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A List of Signs and Symptoms That
Respond to Progesterone Therapy
This section has been removed at the request of the FDA.
In order to read this portion of Dr. Peat's book you must obtain a copy from the
library or purchase a copy of your own. (January 18, 2001).
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"THE PROGESTERONE DECEPTIONS
In the 1930s, it was demonstrated that estrogen, even in small doses, produced
abortions, and that when it is given early enough, even a very small dose will prevent
implantation of the fertilized embryo. Progesterone was known, by the early 1940s, to
protect against the many toxic effects of estrogen, including abortion, but it was also
known as nature's contraceptive, since it prevents pregnancy without harmful side-effects,
by different mechanisms, including prevention of sperm entry into the uterus. That is,
progesterone prevents the miscarriages which result from excess estrogen,(1,2)
but if used before intercourse, it prevents conception, and thus is a true contraceptive,
while estrogen is an abortifacient, not a contraceptive.
In the 1950s, there was a search for chemicals which would prevent ovulation. According
to Carl Djerassi,(3) drug companies were extremely reluctant
to risk a religious backlash against their other products, and so hesitated to market
contraceptives. Obviously, the induction of monthly abortions would have been even harder
to sell.
According to Djerassi,(3) "Until the middle 1940s it
was assumed that progesterone's biological activity was extremely specific and that almost
any alteration of the molecule would diminish or abolish its activity." This would
obviously discourage interest from the drug companies, who could patent a substance which
they had chemically modified, but could not patent a simple natural substance. However,
many substances--even non-steroidal chemicals--turned out to have estrogenic action.(4)
By 1942, Hans Selye had demonstrated that natural steroids retain their activity when
administered orally. But every drug company with a steroid patent had an obvious interest
in having the public believe that there is a reason that the natural steroids cannot be
conveniently used. The doctrine that natural steroids are destroyed by stomach
acid appeared, was promoted, and was accepted. In the manufacture of progesterone, the
precursor steroid is boiled in hydrochloric acid to free it from its glucose residue; no
one seriously believed that stomach acid hurts progesterone, except the public.
The real issue is solubility. Hydrocortisone is reasonably soluble in water, but
progesterone is extremely insoluble in water, and, though it is vastly more soluble in
vegetable oil than in water, it does not stay in solution at room temperature even at the
low concentration of I part in 1000 parts of vegetable oil.
When people speak of an allergy to progesterone (or even to penicillin) they generally
are not aware of the presence of a very toxic solvent.(5) A
few years ago, progesterone was often sold dissolved in benzyl benzoate; the Physician's
Desk Reference warned of possible allergic reaction to progesterone. Now, it is supposedly
sold dissolved in vegetable oil, with about 10% benzyl alcohol as a bacteriostatic agent.
Bacteriostatic water contains 0.9% to 1.9% benzyl - alcohol, and can irreversibly harm
nerves.(6,7) Awareness of benzyl alcohol's toxicity goes
back to 1918 at least; it was proposed as an effective insecticide, and was found to be
toxic to many animal systems. The safe systemic dose(7) is
exceeded with an injection of 150 mg. of progesterone, yet the local concentration is far
higher. It can cause a severe reaction even when used at a lower concentration, in
bacteriostatic water.(5)
Other alcohols, including ethanol, have been used as solvents, but since they (ethanol
even more than benzyl alcohol) have an affinity for water, the solution decomposes in
contact with tissue water. In spite of the toxicity of the vehicle, several beneficial
effects can be obtained with injected progesterone, in serious conditions such as epilepsy
or cancer of the breast or uterus. Many researchers have commented on the very obvious
difficulty of giving very large amounts of progesterone.(8)
My comparisons of oral progesterone in tocopherol with other forms and methods of
administration show a roughly similar efficiency for oral and injected progesterone, and
about 1/20 the effect for suppositories. Crystals of progesterone are visible in the
suppositories I have examined, and this material is obviously wasted.
An old theory of vitamin E's mechanism of action in improving fertility was that it
spares progesterone.(9) It is established that some of the
effects of vitamin E and progesterone are similar; for example, both prevent oxygen waste
and appear to improve mitochondrial coupling of phosphorylation with respiration. I
suspected that if they actually both work at the same mitochondrial site, then they must
have a high mutual solubility. Knowing the long-standing problem of administering large
doses of progesterone without a toxic solvent, I applied for and was granted a patent for
the composition of progesterone in tocopherol. One of my reasons for publishing in the
form of patents is that I have had many years of experience in having my discoveries taken
up by others without acknowledgment. My dissertation research, which established that an
estrogen excess kills the embryo by suffocation, and that progesterone protects the embryo
by promoting the delivery of both oxygen and glucose, didn't strike a responsive
chord in the journals which are heavily influenced by funds from the drug industry.
According to a consultant for a major medical journal, the idea "... of dissolving
progesterone, a fat soluble steroid hormone, in vitamin E which is then incorporated into
chylormicrons absorbed via the lymphatics, and thus avoids the liver on the so called
first pass... ...is so simple it is amazing that the pharmaceutical companies have
not jumped on it "
In the powder form, direct and intimate contact with a mucous membrane allows lipid
phase to lipid phase transfer of progesterone molecules. Instead of by-passing the liver,
much of the progesterone is picked up in the portal circulation, where a major part of it
is glucuronidated, and made water soluble for prompt -excretion. Since this glucuronide
form cross-reacts to some extent with ordinary progesterone in the assay process, and
since 50% of the ordinary free progesteronee is carried inside the red blood cells,(10,
11) and 50% is associated with proteins in the plasma, while the
golucuronide hardly enters the red blood cells at all, it is better to judge by clinical
efficacy when comparing different oral forms. My comparisons show several times higher
potency in the tocopherol composition than in powder form.
Since progesterone's use as a drug antedates the 1938 law requiring special federal
approval, its legal status is similar to that of thyroid hormone. Unfortunately for both
thyroid and progesterone, there is a tendency to cut corners for the sake of a bigger
profit margin.
For example, steroid acetates are generally a little cheaper than the simple natural
steroid. Some people assume that an acetate or butyrate can be substituted for the steroid
itself This can cause dangerous reactions.
Medroxyprogesterone acetate is considered a progestin (though it is not supportive of
gestation), because it modifies the uterus in approximately the way progesterone does, but
it is luteolytic, and lowers the ovaries' production of progesterone while progesterone
itself has a positive effect on the corpus luteum, stimulating progesterone synthesis.
Defining "progestin" in a narrow way allows many synthentics to be sold as
progestagens, though some of them are strongly estrogenic, allowing them to function as
contraceptives--it is odd that contraceptives and agents which suppress progesterone
synthesis should be officially called "supporters of pregnancy," It is probably
partly the acetate group in the medroxyprogesterone acetate molecule which makes it bind
firmly to receptors, yet causes it to block the enzymes which would normally be involved
in progesterone metabolism. (I think testosterone, even, might be a safer progestin than
medroxyprogesterone acetate.) Pregnenolone acetate similarly blocks the enzymes
which normally metabolize pregnenolone.(12) In
aspirin, it has been found that It is the acetyl group which (by a free radical action)
blocks an enzyme involved in prostaglandin synthesis.
If the category called "progestogens" or "progestins" is to be
defined on the basis of a single tissue reaction, then it is possible to classify
progesterone with the toxic synthetic substances, but then it becomes highly deceptive to
imply that progesterone is just a progestin, or that it has any of the other properties of
the toxic synthetics, but this continues to be done. The warnings about "progestins
causing birth defects," for example, cause epileptic women to use conventional
anti-seizure drugs (all of which cause birth defects) during pregnancy, and to avoid
natural progesterone, which generally could control their seizures. Thus, a false message
attached to progesterone creates precisely the harm it claims to want to prevent. In my
communications with the regulatory agencies, I have concluded that their attempts to
deceive are too blatant to ascribe to incompetency. Whether it's the Forest Service or the
FDA, the principle is the same: the regulatory agencies have been captured by the
regulated industries.
Another place to cut costs is in the tocopherol. Tocopherol acetate does have vitamin E
activity, but since it is only about half as efficiently absorbed as the simple
tocopherol,(13) it is a mistake to save a few dollars an
ounce, at the expense of losing half of the therapeutic effect. People who have compared
natural progesterone in natural tocopherols with other compositions have insisted
that the other compositions must not contain progesterone.
The taste of natural vitamin E is stronger than that of the synthetic forms, but since
the mixture is absorbed by any tissue it contacts, including various parts of the bowel,
it can be taken in a capsule. If a small amount of olive oil is used with it, absorption
through the skin is very rapid. Many women use it vaginally, spread onto a diaphragm, to
hold it in contact with the membranes. The efficiency of absorption by all routes is so
high that patients should be warned against its anesthetic effect, until their dosage
requirement is known approximately. Some physicians prefer concentrations higher than 10%,
but the risk of accidental drunkenness or anesthesia is higher with the stronger
solutions.
It is an indication of the tocopherol solution's high availability that medical
researchers such as Roy Hertz,(8) who thought they were
administering maximal doses by combining Injections with suppositories, never mentioned
the problem of an anesthetic effect from an overdose. Similarly, it is evidence of the
extremely poor availabilitv of the micropulverized progesterone that the researchers have
administered hundreds of milligrams per day, without mentioning the symptoms of an
overdose. Because of the. difficulties involved in scientifically studying the clinical
effectiveness of various formulations, I think the most practical way of evaluating the
effectiveness of different progesterone formulations is to measure the amount extractable
from the fed blood cells, a few hours after the peak serum level has been reached. This
will reasonably reflect the amounts reaching brain cells, adrenal glands, and the various
other cells on which progesterone has its therapeutic action.
REFERENCES
I . A. A. Gidley-Baird, et aL, Failure of implantation in human in vitro fertilization
and embryo transfer patients: the effects of altered progesterone/estrogen ratios in
humans and mice, Fertility and sterility 45(1): 69-74. 1986.
2. J. L. Yovich, et al., Early luteal serum progesterone concentrations are higher in
pregnancy cycles, Fertility and Sterility 44(l): 185-189, 1985.
3 . C. Djerassi, The making of the pill. Science 84: 127-129, 1984.
4. R. Kehl, Les Glaudes Endocrines Presses Universitaires de France, Paris, 1952
5. J. A. Grant, et al., New England Journal of Medicine 306(2): 108, 1982, Unsuspected
benzyl alcohol hypersensitivity.
6.T.E. Feasby. et al., Neurotoxicity of bacteriostatic water, New England Journal of
Medicine 308(6): 966-7, 1983,
7. F. T. Kimura, et al., Parenteral toxicity, studies with benzyl alcobol, Toxicol Appl
Pharmacol I8: 60-68, 1971.
8 A. White editor, Symposium on Steroids In Experimental and clinical Practice. The
Blakiston Co., NY., 1951, p. 401.
9. A. Fraschini, 11 Metodo Biologico di Rinvigorimento, Edizioni Minerva Medica, Milan,
1954.
10 F.- Mulder, et al., Metabolism of free and conjugated steroids by intact and
haemolysed mammalian erythrocytes, Biochim. Biophys. Acta 263: 290-297, 1972.
11. M. Holzbauer, The association of steroids with blood cells in vivo J. of Steroid
Biochemistry 3: 579-592 1972.
12. S. Lieberman, et al., A heuristic proposal for understanding steroidogenic
processes, Endocrine Reviews 5(1): 128-148, 1984.
13. L. J. Machlin and E. Gabriel, Kinetics of tissue alpha-tocopherol uptake and
depletion, following administration of high levels of vitamin E, p. 48 in Annals of the
N.Y. Academy of Science 393, B. Lubin and L. J. Machlin, editors, New York. 1982."
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