human prostate epithelial cells in vitro. 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. Also, a high ratio of testosterone to estradiol or of testosterone to prolactin corresponded to better survival 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. 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. 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.”

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. Contrary to the stereotyped ideas, there are suggestions that supplementary androgens could control prostate cancer, and that antagonists to prolactin and estrogen might be appropriately used in hormonal therapy.

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 consistently 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.”

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.”)

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.